J Gastroenterol Hepatol. 2013 Jul;28(7):1202-8.
Salomone F, Li Volti G, Rosso C, Grosso G, Bugianesi E.
http://www.ncbi.nlm.nih.gov/pubmed/23425054

Abstract
Background and Aim: Oxidative stress is considered a key element in the progression of
non-alcoholic fatty liver to non-alcoholic steatohepatitis (NASH). Unconjugated bilirubin
is the main endogenous lipid antioxidant and is cytoprotective in different tissues and
organs. In this study, it was evaluated if unconjugated bilirubin levels are associated with
the degree of liver injury in patients with non-alcoholic fatty liver disease.
Methods: Two hundred and eighty-five patients were retrospectively evaluated with
biopsy-confirmed non-alcoholic fatty liver disease. Multiple logistic regression models
were used to assess the relationship of steatosis, inflammation, and fibrosis levels to the
features of patients.

Results: Unconjugated bilirubin levels differed significantly according to inflammation
and fibrosis scores. Unconjugated bilirubin was lower in patients with moderate-severe
inflammation compared with those with absent-mild (P = 0.001) and in patients with
moderate-severe fibrosis compared with those with absent-mild (P < 0.001), whereas no
difference was observed for steatosis grades. At logistic regression analysis, low unconjugated bilirubin levels were associated with moderate-severe inflammation (odds ratio, 0.11; 95% confidence interval 0.02–0.76; P = 0.025) and moderate-severe fibrosis (odds ratio, 0.013; 95% confidence interval 0.001–0.253; P = 0.004).

Conclusions: Low unconjugated bilirubin levels are independent predictors of advanced
inflammation and fibrosis in patients with steatohepatitis, indicating the lack of antioxidant
protection as a possible molecular determinant for the progression of liver injury.