Treatment of Chronic Delta Hepatitis With Pegylated Interferon

We propose to treat between 10 and 20 patients with chronic delta hepatitis with pegylated alpha interferon for up to five years. Patients with chronic delta hepatitis with raised serum aminotransferases, HBsAg and HDV RNA in serum, and moderate-to-severe chronic hepatitis on liver biopsy with HDV antigen will be enrolled. Patients will be monitored for at least three months with regular testing for ALT levels and will undergo admission for a thorough medical evaluation, portal pressure measurement and percutaneous liver biopsy before treatment. Pegylated interferon will then be started in a dose of 180 mcg weekly. At each clinic visit, patients will be questioned about side effects and symptoms and have blood taken for complete blood counts and routine liver tests (ALT, AST, alkaline phosphatase, direct and total bilirubin, and albumin). At 12-24 week intervals patients will undergo a physical examination and be tested for HBsAg, anti-HBs, HDV RNA, and prothrombin time. The dose of pegylated interferon will be adjusted based upon side effects and changes in ALT levels, aiming for optimal suppression of ALT elevations with acceptable tolerance. At 48 weeks (one year) and every 96 weeks (two years) thereafter, patients will be readmitted to the NIH Clinical Center for repeat thorough medical evaluation, portal pressure measurement and liver biopsy. The primary endpoint of therapy will be improvements in hepatic histology on liver biopsy done after 3 years of pegylated alpha interferon therapy. Several secondary endpoints will be measured, including changes in HDV RNA, loss of HBsAg, HDV staining in the liver biopsy, ALT levels, changes in portal pressures, quality of life, all at 1.3 and 5 years, and hepatic histology at 1 and 5 years. Patients will be maintained on pegylated interferon if it is adequately tolerated and there is an adequate "histological response," as defined by at least 3 point improvement in inflammatory score or 1 point improvement in fibrosis score of the HAI at each liver biopsy. Therapy will be stopped for: (1) intolerance to alpha interferon (which will be carefully defined), (2) lack of improvement in hepatic histology after 1, 3, or 5 years of therapy (histological nonresponse), or (3) a "complete response," i.e. loss of HDV RNA and HBsAg and development of anti-HBs.