Steatosis Is a Cofactor in Liver Injury in Hemochromatosis

Background & Aims: Obesity-related steatosis is an increasingly common histologic finding and often coexists with other chronic liver diseases. Although obesity and steatosis are recognized risk factors for more advanced fibrosis in chronic hepatitis C and alcoholic liver disease, it has not been determined whether these factors influence the progression of other diseases in which steatosis is not a feature of the primary liver insult. Methods: We studied 214 patients with hemochromatosis who were homozygous for the C282Y substitution in HFE and had undergone liver biopsy prior to phlebotomy. Results: Steatosis was present in 41.1% of these patients, and 14.5% had moderate or severe steatosis. Median serum alanine aminotransferase (ALT) and ferritin levels were higher (P < .001), and median transferrin saturation (P = .01) and hepatic iron concentration (HIC) were lower (P = .003) in subjects with steatosis compared with subjects without steatosis. Bivariate analysis revealed a significant association between steatosis and fibrosis (P = .001). Following multiple logistic regression, steatosis was independently associated with fibrosis (odds ratio [OR] 4.3, 95% confidence interval [CI]: 2.1–8.8; P < .001) along with male sex (OR, 5.1; 95% CI: 2.0–12.5; P < .001), excess alcohol consumption (males ≥50 g/day, females ≥40 g/day) (OR, 3.9; 95% CI: 1.8–8.5; P = .001), and hepatic iron content (OR, 1.4; 95% CI: 1.2–1.6; P < .001). Both higher BMI (OR, 3.3; 95% CI: 1.8–6.3; P < .001) and alcohol consumption (males ≥30 g/day, females ≥10 g/day) (OR, 3.4; 95% CI: 1.2–10.0; P = .023) were independently associated with the presence of steatosis. Conclusions: These findings indicate that obesity-related steatosis may have a role as a cofactor in liver injury in hemochromatosis. This has important clinical implications and suggests that obesity should be actively addressed in the management of patients with hemochromatosis, as well as other liver diseases.

Abbreviations used in this paper:  BMI, body mass index , HCV, hepatitis C , HIC, hepatic iron concentration