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Statins associate with better clinical outcomes in chronic hepatitis B patients with HBsAg seroclearance

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Abstract

Introduction

We aimed to describe long-term clinical outcomes in chronic hepatitis B (CHB) patients after HBsAg seroclearance, and identify factors that modify disease outcomes.

Methods

CHB patients with HBsAg seroclearance occurring between 1986 and 2017 were recruited. Primary outcome was cirrhosis/hepatocellular carcinoma (HCC), and secondary outcomes were hepatic decompensation, liver-related death/transplantation, and all-cause mortality. Multivariable Cox model included demographics, prior antivirals, comorbidities, drugs (statins, metformin, proton-pump inhibitors, non-selective beta-blockers), and laboratory parameters (platelet, liver function test, prothrombin time, alpha-fetoprotein [AFP], anti-HBs). Statin users were propensity score matched (PSM) with non-users (1:2 ratio) for survival analysis of all outcomes.

Results

Of 913 patients with HBsAg seroclearance (male: 613 [67.1%]; median age: 53.4 years [18.5–87.0]), 129 (14.1%) were statin users. During median follow-up of 7.7 years (up to 29.1 years), 64/833 (7.7%) developed cirrhosis, 25/905 (2.8%) developed HCC, 3/913 (0.3%) underwent transplantation, and 76/913 (8.3%) died. Statins were associated with lower cirrhosis/HCC risk (adjusted hazard ratio [aHR]: 0.44; 95% CI 0.20–0.96; aHR for every 1-year increase in use: 0.85; 95% CI 0.75–0.97). Statin users had no hepatic decompensation or liver-related death/transplantation (vs 18/778 [2.3%] and 18/784 [2.3%] cases in statin non-users, respectively). Statins were also associated with lower all-cause mortality risk (aHR: 0.21; 95% CI 0.08–0.53). PSM yields consistent results for beneficial effects of statins (log-rank p < 0.05 for all outcomes). Other factors for cirrhosis/HCC included increasing age (aHR: 1.06), diabetes (aHR: 2.03), higher creatinine (aHR: 1.008), GGT > 50U/L (aHR: 3.25), and AFP > 9 ng/mL (aHR: 10.14).

Conclusion

Patients with HBsAg seroclearance have favorable long-term survival. However, liver-related adverse outcomes still develop, necessitating further investigations on beneficial effects of statins.

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Funding

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Authors and Affiliations

  1. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China

    Ka Shing Cheung, Lung Yi Mak, Lok Ka Lam, James Fung, Wai Kay Seto & Man Fung Yuen

  2. Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China

    Ka Shing Cheung & Wai Kay Seto

  3. State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China

    James Fung, Wai Kay Seto & Man Fung Yuen

  4. Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

    Fen Liu

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  1. Ka Shing Cheung
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Contributions

K-SC and W-KS were involved with study concept and design; acquisition of data; analysis and interpretation of data; and drafting of manuscript; LKL was involved with acquisition of data. L-YM and JF were involved with analysis and interpretation of data; and critical revision of the manuscript for important intellectual content. M-FY were involved with the study concept and design; analysis and interpretation of data; drafting of manuscript; critical revision of the manuscript for important intellectual content; and study supervision. The corresponding author had full access to all data, and was fully responsible for the data integrity and statistical analysis. All authors revised the manuscript and approved the final version of this article.

Corresponding authors

Correspondence to Wai Kay Seto or Man Fung Yuen.

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Conflict of interest

W. K. Seto is an advisory board member of AbbVie and Gilead Sciences, and received speaker fees from AbbVie, Gilead Sciences, and Mylan. J. Fung received research funding from Novartis. M. F. Yuen is advisory board member and received speaker’s fees from AbbVie, Janssen, Biocartis NV, Bristol Myers Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp, and Dohme, Sysmex Corporation. M. F. Yuen does consulting for Aligos Pharmaceuticals, Assembly Biosciences, Arbutus Biopharma, Dicerna Pharmaceuticals, Clear-B Therapeutics, GlaxoSmithKline, Immunocore, Springbank Pharmaceuticals and also received research funding from Bristol Myers Squibb and Gilead Sciences. L. Y. Mak is advisory board member of Gilead Sciences. Ka Shing Cheung, Lok Ka Lam and Fen Liu have no conflicts of interest.

Animal research

This study did not involve animal research.

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This is a retrospective cohort study and has been approved by Institutional Review Board, University of Hong Kong and West Cluster of Hospital Authority, Hong Kong.

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Participate identity was anonymized in this study.

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This is not a clinical trial.

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Guarantor of the article: Dr. Ka-Shing Cheung and Prof. Man-Fung Yuen.

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Cheung, K.S., Mak, L.Y., Lam, L.K. et al. Statins associate with better clinical outcomes in chronic hepatitis B patients with HBsAg seroclearance. Hepatol Int 15, 881–891 (2021). https://doi.org/10.1007/s12072-021-10197-4

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