Surveillance for patients at risk of hepatocellular carcinoma: how to improve its cost-effectiveness and expand the role of multidisciplinary tumor board?

Lorenzo Lani , Giacomo Zaccherini , Edoardo G. Giannini , Franco Trevisani

Hepatoma Research ›› 2025, Vol. 11 : 9

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Hepatoma Research ›› 2025, Vol. 11:9 DOI: 10.20517/2394-5079.2024.136
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Surveillance for patients at risk of hepatocellular carcinoma: how to improve its cost-effectiveness and expand the role of multidisciplinary tumor board?

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Abstract

Surveillance for hepatocellular carcinoma (HCC) improves early tumor detection, increases access to curative therapies, and reduces mortality by about 40%. Early diagnosis through surveillance is essential and should be extended to as many at-risk patients as possible to maximize the benefits of multidisciplinary tumor board evaluations. Current guidelines recommend semi-annual abdominal ultrasonography (US), with/without serum alpha-fetoprotein measurement, for patients with cirrhosis and certain subgroups of individuals with pre-cirrhotic chronic liver disease. However, the populations eligible for surveillance include subsets with varying degrees of HCC risk, which may change over time in some individuals. As risk level is a key determinant of cost-effectiveness, the rigid, “one-size-fits-all” strategy appears inadequate. Moreover, certain non-cirrhotic patients - particularly those with advanced liver fibrosis - are currently excluded from surveillance but may benefit from risk stratification to identify those for whom surveillance would be cost-effective. Surveillance strategies must also consider potential harms, and the limitations of US as a screening test. In response, alternative approaches such as biomarkers-based tests and abbreviated magnetic resonance imaging are under investigation. This article reviews the literature advocating for a transition from the current “one-size-fits-all” approach to programs tailored to individual oncological risk (risk-stratified surveillance) or those that also consider the main factors (sex, etiology, phenotype) that influence screening test performance (precision surveillance). Additionally, it presents a seminal proposal for a risk-stratified algorithm designed to optimize cost-effectiveness and the risk-benefit balance by integrating variable screening intervals and modality selection.

Keywords

Surveillance / hepatocellular carcinoma / precision surveillance / DAA / HBV / HCV / HCC risk

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Lorenzo Lani, Giacomo Zaccherini, Edoardo G. Giannini, Franco Trevisani. Surveillance for patients at risk of hepatocellular carcinoma: how to improve its cost-effectiveness and expand the role of multidisciplinary tumor board?. Hepatoma Research, 2025, 11: 9 DOI:10.20517/2394-5079.2024.136

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References

[1]

Singal AG,Llovet JM.Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy.Nat Rev Clin Oncol2023;20:864-84

[2]

Poustchi H,Strasser SI,McCaughan GW.Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed?.Hepatology2011;54:1998-2004

[3]

Singal AG,Narasimman M.HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: a meta-analysis.J Hepatol2022;77:128-39 PMCID:PMC9232881

[4]

Agarwal PD,Hillman L.Multidisciplinary management of hepatocellular carcinoma improves access to therapy and patient survival.J Clin Gastroenterol2017;51:845-9

[5]

Seif El Dahan K,Daher D.Multidisciplinary care for patients with HCC: a systematic review and meta-analysis.Hepatol Commun2023;7:e0143 PMCID:PMC10146543

[6]

Sinn DH,Park HC.Multidisciplinary approach is associated with improved survival of hepatocellular carcinoma patients.PLoS One2019;14:e0210730 PMCID:PMC6331107

[7]

Giannini EG,Plaz Torres MC.Towards an integrated management model for hepatocellular carcinoma.Dig Liver Dis2024;56:2022-4

[8]

Trevisani F, De Notariis S, Rapaccini G, et al; Italian Liver Cancer Group. Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience). Am J Gastroenterol. 2002;97:734-44.

[9]

Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol2018;69:182-236

[10]

Singal AG,Yarchoan M.AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma.Hepatology2023;78:1922-65 PMCID:PMC10663390

[11]

Omata M,Kokudo N.Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update.Hepatol Int2017;11:317-70 PMCID:PMC5491694

[12]

Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma.Clin Mol Hepatol2022;28:583-705 PMCID:PMC9597235

[13]

Hasegawa K, Takemura N, Yamashita T, et al; committee for Revision of the Clinical Practice Guidelines for Hepatocellular Carcinoma, Tokyo, Japan. Clinical practice guidelines for hepatocellular carcinoma: the Japan Society of Hepatology 2021 version (5th JSH-HCC Guidelines). Hepatol Res. 2023;53:383-90.

[14]

Tokushige K,Ono M.Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis 2020.Hepatol Res2021;51:1013-25

[15]

Burak KW.Hepatocellular carcinoma: consensus, controversies and future directions. A report from the Canadian association for the study of the liver hepatocellular carcinoma meeting.Can J Gastroenterol Hepatol2015;29:178-84 PMCID:PMC4444026

[16]

Goossens N,King LY.Cost-effectiveness of risk score-stratified hepatocellular carcinoma screening in patients with cirrhosis.Clin Transl Gastroenterol2017;8:e101 PMCID:PMC5518949

[17]

Singal AG,Obi J.Benefits and harms of hepatocellular carcinoma surveillance in a prospective cohort of patients with cirrhosis.Clin Gastroenterol Hepatol2021;19:1925-32.e1 PMCID:PMC7943645

[18]

Sharma SA,Hansen BE.Toronto HCC risk index: a validated scoring system to predict 10-year risk of HCC in patients with cirrhosis.J Hepatol2017;Epub ahead of print:

[19]

Park J,Tseng TC.Progression rates by age, sex, treatment, and disease activity by AASLD and EASL criteria: data for precision medicine.Clin Gastroenterol Hepatol2022;20:874-85.e4

[20]

Papatheodoridis G,Sypsa V.PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy.J Hepatol2016;64:800-6

[21]

Masuzaki R,Yoshida H.Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography.Hepatology2009;49:1954-61

[22]

Papatheodoridis GV,Dalekos GN.The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B.Hepatology2017;66:1444-53

[23]

Carrat F, Fontaine H, Dorival C, et al; French ANRS CO22 Hepather cohort. Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study. Lancet. 2019;393:1453-64.

[24]

Lockart I,Hajarizadeh B,Danta M.HCC incidence after hepatitis C cure among patients with advanced fibrosis or cirrhosis: a meta-analysis.Hepatology2022;76:139-54 PMCID:PMC9303770

[25]

Ioannou GN.HCC surveillance after SVR in patients with F3/F4 fibrosis.J Hepatol2021;74:458-65

[26]

Kim NJ,Berry K.Hepatocellular carcinoma risk declines but remains high enough for screening in the first 7 years after hepatitis c virus cure with direct-acting antivirals in patients with cirrhosis or high fibrosis-4 score.Gastroenterology2022;163:1104-6.e3 PMCID:PMC9586012

[27]

Izzo F,Albino V.Prospective screening increases the detection of potentially curable hepatocellular carcinoma: results in 8,900 high-risk patients.HPB2013;15:985-90 PMCID:PMC3843617

[28]

Chen Q,Adee MG,Kanwal F.Assessment of incidence of and surveillance burden for hepatocellular carcinoma among patients with hepatitis C in the era of direct-acting antiviral agents.JAMA Netw Open2020;3:e2021173 PMCID:PMC7675109

[29]

Ganne-Carrié N, Chaffaut C, Bourcier V, et al; for CIRRAL Group. Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis. J Hepatol. 2018;69:1274-83.

[30]

Heckley GA,Asamoah BO.How the risk of liver cancer changes after alcohol cessation: a review and meta-analysis of the current literature.BMC Cancer2011;11:446 PMCID:PMC3229519

[31]

Tan DJH, Tamaki N, Kim BK, et al; Global Liver Cancer Consortium. Prevalence of low FIB-4 in MASLD-related hepatocellular carcinoma: a multicentre study. Aliment Pharmacol Ther. 2025;61:278-85.

[32]

Ioannou GN.Epidemiology and risk-stratification of NAFLD-associated HCC.J Hepatol2021;75:1476-84

[33]

Berkan-Kawińska A.Hepatocellular carcinoma in non-alcohol fatty liver disease - changing trends and specific challenges.Curr Med Res Opin2020;36:235-43

[34]

Petta S,Viganò M.Monitoring occurrence of liver-related events and survival by transient elastography in patients with nonalcoholic fatty liver disease and compensated advanced chronic liver disease.Clin Gastroenterol Hepatol2021;19:806-15.e5

[35]

Lee HW,Ahn SH,Choi J.The associations between fibrosis changes and liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.Liver Int2024;44:1448-55

[36]

Bianco C,Pelusi S.Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores.J Hepatol2021;74:775-82 PMCID:PMC7987554

[37]

Ding H, Tu H, Qu C, et al; Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Committee of Hepatology of Chinese Research Hospital Association, Hepatology Society of Chinese Medical Association, Prevention of Infection Related Cancer (PIRCA) Group, Specialist Committee of Cancer Prevention and Control of Chinese Preventive Medicine Association. Guideline for stratified screening and surveillance in patients with high risk of primary liver cancer (2020). HR. 2021;7:17.

[38]

Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD).J Hepatol2024;81:492-542 PMCID:PMC11299976

[39]

Atiq O,Yopp AC.An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis.Hepatology2017;65:1196-205 PMCID:PMC5659110

[40]

Narasimman M,Cerda V.Financial burden of hepatocellular carcinoma screening in patients with cirrhosis.Clin Gastroenterol Hepatol2024;22:760-7.e1

[41]

Narasimman M,Cerda V.Hepatocellular carcinoma surveillance may be associated with potential psychological harms in patients with cirrhosis.Hepatology2024;79:107-17

[42]

Curran C,Datta S,Stanley AJ.Hepatocellular carcinoma risk scores predict patients under surveillance at low risk of benefit and high risk of harm.Dig Dis Sci2023;68:770-7

[43]

Suddle A,Hubner R.British society of gastroenterology guidelines for the management of hepatocellular carcinoma in adults.Gut2024;73:1235-68 PMCID:PMC11287576

[44]

Del Poggio P, Olmi S, Ciccarese F, et al; Italian Liver Cancer (ITA.LI.CA) Group. Factors that affect efficacy of ultrasound surveillance for early stage hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2014;12:1927-33.e2.

[45]

Samoylova ML,Roberts JP.Predictors of ultrasound failure to detect hepatocellular carcinoma.Liver Transpl2018;24:1171-7

[46]

Tzartzeva K,Rich NE.Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis.Gastroenterology2018;154:1706-18.e1 PMCID:PMC5927818

[47]

Harris PS,Gray ME,McGuire BM.Hepatocellular carcinoma surveillance: an evidence-based approach.World J Gastroenterol2019;25:1550-9 PMCID:PMC6452232

[48]

Trevisani F,Morselli-Labate AM.Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status.J Hepatol2001;34:570-5

[49]

Giannini EG, Sammito G, Farinati F, et al; Italian Liver Cancer (ITA.LI.CA) Group. Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical use. Cancer. 2014;120:2150-7.

[50]

Vipani A,Luu M,Singal AG.Decreasing trend of serum α-fetoprotein level in hepatocellular carcinoma.Clin Gastroenterol Hepatol2022;20:1177-9.e4 PMCID:PMC8837708

[51]

Qian X,Long H.Reappraisal of the diagnostic value of alpha-fetoprotein for surveillance of HBV-related hepatocellular carcinoma in the era of antiviral therapy.J Viral Hepat2021;28:20-9 PMCID:PMC7756791

[52]

Gopal P,Waljee AK.Factors that affect accuracy of α-fetoprotein test in detection of hepatocellular carcinoma in patients with cirrhosis.Clin Gastroenterol Hepatol2014;12:870-7 PMCID:PMC3975698

[53]

Biselli M,Gramenzi A.A new approach to the use of α-fetoprotein as surveillance test for hepatocellular carcinoma in patients with cirrhosis.Br J Cancer2015;112:69-76 PMCID:PMC4453600

[54]

Tayob N,Do KA,Feng Z.A Bayesian screening approach for hepatocellular carcinoma using multiple longitudinal biomarkers.Biometrics2018;74:249-59 PMCID:PMC5677596

[55]

Parikh ND,Al-Jarrah T.Barriers to surveillance for hepatocellular carcinoma in a multicenter cohort.JAMA Netw Open2022;5:e2223504 PMCID:PMC9308050

[56]

Zhao C,Le RH.Poor adherence to hepatocellular carcinoma surveillance: a systematic review and meta-analysis of a complex issue.Liver Int2018;38:503-14

[57]

Toyoda H,Shiota S,Tanaka J.Adherence to regular surveillance visits for hepatocellular carcinoma in patients with chronic hepatitis C virus infection who achieved sustained virologic response.Eur J Gastroenterol Hepatol2022;34:693-7

[58]

Rao A,Marrero JA,Singal AG.Diagnostic and therapeutic delays in patients with hepatocellular carcinoma.J Natl Compr Canc Netw2021;19:1063-71

[59]

Govalan R,Lauzon M.Therapeutic underuse and delay in hepatocellular carcinoma: prevalence, associated factors, and clinical impact.Hepatol Commun2022;6:223-36 PMCID:PMC8710787

[60]

Berhane S,Tada T.Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients.Clin Gastroenterol Hepatol2016;14:875-86.e6

[61]

Fujiwara N,Marsh TL.Phase 3 validation of PAaM for hepatocellular carcinoma risk stratification in cirrhosis.Gastroenterology2025;168:556-67.e7

[62]

Pepe MS,Feng Z.Phases of biomarker development for early detection of cancer.J Natl Cancer Inst2001;93:1054-61

[63]

Marsh TL,Roberts LR.A phase 3 biomarker validation of GALAD for the detection of hepatocellular carcinoma in cirrhosis.Gastroenterology2025;168:316-26.e6

[64]

Singal AG,Kanwal F.National liver cancer screening trial (TRACER) study protocol.Hepatol Commun2024;8:e0565 PMCID:PMC11537583

[65]

Parikh ND,Singal AG.Blood-based biomarkers for hepatocellular carcinoma screening: approaching the end of the ultrasound era?.J Hepatol2023;78:207-16 PMCID:PMC10229257

[66]

Park HJ,Kim SY.Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: comparison with ultrasound.J Hepatol2020;72:718-24

[67]

Gupta P,Patel A,Sharma V.Abbreviated MRI for hepatocellular carcinoma screening: a systematic review and meta-analysis.J Hepatol2021;75:108-19

[68]

Giannini EG.Proper assessment and prognostication of patients with hepatocellular carcinoma.Clin Liver Dis2024;23:e0129 PMCID:PMC10919536

[69]

Nahon P, Najean M, Layese R, et al; ANRS CO12 CirVir, ANRS CO22 Hepather, Scientific Committee - Voting members, CIRRAL groups. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis. JHEP Rep. 2021;4:100390. PMCID:PMC8683591

[70]

Kao SZ,Fujiwara N,Parikh ND.Cost-effectiveness of a precision hepatocellular carcinoma surveillance strategy in patients with cirrhosis.EClinicalMedicine2024;75:102755 PMCID:PMC11372615

[71]

Farhang Zangneh H,Sander B.Cost effectiveness of hepatocellular carcinoma surveillance after a sustained virologic response to therapy in patients with hepatitis C virus infection and advanced fibrosis.Clin Gastroenterol Hepatol2019;17:1840-9.e16

[72]

Lani L,Trevisani F.Surveillance for hepatocellular carcinoma in patients with successfully treated viral disease of the liver: a systematic review.Liver Cancer2024;13:376-88 PMCID:PMC11305665

[73]

Chhatwal J,Mueller PP.Hepatocellular carcinoma incidence threshold for surveillance in virologically cured hepatitis C individuals.Clin Gastroenterol Hepatol2024;22:91-101.e6 PMCID:PMC10709527

[74]

EASLTM The Home of Hepatology. EASL policy statement: risk-based surveillance for hepatocellular carcinoma among patients with cirrhosis. Available from: https://easl.eu/publication/easl-policy-statement-risk-based/. [Last accessed on 11 Mar 2025].

[75]

Lim YX,Ho PJ.Breast cancer in Asia: incidence, mortality, early detection, mammography programs, and risk-based screening initiatives.Cancers2022;14:4218 PMCID:PMC9454998

[76]

Ronot M,Rimola J.Screening of liver cancer with abbreviated MRI.Hepatology2023;78:670-86

[77]

Kudo M.Management of hepatocellular carcinoma in Japan as a world-leading model.Liver Cancer2018;7:134-47 PMCID:PMC5985410

[78]

Shiha G,Mousa N.Individualized HCC surveillance using risk stratification scores in advanced fibrosis and cirrhotic HCV patients who achieved SVR: prospective study.Aliment Pharmacol Ther2025;61:99-108

[79]

Nahon P,Ganne-Carrié N.Stratification of hepatocellular carcinoma risk following HCV eradication or HBV control.J Clin Med2021;10:353 PMCID:PMC7832303

[80]

Demirtas CO.Surveillance for hepatocellular carcinoma in chronic viral hepatitis: is it time to personalize it?.World J Gastroenterol2021;27:5536-54 PMCID:PMC8433616

[81]

Tobari M,Taniai M.The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis.J Gastroenterol Hepatol2020;35:862-9

[82]

Luna-Cuadros MA,Hanif H,Khan MM.Risk of hepatocellular carcinoma after hepatitis C virus cure.World J Gastroenterol2022;28:96-107 PMCID:PMC8793019

[83]

Flemming JA,Vittinghoff E,Terrault NA.Risk prediction of hepatocellular carcinoma in patients with cirrhosis: the ADRESS-HCC risk model.Cancer2014;120:3485-93 PMCID:PMC4553222

[84]

Hsu YC,Ho HJ.Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B.J Hepatol2018;69:278-85

[85]

Azzi J, Dorival C, Cagnot C, et al; ANRS-AFEF Hepather Study group. Prediction of hepatocellular carcinoma in hepatitis C patients with advanced fibrosis after sustained virologic response. Clin Res Hepatol Gastroenterol. 2022;46:101923.

[86]

Semmler G,Kozbial K.HCC risk stratification after cure of hepatitis C in patients with compensated advanced chronic liver disease.J Hepatol2022;76:812-21

[87]

Yang HI,Wong GL.Real-world effectiveness from the Asia Pacific rim liver consortium for HBV risk score for the prediction of hepatocellular carcinoma in chronic hepatitis B patients treated with oral antiviral therapy.J Infect Dis2020;221:389-99

[88]

Nardone V,Germani MM.The role of artificial intelligence on tumor boards: perspectives from surgeons, medical oncologists and radiation oncologists.Curr Oncol2024;31:4984-5007 PMCID:PMC11431448

[89]

Gu W,Aubé C.Hepatocellular cancer surveillance in patients with advanced chronic liver disease.NEJM Evid2024;3:EVIDoa2400062

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