title: Unconjugated hyperbilirubinemia is inversely associated with non-alcoholic steatohepatitis (NASH).
abstract: BACKGROUND
  It has been recognised that unconjugated bilirubin contains hepatic anti-fibrogenic and anti-inflammatory properties and is a potent physiological antioxidant cytoprotectant. We believe that unconjugated hyperbilirubinemia may protect against development of non-alcoholic steatohepatitis (NASH).
  
  
  OBJECTIVE
  This study was conducted to assess the association of serum unconjugated bilirubin levels and histological liver damage in non-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  This was a retrospective analysis involving adult patients from a tertiary medical centre undergoing liver biopsy to evaluate suspected NAFLD or NASH and a control group without NAFLD based on normal liver ultrasound, labs and history. Identification of unconjugated hyperbilirubinemia was based on the presence of predominantly unconjugated bilirubin ≥1.0 mg/dL (17.1 μmol/L) while fasting, in the absence of haemolytic disease or other hepatic function alteration.
  
  
  RESULTS
  Six-hundred and forty-one patients were included. Unconjugated hyperbilirubinemia was inversely associated with NASH (OR 16.1, 95% CI 3.7-70.8 P < 0.001). Of the patients without NAFLD (133 patients), 13 (9.8%) had unconjugated hyperbilirubinemia (range 1.0-1.8, mean 1.4). Of the patients with NAFLD without NASH (285 patients), 32 (11.2%) had unconjugated hyperbilirubinemia (range 1.0-3.0, mean 1.4). Of the patients with NASH (223 patients), three (1.3%) had unconjugated hyperbilirubinemia (1.0, 1.1, 1.4).
  
  
  CONCLUSIONS
  Unconjugated hyperbilirubinemia is inversely associated with the histopathological severity of liver damage in non-alcoholic fatty liver disease.
authors.affiliation: Brooke Army Medical Center, Gastroenterology Service, Fort Sam Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hjelkrem
authors.forename: A
authors.initials: A
authors.lastname: Morales
authors.forename: C D
authors.initials: CD
authors.lastname: Williams
authors.forename: S A
authors.initials: SA
authors.lastname: Harrison
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001663:Bilirubin / Q000097:blood*; D001706:Biopsy; D005234:Fatty Liver / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000150:complications*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D001663:Bilirubin