Interferon Treatment of Viral Hepatitis

Interferon Treatment of Viral Hepatitis

By Howard J. Worman, M. D.

This page provides general information on treatment options for viral hepatitis B and C. It is not an endorsement of the any of the products by the author or by any institution with which the author is affiliated.

Various type I interferons administered by intramuscular or subcutaneous injection are indicated for the treatment of chronic hepatitis B and chronic hepatitis C. Interferon alfa is a naturally occurring glycoprotein that is secreted by cells in response to viral infections. It exerts its effects by binding to a membrane receptor. Receptor binding initiates a series of intracellular signaling events that ultimately leads to enhanced expression of certain genes. This leads to the enhancement and induction of certain cellular activities including augmentation of target cell killing by lymphocytes and inhibition of virus replication in infected cells. Various recombinant forms of interferon alpha (interferon alpha-2a and interferon alpha-2b) and a recombinant non-naturally occuring type I interferon (interferon alfacon-1) are approved to treat viral hepatitis.

THIS PAGE PROVIDES ONLY AN INTRODUCTION TO TREATMENT OF CHRONIC HEPATITIS B OR HEPATITIS C WITH INTERFERON. YOU SHOULD CONSULT A PHYSICIAN EXPERIENCED IN THE CARE OF PATIENTS WITH LIVER DISEASES FOR ADDITIONAL INFORMATION.

Chronic Hepatitis B

Interferon alfa-2b is effective in the treatment of adults with chronic hepatitis B virus infection and evidence of viral replication. The patient should have evidence of infection with hepatitis B virus, documented by the presence of hepatitis B surface antigen in the blood, for six months. The patients should also have evidence of virus replication, documented by the presence of hepatitis B e antigen in the blood. Ongoing inflammation of the liver should also be present as documented by an elevation in serum aminotransferase activities. A liver biopsy should also be performed prior to treatment. Patients with severe, decompensated liver disease (eg. encephalopathy, ascites, very high serum bilirubin, prolonged prothrombin time, etc.) should not generally be treated with interferon alfa-2b except in the setting of an approved clinical study.

The recommended dose of interferon alfa-2b for the treatment of chronic hepatitis B is 5,000,000 units daily, administered by subcutaneous or intramuscular injection, for a total of 16 weeks. The patient must be monitored carefully during the treatment period for side effects including flu-like symptoms, depression, rashes, other reactions and abnormal blood counts.

A meta-analysis of several randomized trials of interferon alfa-2b in the treatment of patients with chronic hepatitis B showed such treatment to be cost-effective (Wong et al. Annals Intern. Med. 1995;122:664-675). This analysis showed that treatment with interferon alfa-2b decreased viral replication, documented by loss of serum hepatitis B e antigen, in about 45% of patients compared to less than 10 % of untreated patients. About 8% of patients also lost hepatitis B virus surface antigen (cured) within one year of treatment compared to a rate of about 1% a year for untreated patients.

Interferon alfa-2b treatment of chronic hepatitis B requires careful medical attention. Consult a physician who has experience with this type of treatment for more information.

Chronic Hepatitis C

Interferon alfa-2a (Roferon-A; Hoffmann-La Roche), inteferon alpha-2b (Intron-A; Schering-Plough) and interferon alfacon-1 (Infergen; Amgen) are all approved in the United States for the treatment of adults with chronic hepatitis C. The patient should have evidence of chronic liver disease and infection with hepatitis C virus as documented by the presence of serum antibodies against this virus or serum viral RNA. Inflammation of the liver should also be present as documented by elevations in the serum aminotransferase activities and liver biopsy. Treatment of patients without evidence of inflammation (e.g. normal serum aminotransferase activities), or treatment of patients with decompensated liver disease (e.g. encephalopathy, ascites, very high serum bilirubin, abnormal prothrombin time, etc.), should only be considered in the setting of an approved clinical study.

The recommended dose of interferons alfa-2b and alpha-2a for the treatment of chronic hepatitis C is 3,000,000 units three times a week, administered by subcutaneous or intramuscular injection. For interferon alfacon-1, the recommended dose is 9mcg three times a week for first time treatment. Six months of treatment was originally recommended for interferons alpha 2a and 2b, however, several studies have shown that treatment for a year or longer may be more effective (Poynard et al. Hepatology. 1996;24:778-789). Treatment times of 1 to 2 years with these drugs are now approved by the FDA. For interferon alfacon-1, a six month treatment course of 9 mcg three times a week is approved and a dose of 15 mcg three times a week for another six months is approved for patients who do not respond or relapse. During the treatment periods with any of these recombinant interferons, the patient must be monitored carefully for side effects including flu-like symptoms, depression, rashes, other unusual reactions and abnormal blood counts.

The results of several published clinical studies demonstrate that about 50% to 70% of patients with chronic hepatitis C respond to treatment with interferon alfa-2b as documented by reductions in the serum aminotransferase activities to near normal. Several studies have also shown that about 70% of patients have a decrease in liver inflammation on follow-up liver biopsy. Unfortunately, most patients relapse and have recurrent liver inflammation after treatment is discontinued.

Several studies have tested a combination of interferon alfa-2b and ribavirin. This drug combination was approved by the United States Food and Drug Administation in June, 1998 for patients with chronic hepatitis C who have been treated perviously with interferon alone and "relapsed" after treatment was discontinued. It may also be useful in patients never treated previously or in those who did not respond at all to previous interferon treatment. Study results suggest that a combination of interferon alpha-2b and ribavirin induce a sustained response in more patients than treatment with interferon alpha-2b alone. Patients interested in such treatment should consult their physician.

Interferon treatment of chronic hepatitis C requires careful medical attention. Consult a physician who has experience with this type of treatment for more information.

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