Ulcerative colitis and Crohn’s disease are the two main forms of inflammatory bowel disease (IBD). Here, we report the first trans-ethnic association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East-Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of IBD risk loci, the direction and magnitude of effect is consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by a combination of differences in allele frequencies (NOD2), effect sizes (TNFSF15, ATG16L1) or a combination of both (IL23R, IRGM). Our results provide biological insights into the pathogenesis of IBD, and demonstrate the utility of trans-ethnic association studies for mapping complex disease loci and understanding genetic architecture across diverse populations.
We densely genotyped, using 1000 Genomes Project pilot CEU and additional re-sequencing study variants, 183 reported immune-mediated disease non-HLA risk loci in 12,041 celiac disease cases and 12,228 controls. We identified 13 new celiac disease risk loci at genome wide significance, bringing the total number of known loci (including HLA) to 40. Multiple independent association signals are found at over a third of these loci, attributable to a combination of common, low frequency, and rare genetic variants. In comparison with previously available data such as HapMap3, our dense genotyping in a large sample size provided increased resolution of the pattern of linkage disequilibrium, and suggested localization of many signals to finer scale regions. In particular, 29 of 54 fine-mapped signals appeared localized to specific single genes - and in some instances to gene regulatory elements. We define a complex genetic architecture of risk regions, and refine risk signals, providing a next step towards elucidating causal disease mechanisms.
The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.
Background: The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions. Aim: The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population. Methodology: Data references were identified through indexed journals and non‐indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance. Results: We estimated that 49.3–64.0 million adults in Asia, Australia and Egypt are anti‐HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria. Conclusion: We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection.
Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohn's disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades. This poses unique issues in diagnosis and management which have been scarcely addressed in the literature or in extant guidelines. Depending on the nature of the complaints, investigations to diagnose either form of IBD or to assess disease activity will vary and will also be influenced by geographic variations in other conditions that might mimic IBD. Similarly, therapy varies depending on the phenotype of the disease being treated and available resources. The World Gastroenterology Organization has, accordingly, developed guidelines for diagnosing and treating IBD using a cascade approach to account for variability in resources in countries around the world.
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