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).


This study was conducted to assess the association of serum unconjugated bilirubin levels and histological liver damage in non-alcoholic fatty liver disease (NAFLD).


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.


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).


Unconjugated hyperbilirubinemia is inversely associated with the histopathological severity of liver damage in non-alcoholic fatty liver disease.