Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis.

ABSTRACT

BACKGROUND: Factors responsible for the progression of primary biliary cirrhosis (PBC) are still poorly understood. In the present study, we investigated the associations between the stage of PBC and the immune reaction triggered by oxidative stress; the presence of obesity, steatosis,steatohepatitis; and other toxic, metabolic, or steatogenic factors. METHODS: We studied clinical, laboratory, and histological data for 274 untreated patients with serum antimitochondrial antibody (AMA)-positive PBC. Circulating IgG against human serum albumin adducted with malondialdeyde, the major product of lipid peroxidation, was measured in these patients and in a group of 98 sex-, age and body mass index (BMI)-matched controls. RESULTS: Steatosis was present in 40.5% of all patients. Steatohepatitis was present in 14.9% of all patients. There was a significant association between the frequencies of steatosis and steatohepatitis and the worsening of PBC. Circulating IgG against lipid peroxidation products was significantly higher in the PBC patients than in the controls. Titers of lipid peroxidation-related antibodies were significantly increased in patients with steatosis and inpatients at more advanced stages. Bivariate analysis revealed a significant association between indirect evidence of oxidative stress, steatosis, steatohepatitis, age, BMI, frequency of diabetes, alcohol intake, iron grade after Perl's stain, and PBC stage. Logistic regression analysis confirmed that the titers of antibodies against lipid peroxidation products (odds ratio 4.5, p< .001, 95% confidence interval 3.9­14.4), the presence of steatosis (odds ratio 4.1, 95% confidence interval 2.5­15.4, p< .001), higher BMI (odds ratio 3.9, p< .021, 95%confidence interval 1.4­9.5), and alcohol intake (males ≥ 30 g/day, females ≥ 20 g/day, odds ratio 4.5,95% confidence interval 1.3­19.8, p< .029) were independently associated with more advanced stages of the disease. CONCLUSIONS: The immune reactions triggered by oxidative stress, steatosis, obesity, and alcohol intake are independent predictors of PBC stage progression.