Effect of interferon, ribavirin and ursodeoxycholic acid in patients with hepatitis C infection.
OBJECTIVE
Combination therapy of interferon-alpha (IFNalpha) and the oral nucleoside analog, ribavirin is the standard treatment for individuals suffering from hepatitis C virus (HCV) infection. Several studies have shown combination therapy of IFN and antioxidants is therapeutically beneficial in these patients. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid possessing antioxidant properties. This study evaluated the clinical outcome and extent of oxidative stress in a group of non-responding and disease-relapsed HCV patients treated with IFNalpha, ribavirin and UDCA (triple therapy) for 6 months.


METHODS
Twenty patients with chronic HCV disease were treated with triple therapy for six months. During this period, they were monitored for the presence of HCV RNA, standard serum parameters of liver function and the plasma levels of lipid peroxides (LP) and glutathione (GSH) as indices of oxidative stress. The patients were reassessed six months after completion of treatment.


RESULTS
During the 6-month treatment period, the health status of the patients improved reflected by falls in the serum activities of alanine and aspartate aminotransferases and gamma-glutamyl transpeptidase and an initial lowering of viral (HCV RNA) load. Six months after cessation of treatment, the patients showed biochemical and virological evidence of disease relapse. The elevated plasma LP levels normalized during the treatment period and remained within normal levels 6 months after completion of treatment. Plasma GSH levels fluctuated within the normal range over the 12-month observation period.


CONCLUSIONS
Treatment of individuals with chronic HCV hepatitis with triple therapy comprising IFNalpha, ribavirin and UDCA improves the health status, as well as lowering the extent of oxidative stress in these individuals. This treatment regimen also resulted in a sustained lowering of plasma lipid peroxide levels in the face of laboratory evidence of disease relapse. This preliminary study is unable to provide an apt explanation for the persistence of normal plasma LP levels in the face of evidence of disease relapse 6 months after completion of treatment. However, we believe these preliminary findings are sufficiently intriguing to warrant further study. Such investigations should include more patients with assessment of the extent of hepatic fibrosis during and after completion of treatment to determine whether this treatment can modify the natural progress of the disease.
Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion--Israel Institute of Technology, Haifa, Israel.
Predrag
P
Ljubuncic
Fred M
FM
Konikoff
Laurence M
LM
Blendis
Arieh
A
Bomzon
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D002756:Cholagogues and Choleretics / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005978:Glutathione / Q000097:blood; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008054:Lipid Peroxides / Q000097:blood; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*
D000998:Antiviral Agents; D002756:Cholagogues and Choleretics; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008054:Lipid Peroxides; D011994:Recombinant Proteins; D012254:Ribavirin; D014580:Ursodeoxycholic Acid; D005978:Glutathione