0000000000820289
AUTHOR
Yuji Soejima
An Intention-to-Treat Competing-Risk Model for Candidates with Hepatocellular Cancer Awaiting Liver Transplantation
Background: Since the introduction of the Milan Criteria (MC), all systems, which describe post-transplant prognosis of patients with hepatocellular cancer (HCC), are exclusively based on characteristics available at surgery, and neglect the intention-to-treat principles. This study, based on a large international HCC patient cohort, aimed to develop comprehensive intention-to-treat models through a competing-risk analysis. We used data available at first referral to predict the risk of delisting and HCC-related death after liver transplantation (LT). Methods: Twelve centres in the United States, Europe and Asia created a Derivation Set (n=2,318) and an external Validation Set (n=773) of …
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…
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…