Journal of Gastroenterology

, Volume 45, Issue 10, pp 1053–1062

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

  • Paolo Sorrentino
  • Luigi Terracciano
  • Salvatore D’Angelo
  • Umberto Ferbo
  • Alessandra Bracigliano
  • Luciano Tarantino
  • Alessandro Perrella
  • Oreste Perrella
  • Giovanni De Chiara
  • Luigi Panico
  • Noè De Stefano
  • Mariolina Lepore
  • Raffaela Vecchione
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-010-0249-x

Cite this article as:
Sorrentino, P., Terracciano, L., D’Angelo, S. et al. J Gastroenterol (2010) 45: 1053. doi:10.1007/s00535-010-0249-x

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 cholangitisPrimary biliary cirrhosisOxidative stressLipid peroxidationSteatosisBMIAlcoholIronObesity

Copyright information

© Springer 2010

Authors and Affiliations

  • Paolo Sorrentino
    • 1
    • 4
  • Luigi Terracciano
    • 2
  • Salvatore D’Angelo
    • 1
  • Umberto Ferbo
    • 3
  • Alessandra Bracigliano
    • 4
  • Luciano Tarantino
    • 5
  • Alessandro Perrella
    • 6
    • 7
  • Oreste Perrella
    • 8
  • Giovanni De Chiara
    • 3
  • Luigi Panico
    • 3
    • 4
  • Noè De Stefano
    • 3
  • Mariolina Lepore
    • 3
    • 4
  • Raffaela Vecchione
    • 4
  1. 1.Liver Unit, Clinical and Experimental Hepatology, Department of Internal MedicineS.G. Moscati HospitalAvellinoItaly
  2. 2.Institute of PathologyUniversity of BaselBaselSwitzerland
  3. 3.Institute of PathologyS.G. Moscati HospitalAvellinoItaly
  4. 4.Department of Biomorphological ScienceFederico II University of NaplesNaplesItaly
  5. 5.Hepatology and Interventional Ultrasound Unit S. Giovanni di Dio HospitalNaplesItaly
  6. 6.Department of Infectious DiseaseUniversity of NaplesNaplesItaly
  7. 7.Department of Laparoscopic, Hepatic Surgery and Liver Transplant UnitA. Cardarelli HospitalNaplesItaly
  8. 8.VII Department of Infectious Diseases and ImmunologyD. Cotugno HospitalNaplesItaly