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Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B

  • Grace Lai-Hung Wong
    Correspondence
    Corresponding authors. Address: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong, China. Tel.: +852 9350 3236 (G. Wong), or tel.: +852 3505 1205; fax: +852 2637 3852 (V. Wong).
    Affiliations
    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China

    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

    State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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  • Henry Lik-Yuen Chan
    Affiliations
    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China

    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

    State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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  • Yee-Kit Tse
    Affiliations
    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China

    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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  • Terry Cheuk-Fung Yip
    Affiliations
    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China

    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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  • Kelvin Long-Yan Lam
    Affiliations
    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China

    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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  • Grace Chung-Yan Lui
    Affiliations
    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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  • Vincent Wai-Sun Wong
    Correspondence
    Corresponding authors. Address: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong, China. Tel.: +852 9350 3236 (G. Wong), or tel.: +852 3505 1205; fax: +852 2637 3852 (V. Wong).
    Affiliations
    Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China

    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

    State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
    Search for articles by this author

      Highlights

      • Patients with normal on-treatment ALT after antiviral treatment had lower risk of hepatic events.
      • Adjusted hazard ratios for normal on-treatment ALT at 3, 6, 9 and 12 months were 0.61, 0.54, 0.53 and 0.50 respectively.
      • Similar findings were identified using AASLD, APASL or local laboratory criteria for normal ALT.

      Background & Aims

      Recent studies reveal that the rate of normal on-treatment alanine aminotransferase (ALT) appears different for different nucleos(t)ide analogues (NAs); yet its clinical significance is unclear. We aimed to evaluate the impact of normal on-treatment ALT during antiviral treatment with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB).

      Methods

      A territory-wide cohort of patients with CHB who received ETV and/or TDF in 2005–2016 was identified. Serial on-treatment ALT levels were collected and analyzed. Normal on-treatment ALT (ALT-N) was defined as ALT <30 U/L in males and <19 U/L in females. The primary and secondary outcomes were composite hepatic events (including hepatocellular carcinoma) based on diagnostic codes. Patients with hepatic events before or during the first year of antiviral treatment or follow-up <1 year were excluded.

      Results

      A total of 21,182 patients with CHB (10,437 with and 10,745 without ALT-N at 12 months after antiviral treatment) were identified and followed for 4.0 ± 1.7 years. Patients with and without ALT-N differed in baseline ALT (58 vs. 61 U/L), hepatitis B virus DNA (4.9 vs. 5.1 log10 IU/ml) and cirrhosis status (8.8% vs. 10.5%). A total of 627 (3.0%) patients developed composite hepatic events. Compared to no ALT-N, ALT-N at 3, 6, 9 and 12 months reduced the risk of hepatic events, after adjustment for baseline ALT and other important covariates, with adjusted hazard ratios (95% CI) of 0.61 (0.49–0.77), 0.55 (0.45–0.67), 0.54 (0.44–0.65) and 0.51 (0.42–0.61) respectively (all p <0.001). The cumulative incidence (95% CI) of composite hepatic events at six years was 3.51% (3.06%-4.02%) in ALT-N and 5.70% (5.15%–6.32%) in the no ALT-N group (p <0.001).

      Conclusions

      Normal on-treatment ALT is associated with a lower risk of hepatic events in patients with CHB receiving NA treatment, translating into improved clinical outcomes in these patients.

      Lay summary

      We investigated 21,182 patients with chronic hepatitis B receiving antiviral treatment. Alanine aminotransferase is a laboratory marker of liver function, with raised levels indicating liver dysfunction and in severe cases hepatitis. Normal on-treatment alanine aminotransferase during the first year of treatment in patients with CHB is associated with a lower risk of hepatic events.

      Graphical abstract

      Keywords

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