Clinical Studies With Silymarin: Fibrosis Progression Is the End Point

Abstract

We read with interest the report by Angulo et al. 1 on 27 patients with primary biliary cirrhosis (PBC) who did not respond biochemically to ursodeoxycholic acid (UDCA). In a noncontrolled one-armed study the authors investigated the effect of adding oral silymarin for 1 year to the standard regimen with UDCA. Since silymarin did not alter alkaline phosphatase, bilirubin, aspartate transaminase, albumin, or the Mayo risk score, they concluded that silymarin is not effective in patients with PBC who do not respond to UDCA and that further controlled trials of silymarin in PBC are not warranted. We would take issue with several aspects of the study. 1. The patients were at an early clinical stage of the disease, in which the Mayo score has limited prognostic value. In addition, a treatment time interval of 1 year is generally too short to assess disease progression, with or without medication. 2-7 If one chooses to argue that 1 year is sufficient, then the finding of no progression of disease could be interpreted as evidence for a beneficial effect of silymarin. 2. The outcome parameters for the efficacy of silymarin (alkaline phosphatase, aspartate transaminase, albumin, bilirubin, and the Mayo risk score) are, at best, indirect measures of disease progression and unreliable as predictors of fibrosis, particularly in patients receiving UDCA. 2-7 Since progression of fibrosis ultimately determines the prognosis of PBC, fibrosis-related parameters should be monitored, including sequential histology, aminoterminal procollagen type III peptide, collagen IV, hyaluronic acid, and others. 8 3. The authors failed to note a large experimental study of secondary biliary fibrosis in rats, which showed a highly significant antifibrotic effect of silymarin in early as well as advanced disease. 9 Although not using an exact model of human

Evaluation of antioxidant activity of Manihot esculenta Crantz in wistar rats

“…Silymarin is obtained from the plant sliybon marinum, and it has already proven as an antioxidant and antifibrotic. [ 20 ]…”

Inhibition of hepatic fibrogenesis by matrix metalloproteinase‐9 mutants in mice

“…Main reasons for hepatic fibrogenesis are chronic hepatitis B and C, chronic toxic liver injury including alcoholism, nonalcoholic steatohepatitis, and chronic cholestasis. Some anti-fibrotic agents like silymarin (41), ursodeoxycholic acid (42), or IFN-␣ (43) were tested in clinical trials but as yet a successful therapeutic treatment has not prevailed. A central aspect of progression in liver fibrosis is represented by the accelerated transdifferentiation of perisinusoidal HSC to the activated MFB phenotype.…”

Silymarin treatment of viral hepatitis: a systematic review

“…The study is scheduled to last 2 years, and has fibrosis progression as the primary endpoint. The authors did not state if the study is randomized or placebo‐controlled [72]. The National Centre for Complementary and Alternative Medicine (NCCAM) also lists two phase II trials that are currently investigating silymarin treatment in hepatitis C [73,74].…”