title: 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 3.9–14.4), 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.
authors.affiliation: Liver Unit, Clinical and Experimental Hepatology, Department of Internal Medicine, S.G. Moscati Hospital, Via Pennini, Avellino, Italy. paolosorrmed@tin.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Sorrentino
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Salvatore
authors.initials: S
authors.lastname: D'Angelo
authors.forename: Umberto
authors.initials: U
authors.lastname: Ferbo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bracigliano
authors.forename: Luciano
authors.initials: L
authors.lastname: Tarantino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Perrella
authors.forename: Oreste
authors.initials: O
authors.lastname: Perrella
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Chiara
authors.forename: Luigi
authors.initials: L
authors.lastname: Panico
authors.forename: Noè
authors.initials: N
authors.lastname: De Stefano
authors.forename: Mariolina
authors.initials: M
authors.lastname: Lepore
authors.lastname: Mariolina
authors.forename: Raffaela
authors.initials: R
authors.lastname: Vecchione
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D000906:Antibodies / Q000276:immunology; D016022:Case-Control Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015227:Lipid Peroxidation / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology / Q000503:physiopathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D018384:Oxidative Stress / Q000276:immunology*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G
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