Management of Antiviral Resistance in Patients with Chronic Hepatitis B

TLDR

Antiviral resistance in chronic hepatitis B is monitored through virological and clinical markers, with definitions of primary and secondary treatment failure guiding early diagnosis before disease progression. The meeting aimed to outline current CHB treatments, discuss emerging drug‑resistance issues, and provide a framework for monitoring and managing resistance in patients. Primary failure is defined as <1 log10 IU/ml HBV DNA reduction within 3 months, secondary as ≥1 log10 IU/ml rebound, and resistance is confirmed by sequencing HBV polymerase for specific mutations.

Abstract

A meeting of physicians and scientists involved in the management of chronic hepatitis B (CHB) was held to review current scientific data regarding antiviral resistance in hepatitis B virus (HBV) infection. The goals of the meeting were to describe current treatments for CHB, discuss emerging issues in HBV drug resistance and to delineate patient monitoring, including markers for resistance, during administration of antiviral therapy. The aim of this review article is to provide treating physicians with a framework for the management of CHB in the context of antiviral resistance. Definitions of primary and secondary antiviral treatment failure can be used to aid monitoring and early diagnosis of drug resistance before disease progression occurs as a consequence of viral breakthrough. Primary antiviral treatment failure is defined as failure of a drug to reduce HBV DNA levels by ≥1xlog 10 IU/ml within 3 months following initiation of therapy, and secondary antiviral treatment failure as a rebound of HBV replication of ≥1xlog 10 IU/ml from nadir in patients with an initial antiviral treatment effect (≥1xlog 10 IU/ml decrease in serum HBV DNA). Confirmation of antiviral drug failure can be established by sequencing the HBV DNA polymerase and identifying specific genetic markers of antiviral drug resistance. In addition to virological assays, HBV resistance can be assessed from a clinical perspective including increased serum alanine aminotransferase levels and the development of systemic symptoms or signs of liver failure. Potential strategies to prevent the emergence of resistance and how to manage drug-resistant HBV once it emerges are discussed.