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).

Intervention	Phase
Procedure: Blood Testing  Procedure: Percutaneous Liver Biopsy  Therapy: Lamivudine Therapy	Phase IV

Further Study Details: 

Expected Total Enrollment:  50

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).

Genders Eligible for Study:  Both

Criteria

INCLUSIION CRITERIA:

-Age 18 years or above, male or female

-Presence of HBsAg in serum for at least 6 months.

-Previous liver biopsy histology showing chronic hepatitis with or without cirrhosis.

-Long-term (greater than 1 year) lamivudine therapy in doses of 100 mg daily.

-Normal or near normal (less than twice the upper limit of normal) serum aminotransferase levels.

-HBV DNA levels below 10(5) copies per ml while on lamivudine.

-Written informed consent.

EXCLUSION CRITERIA:

-In women, pregnancy, breast feeding, and, in those capable of bearing children, inability to practice adequate contraception.

-Significant systemic illnesses other than liver disease, including congestive heart failure, renal failure, chronic pancreatitis, or diabetes mellitus with poor control.

-Serum creatinine greater than 1.5 mg/dL and creatinine clearance less than 50 cc/min.

-A history of clinically apparent pancreatitis or evidence of subclinical pancreatitis as shown by serum amylase values twice the upper limits of the normal range and abnormalities of the pancreas on computerized tomography or other imaging studies of the abdomen.

-Severe cirrhosis as defined by Child''''s stage C (Child-Pugh score of 7 or above).

-HIV infection as indicated by presence of anti-HIV in serum.

-Chronic hepatitis C as shown by the presence of anti-HCV and HCV RNA in serum.

-Immunosuppressive therapy requiring use of more than 10 mg of prednisone (or its equivalent) per day.

-Other antiviral therapy for chronic hepatitis B within the previous 3 months.

-Sensory or motor neuropathy apparent from medical history and physical examination.

Please refer to this study by ClinicalTrials.gov identifier  NCT00120354

Maryland
      National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050195; 05-DK-0195
Record last reviewed:  July 7, 2005
Last Updated:  July 14, 2005
Record first received:  July 14, 2005
ClinicalTrials.gov Identifier:  NCT00120354
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-26