Dataset Information

Copy number gain of pro-inflammatory genes in patients with HBV-related acute-on-chronic liver failure.

ABSTRACT: Background: Host genetic factors such as single nucleotide variations may play a crucial role in the onset and progression of HBV-related acute-on-chronic liver failure (ACLF). However, the underlying genomic copy number variations (CNVs) involved in the pathology are currently unclear.

Methods: We genotyped two cohorts with 389 HBV-related ACLF patients and 391 asymptomatic HBV carriers (AsCs), and then carried out CNV-based global burden analysis and a genome-wide association study (GWAS).

Results: For 1874 rare CNVs, HBV-related ACLF patients exhibited a high burden of deletion segments with a size of 100-200 kb (P value?=?0.04), and the related genes were significantly enriched in leukocyte transendothelial migration pathway (P value?=?4.68?×?10^-3). For 352 common CNVs, GWAS predicted 17 significant association signals, and the peak one was a duplication segment located on 1p36.13 (~?38 Kb, P value?=?1.99?×?10^-4, OR?=?2.66). The associated CNVs resulted in more copy number of pro-inflammatory genes (MST1L, DEFB, and HCG4B) in HBV-related ACLF patients than in AsC controls.

Conclusions: Our results suggested that the impact of host CNV on HBV-related ACLF may be through decreasing natural immunity and enhancing host inflammatory response during HBV infection. The findings highlighted the potential importance of gene dosage on excessive hepatic inflammation of this disease.

SUBMITTER: Sun F

PROVIDER: S-EPMC7709420 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Copy number gain of pro-inflammatory genes in patients with HBV-related acute-on-chronic liver failure.

Sun Fengming F Tan Wenting W Dan Yunjie Y Wang Xiuhua X Guo Yanzhi Y Deng Guohong G

BMC medical genomics 20201201 1

<h4>Background</h4>Host genetic factors such as single nucleotide variations may play a crucial role in the onset and progression of HBV-related acute-on-chronic liver failure (ACLF). However, the underlying genomic copy number variations (CNVs) involved in the pathology are currently unclear.<h4>Methods</h4>We genotyped two cohorts with 389 HBV-related ACLF patients and 391 asymptomatic HBV carriers (AsCs), and then carried out CNV-based global burden analysis and a genome-wide association stud ...[more]

PMID: 33261607

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Project description:Summary Background Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients. Methods Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT. Findings In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7–10 had a higher 1-year survival benefit rate from LT (39.2%–64.3%) than those with score <7 or >10. These results were prospectively validated. Interpretation COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7–10 derived a higher net survival benefit from LT. Funding This study was supported by the 10.13039/501100001809National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).

Dataset Information

Copy number gain of pro-inflammatory genes in patients with HBV-related acute-on-chronic liver failure.

Publications

Copy number gain of pro-inflammatory genes in patients with HBV-related acute-on-chronic liver failure.

Similar Datasets

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