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Oral antiviral therapy for HBeAg negative chronic hepatitis B: better stop or continue?
  1. Pietro Lampertico
  1. Correspondence to Dr Pietro Lampertico, 1st Division of Gastroenterology and Hepatology, “A.M. e A. Migliavacca” Center for the Study of Liver Disease, Fondazione IRCCS Ca’ Granda—Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via F. Sforza 35, Milan 20122, Italy; pietro.lampertico{at}

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Treatment cessation is one of the few challenges left to clinicians to deal with after the marketing and widespread use of third generation oral analogues (nucleos(t)ide analogue (NUC)), entecavir (ETV) and tenofovir (TDF) for the treatment of HBeAg negative chronic hepatitis B (CHB). Treatment efficacy is in fact unquestioned as more than 95% of patients, including NUC experienced and resistant ones, achieve complete suppression of viral replication and improvement of hepatic inflammation and fibrosis within the first 5 years of treatment.1–3 As a consequence, in a majority of patients, progression to cirrhosis is prevented, and clinical decompensation and portal hypertension either improved or prevented, with hepatocellular carcinoma (HCC) remaining the only complication in HBeAg negative patients long-term treated for with ETV or TDF.4 Indeed, the yearly attack rates of HCC range between 0.5% and 1% among non-cirrhotics and 2.5% and 4% among compensated cirrhotics, incidence rates not very different from what is expected in untreated patients.4 ,5 In these patients, the recommended stopping rule of NUC therapy is HBsAg seroconversion, defined as HBsAg loss and anti-HBs titres >100–200 IU/L,6–8 which has been proven to be safe in any clinical situation including patients with advanced liver disease, though a minority of patient clearing HBsAg following NUC therapy do not seroconvert to anti-HBs.9 ,10

One major caveat of this stopping rule is the small number of HBeAg negative patients who achieve HBsAg seroconversion, no more than 1% after 5 years and 5% after 10 years of continuous treatment, thereby questioning whether it is appropriate to stop NUC therapy before achieving HBsAg seronegativity. Asian Pacific Association for the Study of the Liver (APASL) guidelines indeed suggest this, but so far clinical evidence supporting these recommendations is more than scanty.

In the study by Seto et al,11 treatment cessation …

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  • Funding Advisory board/speaker bureau for BMS, Roche, Gilead Sciences, GSK and MSD.

  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.

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