A panel of nationally-respected U.S. liver specialists developed comprehensive treatment guidelines – A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the U.S. – that were first published in February 2004, and then revised in August 2006. The update is based on new developments in the understanding of chronic hepatitis B, the availability of more sensitive diagnostic testing, the approval of two new treatments (entecavir and peginterferon), and better understanding of the advantages and disadvantages of the five approved therapies.

This algorithm has been updated where appropriate to include use of the two new drugs and aims to assist treating physicians in answering the practical questions of HBV management based on available evidence; however, where data are lacking, the panel relied on clinical experience and consensus expert opinion.

According to the experts, the primary aim of antiviral therapy is to bring the HBV DNA levels down as low as possible and for as long as possible, to reduce the risk of serious liver disease such as cirrhosis, liver failure and primary liver cancer (hepatocellular cancer, or HCC).

To read the complete “A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the U.S.: An Update 2006”, by Dr. Keeffe, et. al, visit the HBF website at www.hepb.org/pdf/treatmentalgorithm_update.pdf.

EXCERPTS FROM THE UPDATED TREATMENT ALGORITHM CONCLUSION

By Emmet B. Keeffe, et. al, in Clinical Gastroenterology and Hepatology, August 2006

Goal of Therapy

The goal of therapy for patients with chronic HBV infection is to prevent progression of liver disease to cirrhosis and HCC. The primary aim of therapy is durable suppression of serum HBV DNA to the lowest levels possible.

HBV DNA Levels for Treatment Consideration

The HBV DNA levels should be used to establish a patient’s baseline HBV DNA level before treatment and to monitor response to antiviral therapy or viral rebound associated with resistance. The threshold level of HBV DNA for determination of candidates for therapy is:

• HBeAg-positive CHB - 20,000 IU/mL or higher

• HBeAg-negative CHB - 2,000 IU/mL

• Decompensated cirrhosis - 200 IU/mL

Approved Treatments

Adefovir, entecavir, interferon alfa-2b (IFN), lamivudine, and peginterferon alfa-2a are approved as initial therapy for chronic hepatitis B. The issues to consider are efficacy, safety, resistance, method of administration, and cost.

• Adefovir generally has comparable efficacy with lamivudine and is well tolerated. It has the advantage of a delayed and low rate of resistance development.

• Entecavir is the most potent oral agent and has shown superiority to lamivudine in randomized clinical trials. No resistance has been shown after 2 years of therapy in naive patients. However, long-term efficacy and resistance data are not available beyond 2 years.

• The cost of both entecavir and adefovir is higher than that of lamivudine

• IFN and Peginterferon have the advantage of a finite duration of treatment, durable response (in patients who respond), and lack of resistance; however, they are expensive to use, have to be given by injection, and have many side effects. In current practice, peginterferon alfa-2a is likely to supplant standard IFN.

• Lamivudine is well tolerated, with an excellent safety profile and good efficacy, but its long-term use is limited by the development of resistance. Therefore, the panel does not recommend lamivudine for first-line use except in patients receiving short-term antiviral prophylaxis during chemotherapy or in pregnancy, as part of an HIV regimen in patients with HBV/HIV co-infection, or in combination with adefovir in patients with hepatic decompensation.

• Patients requiring therapy for longer than 1 year probably are best treated with adefovir or entecavir, which have much lower incidence rates of resistance.

Future of Combination Therapy

Combination therapy may prove to be more effective than monotherapy in suppressing viral replication and very likely will decrease or delay the incidence of drug resistance. Several large studies are underway in compensated patients.

There are numerous candidate drugs including emtricitabine, telbivudine, and tenofovir currently under evaluation as potential therapies for chronic HBV infection, which should expand the number of treatment options further in the coming years.