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Standard and pegylated interferon for chronic hepatitis B virus infection

Author
Anna SF Lok, MD
Section Editor
Rafael Esteban, MD
Deputy Editor
Jennifer Mitty, MD, MPH

INTRODUCTION

Chronic hepatitis B virus (HBV) infection is a serious liver disorder that can result in cirrhosis, liver failure, and hepatocellular carcinoma. It remains a major global health problem affecting an estimated 248 million persons of whom roughly 600,000 die annually from HBV-related liver disease [1,2].

Interferons (IFN) have antiviral, antiproliferative, and immunomodulatory effects. IFN-alfa and IFN-beta have predominantly antiviral effects, while IFN-gamma has more marked immunomodulatory, but less potent antiviral activity. IFN-alfa is the most widely studied and the only IFN approved for the treatment of HBV in most countries. Although standard IFN was initially used, it has generally been replaced by pegylated interferon (PegIFN). PegIFN alfa-2a is approved in the United States. In many other countries, PegIFN alfa-2b is also used for treatment of chronic HBV.

This topic will review the use of IFN for the treatment of adults with chronic HBV. Topic reviews that provide a more general overview of the treatment of HBV in adults and children are found elsewhere. (See "Hepatitis B virus: Overview of management" and "Overview of hepatitis B virus infection in children and adolescents".)

MECHANISM OF ACTION

Although interferon (IFN) has been used as treatment for chronic hepatitis B virus (HBV) infection for 40 years, its exact mechanisms of action are still unclear. IFN is thought to induce specific genes that interfere with several steps in the HBV lifecycle, including: virus entry; uncoating of the virion; transcription of viral DNA into RNA; translation of viral RNA into proteins; and assembly of nucleocapsids [3]. It may also augment cell-mediated immunity, thereby promoting clearance of HBV-infected hepatocytes. (See "Characteristics of the hepatitis B virus and pathogenesis of infection", section on 'Replication cycle' and "Characteristics of the hepatitis B virus and pathogenesis of infection", section on 'Pathogenesis of infection'.)

IFN's effect on HBV transcription appears to be partly mediated by epigenetic modifications of the HBV covalently closed circular DNA (cccDNA) minichromosome [4,5]. In addition, IFN can induce degradation of cccDNA by induction of APOBEC3s (DNA editing enzymes) that can degrade foreign, but not host, DNAs [6]. These findings may explain why IFN treatment results in a higher rate of hepatitis B e antigen and hepatitis B surface antigen loss, and a more durable response compared with nucleos(t)ide analogue treatment. (See 'Virologic response' below and 'Studies of interferon therapy' below.)

                   

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Literature review current through: Nov 2016. | This topic last updated: Mon Nov 28 00:00:00 GMT+00:00 2016.
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