Roadmap to Functional Cure of Chronic Hepatitis B: An Expert Consensus

Qin Ning; Di Wu; Gui-Qiang Wang; Hong Ren; Zhi-Liang Gao; Peng Hu; Mei-Fang Han; Yan Wang; Wen-Hong Zhang; Feng-Min Lu; Fu-Sheng Wang

Disclosures

J Viral Hepat. 2019;26(10):1146-1155. 

In This Article

Abstract and Introduction

Abstract

Hepatitis B virus (HBV) infection continues to be a major public health issue worldwide. HBsAg loss is associated with functional remission and improved long-term outcome, and is considered to be a 'functional cure' (also referred to as clinical or immunologic cure) for chronic hepatitis B. This ideal goal of therapy can be achieved using optimized combination regimens with direct-acting antivirals [eg nucleos(t)ide analogues (NAs)] and immunomodulators [eg pegylated interferon alpha2a (Peg-IFN)] in selected patients with chronic hepatitis B. Among different combination therapies currently available, those with NA lead-in followed by Peg-IFN in virally suppressed patients has been demonstrated to be effective. This review provides an updated overview of the evidence supporting the use of combination therapies and summarizes expert consensus on the roadmap to attain functional cure for chronic hepatitis B patients.

Introduction

Hepatitis B virus (HBV) infection continues to be a major public health burden. Approximately 240 million people worldwide are chronically infected with HBV, contributing to about 30% of cirrhosis and 45% of hepatocellular carcinoma (HCC) cases.[1,2] The primary goal of hepatitis B treatment is to improve survival by preventing the development of HBV-related cirrhosis, liver failure and HCC.[3–6] HBsAg loss is associated with functional remission and improved long-term outcome[7] and is the ideal goal of therapy (functional cure) recommended by current guidelines.[3–6] However, existing antiviral therapy including immunomodulators [eg pegylated interferon alpha2a (Peg-IFN)] or direct-acting antivirals (DAA) [eg nucleos(t)ide analogues (NAs)] when used alone offers limited capability in delivering functional cure. Curative therapy with the aim of eliminating HBV infection is unlikely to be available in the next decade; thus, there is a pressing need to optimize current therapies. Theoretically, the administration of NA and Peg-IFN with different mechanisms of action in combination against HBV is a promising approach to generate synergistic and complementary effects and could be of importance in future therapeutic regimens. Accumulating data have confirmed virological and serological advantages of combination strategy. This review provides an updated analysis of the clinical data supporting the use of combination therapies and summarizes expert consensus on the roadmap to guide hepatologists' decision-making in attaining functional cure for chronic hepatitis B patients.

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