THYMUS-DERIVED PEPTIDES IN THE TREATMENT OF VIRAL CHRONIC HEPATITIS

The immune system plays a crucial role in the control and eventual cle arance of hepatitis B virus (HBV) infection. Immune mechanisms are now believed to participate in the pathogenesis of the hepatitis C virus (HCV) and to account perhaps for the high frequency of progression fro m acute to chronic disease. Although IFN-alpha has been proven effecti ve in the treatment of viral chronic hepatitis B and C, response rates are low, reactivation of disease is appreciable and side effects of t reatment are, frequent. Both antiviral and immune modulatory activity have been ascribed to IFN-alpha and are believed to account for its th erapeutic effect. Immune-active peptides including those derived from the thymus have also been evaluated over the past 15 years for the tre atment of viral chronic hepatitis. This review summarizes clinical stu dies and experimental observations which provide the rationale for the use of these agents in the treatment of chronic hepatitis associated with HBV and HCV. Primary attention is focused on thymosin-alpha (T al pha l), a synthetic peptide, which has been evaluated in clinical tria ls. T alpha l has in vivo and in vitro immune-modulatory activity on l ymphoid populations as well as the potential of more direct antiviral activity. Preliminary results of clinical trials utilizing combination s of T alpha 1 with various IFN preparations are also reviewed.