Dataset Information

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. OBJECTIVES: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.

SUBMITTER: Almasio PL

PROVIDER: S-EPMC5203613 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort.

Almasio Piero Luigi PL Licata Anna A Maida Marcello M Macaluso Fabio Salvatore FS Costantino Andrea A Alessi Nicola N Grimaudo Stefania S Accardi Giulia G Caruso Calogero C Craxi Antonio A

Hepatitis monthly 20161016 11

<h4>Background</h4>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.<h4>Objectives</h4>We aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy.<h4>Methods</h4>Socio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected. All su ...[more]

PMID: 28070198

Similar Datasets

Project description:Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9-10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13-15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.

Project description:Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation.

Dataset Information

Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort.

Publications

Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets