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Oral antiviral therapy for hepatitis B: the case of besifovir, a new kid on the block with a long way to go
  1. Pietro Lampertico
  1. Correspondence to Dr Pietro Lampertico, 1st Division of Gastroenterology, “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 35-20122 Milan, Italy; pietro.lampertico{at}

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In the last 5 years, the landscape of HBV antiviral treatment has changed significantly to such an extent that most of the clinical problems have been solved for countries where third-generation nucleo s(t)ide analogues (NUC), such as entecavir (ETV) and tenofovir (TDF) are routinely available.13 Indeed, because of the high potency and high genetic barrier of these products, 5–6 years administration of ETV or TDF suppresses viral replication in >95% of the cases, with increasing rates of HBeAg seroconversion (up to 50%) and HBsAg seroconversion (up to 10%). In patients with long-lasting viral suppression, histological fibrosis is reverted, cirrhosis can regress and clinical decompensation is fully prevented, whereas, hepatocellular carcinoma (HCC) remains the only complication leading to anticipated liver-related death and liver transplantation.48 In patients with decompensated cirrhosis, administration of ETV and TDF improves survival, though the early mortality rates and the development HCC despite effective viral suppression do represent major challenges for these delicate patients. Likewise, the management of NUC-resistant (NUC-R) patients has also been revolutionised by the availability of TDF which efficiently suppresses as monotherapy viral replication in most patients, independently of the resistant profile.9 Though efficacy must remain the major endpoint of any anti-HBV therapy, safety has also attracted much of attention in recent years, given that antiviral treatment must be prolonged for several years, even decades, for most patients, as HBsAg clearance remains the best stopping rule even in cirrhotics. Even in this regard, ETV and TDF have shown a good safety profile over extended periods (up to …

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  • Competing interests Advisory Board/Speaker Bureau for BMS, Roche, Gilead Sciences, GlaxoSmithKline and Merck Sharp & Dohme.

  • Provenance and peer review Commissioned; internally peer reviewed.

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