Treatment of Chronic Hepatitis B

Dr. Sherman is a Hepatologist practicing in Toronto, Canada. This paper has been submitted as a contribution to the Update in Liver Disease Conference 1998 and discusses current and future therapies for hepatitis B. (Some clinical information related to lamivudine has been omitted until data publication).

Dr. Morris Sherman

The first licensed therapy for chronic hepatitis B virus infection was interferon. The indications for interferon are very specific. Patients must be HBeAg-positive, and have detectable HBV DNA in the serum, as well as an ALT more than twice the upper limit of normal. When such patients are treated with the standard therapy, namely 30-35 mu interferon/week for 4 months, the response rate is 40-50%. Response is defined as loss of HBeAg, and development of anti-HBe, loss of HBV DNA (by non-PCR assays), and normalization of ALT. This response is usually permanent, and is associated with improvement in histology, and a better long term outcome (fewer patients with cirrhosis and hepatocellular carcinoma).

There are several categories of hepatitis B carrier who are not suitable for interferon, but who nonetheless have active liver disease. these include patients who are anti-HBe-positive, patients who are immunosuppressed, or who have hepatic decompensation. Interferon therapy is controversial in patients who are anti-HBe-positive with elevated enzymes and detectable HBV DNA in serum. Current recommendations are that these patients not be treated, but there is literature suggesting that the response rate is no different that in HBeAg-positive patients. Interferon is ineffective in immunosuppressed patients. Patients with advanced liver disease are at risk for life-threatening complications of infection and deteriorating liver function with interferon therapy. All these groups may be suitable for lamivudine therapy. However, as with the HBeAg-positive group, the duration of therapy is not known. Again, 5 years is the current projected duration of therapy. In these patients seroconversion may not be available to guide stopping therapy. Because of the problem off emerging resistant strains the treatment decision in these patients has to be carefully considered.

Famoiclovir has also been used to treat hepatitis B. Results are available only in abstract form. Famoiclovir will reduce hepatitis B virus replication, but the number of patients who achieve clearance of HBV DNA is less than for lamivudine. In the post-liver transplant situation the emergence of resistance is sometimes associated with progressive liver disease leading to death. It is only a matter of time before this sequence of events is seen in patients with immunosuppression for other reasons.

Two new agents are promising, lobucavir and adefovir. Both are currently undergoing phase II trials, and are about to start phase III trials. In initial studies adefovir was given for three months. The drug cause a universal fall in HBV DNA level to undetectable levels, associated with an improvement in ALT. Adefovir has a major advantage that it is not affected by the mutation which confers resistance to lamivudine. Most patients relapsed after completion of therapy.

Lobucavir was given to patients for one month in initial studies. Like adefovir it induced marked reduction in viral replication levels. Again, most patients relapsed after therapy was stopped. The sensitivity of the lamivudine-resistant hepatitis B mutant to lobucavir is not known.

Both these drugs are also likely to enter the armamentarium against chronic hepatitis B. However, because of the development of resistance it is likely that combination therapy will be the way of the future. The optimal use of these drugs will have to await future trials.

Sharing is caring!

Leave a Comment