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APASL guidance on stopping nucleos(t)ide analogues in chronic hepatitis B patients

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Abstract

Chronic hepatitis B virus (HBV) infection is currently incurable. Long-term treatment with potent and safe nucleos(t)ide analogs (NAs) can reduce hepatocellular carcinoma (HCC) and cirrhosis-related complications through profound viral suppression. However, indefinite therapy raises several crucial issues with pros and cons. Because seroclearance of hepatitis B surface (HBsAg) as functional cure is not easily achievable, a finite therapy including sequential 48-week pegylated interferon therapy may provide an opportunity to facilitate HBsAg seroclearance by the rejuvenation of exhausted immune cells. However, the cost of stopping NA is the high incidence of virological relapse and surge of alanine aminotransferase (ALT) levels, which may increase the risk of adverse outcomes (e.g., decompensation, fibrosis progression, HCC, or liver-related mortality). So far, the APASL criteria to stop NA treatment is undetectable HBV DNA levels with normalization of ALT; however, this criterion for cessation of treatment is associated with various incidence rates of virological/clinical relapse and more than 40% of NA-stoppers eventually receive retreatment. A very intensive follow-up strategy and identification of low-risk patients for virological/clinical relapse by different biomarkers are the keys to stop the NA treatment safely. Recent studies suggested that decreasing HBsAg level at the end-of-treatment to < 100–200 IU/mL seems to be a useful marker for deciding when to discontinue NAs therapy. In addition, several viral and host factors have been reviewed for their potential roles in predicting clinical relapse. Finally, the APASL guidance has proposed rules to stop NA and the subsequent follow-up strategy to achieve a better prognosis after stopping NA. In general, for both HBeAg-positive and HBeAg-negative patients who have stopped treatment, these measurements should be done every 1–3 months at the minimum until 12 months.

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Author notes

  1. Jia-Horng Kao and Tung-Hung Su have contributed equally.

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Jia-Horng Kao & Tung-Hung Su

  2. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    Jia-Horng Kao

  3. Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

    Jia-Horng Kao & Tai-Chung Tseng

  4. Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan

    Wen-Juei Jeng

  5. College of Medicine, Chang Gung University, Taoyuan City, Taiwan

    Wen-Juei Jeng

  6. Department of Infectious Disease, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China

    Qin Ning

  7. Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan

    Yoshiyuki Ueno

  8. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong

    Man-Fung Yuen

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Conflict of interest

JHK: serves as advisor/consultant for AbbVie, Fujirebio Incorporation, Gilead Sciences, GlaxoSmithKline, Janssen, and Sysmex. MFY: serves as advisor/consultant for AbbVie, Aligos therapeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, Roche and receives grant/ research supports from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation, Roche. Others: Nothing to disclose regarding this submission.

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Kao, JH., Jeng, WJ., Ning, Q. et al. APASL guidance on stopping nucleos(t)ide analogues in chronic hepatitis B patients. Hepatol Int 15, 833–851 (2021). https://doi.org/10.1007/s12072-021-10223-5

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