Glycyrrhizin in patients who failed previous interferon alpha-based therapies: biochemical and histological effects after 52 weeks

. Chronic hepatitis C patients often fail to respond to interferon-based therapies. This phase III study aimed at confirming the efficacy and safety of glycyrrhizin in interferon + ribavirin-based therapy non-responders. A randomised, double-blind, placebo-controlled, comparison of glycyrrhizin, administered intravenously 5x/or 3x/week, and 5x/week placebo for 12 weeks to 379 patients, was followed by a randomised, open comparison of glycyrrhizin i.v. 5x/versus 3x/week for 40 weeks. Primary endpoints were: (1) the proportion of patients with =50% ALT (alanine aminotransferase) reduction after 12 weeks double-blind phase, and (2) the proportion of patients with improvement of necro-inflammation after 52 weeks as compared with baseline. The proportion of patients with ALT reduction =50% after 12 weeks was significantly higher with 5x/week glycyrrhizin (28.7%, P < 0.0001) and 3x/week glycyrrhizin (29.0%, P < 0.0001) compared with placebo (7.0%). The proportion of patients with improvement in necro-inflammation after 52 weeks was 44.9% with 5x/week and 46.0% with 3x/week, respectively. Glycyrrhizin exhibited a significantly higher ALT reduction compared to placebo after 12 weeks of therapy and an improvement of necro-inflammation and fibrosis after 52-weeks treatment. Generally, glycyrrhizin treatment was well tolerated.