Lamivudine for chronic delta hepatitis

Chronic delta hepatitis is a severe form of chronic liver disease caused by hepatitis delta virus (HDV) infection superimposed on chronic hepatitis B or the hepatitis B surface antigen (HBsAg) carrier state. Therapy of delta hepatitis is currently unsatisfactory. We have evaluated lamivudine (3-thia cytidine), an oral nucleoside analogue with marked effects against hepatiti s B, as therapy in 5 patients with chronic hepatitis D, Five men, ages 38 t o 65 years, were treated. All had HBsAg, antibody to HDV, and HDV RNA in se rum, as well as persistent elevations in alanine aminotransferase (ALT) lev els and liver histology showing severe chronic hepatitis with fibrosis or c irrhosis. Lamivudine was given in a dose of 100 mg orally daily for 12 mont hs. Patients were monitored carefully and tested for HBsAg, HBV-DNA and HDV -RNA levels serially during the year of treatment and for 6 months thereaft er. Liver biopsies were performed before therapy and repeated after 1 year. Serum levels of HBV DNA fell rapidly in all 5 patients, becoming undetecta ble even by polymerase chain reaction (PCR) in 4. However, all 5 patients r emained HBsAg- and HDV-RNA-positive, and serum ALT levels and liver histolo gy did not improve. All patients tolerated therapy well. When lamivudine wa s stopped, HBV-DNA levels returned to pretreatment values without a change in disease activity. Lamivudine is a potent inhibitor of HBV-DNA replicatio n, but does not improve disease activity or lower HDV-RNA levels in patient s with chronic delta hepatitis.