POLYUNSATURATED PHOSPHATIDYL-CHOLINE AND INTERFERON-ALPHA FOR TREATMENT OF CHRONIC HEPATITIS-B AND HEPATITIS-C - A MULTICENTER, RANDOMIZED,DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Background/Aims: Polyunsaturated phospatidyl-choline (PPC) has been sh own to reduce serum aminotransferases in experimental hepatitis. This multi-center, randomized, double-blind, placebo-controlled trial evalu ated the effects of PPC in patients with chronic hepatitis B and C in combination with interferon alpha 2a or 2b. The diagnosis of chronic v iral hepatitis was based on an abnormal serum alanine aminotransferase (ALT) value (more than twice the upper value of normal), viral replic ation and chronic hepatitis found on liver biopsy. METHODOLOGY: Patien ts received 5 million I.U. (Hepatitis B) and 3 million LU. (hepatitis C) interferon s.c. thrice weekly for 24 weeks, respectively, and were randomly assigned to additional oral medication with either 6 capsules of PPC (total daily dose: 1.8 g) or 6 capsules of placebo per day for 24 weeks. Biochemical response to therapy was defined as a reduction of ALT by more than 50% of pre-treatment values. The responders were t reated for further 24 weeks after cessation of interferon therapy with either PPC or placebo. RESULTS: 176 patients completed the study prot ocol (per-protocol population: 92 in the PPC and 84 in the placebo gro up). A biochemical response (> 50% ALT reduction) was seen in 71% of p atients who were treated with PPC, but only in 56% of patients who rec eived placebo (p<0.05). PPC increased the response rate in particular in patients with hepatitis C: 71% of those patients responded in the P PC group versus 51% in the placebo group (p<0.05). Prolonged PPC thera py given to responders beyond the cessation of interferon therapy tend ed to increase the rate of sustained responders at week 48 in patients with hepatitis C (41% versus 15% in the control group; p=0.064). In c ontrast, PPC did not alter the biochemical response to interferon in p atients with hepatitis B. PPC did not accelerate elimination of HBV-DN A, HBeAg and HCV-RNA. CONCLUSIONS: In conclusion, PPC may be recommend ed in patients with chronic hepatitis C in combination with interferon and after termination of interferon in order to reduce the high relap se rate. PPC may not be recommended for patients with chronic hepatiti s B. In contrast to IFN and other antiviral agents PPC does not carry major risks and is tolerated very well.