Polyunsaturated phosphatidyl-choline and interferon alpha for treatment of chronic hepatitis B and C: a multi-center, randomized, double-blind, placebo-controlled trial. Leich Study Group.
OBJECTIVE
Polyunsaturated phospatidyl-choline (PPC) has been shown to reduce serum aminotransferases in experimental hepatitis. This multi-center, randomized, double-blind, placebo-controlled trial evaluated the effects of PPC in patients with chronic hepatitis B and C in combination with interferon alpha 2a or 2b. The diagnosis of chronic viral hepatitis was based on an abnormal serum alanine aminotransferase (ALT) value (more than twice the upper value of normal), viral replication and chronic hepatitis found on liver biopsy.


METHODS
Patients received 5 million I.U. (Hepatitis B) and 3 million I.U. (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 treated for further 24 weeks after cessation of interferon therapy with either PPC or placebo.


RESULTS
176 patients completed the study protocol (per-protocol population: 92 in the PPC and 84 in the placebo group). A biochemical response (> 50% ALT reduction) was seen in 71% of patients who were treated with PPC, but only in 56% of patients who received placebo (p < 0.05). PPC increased the response rate in particular in patients with hepatitis C: 71% of those patients responded in the PPC group versus 51% in the placebo group (p < 0.05). Prolonged PPC therapy given to responders beyond the cessation of interferon therapy tended 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 contrast, PPC did not alter the biochemical response to interferon in patients with hepatitis B. PPC did not accelerate elimination of HBV-DNA, HBeAg and HCV-RNA.


CONCLUSIONS
In conclusion, PPC may be recommended in patients with chronic hepatitis C in combination with interferon and after termination of interferon in order to reduce the high relapse rate. PPC may not be recommended for patients with chronic hepatitis B. In contrast to IFN and other antiviral agents PPC does not carry major risks and is tolerated very well.
Department of Medicine, Heinrich-Heine-University of Düsseldorf, Germany. claus.niederau@uni-duesseldorf.de
C
C
Niederau
G
G
Strohmeyer
T
T
Heintges
K
K
Peter
E
E
Göpfert
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005069:Evaluation Studies as Topic; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000097:blood / Q000188:drug therapy*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy*; D006521:Hepatitis, Chronic; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D011994:Recombinant Proteins; D013997:Time Factors
D000998:Antiviral Agents; D015415:Biomarkers; D000960:Hypolipidemic Agents; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; C029449:polyene phosphatidylcholine; D000410:Alanine Transaminase