0000000000217977
AUTHOR
Luigi Muratori
Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.
A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).
Primary biliary cholangitis (PBC): The patient journey to diagnosis and through the disease
X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis
Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…
Clinical update on risks and efficacy of anti-SARS-CoV-2 vaccines in patients with autoimmune hepatitis and summary of reports on post-vaccination liver injury
Patients with liver diseases, especially those with cirrhosis, have an increased mortality risk when infected by SARS-CoV-2 and therefore anti-SARS-CoV-2 vaccine has been recommended by leading Scientific Associations for all patients with chronic liver diseases. However, previous reports have shown a reduced antibody response following the full course of vaccination in immunosuppressed patients, including liver transplant recipients and several rheumatic diseases. This document, drafted by an expert panel of hepatologists appointed by the Italian Association for the Study of the Liver (AISF), aims to present the updated scientific data on the safety and efficacy of anti-SARS-CoV-2 mRNA vac…
Primary Biliary Cholangitis: advances in management and treatment of the disease
Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications. The 10Â year mortality is greater than in diseases such as human immunodeficiency virus/Hepatitis C Virus coinfection and breast cancer. Ursodeoxycholic acid is the only treatment available today, b…
Efficacy and safety of Boceprevir-based therapy in HCVG1 treatment-experienced patients with advanced fibrosis/cirrhosis: Italian NPP survey
S. Bruno1, S. Bollani1, A.L. Zignego2, V. Calvaruso3, C. Magni4, S. Landonio4, M. Rizzetto5, A. Ciancio5, A. Mangia6, V. Piazzolla6, M. Caremani7, S. Piovesan8, L. Cavalletto9, S. Babudieri9, A. Moretti 10, C. Colletta11, M. Massari12, S. Fangazio13, F. Mazzotta14, L. Muratori15, A.E. Colombo16, M. Zuin17, A. Traverso18, T. Santantonio19, F. Farina20, E. Marchionne21, G. Serviddio22, M. Russello23, A. Licata24, A. Craxi3, V. Di Marco3 1 Internal Medicine, AO Fatebenefratelli e Oftalmico, Milano, Italy 2 Internal Medicine, Universita di Firenze, Italy 3 Gastroenterology, Universita di Palermo, Italy 4 Infectiuos Diseases, Ospedale Sacco, Milano, Italy 5 Gastroenterology, Universita di Torino…
An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.
[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 77…
HCV E1E 2‐ MF 59 vaccine in chronic hepatitis C patients treated with PEG ‐ IFN α2a and R ibavirin: a randomized controlled trial
Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 μg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte prolife…
Real-world experience with obeticholic acid in patients with primary biliary cholangitis
Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransfer…