Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients With liver cirrhosis

Authors

  • Grace Lai-Hung Wong,

    1. Institute of Digestive Disease, the Chinese University of Hong Kong, Hong Kong SAR, China
    2. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Henry Lik-Yuen Chan,

    1. Institute of Digestive Disease, the Chinese University of Hong Kong, Hong Kong SAR, China
    2. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Christy Wing-Hin Mak,

    1. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Stanley King-Yeung Lee,

    1. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Zoe Man-Yi Ip,

    1. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Andrew Ting-Ho Lam,

    1. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Henry Wing-Hang Iu,

    1. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Joyce May-Sum Leung,

    1. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Jennifer Wing-Yan Lai,

    1. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Angeline Oi-Shan Lo,

    1. Institute of Digestive Disease, the Chinese University of Hong Kong, Hong Kong SAR, China
    2. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Hoi-Yun Chan,

    1. Institute of Digestive Disease, the Chinese University of Hong Kong, Hong Kong SAR, China
    2. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    Search for more papers by this author
  • Vincent Wai-Sun Wong

    Corresponding author
    1. Institute of Digestive Disease, the Chinese University of Hong Kong, Hong Kong SAR, China
    2. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China
    • Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong . E-mail: wongv@cuhk.edu.hk fax: (852)-2637-3852

    Search for more papers by this author

  • Potential conflict of interest: Grace Lai-Hung Wong has served as an advisory committee member for Otsuka and as a speaker for Echosens. Henry Lik-Yuen Chan is a consultant for Abbott, Bristol-Myer Squibb, Gilead, GlaxoSmithKline, Merck, Novartis, and Roche; is on the speakers' bureau of Echosens, GlaxoSmithKline, and Roche; has received lecture honoraria from Abbott, Bristol-Myer Squibb, Echosens, Gilead, Glaxo-Smith-Kline, Merck, Novartis, and Roche; and has received an unrestricted grant from Roche for hepatitis B research. Vincent Wai-Sun Wong has served as an advisory committee member for Roche, Novartis, Gilead, and Otsuka and has served as a speaker for Bristol-Meyers-Squibb, Roche, Novartis, Abbott Diagnostics, and Echosens.

Abstract

Entecavir is a potent antiviral agent with high genetic barrier to resistance, hence it is currently recommended as first-line antiviral therapy for chronic hepatitis B (CHB). The aim of this study was to investigate the efficacy of entecavir on clinical outcomes and deaths. It was a retrospective-prospective cohort study based on two cohorts of patients. The entecavir cohort included consecutive CHB patients who had received entecavir 0.5 mg/day for at least 12 months. The historical control cohort included untreated patients recruited since 1997 who underwent routine clinical care. The primary outcome was the 5-year cumulative probability of hepatic events, defined as any cirrhotic complications, hepatocellular carcinoma (HCC), and/or liver-related mortality. A total of 1,446 entecavir-treated patients (72% men; age, 51 ± 12 years; follow-up, 36 ± 13 months) and 424 treatment-naïve patients (65% men; age, 41 ± 13 years; follow-up, 114 ± 31 months) were studied. Overall, there was no difference in hepatic events between the entecavir and control cohorts. Among patients with liver cirrhosis (482 entecavir-treated, 69 treatment-naïve), entecavir-treated patients had reduced risks of all clinical outcomes when compared with treatment-naïve patients with cirrhosis after adjusted for model for end-stage liver disease score: hepatic events (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.34-0.78; P = 0.002), HCC (HR, 0.55; 95% CI, 0.31-0.99; P = 0.049), liver-related mortality (HR, 0.26; 95% CI, 0.13-0.55; P < 0.001), and all-cause mortality (HR, 0.34; 95% CI, 0.18-0.62; P < 0.001). Entecavir-treated patients with cirrhosis who failed to achieve undetectable hepatitis B virus DNA (105/482 [22%]) had comparable risk of hepatic events as the untreated patients. Conclusion: Entecavir therapy reduces the risks of hepatic events, HCC, liver-related and all-cause mortality of CHB patients with liver cirrhosis in 5 years, particularly among those who had maintained viral suppression. (Hepatology 2013;58:1537–1547)

Ancillary