Trial Information

Long-Term Lamivudine Therapy for Chronic Hepatitis B

The major aims of this study are to evaluate the long-term efficacy and safety of lamivudine
therapy and the possibility of stopping therapy in a cohort of patients with chronic
hepatitis B who have a maintained response to treatment. Lamivudine is a nucleoside
analogue with potent activity against hepatitis B virus (HBV), which is approved for use in
the United States and is used extensively throughout the world to treat HBV and HIV
infection. Lamivudine is well tolerated and adverse events are rare. Its major shortcoming
is the development of antiviral resistance after prolonged therapy which results in loss of
effectiveness, marked by rise in viral levels and return of disease activity. Some
patients, however, have a maintained response to lamivudine therapy and in these individuals
treatment is continued indefinitely or until hepatitis B surface antigen (HBsAg) is lost and
therapy can be permanently stopped. This protocol will allow for the long-term treatment
and evaluation of these patients. Patients will be maintained on lamivudine at a dose of
100 mg daily and seen every three months for interim medical history and serum testing for
aminotransferase levels and hepatitis B markers, with liver biopsies done every 5 years.
Lamivudine will be stopped if HBsAg is lost. The protocol also includes an option to attempt
withdrawal of therapy under controlled conditions focusing on inducing immune reactivity to
HBV and clearance of HBsAg. Patients will stop lamivudine for short periods (1 week, and
later for 2, 4 and 8 weeks) and be monitored during and for 12 weeks afterwards for
aminotransferase levels, HBV DNA levels and CD4+ and CD8+ T cell responses to HBV antigens.
Patients who demonstrate significant worsening of hepatitis will not undergo further
attempts at withdrawal. The endpoint to successful therapy is defined as loss of hepatitis B
surface antigen (HBsAg) and development of antibody (anti-HBs).