title: Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial.
abstract: BACKGROUND
  The burden of non-alcoholic steatohepatitis (NASH) is growing and current pharmacologic treatments are limited by side effects and inconsistent efficacy. Pilot studies suggest that pentoxifylline (PTX) can reduce liver injury in patients with NASH.
  
  
  OBJECTIVE
  We sought to determine the tolerability of PTX and its effect on aminotransferases and liver histology in patients with NASH.
  
  
  METHODS
  Thirty patients with biopsy proven NASH were randomized in a 2:1 fashion to receive 1,200 mg PTX or placebo for 12 months. Metabolic parameters, aminotransferases, liver histology and hepatic gene expression changes were compared.
  
  
  RESULTS
  At baseline the groups were similar. Adverse events were mild, most frequently headache and abdominal cramps, and did not differ between groups (p = NS). After 12 months, ALT and AST decreased from 92 ± 12 IU/L to 67 ± 13 IU/L and 67 ± 6 IU/L to 47 ± 6 IU/L (p < 0.05), respectively in patients treated with PTX. No significant effect was seen with placebo. Steatosis and cellular ballooning improved in the PTX group (p < 0.05), whereas no histological feature of steatohepatitis improved with placebo. However, between groups comparison of both biochemical and histological features were nonsignificant.
  
  
  CONCLUSIONS
  Pentoxifylline is safe, well tolerated and improves transaminases and histology in patients with NASH when compared to baseline and may be a reasonable therapeutic modality for the treatment of NASH. However PTX failed to reduce transaminases compared to placebo and did not positively affect any of the metabolic markers postulated to contribute to NASH. Although animal data and small pilot studies in humans have suggested that PTX may be effective as a treatment for NASH, translating this therapy to clinical practice may prove challenging.
authors.affiliation: Departments of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Van Wagner
authors.forename: Sean W P
authors.initials: SW
authors.lastname: Koppe
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brunt
authors.forename: Jeanne
authors.initials: J
authors.lastname: Gottstein
authors.forename: Konstantina
authors.initials: K
authors.lastname: Gardikiotes
authors.forename: Richard M
authors.initials: RM
authors.lastname: Green
authors.forename: Mary E
authors.initials: ME
authors.lastname: Rinella
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D003085:Colic / Q000139:chemically induced / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006261:Headache / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D010431:Pentoxifylline / Q000009:adverse effects / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D010726:Phosphodiesterase Inhibitors; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010431:Pentoxifylline