COMMENTARY

The Role of Interferon Therapy in Hepatitis B

W. Graham E. Cooksley, MD

Disclosures

March 18, 2004

In This Article

Introduction

Interferon-alfa was approved by the US Food and Drug Administration for treatment of hepatitis B in 1992. Lamivudine was approved in 1998 and, more recently, adefovir dipivoxil was approved in 2002. Because of the side effects associated with interferon and the inconvenience of frequent injections, lamivudine soon became the drug of choice worldwide. However, there are disadvantages associated with use of this agent, including the development of lamivudine resistance as a result of YMDD mutations, as well as some concern regarding the durability of response.

At the time of the National Institutes of Health Workshop on management of hepatitis B in 2000, support for interferon and lamivudine seemed finely balanced,[1] but by the time of the EASL (European Association for the Study of the Liver) Consensus Meeting, held in 2002, the recommendations were in favor of interferon.[2] It was also noted that adefovir seemed to be an effective antiviral agent, and no resistant mutations were detected in patients treated for up to 48 weeks.[3,4] Recently, studies with pegylated interferon have demonstrated better results compared with conventional interferon in this setting.

As well as in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, virus replication and elevated aminotransferases may be seen in patients who remain HBeAg-negative. This phenomenon is due to mutations in the precore region of the virus (precore mutations and core promoter gene mutations) that prevent synthesis of HBeAg, but allow the core proteins to be synthesized; they occur mainly in hepatitis B virus (HBV) genotypes B and C in Asian patients, and in HBV genotype D in Mediterranean patients. These patients are often older with more advanced fibrosis.

In general, patients with HBeAg-positive disease should be treated if there is active viral replication and persistent elevation in their aminotransferase levels (ie, alanine aminotransferase [ALT]) after 3 months of observation. Patients with normal serum ALT or with mild chronic hepatitis should not be treated. These individuals should be monitored, as they may develop progressive liver disease later. In HBeAg-negative disease, differentiation from the inactive "carrier state" may be difficult, and requires monitoring of ALT and HBV DNA levels over a period of 6-12 months. Again, treatment is indicated for patients with moderate or severe disease only. Patients with decompensated cirrhosis, liver transplantation, immunosuppression, coinfection with other viruses, etc. may require specific consideration.[2]

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