Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial

Abstract

Background: Silymarin is the most commonly used herbal product for chronic liver disease; yet, whether silymarin protects against liver disease progression remains unclear.

Aim: To assess the effects of silymarin use on subsequent liver disease progression in 1049 patients of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had advanced fibrosis or cirrhosis and had failed prior peginterferon plus ribavirin treatment.

Methods: Patients recorded their use of silymarin at baseline and were followed up for liver disease progression (two point increase in Ishak fibrosis score across baseline, year 1.5, and year 3.5 biopsies) and over 8.65 years for clinical outcomes.

Results: At baseline, 34% of patients had used silymarin, half of whom were current users. Use of silymarin was associated (P < 0.05) with male gender; oesophageal varices; higher ALT and albumin; and lower AST/ALT ratio, among other features. Baseline users had less hepatic collagen content on study biopsies and had less histological progression (HR: 0.57, 95% CI: 0.33-1.00; P-trend for longer duration of use=0.026). No effect was seen for clinical outcomes.

Conclusions: Silymarin use among patients with advanced hepatitis C-related liver disease is associated with reduced progression from fibrosis to cirrhosis, but has no impact on clinical outcomes (Clinicaltrials.gov #NCT00006164).

Figure 1

Distribution at each biopsy for 621 patients without cirrhosis at baseline (Ishak score of 2, 3, or 4). Repeat protocol biopsies were performed 1.5 years (Biopsy 1, 524 patients) and 3.5 years after randomization (Biopsy 2, 443 patients). The p-values for the distribution of Ishak scores of former vs. never silymarin users were 0.086, 0.30, and 0.47 for baseline, biopsy 1, and biopsy 2, respectively. For current silymarin users vs. never silymarin users, p-values for the distribution of Ishak scores at each biopsy were 0.42, 0.097, and 0.0059, respectively.

Figure 2

Kaplan-Meier survival analysis of time to first clinical outcome by stratum of baseline silymarin use (never, former, and current; P=0.657).