Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

, Volume 45, Issue 10, pp 1053-1062

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

  • Paolo SorrentinoAffiliated withLiver Unit, Clinical and Experimental Hepatology, Department of Internal Medicine, S.G. Moscati HospitalDepartment of Biomorphological Science, Federico II University of Naples Email author 
  • , Luigi TerraccianoAffiliated withInstitute of Pathology, University of Basel
  • , Salvatore D’AngeloAffiliated withLiver Unit, Clinical and Experimental Hepatology, Department of Internal Medicine, S.G. Moscati Hospital
  • , Umberto FerboAffiliated withInstitute of Pathology, S.G. Moscati Hospital
  • , Alessandra BraciglianoAffiliated withDepartment of Biomorphological Science, Federico II University of Naples
  • , Luciano TarantinoAffiliated withHepatology and Interventional Ultrasound Unit S. Giovanni di Dio Hospital
  • , Alessandro PerrellaAffiliated withDepartment of Infectious Disease, University of NaplesDepartment of Laparoscopic, Hepatic Surgery and Liver Transplant Unit, A. Cardarelli Hospital
  • , Oreste PerrellaAffiliated withVII Department of Infectious Diseases and Immunology, D. Cotugno Hospital
  • , Giovanni De ChiaraAffiliated withInstitute of Pathology, S.G. Moscati Hospital
    • , Luigi PanicoAffiliated withInstitute of Pathology, S.G. Moscati HospitalDepartment of Biomorphological Science, Federico II University of Naples
    • , Noè De StefanoAffiliated withInstitute of Pathology, S.G. Moscati Hospital
    • , Mariolina LeporeAffiliated withInstitute of Pathology, S.G. Moscati HospitalDepartment of Biomorphological Science, Federico II University of Naples
    • , Raffaela VecchioneAffiliated withDepartment of Biomorphological Science, Federico II University of Naples

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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 in patients 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 3.9–14.4), the presence of steatosis (odds ratio 4.1, 95% confidence interval 2.5–15.4, p < .001), higher BMI (odds ratio 3.9, p < .021, 95% confidence interval 1.4–9.5), and alcohol intake (males ≥ 30 g/day, females ≥ 20 g/day, odds ratio 4.5, 95% confidence interval 1.3–19.8, 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.

Keywords

Autoimmune cholangitis Primary biliary cirrhosis Oxidative stress Lipid peroxidation Steatosis BMI Alcohol Iron Obesity