title: Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis.
abstract: BACKGROUND
  Non-alcoholic steatohepatitis (NASH) is a common cause of serum alanine aminotransferase (ALT) elevations and chronic liver disease, but it is unclear how well ALT elevations reflect the liver injury.
  
  
  OBJECTIVE
  To assess how well changes in ALT elevations reflect improvements in liver histology in response to vitamin E therapy.
  
  
  METHODS
  The vitamin E and placebo arms of the Pioglitazone vs. Vitamin E vs. Placebo in Non-alcoholic Steatohepatitis (PIVENS) trial were reassessed for associations among changes in ALT levels, body weight and liver histology. An ALT response was defined as a decrease to ≤40 U/L and by ≥30% of baseline. Liver biopsies taken before and after treatment were scored for non-alcoholic fatty liver disease activity (NAS) and fibrosis.
  
  
  RESULTS
  ALT responses were more frequent among vitamin E (48%) than placebo (16%) recipients (P < 0.001). Among vitamin E recipients, ALT responses were associated with decreases in NAS (P < 0.001), but not fibrosis scores (P = 0.34), whereas among placebo recipients, ALT responses were associated with significant decreases in both (P < 0.05). Weight loss (≥2 kg) was also associated with ALT response (P < 0.001), improvements in NAS (P < 0.001) and fibrosis (P < 0.02), but vitamin E had an added effect both with and without weight loss. Weight gain (≥2 kg) was associated with lack of ALT response and worsening NAS and fibrosis scores in patients not on vitamin E.
  
  
  CONCLUSIONS
  Decrease of ALT levels to normal in patients with NASH is usually associated with improved histological activity. Management should stress the value of weight loss and strongly discourage weight gain. Vitamin E can improve both ALT levels and histology with and without weight loss.
  
  
  BACKGROUND
  NCT00063622.
authors.affiliation: Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Hoofnagle
authors.forename: M L
authors.initials: ML
authors.lastname: Van Natta
authors.forename: D E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: J M
authors.initials: JM
authors.lastname: Clark
authors.forename: K V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: R
authors.initials: R
authors.lastname: Loomba
authors.forename: B A
authors.initials: BA
authors.lastname: Neuschwander-Tetri
authors.forename: A J
authors.initials: AJ
authors.lastname: Sanyal
authors.forename: J
authors.initials: J
authors.lastname: Tonascia
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000975:Antioxidants / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014810:Vitamin E / Q000627:therapeutic use*; D015431:Weight Loss
chemical_list: D000975:Antioxidants; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014810:Vitamin E; D000410:Alanine Transaminase; D000077205:Pioglitazone