Impact of Helicobacter pylori Eradication on Clinical and Laboratory Parameters in Non-alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Objective

Helicobacter pylori(HP) infection is associated with non-alcoholic fatty liver disease (NAFLD) and insulin resistance; however, the correlation between HP eradication and NAFLD remains controversial. This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.

Methods

We conducted a literature search of the PubMed, Embase, Scopus, and Web of Science databases through Septem ber 2023 for randomized controlled trials (RCTs) examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone. The primary outcome was the change in steatosis parameters. The secondary endpoints were changes in anthropometric parameters, inflammatory markers (TNF-α), and metabolic parameters (fasting blood glucose, homeostasis model assessment of insulin resistance, AST/ALT, and lipid profile). The random effects model was used to calculate the standardized mean difference (SMD) with associated 95% confidence intervals (CIs) for our desired outcome.

Results

Four RCTs met our inclusion criteria. A total of 453 patients were included (mean age 42.8 years, 58.5% males), 228 (50.3%) of whom were in the HP eradication group and 225 (49.7%) of whom were in the lifestyle modification group. Compared with lifestyle modification alone, HP eradication had a significant effect on reducing liver steatosis and TNF-α levels (SMD: - 0.9; 95% CI - 14.67, - 3.82, I² = 0% and SMD: - 6.3; 95% CI - 9.04, - 3.56, I² = 0%, respectively). No significant effect on other metabolic parameters was found.

Conclusions

HP eradication significantly reduced liver steatosis and TNF-α levels in NAFLD patients. However, HP eradi cation did not significantly affect other metabolic indices compared to lifestyle changes alone.

Keywords

Non-alcoholic fatty liver disease / Helicobacter pylori / Randomized controlled trials / Hepatic steatosis / Anthropometric measurements / Insulin resistance

© The Author(s), under exclusive licence to Huazhong University of Science and Technology 2025

Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s11596-025-00001-x.

Author Contributions Conception and design: Fouad Jaber, Azizullah Beran, Saqr Alsakarneh, Hassan Ghoz, Wendell K. Clarkston, John

H.Helzberg. Provision of study materials or patients: Fouad Jaber, Azizullah Beran, Saqr Alsakarneh, Tala Alsharaeh, Abdelrahman Abdelshafi, Islam Mohamed. Collection and assembly of data: Fouad Jaber, Saqr Alsakarneh, Khaled Elfert, Tala Alsharaeh, Abdelrahman Abdelshafi, Willie Johnson, Ahmed-Jordan Salahat. Data analysis and interpretation: Fouad Jaber, Saqr Alsakarneh, Azizullah Beran, Tala Alsharaeh, Abdelrahman Abdelshafi, Mohamed Ahmed. Supervision and critical review: Mohammad Almeqdadi, Hassan Ghoz, Wendell K. Clarkston, John H. Helzberg. Manuscript writing and editing: Fouad Jaber, Saqr Alsakarneh, Tala Alsharaeh, Abdelrahman Abdelshafi, Willie Johnson, Ahmed-Jordan Salahat, Mohammad Jaber. Final approval of manuscript: All authors.

Availability of Data and Materials The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Conflict of interest All other authors have no conflicts of interest to disclose.

Ethics approval and consent to participate This study was conducted according to the Declaration of Helsinki statement.

Consent for publication Not applicable.

References

[1] Gunji T, Matsuhashi N, Sato H, et al. Helicobacter pylori infection is significantly associated with metabolic syndrome in the Japanese population. Am J Gastroenterol. 2008; 103(12):3005-3010.

[2] Wang L, Cao ZM, Zhang LL, et al. Helicobacter Pylori and Autoimmune Diseases: Involving Multiple Systems. Front Immunol. 2022; 13:833424.

[3] Díaz LA, Fuentes-López E, Ayares G, et al. The establishment of public health policies and the burden of non-alcoholic fatty liver disease in the Americas. Lancet Gastroenterol Hepatol. 2022; 7(6):552-559.

[4] Li M, Shen Z, Li YM. Potential role of Helicobacter pylori infection in nonalcoholic fatty liver disease. World J Gastroenterol, 2013, 19(41):7024-7031.

[5] Cheng H, Hu FL, Lian Zhang L, et al. Prevalence of Helicobacter pylori Infection and Identification of Risk Factors in Rural and Urban Beijing, China. Helicobacter. 2009; 14(2):128-133.

[6] Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, et al. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet. 1991; 338(8776):1175-1176.

[7] Stalke P, Al-Soud WA, Bielawski KP, et al. Detection of Helicobacter species in liver and stomach tissues of patients with chronic liver diseases using polymerase chain reaction-denaturing gradient gel electrophoresis and immunohistochemistry. Scand J Gastroenterol. 2005; 40(9):1032-1041.

[8] PirouzT ZounubiL, Keivani H, et al. Detection of Helicobacter pylori in paraffin-embedded specimens from patients with chronic liver diseases, using the amplification method. Dig Dis Sci. 2009; 54(7):1456-1459.

[9] Cindoruk M, Cirak MY, Unal S, et al. Identification of Helicobacter species by 16SrDNA PCR and sequence analysis in human liver samples from patients with various etiologies of benign liver diseases. Eur J Gastroenterol Hepatol. 2008; 20(1):33-36.

[10] Huang Y, Fan XG, Wang ZM, et al. Identification of helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol. 2004; 57(12):1273-1277.

[11] Ponzetto A, Pellicano R, Leone N, et al. Helicobacter infection and cirrhosis in hepatitis C virus carriage: is it an innocent bystander or a troublemaker? Med Hypotheses. 2000; 54(2):275-277.

[12] Leone N, Pellicano R, Brunello F, et al. Helicobacter pylori seroprevalence in patients with cirrhosis of the liver and hepatocellular carcinoma. Cancer Detect Prev. 2003; 27(6):494-497.

[13] Jamali R MofidA, Vahedi H, et al. The effect of helicobacter pylori eradication on liver fat content in subjects with non-alcoholic Fatty liver disease: a randomized open-label clinical trial. Hepat Mon. 2013; 13(12):14679.

[14] PolyzosSA, Kountouras J, Papatheodorou A, et al. Helicobacter pylori infection in patients with nonalcoholic fatty liver disease. Metabolism. 2013; 62(1):121-126.

[15] Thirumurthi S, Graham DY. Helicobacter pylori infection in India from a western perspective. Indian J Med Res. 2012; 136(4):549-562.

[16] Kusters JG, van Vliet AHM, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. 2006; 19(3):449-490.

[17] Fukuda Y, Bamba H, Okui M, et al. Helicobacter pylori infection increases mucosal permeability of the stomach and intestine. Digestion. 2001; 63(Suppl 1):93-96.

[18] Taylor NS, Fox G, Yan L. In-vitro hepatotoxic factor in Helicobacter hepaticus, H. pylori and other Helicobacter species. J Med Microbiol. 1995; 42(1):48-52.

[19] Gunji T, Matsuhashi N, Sato H, et al. Helicobacter pylori infection significantly increases insulin resistance in the asymptomatic Japanese population. Helicobacter. 2009; 14(5):144-150.

[20] Nwokolo CU, Freshwater DA, O'Hare P, et al. Plasma ghrelin following cure of Helicobacter pylori. Gut. 2003; 2(5):637-640.

[21] Wu MS, Lee WJ, Wang HH, et al. A case-control study of association of Helicobacter pylori infection with morbid obesity in Taiwan. Arch Intern Med. 2005; 165(13):1552-1555.

[22] Takuma Y. Helicobacter pylori infection and liver diseases. Gan To Kagaku Ryoho (Japanese). 2011; 38(3):362-364.

[23] Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009; 151(4):264-269.

[24] Jadad AR, Moore RA, Carroll D. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996; 7(1):1-12.

[25] Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.5 (updated February 2022). Cochrane, 2022. Available from: www.training. cochrane. org/handbook.

[26] Maharshi V, Gupta P, Kumar VL, et al. Effect of Helicobacter pylori-eradication therapy on hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomized-controlled pilot study. Gastroenterol Rep (Oxf). 2020; 8(2):104-110.

[27] Kazemifar AM, Shafikhani AA, Hajinoormohammadi E, et al. Investigating effect of Helicobacter pylori treatment on improvement of non-alcoholic fatty liver parameters: a randomized trial. Egyptian Liver J. 2019; 9(1):2.

[28] Yu YY, Tong YL, Wu LY, et al. Helicobacter pylori infection eradication for nonalcoholic fatty liver disease: a randomized controlled trial. Sci Rep. 2022; 12(1):19530.

[29] Polyzos SA, Nikolopoulos P, Stogianni A, et al. Effect of Helicobacter pylori eradication on hepatic steatosis, NAFLD fibrosis score and HSENSI in patients with nonalcoholic steatohepatitis: a MR imaging-based pilot open-label study. Arq Gastroenterol. 2014; 51(3):261-268.

[30] Cheng DD, He C, Ai HH, et al. The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease. Front Microbiol. 2017; 8:743.

[31] Kalas MA, Chavez L, Leon M, et al. Abnormal liver enzymes: A review for clinicians. World J Hepatol. 2021; 13(11):1688-1698.

[32] HouttuV, Csader S, NieuwdorpM, et al. Dietary Interventions in Patients with Non-alcoholic Fatty Liver Disease: Awithtematic Review and Meta-Analysis. Front Nutr. 2021; 8:716783.

[33] Fernández T, Viñuela M, Vidal C, et al. Lifestyle changes in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. PLoS One. 2022; 17(2):e0263931.

[34] Pepa GD, Vetrani C, Lombardi G, et al. Isocaloric Dietary Changes and Non-Alcoholic Fatty Liver Disease in High Cardiometabolic Risk Individuals. Nutrients. 2017; 9(10):1065.

[35] Sasso M, Beaugrand M, De Ledinghen V, et al. Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol. 2010; 36(11):1825-1835.

[36] de Lédinghen V, Vergniol J, Foucher J, et al. Non-invasive diagnosis of liver steatosis using controlled attenuation parameter (CAP) and transient elastography. Liver Int. 2012; 32(6):911-918.