The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions

Huimin Yuan , Ruochen Xu , Senlin Li , Mengzhu Zheng , Qingyi Tong , Ming Xiang , Yonghui Zhang

MedComm ›› 2025, Vol. 6 ›› Issue (3) : e70121

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MedComm ›› 2025, Vol. 6 ›› Issue (3) : e70121 DOI: 10.1002/mco2.70121
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The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions

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Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, predominantly associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These infections drive persistent liver inflammation, culminating in cellular dysregulation, fibrosis, and cancer. Despite advancements in targeted therapies, drug resistance and the lack of reliable biomarkers for patient stratification still terribly hinder the treatment of viral HCC. To this end, the review delves into the intricate mechanisms underlying the malignant transformation of viral hepatitis to HCC, including viral integration, genomic instability, epigenetic modifications, oxidative stress, gut microbiota dysbiosis, chronic inflammation, immune escape, and abnormal signaling pathways, highlighting their complex interactions and synergies. Cutting-edge preclinical and clinical advancements in HCC management, including lifestyle modifications, drug therapies, immunotherapies, gene-based approaches, and innovative treatments, are further investigated, with particular priority given to their therapeutic potential and future applications in overcoming current limitations. By synthesizing recent scientific and clinical insights, this review aims to deepen the understanding of HCC pathogenesis in the context of chronic viral hepatitis, paving the way for novel therapeutic targets and personalized treatment strategies, ultimately improving patient outcomes.

Keywords

hepatocellular carcinoma / molecular mechanism / malignant transformation / therapeutic intervention / viral hepatitis

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Huimin Yuan, Ruochen Xu, Senlin Li, Mengzhu Zheng, Qingyi Tong, Ming Xiang, Yonghui Zhang. The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions. MedComm, 2025, 6(3): e70121 DOI:10.1002/mco2.70121

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References

[1]

A. G. Singal, F. Kanwal, and J. M. Llovet, “Global Trends in Hepatocellular Carcinoma Epidemiology: Implications for Screening, Prevention and Therapy,” Nature Reviews Clinical Oncology 20, no. 12 (2023): 864–884.

[2]

F. Bray, M. Laversanne, H. Sung, et al., “Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” CA: A Cancer Journal for Clinicians 74, no. 3 (2024): 229–263.

[3]

X. Luo, X. He, X. Zhang, et al., “Hepatocellular Carcinoma: Signaling Pathways, Targeted Therapy, and Immunotherapy,” MedComm 5, no. 2 (2024): e474.

[4]

M. R. Toh, E. Y. T. Wong, S. H. Wong, et al., “Global Epidemiology and Genetics of Hepatocellular Carcinoma,” Gastroenterology 164, no. 5 (2023): 766–782.

[5]

J. M. Llovet, R. Pinyol, R. K. Kelley, et al., “Molecular Pathogenesis and Systemic Therapies for Hepatocellular Carcinoma,” Nature Cancer 3, no. 4 (2022): 386–401.

[6]

K. J. Wangensteen and K. M. Chang, “Multiple Roles for Hepatitis B and C Viruses and the Host in the Development of Hepatocellular Carcinoma,” Hepatology 73 no. Suppl 1 (2021): 27–37.

[7]

C. Peneau, S. Imbeaud, T. La Bella, et al., “Hepatitis B Virus Integrations Promote Local and Distant Oncogenic Driver Alterations in Hepatocellular Carcinoma,” Gut 71, no. 3 (2022): 616–626.

[8]

E. Sivasudhan, N. Blake, Z. Lu, J. Meng, and R. Rong, “Hepatitis B Viral Protein HBx and the Molecular Mechanisms Modulating the Hallmarks of Hepatocellular Carcinoma: A Comprehensive Review,” Cells 11, no. 4 (2022): 741.

[9]

L. Jia, Y. Gao, Y. He, J. D. Hooper, and P. Yang, “HBV Induced Hepatocellular Carcinoma and Related Potential Immunotherapy,” Pharmacological Research 159 (2020): 104992.

[10]

T. G Heredia-Torres, A. R Rincon-Sanchez, S. A. Lozano-Sepulveda, et al., “Unraveling the Molecular Mechanisms Involved in HCV-Induced Carcinogenesis,” Viruses. 14, no. 12 (2022): 2762.

[11]

A. Virzi, A. A. Roca Suarez, T. F. Baumert, and J. Lupberger, “Rewiring Host Signaling: Hepatitis C Virus in Liver Pathogenesis,” Cold Spring Harbor Perspectives in Medicine 10, no. 1 (2020): a037366.

[12]

X. Zhang, C. Li, T. Wen, et al., “The Different Effects of Nucleotide and Nucleoside Analogues on the Prognosis of HBV-Related HCC after Curative Resection,” Journal of Gastrointestinal Surgery 25, no. 6 (2021): 1419–1429.

[13]

D. Q. Huang, A. Tran, M. L. Yeh, et al., “Antiviral Therapy Substantially Reduces HCC Risk in Patients With Chronic hepatitis B Infection in the Indeterminate Phase,” Hepatology 78, no. 5 (2023): 1558–1568.

[14]

G. N. Ioannou, P. K. Green, and K. Berry, “HCV Eradication Induced by Direct-acting Antiviral Agents Reduces the Risk of Hepatocellular Carcinoma,” Journal of Hepatology (2017).

[15]

I. Mikolasevic, T. F. Kanizaj, D. Bozic, et al., “Metabolism of Direct-acting Antiviral Agents (DAAs) in Hepatitis C Therapy: A Review of the Literature,” Current Drug Metabolism 22, no. 2 (2021): 89–98.

[16]

V. Guardigni, A. Toschi, L. Badia, et al., “Patients With HIV and Cirrhosis: The Risk for Hepatocellular Carcinoma After Direct-acting Antivirals for hepatitis C Virus,” Aids 35, no. 12 (2021): 1967–1972.

[17]

R. Deng, S. Liu, S. Shen, H. Guo, and J. Sun, “Circulating HBV RNA: From Biology to Clinical Applications,” Hepatology 76, no. 5 (2022): 1520–1530.

[18]

A. Kostyusheva, S. Brezgin, D. Glebe, D. Kostyushev, and V. Chulanov, “Host-cell Interactions in HBV Infection and Pathogenesis: The Emerging Role of m6A Modification,” Emerging Microbes & Infections 10, no. 1 (2021): 2264–2275.

[19]

N. R. Montanari, R. Ramirez, A. Aggarwal, et al., “Multi-parametric Analysis of human Livers Reveals Variation in Intrahepatic Inflammation Across Phases of Chronic hepatitis B Infection,” Journal of Hepatology 77, no. 2 (2022): 332–343.

[20]

M. Nassal, “HBV cccDNA: Viral Persistence Reservoir and Key Obstacle for a Cure of Chronic hepatitis B,” Gut 64, no. 12 (2015): 1972–1984.

[21]

L. Selzer and A. Zlotnick, “Assembly and Release of Hepatitis B Virus,” Cold Spring Harbor Perspectives in Medicine 5, no. 12 (2015): a021394.

[22]

M. F. Yuen, D. S. Chen, G. M. Dusheiko, et al., “Hepatitis B Virus Infection,” Nature Reviews Disease Primers 4 (2018): 18035.

[23]

L. Wei and A. Ploss, “Mechanism of Hepatitis B Virus cccDNA Formation,” Viruses. 13, no. 8 (2021): 1463.

[24]

S. Tong and P. Revill, “Overview of hepatitis B Viral Replication and Genetic Variability,” Journal of Hepatology 64 no. Suppl 1 (2016): S4–S16.

[25]

T. Tu, M. A. Budzinska, N. A. Shackel, and S. Urban, “HBV DNA Integration: Molecular Mechanisms and Clinical Implications,” Viruses. 9, no. 4 (2017): 75.

[26]

S. H. Wang, S. H. Yeh, and P. J. Chen, “Unique Features of Hepatitis B Virus-Related Hepatocellular Carcinoma in Pathogenesis and Clinical Significance,” Cancers (Basel) 13, no. 10 (2021): 2454.

[27]

J. Lucifora, S. Arzberger, D. Durantel, et al., “Hepatitis B Virus X Protein Is Essential to Initiate and Maintain Virus Replication After Infection,” Journal of Hepatology 55, no. 5 (2011): 996–1003.

[28]

R. Bartenschlager and H. Schaller, “Hepadnaviral Assembly Is Initiated by Polymerase Binding to the Encapsidation Signal in the Viral RNA Genome,” Embo Journal 11, no. 9 (1992): 3413–3420.

[29]

R. Salpini, S. D’Anna, L. Benedetti, et al., “Hepatitis B Virus DNA Integration as a Novel Biomarker of hepatitis B Virus-mediated Pathogenetic Properties and a Barrier to the Current Strategies for hepatitis B Virus Cure,” Frontiers in Microbiology 13 (2022): 972687.

[30]

R. Bartenschlager, V. Lohmann, and F. Penin, “The Molecular and Structural Basis of Advanced Antiviral Therapy for hepatitis C Virus Infection,” Nature Reviews Microbiology 11, no. 7 (2013): 482–496.

[31]

W. X. Bian, Y. Xie, X. N. Wang, et al., “Binding of Cellular Nucleolin With the Viral Core RNA G-quadruplex Structure Suppresses HCV Replication,” Nucleic Acids Research 47, no. 1 (2019): 56–68.

[32]

K. Tabata, C. J. Neufeldt, and R. Bartenschlager, “Hepatitis C Virus Replication,” Cold Spring Harbor Perspectives in Medicine 10, no. 3 (2020): a037093.

[33]

M. C. Metcalf, B. M. Janus, R. Yin, et al., “Structure of Engineered hepatitis C Virus E1E2 Ectodomain in Complex With Neutralizing Antibodies,” Nature Communications 14, no. 1 (2023): 3980.

[34]

K. H. Wrighton, “Structure of the HCV Glycoprotein,” Nature Structural & Molecular Biology 29, no. 12 (2022): 1147.

[35]

N. Alazard-Dany, S. Denolly, B. Boson, and F. L. Cosset, “Overview of HCV Life Cycle With a Special Focus on Current and Possible Future Antiviral Targets,” Viruses 11, no. 1 (2019): 30.

[36]

H. Bley, A. Schobel, and E. Herker, “Whole Lotta Lipids-From HCV RNA Replication to the Mature Viral Particle,” International Journal of Molecular Sciences 21, no. 8 (2020): 2888.

[37]

K. Avula, B. Singh, S. Samantaray, and G. H. Syed, “The Early Secretory Pathway Is Crucial for Multiple Aspects of the Hepatitis C Virus Life Cycle,” Journal of Virology 97, no. 7 (2023): e0018023.

[38]

H. C. Li, C. H. Yang, and S. Y. Lo, “Hepatitis C Viral Replication Complex,” Viruses 13, no. 3 (2021): 520.

[39]

S. Duponchel, L. Monnier, J. Molle, et al., “Hepatitis C Virus Replication Requires Integrity of Mitochondria-associated ER Membranes,” JHEP Reports 5, no. 3 (2023): 100647.

[40]

H. Rumgay, J. Ferlay, C. de Martel, et al., “Global, Regional and National Burden of Primary Liver Cancer by Subtype,” European Journal of Cancer 161 (2022): 108–118.

[41]

Y. C. Hsu, D. Q. Huang, and M. H. Nguyen, “Global Burden of hepatitis B Virus: Current Status, Missed Opportunities and a Call for Action,” Nature Reviews Gastroenterology & Hepatology 20, no. 8 (2023): 524–537.

[42]

J. D. Yang, P. Hainaut, G. J. Gores, A. Amadou, A. Plymoth, and L. R. Roberts, “A Global View of Hepatocellular Carcinoma: Trends, Risk, Prevention and Management,” Nature Reviews Gastroenterology & Hepatology 16, no. 10 (2019): 589–604.

[43]

L. A. Patmore, K. M. A. van Eekhout, M. Buti, et al., “Hepatocellular Carcinoma Risk in sub-Saharan African and Afro-Surinamese Individuals With Chronic hepatitis B Living in Europe,” Journal of Hepatology 80, no. 2 (2024): 243–250.

[44]

B. Jin, S. Du, and H. Yang, “HBsAg Seroclearance Reduces the Risk of Late Recurrence in HBV-related HCC,” Journal of Hepatology 77, no. 5 (2022): 1469–1470.

[45]

R. Huang, J. Liu, J. Wang, J. Li, and C. Wu, “Letter to the Editor: Is HBV Genotype Strongly Associated With HCC Risk in Patients With Chronic hepatitis B?,” Hepatology 75, no. 1 (2022): 233–234.

[46]

M. Khan, S. Khan, M. F. Gondal, et al., “Genetic Diversity in Enhancer II Region of HBV Genotype D and Its Association With Advanced Liver Diseases,” PLoS ONE 17, no. 1 (2022): e0261721.

[47]

C. Polaris Observatory, “Global Prevalence, Cascade of Care, and Prophylaxis Coverage of hepatitis B in 2022: A Modelling Study,” Lancet Gastroenterol Hepatol 8, no. 10 (2023): 879–907.

[48]

X. Mao, K. S. Cheung, C. Peng, et al., “Steatosis, HBV-related HCC, Cirrhosis, and HBsAg Seroclearance: A Systematic Review and Meta-analysis,” Hepatology 77, no. 5 (2023): 1735–1745.

[49]

E. Sagnelli, M. Macera, A. Russo, N. Coppola, and C. Sagnelli, “Epidemiological and Etiological Variations in Hepatocellular Carcinoma,” Infection 48, no. 1 (2020): 7–17.

[50]

M. Cornberg, A. S. Lok, N. A. Terrault, and F. Zoulim, Faculty E-AHTEC, “Guidance for Design and Endpoints of Clinical Trials in Chronic hepatitis B—Report From the 2019 EASL-AASLD HBV Treatment Endpoints Conference(double dagger),” Journal of Hepatology 72, no. 3 (2020): 539–557.

[51]

Panel A-IHG. Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clinical Infectious Diseases 2018; 67(10): 1477–1492.

[52]

Polaris Observatory HCVC. Global Change in hepatitis C Virus Prevalence and Cascade of Care Between 2015 and 2020: A Modelling Study. Lancet Gastroenterol Hepatol 2022; 7(5): 396–415.

[53]

E. Gower, C. Estes, S. Blach, K. Razavi-Shearer, and H. Razavi, “Global Epidemiology and Genotype Distribution of the hepatitis C Virus Infection,” Journal of Hepatology 61 no. Suppl 1 (2014): S45–S57.

[54]

A. J. Freeman, G. J. Dore, M. G. Law, et al., “Estimating Progression to Cirrhosis in Chronic hepatitis C Virus Infection,” Hepatology 34, no. 4 Pt 1 (2001): 809–816.

[55]

F. Kanwal, J. R. Kramer, J. Ilyas, Z. Duan, and H. B. El-Serag, “HCV Genotype 3 Is Associated With an Increased Risk of Cirrhosis and Hepatocellular Cancer in a National Sample of U.S. Veterans With HCV,” Hepatology 60, no. 1 (2014): 98–105.

[56]

C. Stasi, C. Silvestri, and F. Voller, “Update on Hepatitis C Epidemiology: Unaware and Untreated Infected Population Could Be the Key to Elimination,” SN Comprehensive Clinical Medicine 2, no. 12 (2020): 2808–2815.

[57]

J. A. Marrero, L. M. Kulik, C. B. Sirlin, et al., “Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases,” Hepatology 68, no. 2 (2018): 723–750.

[58]

S. H. Yeh, C. L. Li, Y. Y. Lin, et al., “Hepatitis B Virus DNA Integration Drives Carcinogenesis and Provides a New Biomarker for HBV-related HCC,” Cellular and Molecular Gastroenterology and Hepatology 15, no. 4 (2023): 921–929.

[59]

T. Pollicino and G. Caminiti, “HBV-Integration Studies in the Clinic: Role in the Natural History of Infection,” Viruses 13, no. 3 (2021): 368.

[60]

H. Ren, X. Chen, J. Wang, et al., “Temporal and Structural Patterns of hepatitis B Virus Integrations in Hepatocellular Carcinoma,” Journal of Medical Virology 95, no. 10 (2023): e29187.

[61]

X. Lyu, K. M. Sze, J. M. Lee, et al., “Disparity Landscapes of Viral-induced Structural Variations in HCC: Mechanistic Characterization and Functional Implications,” Hepatology (2024).

[62]

J. W. Jang, H. S. Kim, J. S. Kim, et al., “Distinct Patterns of HBV Integration and TERT Alterations Between in Tumor and Non-Tumor Tissue in Patients With Hepatocellular Carcinoma,” International Journal of Molecular Sciences 22, no. 13 (2021): 7056.

[63]

Z. Qian, J. Liang, R. Huang, et al., “HBV Integrations Reshaping Genomic Structures Promote Hepatocellular Carcinoma,” Gut 73, no. 7 (2024): 1169–1182.

[64]

C. K. Y Ng, E. Dazert, T. Boldanova, et al., “Integrative Proteogenomic Characterization of Hepatocellular Carcinoma Across Etiologies and Stages,” Nature Communications 13, no. 1 (2022): 2436.

[65]

K. Zhao, A. Liu, and Y. Xia, “Insights Into Hepatitis B Virus DNA Integration-55 Years After Virus Discovery,” Innovation (Camb) 1, no. 2 (2020): 100034.

[66]

M. F. Yuen, D. K. Wong, J. Fung, et al., “HBsAg Seroclearance in Chronic hepatitis B in Asian Patients: Replicative Level and Risk of Hepatocellular Carcinoma,” Gastroenterology 135, no. 4 (2008): 1192–1199.

[67]

P. An, J. Xu, Y. Yu, and C. A. Winkler, “Host and Viral Genetic Variation in HBV-Related Hepatocellular Carcinoma,” Frontiers in Genetics 9 (2018): 261.

[68]

A. Decorsiere, H. Mueller, P. C. van Breugel, et al., “Hepatitis B Virus X Protein Identifies the Smc5/6 Complex as a Host Restriction Factor,” Nature 531, no. 7594 (2016): 386–389.

[69]

W. A Rios-Ocampo, M. C. Navas, K. N. Faber, T. Daemen, and H. Moshage, “The Cellular Stress Response in hepatitis C Virus Infection: A Balancing Act to Promote Viral Persistence and Host Cell Survival,” Virus Research 263 (2019): 1–8.

[70]

S. Horiike, S. Kawanishi, M. Kaito, et al., “Accumulation of 8-nitroguanine in the Liver of Patients With Chronic hepatitis C,” Journal of Hepatology 43, no. 3 (2005): 403–410.

[71]

T. Chida, S. Watanabe, K. Ohta, et al., “Impact of Amino Acid Substitutions in hepatitis C Virus Core Region on the Severe Oxidative Stress,” Free Radical Biology and Medicine 212 (2024): 199–206.

[72]

Y. L. Chen, Y. M. Jeng, C. N. Chang, et al., “TERT Promoter Mutation in Resectable Hepatocellular Carcinomas: A Strong Association With hepatitis C Infection and Absence of hepatitis B Infection,” International Journal of Surgery 12, no. 7 (2014): 659–665.

[73]

M. M. Hassan, D. Li, Y. Han, et al., “Genome-wide Association Study Identifies High-impact Susceptibility Loci for HCC in North America,” Hepatology 80, no. 1 (2024): 87–101.

[74]

A. Elyamany, R. Ghazala, O. Fayed, Y. Hamed, and A. El-Shendidi, “Mitochondrial DNA Copy Number in Hepatitis C Virus-related Chronic Liver Disease: Impact of Direct-acting Antiviral Therapy,” Scientific Reports 13, no. 1 (2023): 18330.

[75]

M. Gu, B. Ren, Y. Fang, et al., “Epigenetic Regulation in Cancer,” MedComm 5, no. 2 (2024): e495.

[76]

A. L. Mattei, N. Bailly, and A. Meissner, “DNA Methylation: A Historical Perspective,” Trends in Genetics 38, no. 7 (2022): 676–707.

[77]

X. Qiu, L. Zhang, S. Lu, et al., “Upregulation of DNMT1 Mediated by HBx Suppresses RASSF1A Expression Independent of DNA Methylation,” Oncology Reports 31, no. 1 (2014): 202–208.

[78]

I. Y. Park, B. H. Sohn, E. Yu, et al., “Aberrant Epigenetic Modifications in Hepatocarcinogenesis Induced by hepatitis B Virus X Protein,” Gastroenterology 132, no. 4 (2007): 1476–1494.

[79]

L. Rongrui, H. Na, L. Zongfang, J. Fanpu, and J. Shiwen, “Epigenetic Mechanism Involved in the HBV/HCV-related Hepatocellular Carcinoma Tumorigenesis,” Current Pharmaceutical Design 20, no. 11 (2014): 1715–1725.

[80]

S. Liu, S. S. Koh, and C. G. Lee, “Hepatitis B Virus X Protein and Hepatocarcinogenesis,” International Journal of Molecular Sciences 17, no. 6 (2016): 940.

[81]

G. Song, X. Zhu, Z. Xuan, et al., “Hypermethylation of GNA14 and Its Tumor-suppressive Role in hepatitis B Virus-related Hepatocellular Carcinoma,” Theranostics 11, no. 5 (2021): 2318–2333.

[82]

C. Zhang, W. Zhang, Z. Yuan, et al., “Contribution of DNA Methylation to the Risk of hepatitis C Virus-associated Hepatocellular Carcinoma: A Meta-analysis,” Pathology, Research and Practice 238 (2022): 154136.

[83]

M. El-Bendary, D. Nour, M. Arafa, and M. Neamatallah, “Methylation of Tumour Suppressor Genes RUNX3, RASSF1A and E-Cadherin in HCV-related Liver Cirrhosis and Hepatocellular Carcinoma,” British Journal of Biomedical Science 77, no. 1 (2020): 35–40.

[84]

J. Zhang, H. Li, J. P. Yu, S. E. Wang, and X. B. Ren, “Role of SOCS1 in Tumor Progression and Therapeutic Application,” International Journal of Cancer 130, no. 9 (2012): 1971–1980.

[85]

M. Liu, L. Du, X. Cheng, et al., “CpG Island Methylation of Suppressor of Cytokine Signaling-1 Gene Induced by HCV Is Associated with HCV-Related Hepatocellular Carcinoma,” Frontiers in Microbiology 13 (2022): 679593.

[86]

U. Zakir, N. N. Siddiqui, F. U. Naqvi, and R. Khan, “Aberrant STAT1 Methylation as a Non-invasive Biomarker in Blood of HCV Induced Hepatocellular Carcinoma,” Cancer Biomark 34, no. 1 (2022): 95–103.

[87]

D. Sun, X. Gan, L. Liu, et al., “DNA Hypermethylation Modification Promotes the Development of Hepatocellular Carcinoma by Depressing the Tumor Suppressor Gene ZNF334,” Cell Death & Disease 13, no. 5 (2022): 446.

[88]

L. Xiang, L. M. Chen, Y. J. Zhai, et al., “Hypermethylation of Secreted Frizzled Related Protein 2 Gene Promoter Serves as a Noninvasive Biomarker for HBV-associated Hepatocellular Carcinoma,” Life Sciences 270 (2021): 119061.

[89]

F. H. Duong, M. Filipowicz, M. Tripodi, N. La Monica, and M. H. Heim, “Hepatitis C Virus Inhibits Interferon Signaling Through Up-regulation of Protein Phosphatase 2A,” Gastroenterology 126, no. 1 (2004): 263–277.

[90]

Y. Qu, N. Gao, S. Zhang, et al., “Role of N6-methyladenosine RNA Modification in Cancer,” MedComm 5, no. 9 (2024): e715.

[91]

S. Liu, J. Li, M. Qiu, et al., “Genetic Variants of m(6)A Modification Genes Are Associated With Survival of HBV-related Hepatocellular Carcinoma,” Journal of Cellular and Molecular Medicine 28, no. 16 (2024): e18517.

[92]

G. W. Kim and A. Siddiqui, “Hepatitis B Virus X Protein Recruits Methyltransferases to Affect Cotranscriptional N6-methyladenosine Modification of Viral/Host RNAs,” PNAS 118, no. 3 (2021): e2019455118.

[93]

G. W. Kim and A. Siddiqui, “Hepatitis B Virus X Protein Expression Is Tightly Regulated by N6-Methyladenosine Modification of Its mRNA,” Journal of Virology 96, no. 4 (2022): e0165521.

[94]

Y. Yang, Y. Yan, J. Yin, et al., “O-GlcNAcylation of YTHDF2 Promotes HBV-related Hepatocellular Carcinoma Progression in an N(6)-methyladenosine-dependent Manner,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 63.

[95]

S. Qu, L. Jin, H. Huang, J. Lin, W. Gao, and Z. Zeng, “A Positive-feedback Loop Between HBx and ALKBH5 Promotes Hepatocellular Carcinogenesis,” BMC cancer 21, no. 1 (2021): 686.

[96]

G. W. Kim and A. Siddiqui, “The Role of N6-methyladenosine Modification in the Life Cycle and Disease Pathogenesis of hepatitis B and C Viruses,” Experimental & Molecular Medicine 53, no. 3 (2021): 339–345.

[97]

N. S. Gokhale, A. B. R. McIntyre, M. J. McFadden, et al., “N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection,” Cell Host & Microbe 20, no. 5 (2016): 654–665.

[98]

G. W. Kim, H. Imam, M. Khan, and A. Siddiqui, “N(6)-Methyladenosine Modification of hepatitis B and C Viral RNAs Attenuates Host Innate Immunity via RIG-I Signaling,” Journal of Biological Chemistry 295, no. 37 (2020): 13123–13133.

[99]

N. S. Gokhale, A. B. R. McIntyre, M. D. Mattocks, et al., “Altered M(6)A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection,” Molecular Cell 77, no. 3 (2020): 542–555. e8.

[100]

R. Liu, J. Wu, H. Guo, et al., “Post-translational Modifications of Histones: Mechanisms, Biological Functions, and Therapeutic Targets,” MedComm 4, no. 3 (2023): e292.

[101]

Y. Li, X. Chen, and C. Lu, “The Interplay Between DNA and Histone Methylation: Molecular Mechanisms and Disease Implications,” Embo Reports 22, no. 5 (2021): e51803.

[102]

W. Gao, Z. Jia, Y. Tian, et al., “HBx Protein Contributes to Liver Carcinogenesis by H3K4me3 Modification through Stabilizing WD Repeat Domain 5 Protein,” Hepatology 71, no. 5 (2020): 1678–1695.

[103]

C. Garcia-Crespo, I. Francisco-Recuero, I. Gallego, et al., “Hepatitis C Virus Fitness Can Influence the Extent of Infection-mediated Epigenetic Modifications in the Host Cells,” Frontiers in Cellular and Infection Microbiology 13 (2023): 1057082.

[104]

X. Xue, W. Gao, B. Sun, et al., “Vasohibin 2 Is Transcriptionally Activated and Promotes Angiogenesis in Hepatocellular Carcinoma,” Oncogene 32, no. 13 (2013): 1724–1734.

[105]

G. Papadopoulou, S. Petroulia, E. Karamichali, et al., “The Epigenetic Controller Lysine-Specific Demethylase 1 (LSD1) Regulates the Outcome of Hepatitis C Viral Infection,” Cells 12, no. 21 (2023): 2568.

[106]

C. Bernsmeier, F. H. Duong, V. Christen, et al., “Virus-induced Over-expression of Protein Phosphatase 2A Inhibits Insulin Signalling in Chronic hepatitis C,” Journal of Hepatology 49, no. 3 (2008): 429–440.

[107]

M. I. Anwar, N. Li, Q. Zhou, et al., “PPP2R5D promotes hepatitis C Virus Infection by Binding to Viral NS5B and Enhancing Viral RNA Replication,” Virology Journal 19, no. 1 (2022): 118.

[108]

K. Wang, L. Luo, S. Fu, et al., “PHGDH Arginine Methylation by PRMT1 Promotes Serine Synthesis and Represents a Therapeutic Vulnerability in Hepatocellular Carcinoma,” Nature Communications 14, no. 1 (2023): 1011.

[109]

S. L. Berger, “The Complex Language of Chromatin Regulation During Transcription,” Nature 447, no. 7143 (2007): 407–412.

[110]

J. K. Xia, X. Q. Qin, L. Zhang, S. J. Liu, X. L. Shi, and H. Z. Ren, “Roles and Regulation of Histone Acetylation in Hepatocellular Carcinoma,” Frontiers in Genetics 13 (2022): 982222.

[111]

L. Belloni, T. Pollicino, F. De Nicola, et al., “Nuclear HBx Binds the HBV Minichromosome and Modifies the Epigenetic Regulation of cccDNA Function,” PNAS 106, no. 47 (2009): 19975–19979.

[112]

X. Y. Liu, S. H. Tang, S. L. Wu, et al., “Epigenetic Modulation of Insulin-Like Growth Factor-II Overexpression by hepatitis B Virus X Protein in Hepatocellular Carcinoma,” American Journal of Cancer Research 5, no. 3 (2015): 956–978.

[113]

M. Xie, M. Sun, X. Ji, et al., “Overexpression of BACH1 Mediated by IGF2 Facilitates Hepatocellular Carcinoma Growth and Metastasis via IGF1R and PTK2,” Theranostics 12, no. 3 (2022): 1097–1116.

[114]

W. Weichert, “HDAC Expression and Clinical Prognosis in human Malignancies,” Cancer Letters 280, no. 2 (2009): 168–176.

[115]

A. Arzumanyan, T. Friedman, E. Kotei, I. O. Ng, Z. Lian, and M. A. Feitelson, “Epigenetic Repression of E-cadherin Expression by hepatitis B Virus X Antigen in Liver Cancer,” Oncogene 31, no. 5 (2012): 563–572.

[116]

S. Perez, A. Kaspi, T. Domovitz, et al., “Hepatitis C Virus Leaves an Epigenetic Signature post Cure of Infection by Direct-acting Antivirals,” Plos Genetics 15, no. 6 (2019): e1008181.

[117]

N. Hamdane, F. Juhling, E. Crouchet, et al., “HCV-Induced Epigenetic Changes Associated with Liver Cancer Risk Persist after Sustained Virologic Response,” Gastroenterology 156, no. 8 (2019): 2313–2329. e7.

[118]

S. Perez, A. Lavi-Itzkovitz, M. Gidoni, et al., “High-Resolution Genomic Profiling of Liver Cancer Links Etiology with Mutation and Epigenetic Signatures,” Cellular and Molecular Gastroenterology and Hepatology 16, no. 1 (2023): 63–81.

[119]

Y. Zhou, Q. Wang, Q. Yang, et al., “Histone Deacetylase 3 Inhibitor Suppresses Hepatitis C Virus Replication by Regulating Apo-A1 and LEAP-1 Expression,” Virologica Sinica 33, no. 5 (2018): 418–428.

[120]

A. Akil, S. Ezzikouri, A. E. El Feydi, et al., “Associations of Genetic Variants in the Transcriptional Coactivators EP300 and PCAF With Hepatocellular Carcinoma,” Cancer Epidemiology 36, no. 5 (2012): e300–5.

[121]

M. M. Minor and B. L. Slagle, “Hepatitis B Virus HBx Protein Interactions With the Ubiquitin Proteasome System,” Viruses 6, no. 11 (2014): 4683–4702.

[122]

K. Wu, Y. Zhang, Y. Liu, et al., “Phosphorylation of UHRF2 Affects Malignant Phenotypes of HCC and HBV Replication by Blocking DHX9 Ubiquitylation,” Cell Death Discovery 9, no. 1 (2023): 27.

[123]

X. Lin, A. M. Li, Y. H. Li, et al., “Silencing MYH9 Blocks HBx-induced GSK3beta Ubiquitination and Degradation to Inhibit Tumor Stemness in Hepatocellular Carcinoma,” Signal Transduction and Targeted Therapy 5, no. 1 (2020): 13.

[124]

H. You, N. Zhang, T. Yu, et al., “Hepatitis B Virus X Protein Promotes MAN1B1 Expression by Enhancing Stability of GRP78 via TRIM25 to Facilitate Hepatocarcinogenesis,” British Journal of Cancer 128, no. 6 (2023): 992–1004.

[125]

Y. Gao, J. Feng, G. Yang, et al., “Hepatitis B Virus X Protein-elevated MSL2 Modulates hepatitis B Virus Covalently Closed Circular DNA by Inducing Degradation of APOBEC3B to Enhance Hepatocarcinogenesis,” Hepatology 66, no. 5 (2017): 1413–1429.

[126]

J. Wang, N. Li, Z. B. Huang, et al., “HBx Regulates Transcription Factor PAX8 Stabilization to Promote the Progression of Hepatocellular Carcinoma,” Oncogene 38, no. 40 (2019): 6696–6710.

[127]

S. Shin Kim, S. Yeom, J. Kwak, H. J. Ahn, and K. Lib Jang, “Hepatitis B Virus X Protein Induces Epithelial-mesenchymal Transition by Repressing E-cadherin Expression via Upregulation of E12/E47,” Journal of General Virology 97, no. 1 (2016): 134–143.

[128]

J. H. Lim, D. G. Kim, D. Y. Yu, et al., “Stabilization of E2-EPF UCP Protein Is Implicated in hepatitis B Virus-associated Hepatocellular Carcinoma Progression,” Cellular and Molecular Life Sciences 76, no. 13 (2019): 2647–2662.

[129]

J. Hundt, Z. Li, and Q. Liu, “Post-translational Modifications of hepatitis C Viral Proteins and Their Biological Significance,” World Journal of Gastroenterology 19, no. 47 (2013): 8929–8939.

[130]

Y. Liang, G. Zhang, Q. Li, et al., “TRIM26 is a Critical Host Factor for HCV Replication and Contributes to Host Tropism,” Science Advances 7, no. 2 (2021): eabd9732.

[131]

S. Kumar, R. Barouch-Bentov, F. Xiao, et al., “MARCH8 Ubiquitinates the Hepatitis C Virus Nonstructural 2 Protein and Mediates Viral Envelopment,” Cell Reports 26, no. 7 (2019): 1800–1814. e5.

[132]

H. T. Pham, T. T. T. Nguyen, L. P. Nguyen, S. S. Han, Y. S. Lim, and S. B. Hwang, “Hepatitis C Virus Downregulates Ubiquitin-Conjugating Enzyme E2S Expression To Prevent Proteasomal Degradation of NS5A, Leading to Host Cells More Sensitive to DNA Damage,” Journal of Virology 93, no. 2 (2019): e01240.

[133]

L. Deng, Y. Liang, A. Ariffianto, et al., “Hepatitis C Virus-Induced ROS/JNK Signaling Pathway Activates the E3 Ubiquitin Ligase Itch to Promote the Release of HCV Particles via Polyubiquitylation of VPS4A,” Journal of Virology 96, no. 6 (2022): e0181121.

[134]

H. Y. Choi, Y. Zhu, X. Zhao, et al., “NOTCH Localizes to Mitochondria Through the TBC1D15-FIS1 Interaction and Is Stabilized via Blockade of E3 Ligase and CDK8 Recruitment to Reprogram Tumor-initiating Cells,” Experimental & Molecular Medicine 56, no. 2 (2024): 461–477.

[135]

J. Son, M. J. Kim, J. S. Lee, J. Y. Kim, E. Chun, and K. Y. Lee, “Hepatitis B Virus X Protein Promotes Liver Cancer Progression Through Autophagy Induction in Response to TLR4 Stimulation,” Immune Network 21, no. 5 (2021): e37.

[136]

Q. Pan, Y. Xie, Y. Zhang, et al., “EGFR Core Fucosylation, Induced by hepatitis C Virus, Promotes TRIM40-mediated-RIG-I Ubiquitination and Suppresses Interferon-I Antiviral Defenses,” Nature Communications 15, no. 1 (2024): 652.

[137]

K. Nemeth, R. Bayraktar, M. Ferracin, and G. A. Calin, “Non-coding RNAs in Disease: From Mechanisms to Therapeutics,” Nature Reviews Genetics 25, no. 3 (2024): 211–232.

[138]

Y. Y. Wang, J. M. Cao, S. Y. Zhang, et al., “MicroRNA-802 Induces hepatitis B Virus Replication and Replication Through Regulating SMARCE1 Expression in Hepatocellular Carcinoma,” Cell Death & Disease 10 (2019): 783.

[139]

A. K. Mishra, M. M. Hossain, T. N. Sata, et al., “Hepatitis B Virus X Protein Inhibits the Expression of Barrier to Autointegration factor1 via Upregulating miR-203 Expression in Hepatic Cells,” Microbiology Spectrum 11, no. 1 (2023): e0123522.

[140]

S. Hamada-Tsutsumi, Y. Naito, S. Sato, et al., “The Antiviral Effects of human microRNA miR-302c-3p Against hepatitis B Virus Infection,” Alimentary Pharmacology & Therapeutics 49, no. 8 (2019): 1060–1070.

[141]

H. J. Wu, Y. Zhuo, Y. C. Zhou, et al., “miR-29a Promotes hepatitis B Virus Replication and Expression by Targeting SMARCE1 in Hepatoma Carcinoma,” World Journal of Gastroenterology 23, no. 25 (2017): 4569–4578.

[142]

Y. Gao, J. Gu, Y. P. Wang, et al., “Hepatitis B Virus X Protein Boosts Hepatocellular Carcinoma Progression by Downregulating microRNA-137,” Pathology, Research and Practice 216, no. 6 (2020): 152981.

[143]

Y. Nagura, K. Matsuura, E. Iio, et al., “Serum miR-192-5p Levels Predict the Efficacy of Pegylated Interferon Therapy for Chronic hepatitis B,” PLoS ONE 17, no. 2 (2022): e0263844.

[144]

X. Q. Zhao, L. Sun, T. Mu, et al., “An HBV-encoded miRNA Activates Innate Immunity to Restrict HBV Replication,” Journal of Molecular Cell Biology 12, no. 4 (2020): 263–276.

[145]

Z. Q. Li, H. Y. Wang, Q. L. Zeng, et al., “p65/miR-23a/CCL22 Axis Regulated Regulatory T Cells Recruitment in hepatitis B Virus Positive Hepatocellular Carcinoma,” Cancer Medicine-Us 9, no. 2 (2020): 711–723.

[146]

W. B. Chen, J. J. Jiang, L. Gong, et al., “Hepatitis B Virus P Protein Initiates Glycolytic Bypass in HBV-related Hepatocellular Carcinoma via a FOXO3/miRNA-30b-5p/MINPP1 Axis,” Journal of Experimental & Clinical Cancer Research 40, no. 1 (2021): 1.

[147]

B. He, F. Peng, W. Li, and Y. F. Jiang, “Interaction of lncRNA-MALAT1 and miR-124 Regulates HBx-induced Cancer Stem Cell Properties in HepG2 Through PI3K/Akt Signaling,” Journal of Cellular Biochemistry 120, no. 3 (2019): 2908–2918.

[148]

X. C. Wei, Y. R. Xia, P. Zhou, et al., “Hepatitis B Core Antigen Modulates Exosomal miR-135a to Target Vesicle-associated Membrane Protein 2 Promoting Chemoresistance in Hepatocellular Carcinoma,” World Journal of Gastroenterology 27, no. 48 (2021): 8302–8322.

[149]

Y. P. Wei, X. W. Tang, Y. B. Ren, et al., “An RNA-RNA Crosstalk Network Involving HMGB1 and RICTOR Facilitates Hepatocellular Carcinoma Tumorigenesis by Promoting Glutamine Metabolism and Impedes Immunotherapy by PD-L1+Exosomes Activity,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 421.

[150]

Y. F. Qin, Z. Y. Zhou, H. W. Fu, et al., “Hepatitis B Virus Surface Antigen Promotes Stemness of Hepatocellular Carcinoma Through Regulating MicroRNA-203a,” Journal of Clinical and Translational Hepatology 11, no. 1 (2023): 118–129.

[151]

R. Li, T. Xu, H. Wang, et al., “Dysregulation of the miR-325-3p/DPAGT1 Axis Supports HBV-positive HCC Chemoresistance,” Biochemical and Biophysical Research Communications 519, no. 2 (2019): 358–365.

[152]

C. Zhang, P. Liu, and C. B. Zhang, “Hepatitis B virus X Protein Upregulates Alpha-fetoprotein to Promote Hepatocellular Carcinoma by Targeting miR-1236 and miR-329,” Journal of Cellular Biochemistry 121, no. 3 (2020): 2489–2499.

[153]

P. S. Bai, N. Xia, H. Sun, and Y. Kong, “Pleiotrophin, a Target of miR-384, Promotes Proliferation, Metastasis and Lipogenesis in HBV-related Hepatocellular Carcinoma,” Journal of Cellular and Molecular Medicine 21, no. 11 (2017): 3023–3043.

[154]

Q. Chen, S. B. Yang, Y. W. Zhang, et al., “miR-3682-3p Directly Targets FOXO3 and Stimulates Tumor Stemness in Hepatocellular Carcinoma a Positive Feedback Loop Involving FOXO3/PI3K/AKT/c-Myc,” World Journal of Stem Cells 14, no. 7 (2022): 539–555.

[155]

X. Lin, S. Zuo, R. C. Luo, et al., “HBX-induced miR-5188 Impairs FOXO1 to Stimulate β-catenin Nuclear Translocation and Promotes Tumor Stemness in Hepatocellular Carcinoma,” Theranostics 9, no. 25 (2019): 7583–7598.

[156]

Y. X. Liu, J. Y. Feng, M. M. Sun, et al., “Long Non-coding RNA HULC Activates HBV by Modulating HBx/STAT3/miR-539/APOBEC3B Signaling in HBV-related Hepatocellular Carcinoma,” Cancer Letters 454 (2019): 158–170.

[157]

J. J. Hu, W. Song, S. D. Zhang, et al., “HBx-upregulated lncRNA UCA1 Promotes Cell Growth and Tumorigenesis by Recruiting EZH2 and Repressing p27Kip1/CDK2 Signaling,” Scientific Reports-Uk 6 (2016): 23521.

[158]

X. Deng, X. F. Zhao, X. Q. Liang, R. Chen, Y. F. Pan, and J. Liang, “Linc00152 promotes Cancer Progression in hepatitis B Virus-associated Hepatocellular Carcinoma,” Biomedicine & Pharmacotherapy 90 (2017): 100–108.

[159]

X. P. Zhao, H. X. Fan, X. Chen, et al., “Hepatitis B Virus DNA Polymerase Restrains Viral Replication through the CREB1/HOXA Distal Transcript Antisense RNA Homeobox A13 Axis,” Hepatology 73, no. 2 (2021): 503–519.

[160]

J. Ma, T. F. Li, X. W. Han, and H. F. Yuan, “Knockdown of LncRNA ANRIL Suppresses Cell Proliferation, Metastasis, and Invasion via Regulating miR-122-5p Expression in Hepatocellular Carcinoma,” Journal of Cancer Research and Clinical Oncology 144, no. 2 (2018): 205–214.

[161]

F. Zhang, Y. Li, L. P. Gan, et al., “HBx-upregulated MAFG-AS1 Promotes Cell Proliferation and Migration of Hepatoma Cells by Enhancing MAFG Expression and Stabilizing Nonmuscle Myosin IIA,” Faseb Journal 35, no. 5 (2021): e21529.

[162]

J. Bao, X. Q. Chen, Y. G. Hou, G. L. Kang, Q. L. Li, and Y. Xu, “LncRNA DBH-AS1 Facilitates the Tumorigenesis of Hepatocellular Carcinoma by Targeting miR-138 via FAK/Src/ERK Pathway,” Biomedicine & Pharmacotherapy 107 (2018): 824–833.

[163]

B. Jiang, B. Yang, Q. Wang, X. Y. Zheng, Y. Guo, and W. Lu, “lncRNA PVT1 Promotes hepatitis B Virus-positive Liver Cancer Progression by Disturbing Histone Methylation on the c-Myc Promoter,” Oncology Reports 43, no. 2 (2020): 718–726.

[164]

D. Salerno, L. Chiodo, V. Alfano, et al., “Hepatitis B Protein HBx Binds the DLEU2 lncRNA to Sustain cccDNA and Host Cancer-related Gene Transcription,” Gut 69, no. 11 (2020): 2016–2024.

[165]

F. Ren, J. H. Ren, C. L. Song, et al., “LncRNA HOTAIR Modulates hepatitis B Virus Transcription and Replication by Enhancing SP1 Transcription Factor,” Clinical Science 134, no. 22 (2020): 3007–3022.

[166]

T. S. Chen, J. X. Pei, J. J. Wang, et al., “HBx-related Long Non-coding RNA 01152 Promotes Cell Proliferation and Survival by IL-23 in Hepatocellular Carcinoma,” Biomedicine & Pharmacotherapy 115 (2019): 108877.

[167]

Y. J. Jin, D. Wu, W. W. Yang, et al., “Hepatitis B Virus X Protein Induces Epithelial-mesenchymal Transition of Hepatocellular Carcinoma Cells by Regulating Long Non-coding RNA,” Virology Journal 14 (2017): 238.

[168]

J. Y. Feng, G. Yang, Y. X. Liu, et al., “LncRNA PCNAP1 Modulates hepatitis B Virus Replication and Enhances Tumor Growth of Liver Cancer,” Theranostics 9, no. 18 (2019): 5227–5245.

[169]

L. Li, T. Han, K. Liu, C. G. Lei, Z. C. Wang, and G. J. Shi, “LncRNA H19 Promotes the Development of hepatitis B Related Hepatocellular Carcinoma Through Regulating microRNA-22 EMT Pathway,” European Review for Medical and Pharmacological Sciences 23, no. 12 (2019): 5392–5401.

[170]

H. X. Fan, P. Lv, T. Mu, et al., “LncRNA n335586/miR-924/CKMT1A Axis Contributes to Cell Migration and Invasion in Hepatocellular Carcinoma Cells,” Cancer Letters 429 (2018): 89–99.

[171]

D. Lv, Y. Wang, Y. Zhang, P. L. Cui, and Y. Q. Xu, “Downregulated Long Non-coding RNA DREH Promotes Cell Proliferation in hepatitis B Virus-associated Hepatocellular Carcinoma,” Oncology Letters 14, no. 2 (2017): 2025–2032.

[172]

Q. Liu, N. N. Liu, Q. L. Shangguan, et al., “LncRNA SAMD12-AS1 Promotes Cell Proliferation and Inhibits Apoptosis by Interacting With NPM1,” Scientific Reports-Uk 9 (2019): 11593.

[173]

N. N. Liu, Q. Liu, X. H. Yang, et al., “Hepatitis B Virus-Upregulated LNC-HUR1 Promotes Cell Proliferation and Tumorigenesis by Blocking p53 Activity,” Hepatology 68, no. 6 (2018): 2130–2144.

[174]

S. M. Yu, N. Li, Z. B. Huang, et al., “A Novel lncRNA, TCONS_00006195, Represses Hepatocellular Carcinoma Progression by Inhibiting Enzymatic Activity of ENO1,” Cell Death & Disease 9 (2018): 1184.

[175]

S. Y. Susluer, C. Kayabasi, B. O. Yelken, et al., “Analysis of Long Non-coding RNA (lncRNA) Expression in hepatitis B Patients,” Bosnian Journal of Basic Medical Sciences 18, no. 2 (2018): 150–161.

[176]

Q. Q. Hao, Z. Wang, Q. H. Wang, et al., “Identification and Characterization of lncRNA AP000253 in Occult hepatitis B Virus Infection,” Virology Journal 18, no. 1 (2021): 125.

[177]

L. P. Gan, Q. L. Shangguan, F. Zhang, et al., “HBV HBx-Downregulated lncRNA Attenuates Cell Proliferation by Interacting With Vimentin,” International Journal of Molecular Sciences 22, no. 22 (2021): 12497.

[178]

M. J. Chen, X. G. Wang, Z. X. Sun, and X. C. Liu, “Diagnostic Value of LncRNA-MEG3 as a Serum Biomarker in Patients With hepatitis B Complicated With Liver Fibrosis,” European Review for Medical and Pharmacological Sciences 23, no. 10 (2019): 4360–4367.

[179]

Z. G. Hu, P. B. Huang, Y. C. Yan, Z. Y. Zhou, J. Wang, and G. Wu, “Hepatitis B Virus X Protein Related lncRNA WEE2-AS1 Promotes Hepatocellular Carcinoma Proliferation and Invasion,” Biochemical and Biophysical Research Communications 508, no. 1 (2019): 79–86.

[180]

N. Du, K. L. Li, Y. Wang, B. Song, X. Zhou, and S. Duan, “CircRNA circBACH1 Facilitates hepatitis B Virus Replication and Hepatoma Development by Regulating the miR-200a-3p/MAP3K2 Axis,” Histology and Histopathology 37, no. 9 (2022): 863–877.

[181]

Y. Li, R. H. Li, D. Cheng, X. Y. Fu, L. Fu, and S. F. Peng, “The Potential of CircRNA1002 as a Biomarker in hepatitis B Virus-related Hepatocellular Carcinoma,” PeerJ 10 (2022): e13640.

[182]

M. Zhu, Z. Liang, J. Pan, et al., “Hepatocellular Carcinoma Progression Mediated by hepatitis B Virus-encoded circRNA HBV_circ_1 Through Interaction With CDK1,” Molecular Therapy Nucleic Acids 25 (2021): 668–682.

[183]

T. C. Zhou, X. Li, L. J. Chen, et al., “Differential Expression Profile of Hepatic Circular RNAs in Chronic hepatitis B,” Journal of Viral Hepatitis 25, no. 11 (2018): 1341–1351.

[184]

Y. H. Yuan, X. J. Yang, and D. S. Xie, “Role of hsa_circ_0066966 in Proliferation and Migration of hepatitis B Virus-related Liver Cancer Cells,” Experimental and Therapeutic Medicine 23, no. 1 (2022): 87.

[185]

X. Rao, L. L. Lai, X. P. Li, L. Wang, A. I. Li, and Q. Yang, “N-methyladenosine Modification of Circular RNA Circ-ARL3 Facilitates Hepatitis B Virus-associated Hepatocellular Carcinoma via Sponging miR-1305,” Iubmb Life 73, no. 2 (2021): 408–417.

[186]

C. Wu, L. Deng, H. Zhuo, et al., “Circulating circRNA Predicting the Occurrence of Hepatocellular Carcinoma in Patients With HBV Infection,” Journal of Cellular and Molecular Medicine 24, no. 17 (2020): 10216–10222.

[187]

S. S. Wang, S. C. Cui, W. M. Zhao, et al., “Screening and Bioinformatics Analysis of Circular RNA Expression Profiles in hepatitis B-related Hepatocellular Carcinoma,” Cancer Biomark 22, no. 4 (2018): 631–640.

[188]

L. D. Zhang and Z. C. Wang, “Circular RNA hsa_circ_0004812 Impairs IFN-induced Immune Response by Sponging miR-1287-5p to Regulate FSTL1 in Chronic hepatitis B,” Virology Journal 17, no. 1 (2020): 40.

[189]

M. Wang, B. L. Gu, G. L. Yao, P. F. Li, and K. Wang, “Circular RNA Expression Profiles and the Pro-tumorigenic Function of CircRNA_10156 in Hepatitis B Virus-Related Liver Cancer,” International Journal of Medical Sciences 17, no. 10 (2020): 1351–1365.

[190]

S. E. Riad, D. S. Elhelw, H. Shawer, et al., “Disruption of Claudin-1 Expression by miRNA-182 Alters the Susceptibility to Viral Infectivity in HCV Cell Models,” Frontiers in Genetics 9 (2018): 93.

[191]

R. D. Kunden, J. Q. Khan, S. Ghezelbash, and J. A. Wilson, “The Role of the Liver-Specific microRNA, miRNA-122 in the HCV Replication Cycle,” International Journal of Molecular Sciences 21, no. 16 (2020): 5677.

[192]

D. S. Elhelw, S. E. Riad, H. Shawer, et al., “Ectopic Delivery of miR-200c Diminishes hepatitis C Virus Infectivity Through Transcriptional and Translational Repression of Occludin,” Archives of Virology 162, no. 11 (2017): 3283–3291.

[193]

S. Clément, C. Sobolewski, D. Gomes, et al., “Activation of the Oncogenic miR-21-5p Promotes HCV Replication and Steatosis Induced by the Viral Core 3a Protein,” Liver International 39, no. 7 (2019): 1226–1236.

[194]

M. A. Eldosoky, R. Hammad, A. A. Elmadbouly, et al., “Diagnostic Significance of Hsa-miR-21-5p, Hsa-miR-192-5p, Hsa-miR-155-5p, Hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients,” International Journal of Molecular Sciences 24, no. 4 (2023): 3157.

[195]

M. Jamalidoust, M. Shafaati, M. Kalani, M. Zare, and M. Ziyeayan, “MicroRNA Let-7b Inhibits hepatitis C Virus and Induces Apoptosis in human Hepatoma Cells,” Molecular Biology Reports 49, no. 2 (2022): 1273–1280.

[196]

T. Patra, K. Meyer, R. B. Ray, and R. Ray, “Hepatitis C Virus Mediated Inhibition of miR-181c Activates ATM Signaling and Promotes Hepatocyte Growth,” Hepatology 71, no. 3 (2020): 780–793.

[197]

E. B. Lee, P. S. Sung, J. H. Kim, D. J. Park, W. Hur, and S. K. Yoon, “microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and De Novo Lipogenesis,” Viruses-Basel 12, no. 7 (2020): 696.

[198]

N. M. Hany, A. M. A. Hammouda, E. S. Nabih, and S. M. Mohamed, “The Potential Regulatory Role of miR16 to the Interplay Between Interferon and Transforming Growth Factor Beta Pathways Through IRF3 and SMAD7 in hepatitis C Virus Infected Patients,” Journal of Cellular Biochemistry 120, no. 8 (2019): 12694–12701.

[199]

C. L. He, M. Liu, Z. X. Tan, et al., “Hepatitis C Virus Core Protein-induced miR-93-5p Up-regulation Inhibits Interferon Signaling Pathway by Targeting IFNAR1,” World Journal of Gastroenterology 24, no. 2 (2018): 226–236.

[200]

W. F. Gong, X. B. Guo, and Y. M. Zhang, “Depletion of MicroRNA-373 Represses the Replication of Hepatitis C Virus via Activation of Type 1 Interferon Response by Targeting IRF5,” Yonsei Medical Journal 59, no. 10 (2018): 1181–1189.

[201]

C. Sodroski, B. Lowey, L. Hertz, T. J. Liang, and Q. S. Li, “MicroRNA-135a Modulates Hepatitis C Virus Genome Replication Through Downregulation of Host Antiviral Factors,” Virologica Sinica 34, no. 2 (2019): 197–210.

[202]

J. G. Yan, Y. T. Zhang, Y. Su, et al., “microRNA-125a Targets MAVS and TRAF6 to Modulate Interferon Signaling and Promote HCV Infection,” Virus Research 296 (2021): 198336.

[203]

M. B. Yasser, M. Abdellatif, E. Emad, et al., “Circulatory miR-221 & miR-542 Expression Profiles as Potential Molecular Biomarkers in Hepatitis C Virus Mediated Liver Cirrhosis and Hepatocellular Carcinoma,” Virus Research 296 (2021): 198341.

[204]

W. C. Chen, C. K. Wei, and J. C. Lee, “MicroRNA-let-7c Suppresses hepatitis C Virus Replication by Targeting Bach1 for Induction of Haem Oxygenase-1 Expression,” Journal of Viral Hepatitis 26, no. 6 (2019): 655–665.

[205]

Y. J. Wang and Y. Y. Li, “MiR-29c Inhibits HCV Replication Activation of Type I IFN Response by Targeting STAT3 in JFH-1-infected Huh7 Cells,” RSC Advances 8, no. 15 (2018): 8164–8172.

[206]

S. Shwetha, G. Sharma, H. Raheja, A. Goel, R. Aggarwal, and S. Das, “Interaction of miR-125b-5p With Human Antigen R mRNA: Mechanism of Controlling HCV Replication,” Virus Research 258 (2018): 1–8.

[207]

X. Q. Duan, X. Liu, W. T. Li, et al., “Microrna-130a Downregulates HCV Replication Through an atg5-Dependent Autophagy Pathway,” Cells-Basel 8, no. 4 (2019): 338.

[208]

W. Huang, L. Y. Song, J. Y. Zhang, X. Q. Yan, and H. Yan, “Effects of miR-185-5p on Replication of hepatitis C Virus,” Open Life Sciences 16, no. 1 (2021): 752–757.

[209]

A. Y. Elfert, A. Salem, A. M. Abdelhamid, et al., “Implication of miR-122, miR-483, and miR-335 Expression Levels as Potential Signatures in HCV-Related Hepatocellular Carcinoma (HCC) in Egyptian Patients,” Frontiers in Molecular Biosciences 9 (2022): 864839.

[210]

P. B. Devhare, R. Sasaki, S. Shrivastava, A. M. Di Bisceglie, R. B. Ranjit, and R. B. Ray, “Exosome-Mediated Intercellular Communication Between Hepatitis C Virus-Infected Hepatocytes and Hepatic Stellate Cells,” Journal of Virology 91, no. 6 (2017): e02225.

[211]

J. H. Kim, C. H. Lee, and S. W. Lee, “Exosomal Transmission of MicroRNA From HCV Replicating Cells Stimulates Transdifferentiation in Hepatic Stellate Cells,” Molecular Therapy Nucleic Acids 14 (2019): 483–497.

[212]

A. Ullah, I. U. Rehman, K. Ommer, et al., “Circulating miRNA-192 and miR-29a as Disease Progression Biomarkers in Hepatitis C Patients With a Prevalence of HCV Genotype 3,” Genes-Basel 14, no. 5 (2023): 1056.

[213]

R. Horii, M. Honda, T. Shirasaki, et al., “MicroRNA-10a Impairs Liver Metabolism in Hepatitis C Virus-Related Cirrhosis through Deregulation of the Circadian Clock Gene Brain and Muscle Aryl Hydrocarbon Receptor Nuclear Translocator-Like 1,” Hepatology Communications 3, no. 12 (2019): 1687–1703.

[214]

N. M. H Shaheen, N. Zayed, N. M. Riad, et al., “Role of Circulating miR-182 and miR-150 as Biomarkers for Cirrhosis and Hepatocellular Carcinoma Post HCV Infection in Egyptian Patients,” Virus Research 255 (2018): 77–84.

[215]

D. D. Murray, K. Suzuki, M. Law, et al., “Circulating miR-122 and miR-200a as Biomarkers for Fatal Liver Disease in ART-treated, HIV-1-infected Individuals,” Scientific Reports-Uk 7 (2017): 10934.

[216]

N. Van Renne, A. A. R. Suarez, F. H. T. Duong, et al., “miR-135a-5p-mediated Downregulation of Protein Tyrosine Phosphatase Receptor Delta Is a Candidate Driver of HCV-associated Hepatocarcinogenesis,” Gut 67, no. 5 (2018): 953–962.

[217]

T. Y. Shiu, Y. L. Shih, A. C. Feng, et al., “HCV Core Inhibits Hepatocellular Carcinoma Cell Replicative Senescence Through Downregulating microRNA-138 Expression,” Journal of Molecular Medicine 95, no. 6 (2017): 629–639.

[218]

D. E. Nam, A. Angelucci, D. Choi, A. Leigh, H. C. Seong, and Y. S. Hahn, “Elevation of Plasminogen Activator Inhibitor-1 Promotes Differentiation of Cancer Stem-Like Cell State by Hepatitis C Virus Infection,” Journal of Virology 95, no. 10 (2021): e02057.

[219]

E. Miquelestorena-Standley, A. Tallet, C. Collin, et al., “Interest of Variations in microRNA-152 and-122 in a Series of Hepatocellular Carcinomas Related to hepatitis C Virus Infection,” Hepatology Research 48, no. 7 (2018): 566–573.

[220]

L. Wang, D. C. Cao, L. Wang, et al., “HCV-associated Exosomes Promote Myeloid-derived Suppressor Cell Expansion via Inhibiting miR-124 to Regulate T Follicular Cell Differentiation and Function,” Cell Discovery 4 (2018): 51.

[221]

Y. B. Deng, J. C. Wang, M. J. Huang, G. D. Xu, W. J. Wei, and H. J. Qin, “Inhibition of miR-148a-3p Resists Hepatocellular Carcinoma Progress of hepatitis C Virus Infection Through Suppressing and MAPK Pathway,” Journal of Cellular and Molecular Medicine 23, no. 2 (2019): 1415–1426.

[222]

N. M. El Samaloty, M. I. Shabayek, R. S. Ghait, S. A El-Maraghy, S. M. Rizk, and M. M. El-Sawalhi, “Assessment of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and Its mRNA BST2 as Serum Innovative Non-invasive Biomarkers: Recent Insights Into Egyptian Patients With hepatitis C Virus Type 4,” World Journal of Gastroenterology 26, no. 2 (2020): 168–183.

[223]

N. El-Khazragy, A. A. Elshimy, S. S. Hassan, et al., “lnc-HOTAIR Predicts Hepatocellular Carcinoma in Chronic hepatitis C Genotype 4 Following Direct-acting Antivirals Therapy,” Molecular Carcinogenesis 59, no. 12 (2020): 1382–1391.

[224]

G. Sharma, S. K. Tripathi, and S. Das, “lncRNA HULC Facilitates Efficient Loading of HCV-core Protein Onto Lipid Droplets and Subsequent Virus-particle Release,” Cellular Microbiology 21, no. 10 (2019): e13086.

[225]

J. J. Fan, M. Cheng, X. J. Chi, X. Y. Liu, and W. A. Yang, “Human Long Non-coding RNA LncATV Promotes Virus Replication through Restricting RIG-I-Mediated Innate Immunity,” Frontiers in Immunology 10 (2019): 1711.

[226]

Q. Y. Xie, S. W. Chen, R. Y. Tian, et al., “Long Noncoding RNA ITPRIP-1 Positively Regulates the Innate Immune Response Through Promotion of Oligomerization and Activation of MDA5,” Journal of Virology 92, no. 17 (2018): e00507.

[227]

X. Liu, X. Duan, J. A. Holmes, et al., “A Long Noncoding RNA Regulates Hepatitis C Virus Infection through Interferon Alpha-Inducible Protein 6,” Hepatology 69, no. 3 (2019): 1004–1019.

[228]

D. Kung-Chun Chiu, A. Pui-Wah Tse, C. T. Law, et al., “Hypoxia Regulates the Mitochondrial Activity of Hepatocellular Carcinoma Cells Through HIF/HEY1/PINK1 Pathway,” Cell Death & Disease 10, no. 12 (2019): 934.

[229]

H. S. Sabry, S. I. Tayel, M. E. Enar, and N. S. Elabd, “Differential Expression of Long Noncoding RNA in Hepatocellular Carcinoma on Top of Chronic HCV and HBV Infections,” Clinical and Experimental Hepatology 7, no. 4 (2021): 337–350.

[230]

X. Y. Ma, M. L. Mo, H. J. J. Tan, et al., “LINC02499, a Novel Liver-specific Long Non-coding RNA With Potential Diagnostic and Prognostic Value, Inhibits Hepatocellular Carcinoma Cell Proliferation, Migration, and Invasion,” Hepatology Research 50, no. 6 (2020): 726–740.

[231]

E. A. Toraih, A. Ellawindy, S. Y. Fala, et al., “Oncogenic Long Noncoding RNA MALAT1 and HCV-related Hepatocellular Carcinoma,” Biomedicine & Pharmacotherapy 102 (2018): 653–669.

[232]

H. Y. Zeng, L. Li, Y. Gao, G. J. Wu, Z. H. Hou, and S. P. Liu, “Long Noncoding RNA UCA1 Regulates HCV Replication and Antiviral Response via miR-145-5p/SOCS7/IFN Pathway,” International Journal of Biological Sciences 17, no. 11 (2021): 2826–2840.

[233]

C. Zhang, X. Yang, Q. Qi, Y. H. Gao, Q. Wei, and S. W. Han, “lncRNA-HEIH in Serum and Exosomes as a Potential Biomarker in the HCV-related Hepatocellular Carcinoma,” Cancer Biomark 21, no. 3 (2018): 651–659.

[234]

R. M. Golam, M. A. F. Khalil, O. G. Shaker, et al., “The Clinical Significance of Long Non-coding RNAs MALAT1 and CASC2 in the Diagnosis of HCV-related Hepatocellular Carcinoma,” PLoS ONE 19, no. 5 (2024): e0303314.

[235]

M. Mohyeldeen, S. Ibrahim, O. Shaker, and H. Helmy, “Serum Expression and Diagnostic Potential of Long Non-coding RNAs NEAT1 and TUG1 in Viral hepatitis C and Viral hepatitis C-associated Hepatocellular Carcinoma,” Clinical Biochemistry 84 (2020): 38–44.

[236]

H. Bao, Y. T. Jiang, N. Wang, H. Y. Su, and X. J. Han, “Long Noncoding RNAs MALAT1 and HOTTIP Act as Serum Biomarkers for Hepatocellular Carcinoma,” Cancer Control 31 (2024): 10732748241284821.

[237]

N. M. Aborehab, M. A. Kandeil, D. Sabry, R. Rabie, and I. T. Ibrahim, “Circular SERPINA3 and Its Target microRNA-944 as Potential Molecular Biomarkers in hepatitis C Virus-induced Hepatocellular Carcinoma in Egyptian Population,” Non-Coding RNA Research 8, no. 3 (2023): 401–412.

[238]

T. C. Chen, M. Tallo-Parra, Q. M. Cao, et al., “Host-derived Circular RNAs Display Proviral Activities in Hepatitis C Virus-infected Cells,” Plos Pathogens 16, no. 8 (2020): e100834.

[239]

H. M. Bedair, E. A El-Banna, E. A. Ahmed, et al., “Evaluation of Circular RNA SMARCA5 as a Novel Biomarker for Hepatocellular Carcinoma,” Asian Pacific Journal of Cancer Prevention 25, no. 4 (2024): 1411–1417.

[240]

Y. S. Lee and A. Dutta, “MicroRNAs in Cancer,” Annual Review of Pathology: Mechanisms of Disease 4 (2009): 199–227.

[241]

J. Xu, P. An, C. A. Winkler, and Y. Yu, “Dysregulated microRNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Potential as Biomarkers and Therapeutic Targets,” Frontiers in Oncology 10 (2020): 1271.

[242]

K. Ramakrishnan, S. Babu, V. Shaji, et al., “Hepatitis B Virus Modulated Transcriptional Regulatory Map of Hepatic Cellular MicroRNAs,” Omics 27, no. 12 (2023): 581–597.

[243]

M. Bandopadhyay, A. Banerjee, N. Sarkar, et al., “Tumor Suppressor Micro RNA miR-145 and Onco Micro RNAs miR-21 and miR-222 Expressions Are Differentially Modulated by hepatitis B Virus X Protein in Malignant Hepatocytes,” BMC cancer 14 (2014): 721.

[244]

P. Gao, C. C. Wong, E. K. Tung, J. M. Lee, C. M. Wong, and I. O. Ng, “Deregulation of microRNA Expression Occurs Early and Accumulates in Early Stages of HBV-associated Multistep Hepatocarcinogenesis,” Journal of Hepatology 54, no. 6 (2011): 1177–1184.

[245]

H. He, J. Zhou, F. Cheng, H. Li, and Y. Quan, “MiR-3677-3p Promotes Development and Sorafenib Resistance of hepatitis B-related Hepatocellular Carcinoma by Inhibiting FOXM1 Ubiquitination,” Human Cell 36, no. 5 (2023): 1773–1789.

[246]

X. Guo, X. Lv, X. Lv, Y. Ma, L. Chen, and Y. Chen, “Circulating miR-21 Serves as a Serum Biomarker for Hepatocellular Carcinoma and Correlated With Distant Metastasis,” Oncotarget 8, no. 27 (2017): 44050–44058.

[247]

C. H. Li, F. Xu, S. Chow, et al., “Hepatitis B Virus X Protein Promotes Hepatocellular Carcinoma Transformation Through Interleukin-6 Activation of microRNA-21 Expression,” European Journal of Cancer 50, no. 15 (2014): 2560–2569.

[248]

X. Qiu, S. Dong, F. Qiao, et al., “HBx-mediated miR-21 Upregulation Represses Tumor-suppressor Function of PDCD4 in Hepatocellular Carcinoma,” Oncogene 32, no. 27 (2013): 3296–3305.

[249]

T. Kanda, T. Goto, Y. Hirotsu, M. Moriyama, and M. Omata, “Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review,” International Journal of Molecular Sciences 20, no. 6 (2019): 1358.

[250]

M. Panigrahi, M. A. Palmer, and J. A. Wilson, “MicroRNA-122 Regulation of HCV Infections: Insights From Studies of miR-122-Independent Replication,” Pathogens 11, no. 9 (2022): 1005.

[251]

T. Fukuhara and Y. Matsuura, “Role of miR-122 and Lipid Metabolism in HCV Infection,” Journal of Gastroenterology 48, no. 2 (2013): 169–176.

[252]

N. Elfimova, E. Sievers, H. Eischeid, et al., “Control of Mitogenic and Motogenic Pathways by miR-198, Diminishing Hepatoma Cell Growth and Migration,” Biochimica Et Biophysica Acta 1833, no. 5 (2013): 1190–1198.

[253]

H. Zeng, L. Li, Y. Gao, G. Wu, Z. Hou, and S. Liu, “Long Noncoding RNA UCA1 Regulates HCV Replication and Antiviral Response via miR-145-5p/SOCS7/IFN Pathway,” International Journal of Biological Sciences 17, no. 11 (2021): 2826–2840.

[254]

M. T. Chen, J. N. Billaud, M. Sallberg, et al., “A Function of the hepatitis B Virus Precore Protein Is to Regulate the Immune Response to the Core Antigen,” PNAS 101, no. 41 (2004): 14913–14918.

[255]

X. Jin, Y. Zhang, H. Wang, and Y. Zhang, “Expression and Clinical Values of Serum miR-155 and miR-224 in Chinese Patients With HCV Infection,” International Journal of General Medicine 15 (2022): 1393–1403.

[256]

Y. Zhang, W. Wei, N. Cheng, et al., “Hepatitis C Virus-induced Up-regulation of microRNA-155 Promotes Hepatocarcinogenesis by Activating Wnt Signaling,” Hepatology 56, no. 5 (2012): 1631–1640.

[257]

R. T. Marquez, S. Bandyopadhyay, E. B. Wendlandt, et al., “Correlation Between microRNA Expression Levels and Clinical Parameters Associated With Chronic hepatitis C Viral Infection in Humans,” Laboratory Investigation 90, no. 12 (2010): 1727–1736.

[258]

R. Hammad, M. A. Eldosoky, A. A. Elmadbouly, et al., “Monocytes Subsets Altered Distribution and Dysregulated Plasma Hsa-miR-21-5p and Hsa-miR-155-5p in HCV-linked Liver Cirrhosis Progression to Hepatocellular Carcinoma,” Journal of Cancer Research and Clinical Oncology 149, no. 17 (2023): 15349–15364.

[259]

C. J. Liu, X. W. Ma, X. J. Zhang, and S. Q. Shen, “pri-miR-34b/c rs4938723 Polymorphism Is Associated With Hepatocellular Carcinoma Risk: A Case-control Study in a Chinese Population,” International Journal of Molecular Epidemiology and Genetics 8, no. 1 (2017): 1–7.

[260]

Z. Oksuz, L. Gragnani, S. Lorini, G. O. Temel, M. S. Serin, and A. L. Zignego, “Evaluation of Plasma miR-17-5p, miR-24-3p and miRNA-223-3p Profile of Hepatitis C Virus-Infected Patients After Treatment With Direct-Acting Antivirals,” Journal of Personalized Medicine 13, no. 8 (2023): 1188.

[261]

Z. Huang, J. K. Zhou, Y. Peng, W. He, and C. Huang, “The Role of Long Noncoding RNAs in Hepatocellular Carcinoma,” Molecular Cancer 19, no. 1 (2020): 77.

[262]

F. Shi, J. Jiang, B. Wang, et al., “Hepatitis B Virus X Protein Promotes Tumor Glycolysis by Downregulating lncRNA OIP5-AS1/HKDC1 in HCC,” Cell Signalling 119 (2024): 111183.

[263]

J. Wang, G. Yin, H. Bian, et al., “LncRNA XIST Upregulates TRIM25 via Negatively Regulating miR-192 in hepatitis B Virus-related Hepatocellular Carcinoma,” Molecular Medicine 27, no. 1 (2021): 41.

[264]

S. Ahluwalia, B. Ahmad, U. Salim, et al., “Hepatitis B Virus-Encoded HBsAg Contributes to Hepatocarcinogenesis by Inducing the Oncogenic Long Noncoding RNA LINC00665 Through the NF-kappaB Pathway,” Microbiology Spectrum 10, no. 5 (2022): e0273121.

[265]

L. Ruan, L. Huang, L. Zhao, et al., “The Interaction of lncRNA-HEIH and lncRNA-HULC With HBXIP in Hepatitis B Patients,” Gastroenterology Research and Practice 2018 (2018): 9187316.

[266]

B. Zhao, Y. Lu, X. Cao, et al., “MiRNA-124 Inhibits the Proliferation, Migration and Invasion of Cancer Cell in Hepatocellular Carcinoma by Downregulating lncRNA-UCA1,” v 12 (2019): 4509–4516.

[267]

Y. Yao, F. Shu, F. Wang, et al., “Long Noncoding RNA LINC01189 Is Associated With HCV-hepatocellular Carcinoma and Regulates Cancer Cell Proliferation and Chemoresistance Through Hsa-miR-155-5p,” Annals of Hepatology 22 (2021): 100269.

[268]

D. A. Gaber, O. Shaker, A. T. Younis, and M. El-Kassas, “LncRNA HULC and miR-122 Expression Pattern in HCC-Related HCV Egyptian Patients,” Genes (Basel) 13, no. 9 (2022): 1669.

[269]

S. K. Tripathi, A. Pal, S. Ghosh, et al., “LncRNA NEAT1 Regulates HCV-induced Hepatocellular Carcinoma by Modulating the miR-9-BGH3 Axis,” Journal of General Virology 103, no. 12 (2022).

[270]

X. Tang, H. Ren, M. Guo, J. Qian, Y. Yang, and C. Gu, “Review on Circular RNAs and New Insights Into Their Roles in Cancer,” Computational and Structural Biotechnology Journal 19 (2021): 910–928.

[271]

T. C. Zhou, X. Li, L. J. Chen, et al., “Differential Expression Profile of Hepatic Circular RNAs in Chronic hepatitis B,” Journal of Viral Hepatitis 25, no. 11 (2018): 1341–1351.

[272]

L. Zhang and Z. Wang, “Circular RNA hsa_circ_0004812 Impairs IFN-induced Immune Response by Sponging miR-1287-5p to Regulate FSTL1 in Chronic hepatitis B,” Virology Journal 17, no. 1 (2020): 40.

[273]

R. Liao, L. Liu, J. Zhou, X. Wei, and P. Huang, “Current Molecular Biology and Therapeutic Strategy Status and Prospects for circRNAs in HBV-Associated Hepatocellular Carcinoma,” Frontiers in Oncology 11 (2021): 697747.

[274]

X. Y. Huang, Z. L. Huang, P. B. Zhang, et al., “CircRNA-100338 Is Associated with mTOR Signaling Pathway and Poor Prognosis in Hepatocellular Carcinoma,” Frontiers in Oncology 9 (2019): 392.

[275]

X. Rao, L. Lai, X. Li, L. Wang, A. Li, and Q. Yang, “N(6) - methyladenosine Modification of Circular RNA Circ-ARL3 Facilitates Hepatitis B Virus-associated Hepatocellular Carcinoma via Sponging miR-1305,” Iubmb Life 73, no. 2 (2021): 408–417.

[276]

W. Jiang, L. Wang, Y. Zhang, and H. Li, “Circ-ATP5H Induces Hepatitis B Virus Replication and Expression by Regulating miR-138-5p/TNFAIP3 Axis,” Cancer Management and Research 12 (2020): 11031–11040.

[277]

N. M. Aborehab, M. A. Kandeil, D. Sabry, R. Rabie, and I. T. Ibrahim, “Circular SERPINA3 and Its Target microRNA-944 as Potential Biomarkers in hepatitis C Virus-induced Hepatocellular Carcinoma in Egyptian Population,” Non-Coding RNA Research 8, no. 3 (2023): 401–412.

[278]

W. Chen, Y. Quan, S. Fan, et al., “Exosome-transmitted Circular RNA hsa_circ_0051443 Suppresses Hepatocellular Carcinoma Progression,” Cancer Letters 475 (2020): 119–128.

[279]

H. J. Forman and H. Zhang, “Targeting Oxidative Stress in Disease: Promise and Limitations of Antioxidant Therapy,” Nature Reviews Drug Discovery 20, no. 9 (2021): 689–709.

[280]

M. K. Brahma, E. H. Gilglioni, L. Zhou, E. Trepo, P. Chen, and E. N. Gurzov, “Oxidative Stress in Obesity-associated Hepatocellular Carcinoma: Sources, Signaling and Therapeutic Challenges,” Oncogene 40, no. 33 (2021): 5155–5167.

[281]

X. Zhan, R. Wu, X. H. Kong, et al., “Elevated Neutrophil Extracellular Traps by HBV-mediated S100A9-TLR4/RAGE-ROS Cascade Facilitate the Growth and Metastasis of Hepatocellular Carcinoma,” Cancer Commun (Lond) 43, no. 2 (2023): 225–245.

[282]

H. R. Lee, Y. Y. Cho, G. Y. Lee, D. G. You, Y. D. Yoo, and Y. J. Kim, “A Direct Role for hepatitis B Virus X Protein in Inducing Mitochondrial Membrane Permeabilization,” Journal of Viral Hepatitis 25, no. 4 (2018): 412–420.

[283]

T. He, N. Zhang, L. Wang, B. Wan, X. Wang, and L. Zhang, “GPR43 regulates HBV X Protein (HBx)-induced Inflammatory Response in human LO(2) Hepatocytes,” Biomedicine & Pharmacotherapy 123 (2020): 109737.

[284]

Y. M. Choi, S. Y. Lee, and B. J. Kim, “Naturally Occurring Hepatitis B Virus Mutations Leading to Endoplasmic Reticulum Stress and Their Contribution to the Progression of Hepatocellular Carcinoma,” International Journal of Molecular Sciences 20, no. 3 (2019): 597.

[285]

D. Bender and E. Hildt, “Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis,” International Journal of Molecular Sciences 20, no. 18 (2019): 4659.

[286]

A. V. Ivanov, V. T Valuev-Elliston, D. A. Tyurina, et al., “Oxidative Stress, a Trigger of hepatitis C and B Virus-induced Liver Carcinogenesis,” Oncotarget 8, no. 3 (2017): 3895–3932.

[287]

O. A. Smirnova, O. N. Ivanova, F. S. Mukhtarov, et al., “Analysis of the Domains of Hepatitis C Virus Core and NS5A Proteins That Activate the Nrf2/ARE Cascade,” Acta Naturae 8, no. 3 (2016): 123–127.

[288]

A. Jassey, C. H. Liu, C. A. Changou, C. D. Richardson, H. Y. Hsu, and L. T. Lin, “Hepatitis C Virus Non-Structural Protein 5A (NS5A) Disrupts Mitochondrial Dynamics and Induces Mitophagy,” Cells 8, no. 4 (2019): 290.

[289]

Z. Yi and Z. Yuan, “Hepatitis C Virus-Associated Cancers,” Advances in Experimental Medicine and Biology 1018 (2017): 129–146.

[290]

D. Du, C. Liu, M. Qin, et al., “Metabolic Dysregulation and Emerging Therapeutical Targets for Hepatocellular Carcinoma,” Acta Pharmaceutica Sinica B 12, no. 2 (2022): 558–580.

[291]

A. Allameh, R. Niayesh-Mehr, A. Aliarab, G. Sebastiani, and K. Pantopoulos, “Oxidative Stress in Liver Pathophysiology and Disease,” Antioxidants (Basel) 12, no. 9 (2023): 1653.

[292]

H. Cai, Z. Meng, and F. Yu, “The Involvement of ROS-regulated Programmed Cell Death in Hepatocellular Carcinoma,” Critical Reviews in Oncology/Hematology 197 (2024): 104361.

[293]

P. Bellot, R. Frances, and J. Such, “Pathological Bacterial Translocation in Cirrhosis: Pathophysiology, Diagnosis and Clinical Implications,” Liver International 33, no. 1 (2013): 31–39.

[294]

T. Reiberger, A. Ferlitsch, B. A. Payer, et al., “Non-selective Betablocker Therapy Decreases Intestinal Permeability and Serum Levels of LBP and IL-6 in Patients With Cirrhosis,” Journal of Hepatology 58, no. 5 (2013): 911–921.

[295]

A. Albillos, A. de Gottardi, and M. Rescigno, “The Gut-liver Axis in Liver Disease: Pathophysiological Basis for Therapy,” Journal of Hepatology 72, no. 3 (2020): 558–577.

[296]

Q. Liu, F. Li, Y. Zhuang, et al., “Alteration in Gut Microbiota Associated With hepatitis B and non-hepatitis Virus Related Hepatocellular Carcinoma,” Gut Pathogens 11 (2019): 1.

[297]

H. Huang, Z. Ren, X. Gao, et al., “Integrated Analysis of Microbiome and Host Transcriptome Reveals Correlations Between Gut Microbiota and Clinical Outcomes in HBV-related Hepatocellular Carcinoma,” Genome Medicine 12, no. 1 (2020): 102.

[298]

C. Zheng, F. Lu, B. Chen, et al., “Gut Microbiome as a Biomarker for Predicting Early Recurrence of HBV-related Hepatocellular Carcinoma,” Cancer Science 114, no. 12 (2023): 4717–4731.

[299]

T. Preveden, E. Scarpellini, N. Milic, F. Luzza, and L. Abenavoli, “Gut Microbiota Changes and Chronic hepatitis C Virus Infection,” Expert Review of Gastroenterology & Hepatology 11, no. 9 (2017): 813–819.

[300]

L. Li and J. Ye, “Characterization of Gut Microbiota in Patients With Primary Hepatocellular Carcinoma Received Immune Checkpoint Inhibitors: A Chinese Population-based Study,” Medicine 99, no. 37 (2020): e21788.

[301]

C. Cosseau, D. A. Devine, E. Dullaghan, et al., “The Commensal Streptococcus Salivarius K12 Downregulates the Innate Immune Responses of human Epithelial Cells and Promotes Host-microbe Homeostasis,” Infection and Immunity 76, no. 9 (2008): 4163–4175.

[302]

Y. Zhou, L. Hu, W. Tang, et al., “Hepatic NOD2 Promotes Hepatocarcinogenesis via a RIP2-mediated Proinflammatory Response and a Novel Nuclear Autophagy-mediated DNA Damage Mechanism,” Journal of Hematology & Oncology 14, no. 1 (2021): 9.

[303]

C. Hu, B. Xu, X. Wang, et al., “Gut Microbiota-derived Short-chain Fatty Acids Regulate Group 3 Innate Lymphoid Cells in HCC,” Hepatology 77, no. 1 (2023): 48–64.

[304]

J. Behary, N. Amorim, X. T. Jiang, et al., “Gut Microbiota Impact on the Peripheral Immune Response in Non-alcoholic Fatty Liver Disease Related Hepatocellular Carcinoma,” Nature Communications 12, no. 1 (2021): 187.

[305]

Q. Song, X. Zhang, W. Liu, et al., “Bifidobacterium Pseudolongum-generated Acetate Suppresses Non-alcoholic Fatty Liver Disease-associated Hepatocellular Carcinoma,” Journal of Hepatology 79, no. 6 (2023): 1352–1365.

[306]

H. Ma, L. Yang, Y. Liang, et al., “B. thetaiotaomicron-derived Acetic Acid Modulate Immune Microenvironment and Tumor Growth in Hepatocellular Carcinoma,” Gut Microbes 16, no. 1 (2024): 2297846.

[307]

M. Zare-Bidaki, K. Tsukiyama-Kohara, and M. K. Arababadi, “Toll-Like Receptor 4 and hepatitis B Infection: Molecular Mechanisms and Pathogenesis,” Viral Immunology 27, no. 7 (2014): 321–326.

[308]

A. E. Stone, S. Giugliano, G. Schnell, et al., “Hepatitis C Virus Pathogen Associated Molecular Pattern (PAMP) Triggers Production of Lambda-interferons by human Plasmacytoid Dendritic Cells,” Plos Pathogens 9, no. 4 (2013): e1003316.

[309]

A. Kell, M. Stoddard, H. Li, J. Marcotrigiano, G. M. Shaw, and M. Gale, “Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length,” Journal of Virology 89, no. 21 (2015): 11056–11068.

[310]

S. Lee, A. Goyal, A. S. Perelson, Y. Ishida, and T. Saito, “Suppression of hepatitis B Virus Through Therapeutic Activation of RIG-I and IRF3 Signaling in Hepatocytes,” Iscience 24, no. 1 (2021): 101969.

[311]

A. Suslov, T. Boldanova, X. Wang, S. Wieland, and M. H. Heim, “Hepatitis B Virus Does Not Interfere with Innate Immune Responses in the Human Liver,” Gastroenterology 154, no. 6 (2018): 1778–1790.

[312]

D. Stadler, M. Kachele, A. N. Jones, et al., “Interferon-induced Degradation of the Persistent hepatitis B Virus cccDNA Form Depends on ISG20,” Embo Reports 22, no. 6 (2021): e49568.

[313]

J. Brownell, J. Wagoner, E. S. Lovelace, et al., “Independent, Parallel Pathways to CXCL10 Induction in HCV-infected Hepatocytes,” Journal of Hepatology 59, no. 4 (2013): 701–708.

[314]

S. J. Park and Y. S. Hahn, “Hepatocytes Infected With hepatitis C Virus Change Immunological Features in the Liver Microenvironment,” Clinical and Molecular Hepatology 29, no. 1 (2023): 65–76.

[315]

O. K. Kim, D. E. Nam, and Y. S. Hahn, “The Pannexin 1/Purinergic Receptor P2×4 Pathway Controls the Secretion of MicroRNA-Containing Exosomes by HCV-Infected Hepatocytes,” Hepatology 74, no. 6 (2021): 3409–3426.

[316]

L. Wang, D. Cao, L. Wang, et al., “HCV-associated Exosomes Promote Myeloid-derived Suppressor Cell Expansion via Inhibiting miR-124 to Regulate T Follicular Cell Differentiation and Function,” Cell Discovery 4 (2018): 51.

[317]

L. He, H. Yuan, J. Liang, J. Hong, and C. Qu, “Expression of Hepatic Stellate Cell Activation-related Genes in HBV-, HCV-, and Nonalcoholic Fatty Liver Disease-associated Fibrosis,” PLoS ONE 15, no. 5 (2020): e0233702.

[318]

W. Li, X. Duan, C. Zhu, et al., “Hepatitis B and Hepatitis C Virus Infection Promote Liver Fibrogenesis Through a TGF-beta1-Induced OCT4/Nanog Pathway,” Journal of Immunology 208, no. 3 (2022): 672–684.

[319]

R. Sahu, S. Goswami, G. Narahari Sastry, and R. K. Rawal, “The Preventive and Therapeutic Potential of the Flavonoids in Liver Cirrhosis: Current and Future Perspectives,” Chemistry and Biodiversity 20, no. 2 (2023): e202201029.

[320]

C. Brenner, L. Galluzzi, O. Kepp, and G. Kroemer, “Decoding Cell Death Signals in Liver Inflammation,” Journal of Hepatology 59, no. 3 (2013): 583–594.

[321]

J. Li, S. You, S. Zhang, et al., “Elevated N-methyltransferase Expression Induced by Hepatic Stellate Cells Contributes to the Metastasis of Hepatocellular Carcinoma via Regulation of the CD44v3 Isoform,” Molecular Oncology 13, no. 9 (2019): 1993–2009.

[322]

P. Rawal, H. Siddiqui, M. Hassan, et al., “Endothelial Cell-Derived TGF-beta Promotes Epithelial-Mesenchymal Transition via CD133 in HBx-Infected Hepatoma Cells,” Frontiers in Oncology 9 (2019): 308.

[323]

Y. Cheng, B. Gunasegaran, H. D. Singh, et al., “Non-terminally Exhausted Tumor-resident Memory HBV-specific T Cell Responses Correlate With Relapse-free Survival in Hepatocellular Carcinoma,” Immunity 54, no. 8 (2021): 1825–1840. e7.

[324]

Y. Chen, M. Cheng, and Z. Tian, “Hepatitis B Virus Down-regulates Expressions of MHC Class I Molecules on Hepatoplastoma Cell Line,” Cellular & Molecular Immunology 3, no. 5 (2006): 373–378.

[325]

K. Esser-Nobis, J. Schmidt, K. Nitschke, C. Neumann-Haefelin, R. Thimme, and V. Lohmann, “The Cyclophilin-inhibitor Alisporivir Stimulates Antigen Presentation Thereby Promoting Antigen-specific CD8(+) T Cell Activation,” Journal of Hepatology 64, no. 6 (2016): 1305–1314.

[326]

Y. Jia, J. Zhao, C. Wang, et al., “HBV DNA Polymerase Upregulates the Transcription of PD-L1 and Suppresses T Cell Activity in Hepatocellular Carcinoma,” Journal of Translational Medicine 22, no. 1 (2024): 272.

[327]

W. Xiao, L. F. Jiang, X. Z. Deng, et al., “PD-1/PD-L1 Signal Pathway Participates in HCV F Protein-induced T Cell Dysfunction in Chronic HCV Infection,” Immunologic Research 64, no. 2 (2016): 412–423.

[328]

K. Heim, Sagar, O. Sogukpinar, et al., “Attenuated Effector T Cells Are Linked to Control of Chronic HBV Infection,” Nature Immunology 25, no. 9 (2024): 1650–1662.

[329]

A. M. van der Leun, D. S. Thommen, and T. N. Schumacher, “CD8(+) T Cell States in human Cancer: Insights From Single-cell Analysis,” Nature Reviews Cancer 20, no. 4 (2020): 218–232.

[330]

P. Fisicaro, V. Barili, M. Rossi, et al., “Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches,” Frontiers in Immunology 11 (2020): 849.

[331]

J. Shi, G. Li, L. Liu, et al., “Establishment and Validation of Exhausted CD8+ T Cell Feature as a Prognostic Model of HCC,” Frontiers in Immunology 14 (2023): 1166052.

[332]

L. Zhao, Y. Jin, C. Yang, and C. Li, “HBV-specific CD8 T Cells Present Higher TNF-alpha Expression but Lower Cytotoxicity in Hepatocellular Carcinoma,” Clinical and Experimental Immunology 201, no. 3 (2020): 289–296.

[333]

Q. Bai, R. Li, X. He, et al., “Single-cell Landscape of Immune Cells During the Progression From HBV Infection to HBV Cirrhosis and HBV-associated Hepatocellular Carcinoma,” Frontiers in Immunology 14 (2023): 1320414.

[334]

D. De Battista, F. Zamboni, H. Gerstein, et al., “Molecular Signature and Immune Landscape of HCV-Associated Hepatocellular Carcinoma (HCC): Differences and Similarities With HBV-HCC,” Journal of Hepatocellular Carcinoma 8 (2021): 1399–1413.

[335]

M. Hofmann, C. Tauber, N. Hensel, and R. Thimme, “CD8(+) T Cell Responses During HCV Infection and HCC,” Journal of Clinical Medicine 10, no. 5 (2021): 991.

[336]

Q. Zhang, L. Yang, S. Liu, M. Zhang, and Z. Jin, “Interleukin-35 Suppresses Interleukin-9-Secreting CD4(+) T Cell Activity in Patients with Hepatitis B-Related Hepatocellular Carcinoma,” Frontiers in Immunology 12 (2021): 645835.

[337]

Y. Miao, Z. Li, J. Feng, et al., “The Role of CD4(+)T Cells in Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma,” International Journal of Molecular Sciences 25, no. 13 (2024): 6895.

[338]

R. Saxena and J. Kaur, “Th1/Th2 cytokines and Their Genotypes as Predictors of hepatitis B Virus Related Hepatocellular Carcinoma,” World Journal of Hepatology 7, no. 11 (2015): 1572–1580.

[339]

J. Yan, X. L. Liu, G. Xiao, et al., “Prevalence and Clinical Relevance of T-helper Cells, Th17 and Th1, in hepatitis B Virus-related Hepatocellular Carcinoma,” PLoS ONE 9, no. 5 (2014): e96080.

[340]

Y. Shen, S. D. Wu, Y. Chen, et al., “Alterations in Gut Microbiome and Metabolomics in Chronic hepatitis B Infection-associated Liver Disease and Their Impact on Peripheral Immune Response,” Gut Microbes 15, no. 1 (2023): 2155018.

[341]

Y. Ye, X. Xie, J. Yu, et al., “Involvement of Th17 and Th1 Effector Responses in Patients With Hepatitis B,” Journal of Clinical Immunology 30, no. 4 (2010): 546–555.

[342]

K. Benova, M. Hanckova, K. Koci, M. Kudelova, and T. Betakova, “T Cells and Their Function in the Immune Response to Viruses,” Acta Virologica 64, no. 2 (2020): 131–143.

[343]

S. G. Tangye, C. S. Ma, R. Brink, and E. K. Deenick, “The Good, the Bad and the Ugly—TFH Cells in human Health and Disease,” Nature Reviews Immunology 13, no. 6 (2013): 412–426.

[344]

Z. Q. Zhou, D. N. Tong, J. Guan, et al., “Follicular Helper T Cell Exhaustion Induced by PD-L1 Expression in Hepatocellular Carcinoma Results in Impaired Cytokine Expression and B Cell Help, and Is Associated With Advanced Tumor Stages,” American Journal of Translational Research 8, no. 7 (2016): 2926–2936.

[345]

J. Fu, Z. Zhang, L. Zhou, et al., “Impairment of CD4+ Cytotoxic T Cells Predicts Poor Survival and High Recurrence Rates in Patients With Hepatocellular Carcinoma,” Hepatology 58, no. 1 (2013): 139–149.

[346]

K. Dai, L. Huang, X. Sun, L. Yang, and Z. Gong, “Hepatic CD206-positive Macrophages Express Amphiregulin to Promote the Immunosuppressive Activity of Regulatory T Cells in HBV Infection,” Journal of Leukocyte Biology 98, no. 6 (2015): 1071–1080.

[347]

M. Smits, K. Zoldan, N. Ishaque, et al., “Follicular T Helper Cells Shape the HCV-specific CD4+ T Cell Repertoire After Virus Elimination,” Journal of Clinical Investigation 130, no. 2 (2020): 998–1009.

[348]

Y. Gao, M. You, J. Fu, et al., “Intratumoral Stem-Like CCR4+ Regulatory T Cells Orchestrate the Immunosuppressive Microenvironment in HCC Associated With hepatitis B,” Journal of Hepatology 76, no. 1 (2022): 148–159.

[349]

C. J. Lim, Y. H. Lee, L. Pan, et al., “Multidimensional Analyses Reveal Distinct Immune Microenvironment in hepatitis B Virus-related Hepatocellular Carcinoma,” Gut 68, no. 5 (2019): 916–927.

[350]

V. Engelhard, J. R Conejo-Garcia, R. Ahmed, et al., “B Cells and Cancer,” Cancer Cell 39, no. 10 (2021): 1293–1296.

[351]

Y. Chen and Z. Tian, “HBV-Induced Immune Imbalance in the Development of HCC,” Frontiers in Immunology 10 (2019): 2048.

[352]

Y. Cai and W. Yin, “The Multiple Functions of B Cells in Chronic HBV Infection,” Frontiers in Immunology 11 (2020): 582292.

[353]

A. P. Underwood, M. Gupta, B. R. Wu, et al., “B-cell Characteristics Define HCV Reinfection Outcome,” Journal of Hepatology 81, no. 3 (2024): 415–428.

[354]

H. F. Hetta, M. A. Mekky, A. M. Zahran, et al., “Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association With Regulatory T Cells and Disease Progression,” Vaccines (Basel) 8, no. 3 (2020): 380.

[355]

Y. Liu, Y. Luo, T. Zhu, et al., “Regulatory B Cells Dysregulated T Cell Function in an IL-35-Dependent Way in Patients with Chronic Hepatitis B,” Frontiers in Immunology 12 (2021): 653198.

[356]

A. M. Zahran, H. F. Hetta, A. Rayan, et al., “Differential Expression of Tim-3, PD-1, and CCR5 on Peripheral T and B Lymphocytes in hepatitis C Virus-related Hepatocellular Carcinoma and Their Impact on Treatment Outcomes,” Cancer Immunology, Immunotherapy 69, no. 7 (2020): 1253–1263.

[357]

V. Cazzetta, S. Franzese, C. Carenza, S. Della Bella, J. Mikulak, and D. Mavilio, “Natural Killer-Dendritic Cell Interactions in Liver Cancer: Implications for Immunotherapy,” Cancers (Basel) 13, no. 9 (2021): 2184.

[358]

F. Lebosse, B. Testoni, J. Fresquet, et al., “Intrahepatic Innate Immune Response Pathways Are Downregulated in Untreated Chronic hepatitis B,” Journal of Hepatology 66, no. 5 (2017): 897–909.

[359]

M. Sajid, L. Liu, and C. Sun, “The Dynamic Role of NK Cells in Liver Cancers: Role in HCC and HBV Associated HCC and Its Therapeutic Implications,” Frontiers in Immunology 13 (2022): 887186.

[360]

Y. Chen, X. Hao, R. Sun, H. Wei, and Z. Tian, “Natural Killer Cell-Derived Interferon-Gamma Promotes Hepatocellular Carcinoma through the Epithelial Cell Adhesion Molecule-Epithelial-to-Mesenchymal Transition Axis in Hepatitis B Virus Transgenic Mice,” Hepatology 69, no. 4 (2019): 1735–1750.

[361]

B. Zheng, Y. Yang, Q. Han, C. Yin, Z. Pan, and J. Zhang, “STAT3 directly Regulates NKp46 Transcription in NK Cells of HBeAg-negative CHB Patients,” Journal of Leukocyte Biology 106, no. 4 (2019): 987–996.

[362]

W. C. Huang, N. J. Easom, X. Z. Tang, et al., “T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System,” Journal of Immunology 198, no. 3 (2017): 1172–1182.

[363]

M. O. Diniz, A. Schurich, S. K. Chinnakannan, et al., “NK Cells Limit Therapeutic Vaccine-induced CD8(+)T Cell Immunity in a PD-L1-dependent Manner,” Science Translational Medicine 14, no. 640 (2022): eabi4670.

[364]

Z. Jin, R. Sun, H. Wei, X. Gao, Y. Chen, and Z. Tian, “Accelerated Liver Fibrosis in hepatitis B Virus Transgenic Mice: Involvement of Natural Killer T Cells,” Hepatology 53, no. 1 (2011): 219–229.

[365]

G. F. Njiomegnie, S. A. Read, N. Fewings, J. George, F. McKay, and G. Ahlenstiel, “Immunomodulation of the Natural Killer Cell Phenotype and Response During HCV Infection,” Journal of Clinical Medicine 9, no. 4 (2020): 1030.

[366]

J. Nattermann, G. Feldmann, G. Ahlenstiel, B. Langhans, T. Sauerbruch, and U. Spengler, “Surface Expression and Cytolytic Function of Natural Killer Cell Receptors Is Altered in Chronic hepatitis C,” Gut 55, no. 6 (2006): 869–877.

[367]

C. Zhang, X. M. Wang, S. R. Li, et al., “NKG2A is a NK Cell Exhaustion Checkpoint for HCV Persistence,” Nature Communications 10, no. 1 (2019): 1507.

[368]

T. Miyagi, T. Takehara, K. Nishio, et al., “Altered Interferon-alpha-signaling in Natural Killer Cells From Patients With Chronic hepatitis C Virus Infection,” Journal of Hepatology 53, no. 3 (2010): 424–430.

[369]

S. Crotta, A. Stilla, A. Wack, et al., “Inhibition of Natural Killer Cells Through Engagement of CD81 by the Major hepatitis C Virus Envelope Protein,” Journal of Experimental Medicine 195, no. 1 (2002): 35–41.

[370]

C. T. Tseng and G. R. Klimpel, “Binding of the hepatitis C Virus Envelope Protein E2 to CD81 Inhibits Natural Killer Cell Functions,” Journal of Experimental Medicine 195, no. 1 (2002): 43–49.

[371]

D. Xu, Q. Han, Z. Hou, C. Zhang, and J. Zhang, “miR-146a Negatively Regulates NK Cell Functions via STAT1 Signaling,” Cellular & Molecular Immunology 14, no. 8 (2017): 712–720.

[372]

L. Santangelo, V. Bordoni, C. Montaldo, et al., “Hepatitis C Virus Direct-acting Antivirals Therapy Impacts on Extracellular Vesicles microRNAs Content and on Their Immunomodulating Properties,” Liver International 38, no. 10 (2018): 1741–1750.

[373]

Y. Yang, Q. Han, Z. Hou, C. Zhang, Z. Tian, and J. Zhang, “Exosomes Mediate hepatitis B Virus (HBV) Transmission and NK-cell Dysfunction,” Cellular & Molecular Immunology 14, no. 5 (2017): 465–475.

[374]

K. Cheng, N. Cai, J. Zhu, X. Yang, H. Liang, and W. Zhang, “Tumor-associated Macrophages in Liver Cancer: From Mechanisms to Therapy,” Cancer Commun (Lond) 42, no. 11 (2022): 1112–1140.

[375]

F. Tacke, “Targeting Hepatic Macrophages to Treat Liver Diseases,” Journal of Hepatology 66, no. 6 (2017): 1300–1312.

[376]

G. Song, Y. Shi, M. Zhang, et al., “Global Immune Characterization of HBV/HCV-related Hepatocellular Carcinoma Identifies Macrophage and T-cell Subsets Associated With Disease Progression,” Cell Discovery 6, no. 1 (2020): 90.

[377]

C. L. Yang, R. Song, J. W. Hu, et al., “Integrating Single-cell and Bulk RNA Sequencing Reveals CK19 + Cancer Stem Cells and Their Specific SPP1 + Tumor-associated Macrophage Niche in HBV-related Hepatocellular Carcinoma,” Hepatology International 18, no. 1 (2024): 73–90.

[378]

S. K. Qin, Q. Li, J. Ming Xu, et al., “Icaritin-induced Immunomodulatory Efficacy in Advanced hepatitis B Virus-related Hepatocellular Carcinoma: Immunodynamic Biomarkers and Overall Survival,” Cancer Science 111, no. 11 (2020): 4218–4231.

[379]

Y. Mu, X. H. Ren, D. Han, et al., “Codelivery of HBx-siRNA and Plasmid Encoding IL-12 for Inhibition of Hepatitis B Virus and Reactivation of Antiviral Immunity,” Pharmaceutics 14, no. 7 (2022): 1439.

[380]

E. A. Said, I. Al-Reesi, M. Al-Riyami, et al., “Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells During Chronic HBV Infection,” PLoS ONE 11, no. 6 (2016): e0158265.

[381]

X. Xiang, Y. Wu, X. Q. Lv, et al., “Hepatitis B Virus Infection Promotes M2 Polarization of Macrophages by Upregulating the Expression of B7x in Vivo and in Vitro,” Viral Immunology 35, no. 9 (2022): 597–608.

[382]

P. S. Sung and E. C. Shin, “Immunological Mechanisms for Hepatocellular Carcinoma Risk After Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection,” Journal of Clinical Medicine 10, no. 2 (2021): 221.

[383]

S. J. Rau, E. Hildt, K. Himmelsbach, et al., “CD40 inhibits Replication of hepatitis C Virus in Primary human Hepatocytes by c-Jun N Terminal Kinase Activation Independent From the Interferon Pathway,” Hepatology 57, no. 1 (2013): 23–36.

[384]

G. Swaminathan, D. Pascual, G. Rival, R. Perales-Linares, J. Martin-Garcia, and S. Navas-Martin, “Hepatitis C Virus Core Protein Enhances HIV-1 Replication in human Macrophages Through TLR2, JNK, and MEK1/2-dependent Upregulation of TNF-alpha and IL-6,” Febs Letters 588, no. 18 (2014): 3501–3510.

[385]

B. Saha, K. Kodys, and G. Szabo, “Hepatitis C Virus-Induced Monocyte Differentiation into Polarized M2 Macrophages Promotes Stellate Cell Activation via TGF-beta,” Cellular and Molecular Gastroenterology and Hepatology 2, no. 3 (2016): 302–316. e8.

[386]

Y. Fei, Z. Wang, M. Huang, et al., “MiR-155 Regulates M2 Polarization of hepatitis B Virus-infected Tumour-associated Macrophages Which in Turn Regulates the Malignant Progression of Hepatocellular Carcinoma,” Journal of Viral Hepatitis 30, no. 5 (2023): 417–426.

[387]

Q. Zhang, Y. M. Tsui, V. X. Zhang, et al., “Reciprocal Interactions Between Malignant Cells and Macrophages Enhance Cancer Stemness and M2 Polarization in HBV-associated Hepatocellular Carcinoma,” Theranostics 14, no. 2 (2024): 892–910.

[388]

W. Li, G. Chen, H. Peng, et al., “Research Progress on Dendritic Cells in Hepatocellular Carcinoma Immune Microenvironments,” Biomolecules 14, no. 9 (2024): 1161.

[389]

B. Shi, G. Ren, Y. Hu, S. Wang, Z. Zhang, and Z. Yuan, “HBsAg Inhibits IFN-alpha Production in Plasmacytoid Dendritic Cells Through TNF-alpha and IL-10 Induction in Monocytes,” PLoS ONE 7, no. 9 (2012): e44900.

[390]

C. De Pasquale, S. Campana, C. Barberi, et al., “Human Hepatitis B Virus Negatively Impacts the Protective Immune Crosstalk between Natural Killer and Dendritic Cells,” Hepatology 74, no. 2 (2021): 550–565.

[391]

A. Schurich, L. J. Pallett, M. Lubowiecki, et al., “The Third Signal Cytokine IL-12 Rescues the Anti-viral Function of Exhausted HBV-specific CD8 T Cells,” Plos Pathogens 9, no. 3 (2013): e1003208.

[392]

A. Sacchi, N. Tumino, F. Turchi, et al., “Dendritic Cells Activation Is Associated With Sustained Virological Response to Telaprevir Treatment of HCV-infected Patients,” Clinical Immunology 183 (2017): 82–90.

[393]

S. N. Waggoner, C. H. Hall, and Y. S. Hahn, “HCV Core Protein Interaction With gC1q Receptor Inhibits Th1 Differentiation of CD4+ T Cells via Suppression of Dendritic Cell IL-12 Production,” Journal of Leukocyte Biology 82, no. 6 (2007): 1407–1419.

[394]

S. Zhang, K. Kodys, G. J. Babcock, and G. Szabo, “CD81/CD9 tetraspanins Aid Plasmacytoid Dendritic Cells in Recognition of hepatitis C Virus-infected Cells and Induction of Interferon-alpha,” Hepatology 58, no. 3 (2013): 940–949.

[395]

S. Zhang, B. Saha, K. Kodys, and G. Szabo, “IFN-gamma Production by human Natural Killer Cells in Response to HCV-infected Hepatoma Cells Is Dependent on Accessory Cells,” Journal of Hepatology 59, no. 3 (2013): 442–449.

[396]

Y. Kondo and T. Shimosegawa, “Significant Roles of Regulatory T Cells and Myeloid Derived Suppressor Cells in hepatitis B Virus Persistent Infection and hepatitis B Virus-related HCCs,” International Journal of Molecular Sciences 16, no. 2 (2015): 3307–3322.

[397]

Y. Wang, T. Zhang, M. Sun, et al., “Therapeutic Values of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma: Facts and Hopes,” Cancers (Basel) 13, no. 20 (2021): 5127.

[398]

L. J. Pallett, U. S. Gill, A. Quaglia, et al., “Metabolic Regulation of hepatitis B Immunopathology by Myeloid-derived Suppressor Cells,” Nature Medicine 21, no. 6 (2015): 591–600.

[399]

S. Pal, D. Dey, B. C. Chakraborty, et al., “Diverse Facets of MDSC in Different Phases of Chronic HBV Infection: Impact on HBV-specific T-cell Response and Homing,” Hepatology 76, no. 3 (2022): 759–774.

[400]

M. S. Hayden and S. Ghosh, “Shared Principles in NF-kappaB Signaling,” Cell 132, no. 3 (2008): 344–362.

[401]

L. X. Yu, Y. Ling, and H. Y. Wang, “Role of Nonresolving Inflammation in Hepatocellular Carcinoma Development and Progression,” NPJ Precision Oncology 2, no. 1 (2018): 6.

[402]

L. Ye, T. Chen, J. Cao, L. Sun, W. Li, and C. Zhang, “Short Hairpin RNA Attenuates Liver Fibrosis by Regulating the PPAR-Gamma and NF-kappaB Pathways in HBV-Induced Liver Fibrosis in Mice,” International Journal of Oncology 57, no. 5 (2020): 1116–1128.

[403]

S. Shokri, S. Mahmoudvand, R. Taherkhani, F. Farshadpour, and F. A. Jalalian, “Complexity on Modulation of NF-kappaB Pathways by hepatitis B and C: A Double-edged Sword in Hepatocarcinogenesis,” Journal of Cellular Physiology 234, no. 9 (2019): 14734–14742.

[404]

H. R. Kim, S. H. Lee, and G. Jung, “The hepatitis B Viral X Protein Activates NF-kappaB Signaling Pathway Through the Up-regulation of TBK1,” Febs Letters 584, no. 3 (2010): 525–530.

[405]

X. Wu, B. Cai, W. Lu, et al., “HBV Upregulated Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) Expression on Monocytes Participated in Disease Progression Through NF-Kb Pathway,” Clinical Immunology 223 (2021): 108650.

[406]

M. X. Luo, S. H. Wong, M. T. Chan, et al., “Autophagy Mediates HBx-Induced Nuclear Factor-kappaB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes,” Journal of Cellular Physiology 230, no. 10 (2015): 2382–2389.

[407]

L. Chen, X. Lin, Y. Lei, et al., “Aerobic Glycolysis Enhances HBx-initiated Hepatocellular Carcinogenesis via NF-kappaBp65/HK2 Signalling,” Journal of Experimental & Clinical Cancer Research 41, no. 1 (2022): 329.

[408]

X. Song, X. Gao, Y. Wang, et al., “HCV Core Protein Induces Chemokine CCL2 and CXCL10 Expression through NF-kappaB Signaling Pathway in Macrophages,” Frontiers in Immunology 12 (2021): 654998.

[409]

H. C. Lee, S. S. Sung, P. D. Krueger, et al., “Hepatitis C Virus Promotes T-helper (Th)17 Responses Through Thymic Stromal Lymphopoietin Production by Infected Hepatocytes,” Hepatology 57, no. 4 (2013): 1314–1324.

[410]

M. Schank, J. Zhao, L. Wang, et al., “Oxidative Stress Induces Mitochondrial Compromise in CD4 T Cells from Chronically HCV-Infected Individuals,” Frontiers in Immunology 12 (2021): 760707.

[411]

Y. Chen, L. He, Y. Peng, et al., “The hepatitis C Virus Protein NS3 Suppresses TNF-alpha-stimulated Activation of NF-kappaB by Targeting LUBAC,” Science Signaling 8, no. 403 (2015): ra118.

[412]

H. Park, S. Lee, J. Lee, H. Moon, and S. W. Ro, “Exploring the JAK/STAT Signaling Pathway in Hepatocellular Carcinoma: Unraveling Signaling Complexity and Therapeutic Implications,” International Journal of Molecular Sciences 24, no. 18 (2023): 13764.

[413]

M. Ringelhan, S. Schuehle, M. van de Klundert, et al., “HBV-related HCC Development in Mice Is STAT3 Dependent and Indicates an Oncogenic Effect of HBx,” JHEP Reports 6, no. 10 (2024): 101128.

[414]

J. Teng, X. Wang, Z. Xu, and N. Tang, “HBx-dependent Activation of Twist Mediates STAT3 Control of Epithelium-mesenchymal Transition of Liver Cells,” Journal of Cellular Biochemistry 114, no. 5 (2013): 1097–1104.

[415]

J. Lokau, V. Schoeder, J. Haybaeck, and C. Garbers, “Jak-Stat Signaling Induced by Interleukin-6 Family Cytokines in Hepatocellular Carcinoma,” Cancers (Basel) 11, no. 11 (2019): 1704.

[416]

S. A. Lee, H. Kim, Y. S. Won, et al., “Male-specific hepatitis B Virus Large Surface Protein Variant W4P Potentiates Tumorigenicity and Induces Gender Disparity,” Molecular Cancer 14, no. 1 (2015): 23.

[417]

R. S. Tacke, A. Tosello-Trampont, V. Nguyen, D. W. Mullins, and Y. S. Hahn, “Extracellular hepatitis C Virus Core Protein Activates STAT3 in human Monocytes/Macrophages/Dendritic Cells via an IL-6 Autocrine Pathway,” Journal of Biological Chemistry 286, no. 12 (2011): 10847–10855.

[418]

G. Xu, F. Yang, C. L. Ding, et al., “MiR-221 Accentuates IFN׳s Anti-HCV Effect by Downregulating SOCS1 and SOCS3,” Virology 462-463 (2014): 343–350.

[419]

L. Y. Tian, D. J. Smit, and M. Jucker, “The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism,” International Journal of Molecular Sciences 24, no. 3 (2023): 2652.

[420]

Z. Chen, W. Yu, Q. Zhou, et al., “A Novel lncRNA IHS Promotes Tumor Proliferation and Metastasis in HCC by Regulating the ERK-and AKT/GSK-3beta-Signaling Pathways,” Molecular Therapy Nucleic Acids 16 (2019): 707–720.

[421]

W. P. Lee, K. H. Lan, C. P. Li, Y. Chao, H. C. Lin, and S. D. Lee, “Pro-apoptotic or Anti-apoptotic Property of X Protein of hepatitis B Virus Is Determined by Phosphorylation at Ser31 by Akt,” Archives of Biochemistry and Biophysics 528, no. 2 (2012): 156–162.

[422]

M. Zhu, W. Li, Y. Lu, et al., “HBx Drives Alpha Fetoprotein Expression to Promote Initiation of Liver Cancer Stem Cells Through Activating PI3K/AKT Signal Pathway,” International Journal of Cancer 140, no. 6 (2017): 1346–1355.

[423]

S. Rawat and M. J. Bouchard, “The hepatitis B Virus (HBV) HBx Protein Activates AKT to Simultaneously Regulate HBV Replication and Hepatocyte Survival,” Journal of Virology 89, no. 2 (2015): 999–1012.

[424]

J. Zhao, T. Zhang, G. Chen, et al., “Non-Structural Protein 3 of Duck Tembusu Virus Induces Autophagy via the ERK and PI3K-AKT-mTOR Signaling Pathways,” Frontiers in Immunology 13 (2022): 746890.

[425]

Y. C. Kuo, I. Y. Chen, S. C. Chang, et al., “Hepatitis C Virus NS5A Protein Enhances Gluconeogenesis Through Upregulation of Akt-/JNK-PEPCK Signalling Pathways,” Liver International 34, no. 9 (2014): 1358–1368.

[426]

H. Nakamura, H. Aoki, O. Hino, and M. Moriyama, “HCV Core Protein Promotes Heparin Binding EGF-Like Growth Factor Expression and Activates Akt,” Hepatology Research 41, no. 5 (2011): 455–462.

[427]

H. Moon and S. W. Ro, “MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma,” Cancers (Basel) 13, no. 12 (2021): 3026.

[428]

R. Chin, L. Earnest-Silveira, B. Koeberlein, et al., “Modulation of MAPK Pathways and Cell Cycle by Replicating hepatitis B Virus: Factors Contributing to Hepatocarcinogenesis,” Journal of Hepatology 47, no. 3 (2007): 325–337.

[429]

J. Torresi, B. M. Tran, D. Christiansen, L. Earnest-Silveira, R. H. M. Schwab, and E. Vincan, “HBV-related Hepatocarcinogenesis: The Role of Signalling Pathways and Innovative Ex Vivo Research Models,” BMC Cancer 19, no. 1 (2019): 707.

[430]

R. Chin, U. Nachbur, L. Earnest-Silveira, et al., “Dysregulation of Hepatocyte Cell Cycle and Cell Viability by hepatitis B Virus,” Virus Research 147, no. 1 (2010): 7–16.

[431]

L. Stockl, A. Berting, B. Malkowski, R. Foerste, P. H. Hofschneider, and E. Hildt, “Integrity of c-Raf-1/MEK Signal Transduction Cascade Is Essential for hepatitis B Virus Gene Expression,” Oncogene 22, no. 17 (2003): 2604–2610.

[432]

M. Benkheil, J. Paeshuyse, J. Neyts, M. Van Haele, T. Roskams, and S. Liekens, “HCV-induced EGFR-ERK Signaling Promotes a Pro-inflammatory and Pro-angiogenic Signature Contributing to Liver Cancer Pathogenesis,” Biochemical Pharmacology 155 (2018): 305–315.

[433]

L. Zhao, X. Sun, L. Chen, et al., “Hepatitis C Virus Core Protein Promotes the Metastasis of Human Hepatocytes by Activating the MAPK/ERK/PEA3-SRF/c-Fos/MMPs Axis,” Archives of Medical Research 53, no. 5 (2022): 469–482.

[434]

M. Atif, M. A. Mustaan, S. Falak, A. Ghaffar, and B. Munir, “Targeting the Effect of Sofosbuvir on Selective Oncogenes Expression Level of Hepatocellular Carcinoma Ras/Raf/MEK/ERK Pathway in Huh7 Cell Line,” Saudi Journal of Biological Sciences 29, no. 8 (2022): 103332.

[435]

L. Kalantari, Z. R. Ghotbabadi, A. Gholipour, et al., “A state-of-the-art Review on the NRF2 in Hepatitis Virus-associated Liver Cancer,” Cell Communication and Signaling 21, no. 1 (2023): 318.

[436]

W. W. Wasserman and W. E. Fahl, “Functional Antioxidant Responsive Elements,” PNAS 94, no. 10 (1997): 5361–5366.

[437]

S. Schaedler, J. Krause, K. Himmelsbach, et al., “Hepatitis B Virus Induces Expression of Antioxidant Response Element-regulated Genes by Activation of Nrf2,” Journal of Biological Chemistry 285, no. 52 (2010): 41074–41086.

[438]

X. Xiang, H. G. Qin, X. M. You, et al., “Expression of P62 in Hepatocellular Carcinoma Involving hepatitis B Virus Infection and Aflatoxin B1 Exposure,” Cancer Medicine 6, no. 10 (2017): 2357–2369.

[439]

M. L. Cheng, Y. F. Lu, H. Chen, Z. Y. Shen, and J. Liu, “Liver Expression of Nrf2-related Genes in Different Liver Diseases,” Hepatobiliary & Pancreatic Diseases International 14, no. 5 (2015): 485–491.

[440]

Y. Jiang, H. Bao, Y. Ge, et al., “Therapeutic Targeting of GSK3beta Enhances the Nrf2 Antioxidant Response and Confers Hepatic Cytoprotection in hepatitis C,” Gut 64, no. 1 (2015): 168–179.

[441]

H. Shi, Y. Zou, W. Zhong, et al., “Complex Roles of Hippo-YAP/TAZ Signaling in Hepatocellular Carcinoma,” Journal of Cancer Research and Clinical Oncology 149, no. 16 (2023): 15311–15322.

[442]

I. M. Moya and G. Halder, “Hippo-YAP/TAZ Signalling in Organ Regeneration and Regenerative Medicine,” Nature Reviews Molecular Cell Biology 20, no. 4 (2019): 211–226.

[443]

N. Liu, J. Zhang, X. Yang, et al., “HDM2 Promotes NEDDylation of Hepatitis B Virus HBx To Enhance Its Stability and Function,” Journal of Virology 91, no. 16 (2017): e00340.

[444]

C. Oda, K. Kamimura, O. Shibata, et al., “HBx and YAP Expression Could Promote Tumor Development and Progression in HBV-related Hepatocellular Carcinoma,” Biochemistry and Biophysics Reports 32 (2022): 101352.

[445]

P. Liu, H. Zhang, X. Liang, et al., “HBV preS2 Promotes the Expression of TAZ via miRNA-338-3p to Enhance the Tumorigenesis of Hepatocellular Carcinoma,” Oncotarget 6, no. 30 (2015): 29048–29059.

[446]

D. Sweed, A. Abd-Elbary, E. Sweed, et al., “Expression of Cyclo-oxygenase-2 and Yap/Taz in Hepatocellular Carcinoma in Untreated and Treated hepatitis C Virus Patients,” Polish Journal of Pathology 73, no. 2 (2022): 88–98.

[447]

Y. Xue, W. M. Mars, W. Bowen, A. D. Singhi, J. Stoops, and G. K. Michalopoulos, “Hepatitis C Virus Mimics Effects of Glypican-3 on CD81 and Promotes Development of Hepatocellular Carcinomas via Activation of Hippo Pathway in Hepatocytes,” American Journal of Pathology 188, no. 6 (2018): 1469–1477.

[448]

Y. Xue, B. Bhushan, W. M. Mars, et al., “Phosphorylated Ezrin (Thr567) Regulates Hippo Pathway and Yes-Associated Protein (Yap) in Liver,” American Journal of Pathology 190, no. 7 (2020): 1427–1437.

[449]

C. Xu, Z. Xu, Y. Zhang, M. Evert, D. F. Calvisi, and X. Chen, “beta-Catenin Signaling in Hepatocellular Carcinoma,” Journal of Clinical Investigation 132, no. 4 (2022): e154515.

[450]

S. S. Kim, H. J. Cho, H. Y. Lee, et al., “Genetic Polymorphisms in the Wnt/Beta-catenin Pathway Genes as Predictors of Tumor Development and Survival in Patients With hepatitis B Virus-associated Hepatocellular Carcinoma,” Clinical Biochemistry 49, no. 10-11 (2016): 792–801.

[451]

S. W. Li, L. F. Han, Y. He, and X. S. Wang, “Immunological Classification of hepatitis B Virus-positive Hepatocellular Carcinoma by Transcriptome Analysis,” World Journal of Hepatology 14, no. 12 (2022): 1997–2011.

[452]

H. Yoon and K. L. Jang, “Hepatitis B Virus X Protein and hepatitis C Virus Core Protein Cooperate to Repress E-cadherin Expression via DNA Methylation,” Heliyon 8, no. 7 (2022): e09881.

[453]

P. Huang, Q. Xu, Y. Yan, et al., “HBx/ERalpha Complex-mediated LINC01352 Downregulation Promotes HBV-related Hepatocellular Carcinoma via the miR-135b-APC Axis,” Oncogene 39, no. 18 (2020): 3774–3789.

[454]

W. Chung, M. Kim, S. de la Monte, et al., “Activation of Signal Transduction Pathways During Hepatic Oncogenesis,” Cancer Letters 370, no. 1 (2016): 1–9.

[455]

F. Pezzuto, L. Buonaguro, F. M. Buonaguro, and M. L. Tornesello, “Frequency and Geographic Distribution of TERT Promoter Mutations in Primary Hepatocellular Carcinoma,” Infectious Agents and Cancer 12 (2017): 27.

[456]

S. Mahmoudvand, S. Shokri, R. Taherkhani, and F. Farshadpour, “Hepatitis C Virus Core Protein Modulates Several Signaling Pathways Involved in Hepatocellular Carcinoma,” World Journal of Gastroenterology 25, no. 1 (2019): 42–58.

[457]

W. Wang, Q. Pan, G. M. Fuhler, R. Smits, and M. P. Peppelenbosch, “Action and Function of Wnt/Beta-catenin Signaling in the Progression From Chronic hepatitis C to Hepatocellular Carcinoma,” Journal of Gastroenterology 52, no. 4 (2017): 419–431.

[458]

X. Wang, Y. Zhou, C. Wang, et al., “HCV Core Protein Represses DKK3 Expression via Epigenetic Silencing and Activates the Wnt/Beta-catenin Signaling Pathway During the Progression of HCC,” Clinical & Translational Oncology 24, no. 10 (2022): 1998–2009.

[459]

M. A. Rana, B. Ijaz, M. Daud, S. Tariq, T. Nadeem, and T. Husnain, “Interplay of Wnt Beta-catenin Pathway and miRNAs in HBV Pathogenesis Leading to HCC,” Clinics and Research in Hepatology and Gastroenterology 43, no. 4 (2019): 373–386.

[460]

C. Y. Park, S. H. Choi, S. M. Kang, et al., “Nonstructural 5A Protein Activates Beta-catenin Signaling Cascades: Implication of hepatitis C Virus-induced Liver Pathogenesis,” Journal of Hepatology 51, no. 5 (2009): 853–864.

[461]

K. Engeland, “Cell Cycle Arrest Through Indirect Transcriptional Repression by p53: I Have a DREAM,” Cell Death and Differentiation 25, no. 1 (2018): 114–132.

[462]

S. Knoll, K. Furst, S. Thomas, et al., “Dissection of Cell Context-dependent Interactions Between HBx and p53 family Members in Regulation of Apoptosis: A Role for HBV-induced HCC,” Cell Cycle 10, no. 20 (2011): 3554–3565.

[463]

F. Zhao, N. B. Hou, T. Song, et al., “Cellular DNA Repair Cofactors Affecting hepatitis B Virus Infection and Replication,” World Journal of Gastroenterology 14, no. 32 (2008): 5059–5065.

[464]

S. G. Li, Q. W. Shi, L. Y. Yuan, et al., “C-Myc-dependent Repression of Two Oncogenic miRNA Clusters Contributes to Triptolide-induced Cell Death in Hepatocellular Carcinoma Cells,” Journal of Experimental & Clinical Cancer Research 37, no. 1 (2018): 51.

[465]

X. Xu, Z. Fan, L. Kang, et al., “Hepatitis B Virus X Protein Represses miRNA-148a to Enhance Tumorigenesis,” Journal of Clinical Investigation 123, no. 2 (2013): 630–645.

[466]

X. W. Wang, K. Forrester, H. Yeh, M. A. Feitelson, J. R. Gu, and C. C. Harris, “Hepatitis B Virus X Protein Inhibits p53 Sequence-specific DNA Binding, Transcriptional Activity, and Association With Transcription Factor ERCC3,” PNAS 91, no. 6 (1994): 2230–2234.

[467]

C. Ye, H. Tang, Z. Zhao, et al., “MDM2 mediates Fibroblast Activation and Renal Tubulointerstitial Fibrosis via a p53-independent Pathway,” American Journal of Physiology. Renal Physiology 312, no. 4 (2017): F760–F768.

[468]

W. S. Mason, U. S. Gill, S. Litwin, et al., “HBV DNA Integration and Clonal Hepatocyte Expansion in Chronic Hepatitis B Patients Considered Immune Tolerant,” Gastroenterology 151, no. 5 (2016): 986–998. e4.

[469]

Y. L. Seo, S. Heo, and K. L. Jang, “Hepatitis C Virus Core Protein Overcomes H2O2-induced Apoptosis by Downregulating p14 Expression via DNA Methylation,” Journal of General Virology 96, no. Pt 4 (2015): 822–832.

[470]

F. A. Dick and S. M. Rubin, “Molecular Mechanisms Underlying RB Protein Function,” Nature Reviews Molecular Cell Biology 14, no. 5 (2013): 297–306.

[471]

A. D. Dearborn and J. Marcotrigiano, “Hepatitis C Virus Structure: Defined by What It Is Not,” Cold Spring Harbor Perspectives in Medicine 10, no. 1 (2020): a036822.

[472]

H. Cao, X. Chen, Z. Wang, L. Wang, Q. Xia, and W. Zhang, “The Role of MDM2-p53 Axis Dysfunction in the Hepatocellular Carcinoma Transformation,” Cell Death Discovery 6 (2020): 53.

[473]

R. S. Apte, D. S. Chen, and N. Ferrara, “VEGF in Signaling and Disease: Beyond Discovery and Development,” Cell 176, no. 6 (2019): 1248–1264.

[474]

S. X. Wu, S. S. Ye, Y. X. Hong, et al., “Hepatitis B Virus Small Envelope Protein Promotes Hepatocellular Carcinoma Angiogenesis via Endoplasmic Reticulum Stress Signaling To Upregulate the Expression of Vascular Endothelial Growth Factor A,” Journal of Virology 96, no. 4 (2022): e0197521.

[475]

I. J. Su, L. H. Wang, W. C. Hsieh, et al., “The Emerging Role of hepatitis B Virus Pre-S2 Deletion Mutant Proteins in HBV Tumorigenesis,” Journal of Biomedical Science 21, no. 1 (2014): 98.

[476]

Z. B. Chen, S. Q. Shen, Y. M. Ding, et al., “The Angiogenic and Prognostic Implications of VEGF, Ang-1, Ang-2, and MMP-9 for Hepatocellular Carcinoma With Background of hepatitis B Virus,” Medical Oncology 26, no. 3 (2009): 365–371.

[477]

T. Vescovo, G. Refolo, G. Vitagliano, G. M. Fimia, and M. Piacentini, “Molecular Mechanisms of hepatitis C Virus-induced Hepatocellular Carcinoma,” Clinical Microbiology and Infection 22, no. 10 (2016): 853–861.

[478]

Y. Li, J. Chen, C. Wu, L. Wang, M. Lu, and X. Chen, “Hepatitis B Virus/hepatitis C Virus Upregulate Angiopoietin-2 Expression Through Mitogen-activated Protein Kinase Pathway,” Hepatology Research 40, no. 10 (2010): 1022–1033.

[479]

S. C. R Carvalho, L. R. S. Vasconcelos, L. D. Fonseca, et al., “Methylene Tetrahydrofolate Reductase (MTHFR) and Vascular Endothelial Growth Factor (VEGF) Polymorphisms in Brazilian Patients With Hepatitis C Virus (HCV)-related Hepatocellular Carcinoma (HCC),” Clinics (Sao Paulo) 76 (2021): e2881.

[480]

T. Kanda, R. Steele, R. Ray, and R. B. Ray, “Hepatitis C Virus Core Protein Augments Androgen Receptor-mediated Signaling,” Journal of Virology 82, no. 22 (2008): 11066–11072.

[481]

Y. Y. Shao, M. S. Hsieh, H. Y. Wang, et al., “Hepatitis C Virus Core Protein Potentiates Proangiogenic Activity of Hepatocellular Carcinoma Cells,” Oncotarget 8, no. 49 (2017): 86681–86692.

[482]

M. T. Ngo, H. Y. Jeng, Y. C. Kuo, et al., “The Role of IGF/IGF-1R Signaling in Hepatocellular Carcinomas: Stemness-Related Properties and Drug Resistance,” International Journal of Molecular Sciences 22, no. 4 (2021): 1931.

[483]

Y. Ji, Z. Wang, H. Chen, L. Zhang, F. Zhuo, and Q. Yang, “Serum From Chronic Hepatitis B Patients Promotes Growth and Proliferation via the IGF-II/IGF-IR/MEK/ERK Signaling Pathway in Hepatocellular Carcinoma Cells,” Cellular Physiology and Biochemistry 47, no. 1 (2018): 39–53.

[484]

P. Scalia, A. Giordano, and S. J. Williams, “The IGF-II-Insulin Receptor Isoform-A Autocrine Signal in Cancer: Actionable Perspectives,” Cancers (Basel) 12, no. 2 (2020): 366.

[485]

W. W. Su, K. T. Lee, Y. T. Yeh, et al., “Association of Circulating Insulin-Like Growth Factor 1 With Hepatocellular Carcinoma: One Cross-sectional Correlation Study,” Journal of Clinical Laboratory Analysis 24, no. 3 (2010): 195–200.

[486]

S. Lacin, S. Yalcin, Y. Karakas, et al., “Prognostic Significance of Serum Insulin-Like Growth Factor-1 in Hepatocellular Cancer Patients: A Validation Study,” J Hepatocell Carcinoma 7 (2020): 143–153.

[487]

M. A. Abu El-Makarem, M. F. Kamel, A. A. Mohamed, et al., “Down-regulation of Hepatic Expression of GHR/STAT5/IGF-1 Signaling Pathway Fosters Development and Aggressiveness of HCV-related Hepatocellular Carcinoma: Crosstalk With Snail-1 and Type 2 Transforming Growth Factor-beta Receptor,” PLoS ONE 17, no. 11 (2022): e0277266.

[488]

T. S. Chang, Y. C. Wu, C. C. Chi, et al., “Activation of IL6/IGFIR Confers Poor Prognosis of HBV-related Hepatocellular Carcinoma Through Induction of OCT4/NANOG Expression,” Clinical Cancer Research 21, no. 1 (2015): 201–210.

[489]

J. F. Hu, Z. Cheng, F. V. Chisari, T. H. Vu, A. R. Hoffman, and T. C. Campbell, “Repression of hepatitis B Virus (HBV) Transgene and HBV-induced Liver Injury by Low Protein Diet,” Oncogene 15, no. 23 (1997): 2795–2801.

[490]

L. S. Yang, L. J. Yan, G. X. Meng, et al., “The Association of Glycemic Index, Glycemic Load, and Daily Carbohydrates Intake With the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis,” Nutrition and Cancer 75, no. 2 (2023): 461–469.

[491]

W. P. Koh, Y. Y. Dan, G. B. Goh, A. Jin, R. Wang, and J. M. Yuan, “Dietary Fatty Acids and Risk of Hepatocellular Carcinoma in the Singapore Chinese Health Study,” Liver International 36, no. 6 (2016): 893–901.

[492]

C. X. Yu, Y. S. Chen, Z. J. Ge, et al., “Dietary Habits and Risk of Hepatocellular Carcinoma Among hepatitis B Surface Antigen Carriers: A Prospective Cohort Study in China,” Journal of Digestive Diseases 21, no. 7 (2020): 406–415.

[493]

Y. Li, S. C. Chang, B. Y. Goldstein, et al., “Green Tea Consumption, Inflammation and the Risk of Primary Hepatocellular Carcinoma in a Chinese Population,” Cancer Epidemiology 35, no. 4 (2011): 362–368.

[494]

Y. Shadi, B. Heshmati, and J. Poorolajal, “Interaction Between hepatitis B, hepatitis C and Smoking in the Development of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis,” Journal of Public Health (Oxford, England) 46, no. 1 (2024): 51–60.

[495]

Y. H. Wang, Y. H. Chuang, C. F. Wu, et al., “Smoking and Hepatitis B Virus-Related Hepatocellular Carcinoma Risk: The Mediating Roles of Viral Load and Alanine Aminotransferase,” Hepatology 69, no. 4 (2019): 1412–1425.

[496]

A. Iida-Ueno, M. Enomoto, A. Tamori, and N. Kawada, “Hepatitis B Virus Infection and Alcohol Consumption,” World Journal of Gastroenterology 23, no. 15 (2017): 2651–2659.

[497]

S. Yapali, N. Talaat, and A. S. Lok, “Management of hepatitis B: Our Practice and How It Relates to the Guidelines,” Clinical Gastroenterology and Hepatology 12, no. 1 (2014): 16–26.

[498]

Q. Zhao, H. Liu, L. D. Tang, et al., “Mechanism of Interferon Alpha Therapy for Chronic hepatitis B and Potential Approaches to Improve Its Therapeutic Efficacy,” Antiviral Research 221 (2024): 105782.

[499]

S. K. Kim, T. Fujii, S. R. Kim, et al., “Hepatitis B Virus Treatment and Hepatocellular Carcinoma-controversies and Approaches to Consensus,” Liver Cancer 11, no. 6 (2022): 497–510.

[500]

Y. N. Lamb, “Glecaprevir/Pibrentasvir: First Global Approval,” Drugs 77, no. 16 (2017): 1797–1804.

[501]

Z. T. Al-Salama and E. D. Deeks, “Elbasvir/Grazoprevir: A Review in Chronic HCV Genotypes 1 and 4,” Drugs 77, no. 8 (2017): 911–921.

[502]

O. M. Klibanov, S. E. Gale, and B. Santevecchi, “Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir Tablets for Hepatitis C Virus Genotype 1 Infection,” Annals of Pharmacotherapy 49, no. 5 (2015): 566–581.

[503]

Z. Li, F. Yao, G. Xue, et al., “Antiviral Effects of Simeprevir on Multiple Viruses,” Antiviral Research 172 (2019): 104607.

[504]

E. B. Chahine, D. Kelley, and L. M. Childs-Kean, “Sofosbuvir/Velpatasvir/Voxilaprevir: A Pan-Genotypic Direct-Acting Antiviral Combination for Hepatitis C,” Annals of Pharmacotherapy 52, no. 4 (2018): 352–363.

[505]

N. Sabry, A. M. Kamel, A. Cordie, and G. Esmat, “Daclatasvir as a hepatitis C Infection Treatment Option: An up-to-date Evaluation,” Expert Opinion on Pharmacotherapy 24, no. 2 (2023): 159–170.

[506]

E. S. Rosenthal, S. Kottilil, and M. A. Polis, “Sofosbuvir and Ledipasvir for HIV/HCV co-infected Patients,” Expert Opinion on Pharmacotherapy 17, no. 5 (2016): 743–749.

[507]

S. Ahmed, N. Ullah, S. Parveen, et al., “Effect of Silymarin as an Adjunct Therapy in Combination With Sofosbuvir and Ribavirin in Hepatitis C Patients: A Miniature Clinical Trial,” Oxidative Medicine and Cellular Longevity 2022 (2022): 9199190.

[508]

R. Dong, R. Zhang, C. Shen, et al., “Urinary Caffeine and Its Metabolites in Association With Advanced Liver Fibrosis and Liver Steatosis: A Nationwide Cross-sectional Study,” Food & Function 15, no. 4 (2024): 2064–2077.

[509]

E. E Vargas-Pozada, E. Ramos-Tovar, C. Acero-Hernandez, et al., “Caffeine Mitigates Experimental Nonalcoholic Steatohepatitis and the Progression of Thioacetamide-induced Liver Fibrosis by Blocking the MAPK and TGF-beta/Smad3 Signaling Pathways,” Annals of Hepatology 27, no. 2 (2022): 100671.

[510]

E. E Vargas-Pozada, E. Ramos-Tovar, J. D Rodriguez-Callejas, et al., “Caffeine Inhibits NLRP3 Inflammasome Activation by Downregulating TLR4/MAPK/NF-κB Signaling Pathway in an Experimental NASH Model,” International Journal of Molecular Sciences 23, no. 17 (2022): 9954.

[511]

J. Z. Yi, S. Y. Wu, S. W. Tan, et al., “Berberine Alleviates Liver Fibrosis Through Inducing Ferrous Redox to Activate ROS-mediated Hepatic Stellate Cells Ferroptosis,” Cell Death Discov 7, no. 1 (2021): 374.

[512]

X. Z. Liu, L. F. Wang, S. W. Tan, Z. B. Chen, B. Wu, and X. Y. Wu, “Therapeutic Effects of Berberine on Liver Fibrosis Are Associated with Lipid Metabolism and Intestinal Flora,” Frontiers in Pharmacology 13 (2022): 814871.

[513]

D. S. Kong, Z. L. Zhang, L. P. Chen, et al., “Curcumin Blunts Epithelial-mesenchymal Transition of Hepatocytes to Alleviate Hepatic Fibrosis Through Regulating Oxidative Stress and Autophagy,” Redox Biology 36 (2020): 101600.

[514]

M. M. Guo, Z. D. Wang, J. Y. Dai, et al., “Glycyrrhizic Acid Alleviates Liver Fibrosis and via Activating CUGBP1-mediated IFN-γ/STAT1/Smad7 Pathway,” Phytomedicine 112 (2023): 154587.

[515]

D. J. Xiang, J. Zou, X. Y. Zhu, et al., “Physalin D Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis by Blocking TGF-β/Smad and YAP Signaling,” Phytomedicine 78 (2020): 153294.

[516]

K. Chen, W. R. Guo, R. X. Li, Y. Q. Han, Q. Gao, and S. Z. Wang, “Demethylzeylasteral Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis by Inhibiting AGAP2 Mediated Signaling,” Phytomedicine 105 (2022): 154349.

[517]

P. P. Chen, R. Wang, F. B. Liu, et al., “Schizandrin C Regulates Lipid Metabolism and Inflammation in Liver Fibrosis by NF-κB and p38/ERK MAPK Signaling Pathways,” Frontiers in Pharmacology 14 (2023): 1092151.

[518]

M. Shi, Y. Y. Li, R. N. Xu, et al., “Mesenchymal Stem Cell Therapy in Decompensated Liver Cirrhosis: A Long-term Follow-up Analysis of the Randomized Controlled Clinical Trial,” Hepatology International 15, no. 6 (2021): 1431–1441.

[519]

H. Salama, A. R. N. Zekri, E. Medhat, et al., “Peripheral Vein Infusion of Autologous Mesenchymal Stem Cells in Egyptian HCV-positive Patients With End-stage Liver Disease,” Stem Cell Research & Therapy 8 (2014): 70.

[520]

P. Chen, M. Q. Yuan, L. C. Yao, et al., “Human Umbilical Cord-derived Mesenchymal Stem Cells Ameliorate Liver Fibrosis by Improving Mitochondrial Function via Slc25a47-Sirt3 Signaling Pathway,” Biomedicine & Pharmacotherapy 171 (2024): 116133.

[521]

W. Y. Chen, F. Y. Lin, X. D. Feng, et al., “MSC-derived Exosomes Attenuate Hepatic Fibrosis in Primary Sclerosing Cholangitis Through Inhibition of Th17 Differentiation,” Asian Journal of Pharmaceutical Sciences 19, no. 1 (2024): 100889.

[522]

F. Cheng, F. J. Yang, Y. J. Wang, J. Zhou, H. Qian, and Y. M. Yan, “Mesenchymal Stem Cell-derived Exosomal miR-27b-3p Alleviates Liver Fibrosis via Downregulating YAP/LOXL2 Pathway,” Journal of Nanbiotechnology 21, no. 1 (2023): 195.

[523]

Y. H. Li, S. Shen, T. Shao, et al., “Mesenchymal Stem Cells Attenuate Liver Fibrosis by Targeting Ly6C(hi/lo) Macrophages Through Activating the Cytokine-paracrine and Apoptotic Pathways,” Cell Death Discovery 7, no. 1 (2021): 239.

[524]

J. Kim, C. B. Lee, Y. B. Shin, et al., “sEVs From Tonsil-derived Mesenchymal Stromal Cells Alleviate Activation of Hepatic Stellate Cells and Liver Fibrosis Through miR-486-5p,” Molecular Therapy 29, no. 4 (2020): 1471–1486.

[525]

Q. Q. Fan, H. Tian, J. X. Cheng, et al., “Research Progress of sorafenib Drug Delivery System in the Treatment of Hepatocellular Carcinoma: An Update,” Biomedicine & Pharmacotherapy 177 (2024): 117118.

[526]

Z. T Al-Salama, Y. Y. Syed, and L. J. Scott, “Lenvatinib: A Review in Hepatocellular Carcinoma,” Drugs 79, no. 6 (2019): 665–674.

[527]

J. Garcia, H. I. Hurwitz, A. B. Sandler, et al., “Bevacizumab (Avastin(R)) in Cancer Treatment: A Review of 15 Years of Clinical Experience and Future Outlook,” Cancer Treatment Reviews 86 (2020): 102017.

[528]

S. J. Keam and S. Duggan, “Donafenib: First Approval,” Drugs 81, no. 16 (2021): 1915–1920.

[529]

A. Granito, A. Forgione, S. Marinelli, et al., “Experience With regorafenib in the Treatment of Hepatocellular Carcinoma,” Therapeutic Advances in Gastroenterology 14 (2021): 17562848211016959.

[530]

R. Z. Shang, X. H. Song, P. Wang, et al., “Cabozantinib-based Combination Therapy for the Treatment of Hepatocellular Carcinoma,” Gut 70, no. 9 (2021): 1746–1757.

[531]

Y. Y. Syed, “Ramucirumab: A Review in Hepatocellular Carcinoma,” Drugs 80, no. 3 (2020): 315–322.

[532]

X. H. Zhang, M. Q. Cao, X. X. Li, and T. Zhang, “Apatinib as an Alternative Therapy for Advanced Hepatocellular Carcinoma,” World Journal of Hepatology 12, no. 10 (2020): 766–774.

[533]

R. K. Kelley, B. Sangro, W. Harris, et al., “Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients with Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study,” Journal of Clinical Oncology 39, no. 27 (2021): 2991.

[534]

T. Yau, Y. K. Kang, T. Y. Kim, et al., “Efficacy and Safety of Nivolumab plus Ipilimumab in Patients with Advanced Hepatocellular Carcinoma Previously Treated with Sorafenib the CheckMate 040 Randomized Clinical Trial,” JAMA Oncology 6, no. 11 (2020): e204564.

[535]

S. K. Qin, Z. D. Chen, W. J. Fang, et al., “Pembrolizumab versus Placebo as Second-Line Therapy in Patients from Asia with Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial,” Journal of Clinical Oncology 41, no. 7 (2023): 1434.

[536]

S. K. Qin, M. Kudo, T. Meyer, et al., “Tislelizumab vs Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma a Phase 3 Randomized Clinical Trial,” JAMA Oncology 9, no. 12 (2023): 1651–1659.

[537]

A. X. Zhu, A. R. Abbas, M. R. de Galarreta, et al., “Molecular Correlates of Clinical Response and Resistance to atezolizumab in Combination With Bevacizumab in Advanced Hepatocellular Carcinoma,” Nature Medicine 28, no. 8 (2022): 1599.

[538]

M. H. Nguyen, G. Wong, E. Gane, J. H. Kao, and G. Dusheiko, “Hepatitis B Virus: Advances in Prevention, Diagnosis, and Therapy,” Clinical Microbiology Reviews 33, no. 2 (2020): e00046.

[539]

M. L. Yeh, J. F. Huang, C. Y. Dai, M. L. Yu, and W. L. Chuang, “Pharmacokinetics and Pharmacodynamics of Pegylated Interferon for the Treatment of hepatitis B,” Expert Opinion on Drug Metabolism & Toxicology 15, no. 10 (2019): 779–785.

[540]

S. K. Lee, J. H. Kwon, S. W. Lee, et al., “Sustained off Therapy Response After Peglyated Interferon Favours Functional Cure and no Disease Progression in Chronic hepatitis B,” Liver International 41, no. 2 (2021): 288–294.

[541]

L. Wu, H. Deng, X. Feng, et al., “Interferon-gamma(+) Th1 Activates Intrahepatic Resident Memory T Cells to Promote HBsAg Loss by Inducing M1 Macrophage Polarization,” Journal of Medical Virology 96, no. 5 (2024): e29627.

[542]

J. X. Luo, Y. Zhang, X. Y. Hu, and N. Xiang, “Interferon Therapy Improves Survival in Patients With hepatitis B Virus-related Hepatocellular Carcinoma After Curative Surgery: A Meta-analysis,” Hepatology International 18, no. 1 (2024): 63–72.

[543]

S. R. R Butt, T. Satnarine, P. Ratna, et al., “A Systematic Review on Current Trends in the Treatment of Chronic Hepatitis B to Predict Disease Remission and Relapse,” The Cureus Journal of Medical Science 14, no. 12 (2022): e32247.

[544]

M. Cornberg, A. S. F. Lok, N. A. Terrault, et al., “Guidance for Design and Endpoints of Clinical Trials in Chronic hepatitis B—Report From the 2019 EASL-AASLD HBV Treatment Endpoints Conferences,” Journal of Hepatology 72, no. 3 (2020): 539–557.

[545]

H. Nishikawa, S. K. Kim, and A. Asai, “Liver Carcinogenesis Suppression in Chronic Hepatitis B in the Nucleoside Analogues Era,” In Vivo (Athens, Greece) 38, no. 1 (2024): 40–47.

[546]

V. W. K Hui, S. L. Chan, V. W. S. Wong, et al., “Increasing Antiviral Treatment Uptake Improves Survival in Patients With HBV-related HCC,” JHEP Reports 2, no. 6 (2020): 100152.

[547]

Y. X. Liang, D. Y. Zhong, Z. L. Zhang, et al., “Impact of Preoperative Antiviral Therapy on the Prognosis of hepatitis B Virus-related Hepatocellular Carcinoma,” BMC Cancer 24, no. 1 (2024): 291.

[548]

Z. H. Huang, G. Y. Lu, L. X. Qiu, et al., “Risk of Hepatocellular Carcinoma in Antiviral Treatment-naive Chronic hepatitis B Patients Treated With Entecavir or Tenofovir Disoproxil Fumarate: A Network Meta-analysis,” BMC Cancer 22, no. 1 (2022): 287.

[549]

F. Carrat, H. Fontaine, C. Dorival, et al., “Clinical Outcomes in Patients With Chronic hepatitis C After Direct-acting Antiviral Treatment: A Prospective Cohort Study,” Lancet 393, no. 10179 (2019): 1453–1464.

[550]

Liver EAS. EASL Recommendations on Treatment of Hepatitis C 2018. Journal of Hepatology 2018; 69(2): 461–511.

[551]

M. Zajac, I. Muszalska, A. Sobczak, A. Dadej, S. Tomczak, and A. Jelinska, “Hepatitis C—New Drugs and Treatment Prospects,” European Journal of Medicinal Chemistry 165 (2019): 225–249.

[552]

W. Sohn, S. Y. Park, T. H. Lee, et al., “Effect of Direct-acting Antivirals on Disease Burden of hepatitis C Virus Infection in South Korea in 2007–2021: A Nationwide, Multicentre, Retrospective Cohort Study,” Eclinicalmedicine 73 (2024): 102671.

[553]

H. W. Yoo, J. Y. Park, S. G. Kim, et al., “Regression of Liver Fibrosis and Hepatocellular Carcinoma Development After HCV Eradication With Oral Antiviral Agents,” Scientific Reports-Uk 12, no. 1 (2022): 193.

[554]

D. Y. Zhang, Y. G. Zhang, and B. Sun, “The Molecular Mechanisms of Liver Fibrosis and Its Potential Therapy in Application,” International Journal of Molecular Sciences 23, no. 20 (2022): 12572.

[555]

D. Q. Hu, P. Wang, X. J. Wang, et al., “The Efficacy of Antiviral Treatment in Chronic hepatitis B Patients With Hepatic Steatosis,” Heliyon 10, no. 7 (2024): e28653.

[556]

O. Koppandi, D. Iovanescu, B. Miuescu, et al., “Prospective Assessment of Serum Lipid Alterations in Chronic Hepatitis C Patients Treated With Direct Acting Antivirals: Insights Six Months Post Sustained Virological Response,” Medicina-Lithuania 60, no. 8 (2024): 1295.

[557]

L. Radmanic, P. S. Simicic, K. Bodulic, A. Vince, and S. Z. Lepej, “Antiviral Treatment Significantly Reduces the Levels of CXCL9, CXCL10 and CXCL11 in Chronic hepatitis C,” Cytokine 176 (2024): 156529.

[558]

A. Gillessen and H. H. J. Schmidt, “Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review,” Advances in Therapy 37, no. 4 (2020): 1279–1301.

[559]

S. C. Zhao, J. D. Li, X. X. Xing, J. X. Chen, Q. Zhou, and J. J. Sun, “Oxyberberine Suppressed the Carbon Tetrachloride-induced Liver Fibrosis by Inhibiting Liver Inflammation in a Sirtuin 3-dependent Manner in Mice,” International Immunopharmacology 116 (2023): 109876.

[560]

P. Liu, Y. R. Qian, X. Liu, et al., “Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Liver Fibrosis,” Frontiers in Immunology 13 (2023): 1096402.

[561]

M. Reig, A. Forner, J. Rimola, et al., “BCLC Strategy for Prognosis Prediction and Treatment Recommendation: The 2022 Update,” Journal of Hepatology 76, no. 3 (2022): 681–693.

[562]

J. Garcia, H. I. Hurwitz, A. B. Sandler, et al., “Bevacizumab (Avastin®) in Cancer Treatment: A Review of 15 Years of Clinical Experience and Future Outlook,” Cancer Treatment Reviews 86 (2020): 102017.

[563]

R. S. Finn, S. Qin, M. Ikeda, et al., “Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma,” New England Journal of Medicine 382, no. 20 (2020): 1894–1905.

[564]

M. Li, S. Bhoori, N. Mehta, and V. Mazzaferro, “Immunotherapy for Hepatocellular Carcinoma: The next Evolution in Expanding Access to Liver Transplantation,” Journal of Hepatology 81, no. 4 (2024): 743–755.

[565]

D. H. Shi, Y. P. Shi, A. O. Kaseb, et al., “Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I Trials,” Clinical Cancer Research 26, no. 15 (2020): 3979–3989.

[566]

L. L. Lu, S. X. Xiao, Z. Y. Lin, et al., “GPC3-IL7-CCL19-CAR-T Primes Immune Microenvironment Reconstitution for Hepatocellular Carcinoma Therapy,” Cell Biology and Toxicology 39, no. 6 (2023): 3101–3119.

[567]

H. R. Dai, C. Tong, D. W. Shi, et al., “Efficacy and Biomarker Analysis of CD133-directed CAR T Cells in Advanced Hepatocellular Carcinoma: A Single-arm, Open-label, Phase II Trial,” Oncoimmunology 9, no. 1 (2020): 1846926.

[568]

D. Z. Li, J. Qin, T. Zhou, et al., “Bispecific GPC3/PD-1 CAR-T Cells for the Treatment of HCC,” International Journal of Oncology 62, no. 4 (2023): 53.

[569]

F. Zou, J. Z. Tan, T. Liu, et al., “The CD39 HBV Surface Protein-targeted CAR-T and Personalized Tumor-reactive CD8 T Cells Exhibit Potent Anti-HCC Activity,” Molecular Therapy 29, no. 5 (2021): 1794–1807.

[570]

Y. Y. Zhai, K. Y. He, L. Y. Huang, et al., “DLK1-directed Chimeric Antigen Receptor T-cell Therapy for Hepatocellular Carcinoma,” Liver International 42, no. 11 (2022): 2524–2537.

[571]

M. Yarchoan, E. J. Gane, T. U. Marron, et al., “Personalized Neoantigen Vaccine and Pembrolizumab in Advanced Hepatocellular Carcinoma: A Phase 1/2 Trial,” Nature Medicine 30, no. 3 (2024): 1044–1053.

[572]

M. Nakajima, S. Hazama, Y. Tokumitsu, et al., “Phase I Study of a Novel Therapeutic Vaccine as Perioperative Treatment for Patients With Surgically Resectable Hepatocellular Carcinoma: The YCP02 Trial,” Hepatology Research 53, no. 7 (2023): 649–660.

[573]

S. Peng, S. L. Chen, W. Hu, et al., “Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses against Recurrence of Hepatocellular Carcinoma,” Cancer Immunology Research 10, no. 6 (2022): 728–744.

[574]

M. W. Loffler, S. Gori, F. Izzo, et al., “Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma,” Clinical Cancer Research 28, no. 12 (2022): 2555–2566.

[575]

M. Taniguchi, S. Mizuno, T. Yoshikawa, et al., “Peptide Vaccine as an Adjuvant Therapy for Glypican-3-positive Hepatocellular Carcinoma Induces Peptide-specific CTLs and Improves Long Prognosis,” Cancer Science 111, no. 8 (2020): 2747–2759.

[576]

Z. X. Cai, X. P. Su, L. M. Qiu, et al., “Personalized Neoantigen Vaccine Prevents Postoperative Recurrence in Hepatocellular Carcinoma Patients With Vascular Invasion,” Molecular Cancer 20, no. 1 (2021): 164.

[577]

P. Li, Z. H. Zhai, J. W. Fang, et al., “PLGA Micro/Nanoparticle Vaccination Elicits Non-tumor Antigen Specific Resident Memory CD8 T Cell Protection From Hepatocellular Carcinoma,” Nanoscale 16, no. 25 (2024): 12149–12162.

[578]

Z. Tian, Q. T. Hu, Z. Y. Sun, et al., “A Booster for Radiofrequency Ablation: Advanced Adjuvant Therapy via Nanovaccine Synergized With Anti-programmed Death Ligand 1 Immunotherapy for Systemically Constraining Hepatocellular Carcinoma,” Acs Nano 17, no. 19 (2023): 19441–19458.

[579]

S. F. Yang, M. T. Weng, J. D. Liang, et al., “Neoantigen Vaccination Augments Antitumor Effects of Anti-PD-1 on Mouse Hepatocellular Carcinoma,” Cancer Letters 563 (2023): 216192.

[580]

M. T. Weng, S. F. Yang, S. Y. Liu, et al., “vaccination Followed by Intramuscular Poly-ICLC Injections for the Treatment of Hepatocellular Carcinoma in Mouse Models,” Pharmacological Research 188 (2023): 106646.

[581]

Y. H. Wang, Q. F. Zhao, B. Y. Zhao, et al., “Remodeling Tumor-Associated Neutrophils to Enhance Dendritic Cell-Based HCC Neoantigen Nano-Vaccine Efficiency,” Advancement of Science 9, no. 11 (2022): e2105631.

[582]

L. Yi, Z. Ning, L. Xu, et al., “The Combination Treatment of Oncolytic adenovirus H101 With nivolumab for Refractory Advanced Hepatocellular Carcinoma: An Open-label, Single-arm, Pilot Study,” Esmo Open 9, no. 2 (2024): 102239.

[583]

M. J. Webb, T. Sangsuwannukul, J. van Vloten, et al., “Expression of Tumor Antigens Within an Oncolytic Virus Enhances the Anti-tumor T Cell Response,” Nature Communications 15, no. 1 (2024): 5442.

[584]

H. Y. Yu, F. Sun, Y. Xu, et al., “Combination Immunotherapy of Oncolytic Flu-Vectored Virus and Programmed Cell Death 1 Blockade Enhances Antitumor Activity in Hepatocellular Carcinoma,” Human Gene Therapy 35, no. 5-6 (2024): 177–191.

[585]

C. Li, Y. Tian, F. Sun, et al., “A Recombinant Oncolytic Influenza Virus Carrying GV1001 Triggers an Antitumor Immune Response,” Human Gene Therapy 35, no. 1-2 (2024): 48–58.

[586]

F. Sun, Y. Xu, Z. Y. Deng, and P. H. Yang, “A Recombinant Oncolytic Influenza Virus Expressing a PD-L1 Antibody Induces CD8+T-cell Activation via the cGas-STING Pathway in Mice With Hepatocellular Carcinoma,” International Immunopharmacology 120 (2023): 110323.

[587]

J. Liu, Y. Y. Hu, Q. Y. Zhang, et al., “Attenuated WNV-poly(A) Exerts a Broad-spectrum Oncolytic Effect by Selective Virus Replication and CD8+T Cell-dependent Immune Response,” Biomedicine & Pharmacotherapy 158 (2023): 114094.

[588]

N. A. Alturki, “Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment,” Journal of Clinical Medicine 12, no. 13 (2023): 4301.

[589]

A. L. Cheng, S. Qin, M. Ikeda, et al., “Updated Efficacy and Safety Data From IMbrave150: Atezolizumab plus Bevacizumab vs. sorafenib for Unresectable Hepatocellular Carcinoma,” Journal of Hepatology 76, no. 4 (2022): 862–873.

[590]

B. Sangro, S. L. Chan, R. K. Kelley, et al., “Four-year Overall Survival Update From the Phase III HIMALAYA Study of tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma,” Annals of Oncology 35, no. 5 (2024): 448–457.

[591]

Q. Du, J. Yuan, and Z. G. Ren, “Hepatocellular Carcinoma Patients With Hepatitis B Virus Infection Exhibited Favorable Survival From Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis,” Liver Cancer 13, no. 4 (2024): 344–354.

[592]

H. C. Mon, P. C. Lee, Y. P. Hung, et al., “Functional Cure of hepatitis B in Patients With Cancer Undergoing Immune Checkpoint Inhibitor Therapy,” Journal of Hepatology 82, no. 1 (2024): 51–61.

[593]

R. C. Sterner and R. M. Sterner, “CAR-T Cell Therapy: Current Limitations and Potential Strategies,” Blood Cancer Journal 11, no. 4 (2021): 69.

[594]

T. Nishida and H. Kataoka, “Glypican 3-Targeted Therapy in Hepatocellular Carcinoma,” Cancers 11, no. 9 (2019): 1339.

[595]

D. Li, N. Li, Y. F. Zhang, et al., “Persistent Polyfunctional Chimeric Antigen Receptor T Cells That Target Glypican 3 Eliminate Orthotopic Hepatocellular Carcinomas in Mice,” Gastroenterology 158, no. 8 (2020): 2250.

[596]

A. T. Tan, N. H. Yang, T. L. Krishnamoorthy, et al., “Use of Expression Profiles of HBV-DNA Integrated into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy,” Gastroenterology 156, no. 6 (2019): 1862.

[597]

G. A. Sautto, K. Wisskirchen, N. Clementi, et al., “Chimeric Antigen Receptor (CAR)-engineered T Cells Redirected Against hepatitis C Virus (HCV) E2 Glycoprotein,” Gut 65, no. 3 (2016): 512–U195.

[598]

G. L. H Wong, V. W. K. Hui, T. C. F. Yip, et al., “Universal HBV Vaccination Dramatically Reduces the Prevalence of HBV Infection and Incidence of Hepatocellular Carcinoma,” Alimentary Pharmacology & Therapeutics 56, no. 5 (2022): 869–877.

[599]

G. L. Costa and G. A. Sautto, “Exploring T-Cell Immunity to Hepatitis C Virus: Insights From Different Vaccine and Antigen Presentation Strategies,” Vaccines-Basel 12, no. 8 (2024): 890.

[600]

C. Boni, H. L. A. Janssen, M. Rossi, et al., “Combined GS-4774 and Tenofovir Therapy Can Improve HBV-Specific T-Cell Responses in Patients with Chronic Hepatitis,” Gastroenterology 157, no. 1 (2019): 227–241. e7.

[601]

A. Notarpaolo, R. Layese, P. Magistri, et al., “Validation of the AFP Model as a Predictor of HCC Recurrence in Patients With Viral hepatitis-related Cirrhosis Who Had Received a Liver Transplant for HCC,” Journal of Hepatology 66, no. 3 (2017): 552–559.

[602]

X. J. Lu, S. S. Deng, J. J. Xu, et al., “Combination of AFP Vaccine and Immune Checkpoint Inhibitors Slows Hepatocellular Carcinoma Progression in Preclinical Models,” Journal of Clinical Investigation 133, no. 11 (2023): e163291.

[603]

D. Reparaz, B. Aparicio, D. Llopiz, S. Hervas-Stubbs, and P. Sarobe, “Therapeutic Vaccines Against Hepatocellular Carcinoma in the Immune Checkpoint Inhibitor Era: Time for Neoantigens?,” International Journal of Molecular Sciences 23, no. 4 (2022): 2022.

[604]

Z. Sas, E. Cendrowicz, I. Weinhäuser, and T. P. Rygiel, “Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options,” International Journal of Molecular Sciences 23, no. 7 (2022): 3778.

[605]

R. Xiao, H. Jin, F. Huang, B. Huang, H. Wang, and Y. G. Wang, “Oncolytic Virotherapy for Hepatocellular Carcinoma: A Potent Immunotherapeutic Landscape,” World Journal of Gastrointestinal Oncology 16, no. 7 (2024): 2867–2876.

[606]

G. Liu, Q. F. Hu, S. G. Peng, et al., “The Spatial and Single-cell Analysis Reveals Remodeled Immune Microenvironment Induced by Synthetic Oncolytic adenovirus Treatment,” Cancer Letters 581 (2024): 216485.

[607]

Y. Z. Liang, B. Wang, Q. J. Chen, et al., “Systemic Delivery of Glycosylated-PEG-masked Oncolytic Virus Enhances Targeting of Antitumor Immuno-virotherapy and Modulates T and NK Cell Infiltration,” Theranostics 13, no. 15 (2023): 5452–5468.

[608]

X. W. Shi, K. Y. X. Sun, L. Li, et al., “Oncolytic Activity of Sindbis Virus With the Help of GM-CSF in Hepatocellular Carcinoma,” International Journal of Molecular Sciences 25, no. 13 (2024): 7195.

[609]

S. Manzoor, I. R. Malik, S. Jahan, et al., “Serum MicroRNAs as Predictors for HCV Progression and Response to Treatment in Pakistani Patients,” Genes-Basel 14, no. 2 (2023): 441.

[610]

A. Morishita, K. Fujita, H. Iwama, et al., “Role of microRNA-210-3p in hepatitis B Virus-related Hepatocellular Carcinoma,” American Journal of Physiology-Gastrointestinal and Liver 318, no. 3 (2020): G401–G409.

[611]

S. A El-Maraghy, O. Adel, N. Zayed, A. Yosry, S. M El-Nahaas, and A. A. Gibriel, “Circulatory miRNA-484, 524, 615 and 628 Expression Profiling in HCV Mediated HCC Among Egyptian Patients; Implications for Diagnosis and Staging of Hepatic Cirrhosis and Fibrosis,” Journal of Advanced Research 22 (2020): 57–66.

[612]

Y. L. Deng, F. Campbell, K. L. Han, et al., “Randomized Clinical Trials towards a Single-visit Cure for Chronic hepatitis C: Oral GSK2878175 and Injectable RG-101 in Chronic hepatitis C Patients and Long-acting Injectable GSK2878175 in Healthy Participants,” Journal of Viral Hepatitis 27, no. 7 (2020): 699–708.

[613]

M. Hassan, M. Elzallat, T. Aboushousha, Y. Elhusseny, and E. El-Ahwany, “MicroRNA-122 Mimic/microRNA-221 Inhibitor Combination as a Novel Therapeutic Tool Against Hepatocellular Carcinoma,” Non-Coding RNA Research 8, no. 1 (2023): 126–134.

[614]

J. C. Wischhusen, S. M. Chowdhury, T. Lee, et al., “Ultrasound-mediated Delivery of miRNA-122 and Anti-miRNA-21 Therapeutically Immunomodulates Murine Hepatocellular Carcinoma,” Journal of Controlled Release 321 (2020): 272–284.

[615]

H. Wang, Z. Hu, U. K. Sukumar, et al., “Ultrasound-Guided Microbubble-Mediated Locoregional Delivery of Multiple MicroRNAs Improves Chemotherapy in Hepatocellular Carcinoma,” Nanotheranostics 6, no. 1 (2022): 62–78.

[616]

L. Lumkul, P. Jantaree, K. Jaisamak, et al., “Combinatorial Gene Expression Profiling of Serum, and lncRNAs to Differentiate Hepatocellular Carcinoma From Liver Diseases: A Systematic Review and Meta-Analysis,” International Journal of Molecular Sciences 25, no. 2 (2024): 1258.

[617]

D. D. Zhou, Y. Wang, H. F. Hu, et al., “lncRNA MALAT1 Promotes HCC Metastasis Through the Peripheral Vascular Infiltration via miRNA-613: A Primary Study Using Contrast Ultrasound,” World Journal of Surgical Oncology 20, no. 1 (2022): 203.

[618]

Z. Jiang and H. Liu, “Metformin Inhibits Tumorigenesis in HBV-induced Hepatocellular Carcinoma by Suppressing HULC Overexpression Caused by HBX,” Journal of Cellular Biochemistry 119, no. 6 (2018): 4482–4495.

[619]

C. J. Shi, Y. B. Zheng, F. F. Pan, F. W. Zhang, P. Zhuang, and W. M. Fu, “Gallic Acid Suppressed Tumorigenesis by an LncRNA MALAT1-Wnt/Beta-Catenin Axis in Hepatocellular Carcinoma,” Frontiers in Pharmacology 12 (2021): 708967.

[620]

T. Wang, Q. Y. Li, R. Xu, et al., “Nanoparticles (NPs)-mediated lncMALAT1 Silencing to Reverse Cisplatin Resistance for Effective Hepatocellular Carcinoma Therapy,” Frontiers in Pharmacology 15 (2024): 1437071.

[621]

S. M. Qu, J. Li, H. F. Huang, J. Lin, W. W. Gao, and Z. Zeng, “A Positive-feedback Loop Between HBx and ALKBH5 Promotes Hepatocellular Carcinogenesis,” BMC Cancer 21, no. 1 (2021): 686.

[622]

Y. X. Du, Y. R. Ma, Q. Zhu, et al., “An m6A-Related Prognostic Biomarker Associated with the Hepatocellular Carcinoma Immune Microenvironment,” Frontiers in Pharmacology 12 (2021): 707930.

[623]

T. Guo, K. He, Y. F. Wang, J. J. Sun, Y. Chen, and Z. L. Yang, “Prognostic Signature of Hepatocellular Carcinoma and Analysis of Immune Infiltration Based on m6A-Related lncRNAs,” Frontiers in Oncology 11 (2021): 691372.

[624]

H. Imam, G. W. Kim, S. A. Mir, M. Khan, and A. Siddiqui, “Interferon-stimulated Gene 20 (ISG20) Selectively Degrades N6-methyladenosine Modified Hepatitis B Virus Transcripts,” Plos Pathogens 16, no. 2 (2020): e1008338.

[625]

X. Y. Zhang, T. H. Su, Y. F. Wu, et al., “Methyladenosine Reader YTHDF1 Promotes Stemness and Therapeutic Resistance in Hepatocellular Carcinoma by Enhancing NOTCH1 Expression,” Cancer Research 84, no. 6 (2024): 827–840.

[626]

Z. C. Xiao, T. Li, X. Y. Zheng, et al., “Nanodrug Enhances Post-ablation Immunotherapy of Hepatocellular Carcinoma via Promoting Dendritic Cell Maturation and Antigen Presentation,” Bioact Mater 21 (2023): 57–68.

[627]

S. J. Yu, R. R. Zhao, B. C. Zhang, et al., “Research Progress and Application of the CRISPR/Cas9 Gene-editing Technology Based on Hepatocellular Carcinoma,” Asian Journal of Pharmaceutical Sciences 18, no. 4 (2023): 100828.

[628]

U. I. Bartosh, A. S. Dome, N. V. Zhukova, P. E. Karitskaya, and G. A. Stepanov, “CRISPR/Cas9 as a New Antiviral Strategy for Treating Hepatitis Viral Infections,” International Journal of Molecular Sciences 25, no. 1 (2024): 334.

[629]

P. Rawal, D. M. Tripathi, H. Hemati, et al., “Targeted HBx Gene Editing by CRISPR/Cas9 System Effectively Reduces Epithelial to Mesenchymal Transition and HBV Replication in Hepatoma Cells,” Liver International 44, no. 2 (2024): 614–624.

[630]

Y. Kato, H. Tabata, K. Sato, M. Nakamura, I. Saito, and T. Nakanishi, “Adenovirus Vectors Expressing Eight Multiplex Guide RNAs of CRISPR/Cas9 Efficiently Disrupted Diverse Hepatitis B Virus Gene Derived From Heterogeneous Patient,” International Journal of Molecular Sciences 22, no. 19 (2021): 10570.

[631]

S. Duponchel, L. Monnier, J. Molle, et al., “Hepatitis C Virus Replication Requires Integrity of Mitochondria-associated ER Membranes,” Jhep Reports 5, no. 3 (2023): 100647.

[632]

M. Kim, Y. Hwang, S. Lim, H. K. Jang, and H. O. Kim, “Advances in Nanoparticles as Non-Viral Vectors for Efficient Delivery of CRISPR/Cas9,” Pharmaceutics 16, no. 9 (2024): 1197.

[633]

B. C. Zhang, B. Y. Luo, J. J. Zou, et al., “Co-delivery of Sorafenib and CRISPR/Cas9 Based on Targeted Core-Shell Hollow Mesoporous Organosilica Nanoparticles for Synergistic HCC Therapy,” ACS Applied Materials & Interfaces 12, no. 51 (2020): 57362–57372.

[634]

Y. Myojin, H. Hikita, Y. Tahata, et al., “Serum Growth Differentiation Factor 15 Predicts Hepatocellular Carcinoma Occurrence After hepatitis C Virus Elimination,” Alimentary pharmacology & therapeutics 55, no. 4 (2022): 422–433.

[635]

L. He, Z. Z. Li, D. J. Su, et al., “Tumor Microenvironment-Responsive Nanocapsule Delivery CRISPR/Cas9 to Reprogram the Immunosuppressive Microenvironment in Hepatoma Carcinoma,” Advancement of Science 11, no. 26 (2024): e2403858.

[636]

B. C. Zhang, C. M. Lai, B. Y. Luo, and J. W. Shao, “Triterpenoids-templated Self-assembly Nanosystem for Biomimetic Delivery of CRISPR/Cas9 Based on the Synergy of TLR-2 and ICB to Enhance HCC Immunotherapy,” Acta Pharmaceutica Sinica B 14, no. 7 (2024): 3205–3217.

[637]

W. N. Guo, X. Zhou, X. R. Li, et al., “Depletion of Gut Microbiota Impairs Gut Barrier Function and Antiviral Immune Defense in the Liver,” Frontiers in Immunology 12 (2021): 636803.

[638]

R. Huo, W. J. Yang, Y. Liu, et al., “Stigmasterol: Remodeling Gut Microbiota and Suppressing Tumor Growth Through Treg and CD8+T Cells in Hepatocellular Carcinoma,” Phytomedicine 129 (2024): 155225.

[639]

G. X. Jing, W. Q. Xu, W. Ma, et al., “polysaccharide Intervene in Hepatocellular Carcinoma via Modulation of Gut Microbiota to Inhibit TLR4/NF-κB Pathway,” International Journal of Biological Macromolecules 261 (2024): 129917.

[640]

H. C. Yao, S. Ma, J. J. Huang, et al., “Trojan-Horse Strategy Targeting the Gut-Liver Axis Modulates Gut Microbiome and Reshapes Microenvironment for Orthotopic Hepatocellular Carcinoma Therapy,” Advancement of Science 11, no. 44 (2024): e2310002.

[641]

S. K. Dogra, J. Doré, and S. Damak, “Gut Microbiota Resilience: Definition, Link to Health and Strategies for Intervention,” Frontiers in Microbiology 11 (2020): 572921.

[642]

J. Yang, H. Gao, T. T. Zhang, et al., “In Vitro Lactic Acid Bacteria Anti-Hepatitis B Virus (HBV) Effect and Modulation of the Intestinal Microbiota in Fecal Cultures From HBV-Associated Hepatocellular Carcinoma Patients,” Nutrients 16, no. 5 (2024): 600.

[643]

H. Yu, G. Lin, J. Jiang, et al., “Synergistic Activity of Enterococcus Faecium-induced Ferroptosis via Expansion of IFN-gamma(+)CD8(+) T Cell Population in Advanced Hepatocellular Carcinoma Treated With sorafenib,” Gut Microbes 16, no. 1 (2024): 2410474.

[644]

B. Kalyanaraman, G. Cheng, and M. Hardy, “The Role of Short-chain Fatty Acids in Cancer Prevention and Cancer Treatment,” Archives of Biochemistry and Biophysics 761 (2024): 110172.

[645]

Y. B. Che, G. Y. Chen, Q. Q. Guo, Y. R. Duan, H. Z. Feng, and Q. Xia, “Gut Microbial Metabolite Butyrate Improves Anticancer Therapy by Regulating Intracellular Calcium Homeostasis,” Hepatology 78, no. 1 (2023): 88–102.

[646]

Y. Y. Zhao, C. Gong, J. Xu, et al., “Research Progress of Fecal Microbiota Transplantation in Liver Diseases,” Journal of Clinical Medicine 12, no. 4 (2023): 1683.

[647]

Y. D. Ren, Z. S. Ye, L. Z. Yang, et al., “Fecal Microbiota Transplantation Induces Hepatitis B Virus E-Antigen (HBeAg) Clearance in Patients with Positive HBeAg after Long-Term Antiviral Therapy,” Hepatology 65, no. 5 (2017): 1765–1768.

[648]

L. S. Deng, X. Z. Guo, J. H. Chen, et al., “Effect of Intestinal Microbiota Transplantation on Chronic hepatitis B Virus Infection Associated Liver Disease,” Frontiers in Microbiology 15 (2024): 1458754.

[649]

J. Calderaro, T. P. Seraphin, T. Luedde, and T. G. Simon, “Artificial Intelligence for the Prevention and Clinical Management of Hepatocellular Carcinoma,” Journal of Hepatology 76, no. 6 (2022): 1348–1361.

[650]

H. Y. Kim, P. Lampertico, J. Y. Nam, et al., “An Artificial Intelligence Model to Predict Hepatocellular Carcinoma Risk in Korean and Caucasian Patients With Chronic hepatitis B,” Journal of Hepatology 76, no. 2 (2022): 311–318.

[651]

A. Hiraoka, T. Kumada, T. Tada, et al., “Attempt to Establish Prognostic Predictive System for Hepatocellular Carcinoma Using Artificial Intelligence for Assistance With Selection of Treatment Modality,” Liver Cancer 12, no. 6 (2023): 565–575.

[652]

T. Minami, M. Sato, H. Toyoda, et al., “Machine Learning for Individualized Prediction of Hepatocellular Carcinoma Development After the Eradication of hepatitis C Virus With Antivirals,” Journal of Hepatology 79, no. 4 (2023).

[653]

H. P. Lin, G. L. Li, A. Delamarre, et al., “A Liver Stiffness-Based Etiology-Independent Machine Learning Algorithm to Predict Hepatocellular Carcinoma,” Clinical Gastroenterology and Hepatology 22, no. 3 (2024): 602–610.

[654]

R. Yamashita, J. Long, A. Saleem, D. L. Rubin, and J. Shen, “Deep Learning Predicts Postsurgical Recurrence of Hepatocellular Carcinoma From Digital Histopathologic Images,” Scientific Reports-Uk 11, no. 1 (2021): 2047.

[655]

Y. Z. Li, Z. M. Xu, C. An, H. J. Chen, and X. Li, “Multi-Task Deep Learning Approach for Simultaneous Objective Response Prediction and Tumor Segmentation in HCC Patients With Transarterial Chemoembolization,” Journal of Personalized Medicine 12, no. 2 (2022): 248.

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