title: Oltipraz therapy in patients with liver fibrosis or cirrhosis: a randomized, double-blind, placebo-controlled phase II trial.
abstract: OBJECTIVE
  Oltipraz, a cancer chemopreventive agent, has an anticirrhotic effect in animals. A phase II trial was designed to investigate the preliminary efficacy of oltipraz therapy in liver fibrosis or cirrhosis.
  
  
  METHODS
  Of 83 patients who were randomized to receive placebo, oltipraz 60 mg bid or oltipraz 90 mg qd for 24 weeks, 68 completed the study without any major protocol violation. Pre- and post-treatment liver biopsies, and blood fibrosis markers were assessed.
  
  
  RESULTS
  Twenty-four weeks of oltipraz treatment showed no significant differences in the proportions of patients showing an improvement in histological outcomes, including Ishak fibrosis score. In the oltipraz 60 mg bid group, there was a trend of decreases in hepatic collagen area and plasma transforming growth factor-β1 (TGF-β1, a blood fibrosis marker) levels from baseline to week 24. In the per-protocol population (n = 68), decreases in plasma TGF-β1 correlated with those in the Ishak fibrosis score, suggesting that circulating TGF-β1 serves a possible indicator for fibrosis treatment.
  
  
  CONCLUSIONS
  No significant differences in liver histological outcomes were seen among the three treatment groups in this 24-week pilot study. Our finding indicates an association between TGF-β1 repression and improvement in the histological index of fibrosis.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea. sgk@snu.ac.kr
authors.forename: Sang Geon
authors.initials: SG
authors.lastname: Kim
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Joon-Yeol
authors.initials: JY
authors.lastname: Han
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Jang
authors.forename: Se-Hyun
authors.initials: SH
authors.lastname: Cho
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Dong Hoo
authors.initials: DH
authors.lastname: Lee
authors.forename: Ja-June
authors.initials: JJ
authors.lastname: Jang
authors.forename: Eunsil
authors.initials: E
authors.lastname: Yu
authors.forename: Young Sok
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000328:Adult; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003094:Collagen / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D013871:Thiones; D013876:Thiophenes; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D016588:Anticarcinogenic Agents; D015415:Biomarkers; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D053773:Transforming Growth Factor beta1; C026209:oltipraz; D003094:Collagen