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Nucleos(t)ide analogues in patients with chronic hepatitis B: to stop or not to stop?
  1. Jia-Horng Kao1,
  2. Thomas Berg2
  1. 1Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
  2. 2Clinic and Polyclinic of Gastroenterology, Hepatology, Infectiology and Pneumology, University Hospital Leipzig, Leipzig, Germany
  1. Correspondence to Prof. Dr Thomas Berg, Clinic and Polyclinic for Gastroenterology, Hepatology, Infectiology and Pneumology, Univeristy Hospital Leipzig, Liebigstr. 20; 04103 Leipzig, Germany; thomas.berg{at}medizin.uni-leipzig.de

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Chronic HBV infection is a treatable but not curable disease. Long-term treatment with potent and safe nucleos(t)ide analogues (NA) with a high genetic barrier to drug resistance helps to reduce cirrhosis, hepatocellular carcinoma and liver-related mortality by profound viral suppression.1 Nevertheless, several controversial issues of chronic hepatitis B (CHB) management still exist and deserve further studies, including the selection of best candidates for a finite approach of NA therapy (box 1).

Box 1

Controversial issues and unmet needs of chronic hepatitis B management

  • A finite approach of NA treatment.

  • Risk stratification of HCC under long-term NA therapy.

  • Combination therapy with NA and interferon.

  • Treatment of immune-tolerant or HBeAg-positive patients with chronic HBV infection.

  • Novel biomarkers to optimise chronic hepatitis B management.

  • HBeAg, hepatitis B e antigen; HCC, hepatocellular carcinoma; NA, nucleos(t)ide analogue.

International practising guidelines recommend that NA therapy should continue until HBsAg loss, at least in patients with HBeAg-negative CHB. However, a finite NA therapy has been practised in resource-limited regions, especially in Asia. The recent European Association for the Study of the Liver (EASL) guideline suggested NA may be stopped in HBeAg-positive non-cirrhotic patients who achieve HBeAg seroconversion with undetectable HBV DNA for at least 12 months, or in HBeAg-negative non-cirrhotic patients with persistent virological remission for >/=3 years.2 The pros of stopping NA are a finite treatment duration, with improved adherence, reduced costs and minimisation of renal and bone toxicity. The cons are the risk of reactivation of suppressed HBV, resulting in an unpredictable worsening of disease and possible development of severe hepatitis or even acute-on-chronic liver failure. The off-therapy relapse is common and up …

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