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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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Authors and Affiliations

  1. Liver Unit, Clinical and Experimental Hepatology, Department of Internal Medicine, S.G. Moscati Hospital, Via Pennini, 83100, Avellino, Italy

    Paolo Sorrentino & Salvatore D’Angelo

  2. Institute of Pathology, University of Basel, Basel, Switzerland

    Luigi Terracciano

  3. Institute of Pathology, S.G. Moscati Hospital, Avellino, Italy

    Umberto Ferbo, Giovanni De Chiara, Luigi Panico, Noè De Stefano & Mariolina Lepore

  4. Department of Biomorphological Science, Federico II University of Naples, Naples, Italy

    Paolo Sorrentino, Alessandra Bracigliano, Luigi Panico, Mariolina Lepore & Raffaela Vecchione

  5. Hepatology and Interventional Ultrasound Unit S. Giovanni di Dio Hospital, ASL 3 Frattamaggiore, Naples, Italy

    Luciano Tarantino

  6. Department of Infectious Disease, University of Naples, Naples, Italy

    Alessandro Perrella

  7. Department of Laparoscopic, Hepatic Surgery and Liver Transplant Unit, A. Cardarelli Hospital, Naples, Italy

    Alessandro Perrella

  8. VII Department of Infectious Diseases and Immunology, D. Cotugno Hospital, Naples, Italy

    Oreste Perrella

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  1. Paolo Sorrentino
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  2. Luigi Terracciano
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  3. Salvatore D’Angelo
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  9. Giovanni De Chiara
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Correspondence to Paolo Sorrentino.

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Sorrentino, P., Terracciano, L., D’Angelo, S. et al. Oxidative stress and steatosis are cofactors of liver injury in primary biliary cirrhosis. J Gastroenterol 45, 1053–1062 (2010). https://doi.org/10.1007/s00535-010-0249-x

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  • DOI: https://doi.org/10.1007/s00535-010-0249-x

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