The Hep573 Study: a randomised, double-blind, placebo-controlled clinical trial of silymarin alone, and silymarin combined with antioxidants in chronic hepatitis C

Oxidative stress (OS) is a key mechanism by which liver injury occurs in chronic hepatitis C (CHC) virus infection. For this Study, it was hypothesised the use of antioxidant compounds would reduce OS, hepatic necroinflammation and hepatic fibrosis in CHC patients. To test this hypothesis, a randomised, double-blind, placebo-controlled clinical trial (termed the 'Hep573 Study') was conducted in three Australian teaching hospitals in New South Wales. One hundred and eighteen participants were recruited through the liver outpatient clinics at the hospitals from July, 2003 to March, 2006. They were randomised to treatment in blocks of six to one of three groups: placebo; silymarin (720 mg silybin/day); and silymarin with antioxidants (720 mg silybin plus 13 other ingredients). Study duration was 48 weeks: 24 weeks on active treatment or placebo, and 24 weeks follow-up post treatment. The primary outcome measure was the proportion of patients with alanine aminotransferase (ALT) normalisation at Week 24 (Fisher‟s exact test). Secondary outcome measures were the percentage change from baseline to Week 24 in F₂₋isoprostanes, and to Week 24 and Week 48 in ALT, HCV viral load (HCV RNA) and FibroTest (Linear Mixed Effects). Results were analysed on an intention-to-treat basis. In patients with compensated CHC, the use of silymarin and antioxidant compounds achieved a higher rate of ALT normalisation than placebo (P=0.02) or silymarin (P=0.003) at Week 24. This result could not be attributed to alcohol, diet or caffeine, as intake across the groups did not change throughout the Study. In addition, there was a significant improvement in the overall mental-health score (Mental Component Summary), QualityMetric Hepatitis Quality of Life Questionnaire™ (HQLQ) in the silymarin and antioxidant (SOX) group (P=0.002). This novel randomised, double-blind, placebo-controlled trial of oral silymarin and oral antioxidants has shown a reduction in hepatic necroinflammation and an improvement in overall mental-health status in a specific CHC population.