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Standard and pegylated interferon for chronic hepatitis B virus infection

INTRODUCTION

Chronic hepatitis B virus (HBV) infection is a serious liver disorder which may result in cirrhosis and hepatocellular carcinoma (HCC). It is an immense health problem globally that affects 300 million individuals or 5 percent of the world's population.

Interferons (IFN) have antiviral, antiproliferative, and immunomodulatory effects. IFN-alfa (IFNa) and IFN-beta have predominantly antiviral effects, while IFN-gamma has more marked immunoregulatory but less potent antiviral activity.

IFNa was the first treatment approved for chronic HBV infection in most countries. More recently, pegylated interferon (pegIFN alfa-2a only in the United States and pegIFN alfa-2a as well as pegIFN alfa-2b in many countries outside the US) was approved for treatment of chronic HBV. This topic review will discuss the treatment of chronic hepatitis B with standard or pegylated interferon. A general approach to patients with hepatitis B (including other treatment options) is presented separately. (See "Overview of the management of chronic hepatitis B and case examples".)

ENDPOINTS OF THERAPY

Several endpoints are used to assess the efficacy of hepatitis B treatment (table 1). A report from a NIH workshop on the management of hepatitis B proposes that responses to antiviral therapy of chronic hepatitis B should be categorized as biochemical, virological, or histological, and as on-therapy or sustained off-therapy [1]. A positive response in most clinical trials was defined as the loss of viral replication markers (HBeAg [in patients who were HBeAg-positive] and serum HBV DNA) within 12 months after the initiation of treatment. Clearance of serum HBV DNA usually occurs during treatment but loss of HBeAg and seroconversion to HBe antibody (anti-HBe) may be delayed. In most trials, spontaneous loss of HBeAg and serum HBV DNA occurs in 5 to 10 percent of untreated controls.

IFN therapy is associated with flares (at least twofold increase over baseline) in serum alanine aminotransferase (ALT) concentrations in 30 to 50 percent of patients [2,3]. This response is thought to reflect immune-mediated lysis of infected hepatocytes. (See "Characteristics of the hepatitis B virus and pathogenesis of infection".) IFN may need to be discontinued or the dose reduced if the flare is severe and accompanied by symptoms or an increase in the serum bilirubin concentration. A successful antiviral response is usually associated with normalization of serum ALT and decreased necroinflammatory activity.
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