Genome-wide association study identiﬁes HLA-DR variants conferring risk of HBV-related acute-on-chronic liver failure

Tan, Wenting; Xia, Jie; Dan, Yunjie; Meng-ying, LI; Lin, Shide; Pan, Xingnan; Wang, Huifen; Tang, Yu; Liu, Nana; Tan, Shun; Liu, Ming; He, Wei; Zhang, Weihua; Mao, Qing; Wang, Yuming; Deng, Guohong

doi:10.1136/gutjnl-2016-313035

Cited by 28 publications

(31 citation statements)

References 35 publications

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“…As reported, CD4 + T‐cell priming is pivotal to activate professional antigen‐presenting cells necessary for the induction of CD8 + T‐cell responses . And a recent genome‐wide association study identified that HLA‐DR, which is involved in HLA class II‐restricted CD4 + T‐cell immunity, is the major locus that contributes to susceptibility to HB‐ACLF . Therefore, it suggested that the polymorphism of CD4 + T‐cell priming determined the magnitude and quality of CD8 + T‐cell response and hepatic damage.…”

Section: Discussionmentioning

confidence: 91%

Characteristics of systemic inflammation in hepatitis B‐precipitated ACLF: Differentiate it from No‐ACLF

Yan

Zhao

et al. 2017

Liver International

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Section: Discussionmentioning

confidence: 91%

Characteristics of systemic inflammation in hepatitis B‐precipitated ACLF: Differentiate it from No‐ACLF

Yan

Zhao

et al. 2017

Liver International

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“…Genetic variations in HLA class II loci (HLA-DP and HLA-DQ) were significantly associated with susceptibility to chronic HBV infection and with HBV-related HCC (Mbarek et al, 2011;Kamatani et al, 2009;Nishida et al, 2012;Jiang et al, 2013;Jiang et al, 2015;Li et al, 2012;Kim et al, 2013;Hu et al, 2013;Chang et al, 2014;Tan et al, 2017) ( Table 1, Fig. 2).…”

Section: Hbv and Hcvmentioning

confidence: 98%

Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches

Mozzi

Pontremoli

Sironi

2018

Infection, Genetics and Evolution

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Genome-wide association studies (GWASs) have been widely applied to identify genetic factors that affect complex diseases or traits. Presently, the GWAS Catalog includes >2800 human studies. Of these, only a minority have investigated the susceptibility to infectious diseases or the response to therapies for the treatment or prevention of infections. Despite their limited application in the field, GWASs have provided valuable insights by pinpointing associations to both innate and adaptive immune response loci, as well as novel unexpected risk factors for infection susceptibility. Herein, we discuss some issues and caveats of GWASs for infectious diseases, we review the most recent findings ensuing from these studies, and we provide a brief summary of selected GWASs for infections in non-human mammals. We conclude that, although the general trend in the field of complex traits is to shift from GWAS to next-generation sequencing, important knowledge on infectious disease-related traits can be still gained by GWASs, especially for those conditions that have never been investigated using this approach. We suggest that future studies will benefit from the leveraging of information from the host's and pathogen's genomes, as well as from the exploration of models that incorporate heterogeneity across populations and phenotypes. Interactions within HLA genes or among HLA variants and polymorphisms located outside the major histocompatibility complex may also play an important role in shaping the susceptibility and response to invading pathogens.

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“…Excess innate immune responses to viral antigens mediated by pathogen‐associated molecular patterns and damage‐associated molecular patterns (DAMPs) may play a role in the development of ACLF . Host and virus genetic factors have also been shown to predispose certain individuals to ACLF due to HBV . However, our ability to predict ACLF due to HBV still remains poor.…”

Section: Viral Hepatitismentioning

confidence: 99%

Precipitants of Acute‐on‐Chronic Liver Failure: An Opportunity for Preventative Measures to Improve Outcomes

et al. 2020

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Acute-on-chronic liver failure (ACLF) is a feared complication that can develop at any stage of chronic liver disease. The incidence of ACLF is increasing, leading to a significant burden to both the affected individual and health care systems. To date, our understanding of ACLF suggests that it may be initiated by precipitants such as systemic infection, alcohol use, or viral hepatitis. The prevalence of these vary significantly by geography and underlying liver disease, and these precipitants have a varying impact on patient prognosis. Herein, we present a review of our current understanding of the precipitants of ACLF, including gaps in current data and opportunities for meaningful intervention and areas of future research. Liver Transplantation 26 283-293 2020 AASLD.liveR tRAnsplAntAtion, vol. 26, no. 2, 2020 cullARo et Al.

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Genome-wide association study identiﬁes HLA-DR variants conferring risk of HBV-related acute-on-chronic liver failure

Abstract: Our genome-wide association study identified as the major locus for susceptibility to HBV-related ACLF. Our findings highlight the importance of HLA class II restricted CD4+ T-cell pathway on the immunopathogenesis of HBV-related ACLF.

Cited by 28 publications

References 35 publications

Characteristics of systemic inflammation in hepatitis B‐precipitated ACLF: Differentiate it from No‐ACLF

Characteristics of systemic inflammation in hepatitis B‐precipitated ACLF: Differentiate it from No‐ACLF

Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches

Precipitants of Acute‐on‐Chronic Liver Failure: An Opportunity for Preventative Measures to Improve Outcomes

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