title: Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort.
abstract: BACKGROUND
  Natural history of primary biliary cirrhosis (PBC) is partially characterized in patients from the Mediterranean area whose genetic background differs from that of Northern Europeans.
  
  
  OBJECTIVE
  We aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy.
  
  
  METHODS
  Socio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected. All subjects were treated with Ursodeoxycholic acid at a dose of 15 mg/kg. HLA class II DRB1 alleles were compared with those of 237 healthy control subjects. IL28B genotyping for IL28B rs12979860 C/T and rs80899917 G/T was performed in a sub-group of patients.
  
  
  RESULTS
  HLA-DRB1*07 (RR 5.3, P = 0.0008) and HLA-DRB1*08 (RR n.c. P = 0.0005) were significantly associated with the risk of PBC development. Patients younger than 45 years had significantly higher alanine aminotransferase (P = 0.038) and alkaline phosphatase levels (P = 0.047) than older cases. In comparison to non-CC rs12979860, patients with CC rs12979860 genotype showed an early histological stage at onset (93.8% vs. 62.5%, P = 0.03). After a mean follow-up of 61 months, three patients died, one underwent liver transplantation and sixteen (21.9%) had progression of the disease. At multivariate analysis, extrahepatic autoimmune disease (P = 0.04), pruritus (P = 0.008) and advanced histological stage (P < 0.0001) were independent risk factors for disease progression.
  
  
  CONCLUSIONS
  HLA-DRB1*07 and HLA-DRB1*08 alleles increase susceptibility to disease development. At onset, higher biochemical activity was observed in younger patients, whereas rs12979860 CC genotype was associated with milder histological stage. Pruritus and coexistence of extrahepatic autoimmune diseases were significantly associated with poorer prognosis.
authors.affiliation: Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors.forename: Piero Luigi
authors.initials: PL
authors.lastname: Almasio
authors.affiliation: Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Licata
authors.affiliation: Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maida
authors.affiliation: Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors.forename: Fabio Salvatore
authors.initials: FS
authors.lastname: Macaluso
authors.affiliation: Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Costantino
authors.affiliation: Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Alessi
authors.affiliation: Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Palermo, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Accardi
authors.affiliation: Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Palermo, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
authors.affiliation: Sezione di Gastroenterologia ed Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxi
keywords: Genetic; Natural History; Primary Biliary Cirrhosis