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Meta-Analysis
. 2023 Jul;29(3):705-720.
doi: 10.3350/cmh.2023.0004. Epub 2023 May 8.

Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis

Yu Jun Wong  1   2 , Vy H Nguyen  3   4 , Hwai-I Yang  5   6   7   8 , Jie Li  9 , Michael Huan Le  3   10 , Wan-Jung Wu  11 , Nicole Xinrong Han  12 , Khi Yung Fong  12 , Elizebeth Chen  1 , Connie Wong  13 , Fajuan Rui  14 , Xiaoming Xu  14 , Qi Xue  15 , Xin Yu Hu  16 , Wei Qiang Leow  17 , George Boon-Bee Goh  2   18 , Ramsey Cheung  19   20 , Grace Wong  21 , Vincent Wai-Sun Wong  21 , Ming-Whei Yu  11 , Mindie H Nguyen  20   22
Affiliations
Meta-Analysis

Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis

Yu Jun Wong et al. Clin Mol Hepatol. 2023 Jul.

Abstract

Background/aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.

Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.

Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).

Conclusion: IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Keywords: Cirrhosis; Fibrosis; HBsAg seroclearance; Hepatocellular carcinoma; Mortality; Non-alcoholic fatty liver disease.

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Conflict of interest statement

Conflicts of Interest

WYJ: Research/grant: Nurturing Clinician Scientist Scheme, Medicine Academic Clinical Program, SingHealth, Speaker’s fee: Gilead & AbbVie; RK: Research/grant: SingHealth foundation grant, Consulting/advisory board: Gilead Sciences, Speaker bureau: Gilead Sciences, AbbVie; VW: Consultancy: AbbVie, Boehringer Ingelheim, Echosens, Intercept, Inventiva, Novo Nordisk, Pfizer, TARGET PharmaSolutions, Lectures: Abbott, AbbVie, Gilead Sciences, Novo Nordisk, Research grants: Gilead Sciences, Stock: Co-founder of Illuminatio Medical Technology Limited; GW: Research/grant: Gilead Sciences, Consulting/Advisory board: Gilead Sciences, Janssen, Speaker’s bureau: Abbott, AbbVie, Bristol-Myers Squibb, Echosens & Furui, Gilead, Janssen, Roche; MHN: Research support: Pfizer, Enanta, CurveBio, Gilead, Exact Sciences, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, B.K. Kee Foundation; Consulting and/or Advisory Board: Intercept, Exact Science, Gilead, GSK, Eli Lilly, Laboratory of Advanced Medicine, Janssen

Figures

Figure 1.
Figure 1.
PRISMA flow diagram. HBV, hepatitis B virus, HCC, hepatocellular carcinoma, MA, meta-analysis, IPD-MA, individual patient data meta-analysis; HBsAg, hepatitis B surface antigen. *Some studies may have more than 1 study outcomes.
Figure 2.
Figure 2.
Conventional aggregated study-level data meta-analysis: The pooled incidence of clinical outcomes in chronic hepatitis B patients with or without concomitant fatty liver; (A) Hepatocellular carcinoma, (B) Liver cirrhosis, (C) Mortality and (D) HBsAg seroclerance.
Figure 3.
Figure 3.
Individual patient-level data meta-analysis: Cumulative incidence of clinical outcomes in the total cohort of patients with chronic hepatitis B with and without fatty liver: (A) Hepatocellular carcinoma (HCC), (B) Cirrhosis, (C) Mortality, and (D) HBsAg seroconversion.
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