Dataset Information

HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

ABSTRACT:

Background

Diversity in the HLA genes might be associated with disease outcomes-the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).

Methods

We utilized DNA from > 10 000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as homozygotes at a given locus when imputed to carry the same 4-digit allele for the 2 HLA alleles at that locus.

Results

Increase in number of homozygous HLA class II loci was associated with an increased risk of chronic HBV infection (Ptrend = 1.18 × 10-7). Among chronic HBV carriers, increase in number of homozygous HLA class II loci was also associated with an increased risk of HBV-associated HCC (Ptrend = .031). For individual HLA loci, HLA-DQB1 homozygosity was significantly associated with HCC risk (adjusted hazard ratio = 1.40; 95% confidence interval, 1.06-1.84). We also found that zygosity affects risk of HCC through its ability to affect viral control.

Conclusions

Homozygosity at HLA class II loci, particularly HLA-DQB1, is associated with a higher risk of HBV-associated HCC.

SUBMITTER: Liu Z

PROVIDER: S-EPMC9633721 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Liu Zhiwei Z Huang Chih-Jen CJ Huang Yu-Han YH Pan Mei-Hung MH Lee Mei-Hsuan MH Yu Kelly J KJ Pfeiffer Ruth M RM Viard Mathias M Yuki Yuko Y Gao Xiaojiang X Carrington Mary M Chen Chien-Jen CJ Hildesheim Allan A Yang Hwai-I HI

The Journal of infectious diseases 20211101 10

<h4>Background</h4>Diversity in the HLA genes might be associated with disease outcomes-the heterozygote advantage hypothesis. We tested this hypothesis in relation to hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).<h4>Methods</h4>We utilized DNA from > 10 000 Taiwanese individuals with current or past HBV infection to examine the association between HLA diversity and critical natural history steps in the progression from HBV infection to HCC. Individuals were classified as ho ...[more]

PMID: 33852009

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Project description:BackgroundDespite the recent identification of several prognostic gene signatures, the lack of common genes among experimental cohorts has posed a considerable challenge in uncovering the molecular basis underlying hepatocellular carcinoma (HCC) recurrence for application in clinical purposes. To overcome the limitations of individual gene-based analysis, we applied a pathway-based approach for analysis of HCC recurrence.ResultsBy implementing a permutation-based semi-supervised principal component analysis algorithm using the optimal principal component, we selected sixty-four pathways associated with hepatitis B virus (HBV)-positive HCC recurrence (p < 0.01), from our microarray dataset composed of 142 HBV-positive HCCs. In relation to the public HBV- and public hepatitis C virus (HCV)-positive HCC datasets, we detected 46 (71.9%) and 18 (28.1%) common recurrence-associated pathways, respectively. However, overlap of recurrence-associated genes between datasets was rare, further supporting the utility of the pathway-based approach for recurrence analysis between different HCC datasets. Non-supervised clustering of the 64 recurrence-associated pathways facilitated the classification of HCC patients into high- and low-risk subgroups, based on risk of recurrence (p < 0.0001). The pathways identified were additionally successfully applied to discriminate subgroups depending on recurrence risk within the public HCC datasets. Through multivariate analysis, these recurrence-associated pathways were identified as an independent prognostic factor (p < 0.0001) along with tumor number, tumor size and Edmondson's grade. Moreover, the pathway-based approach had a clinical advantage in terms of discriminating the high-risk subgroup (N = 12) among patients (N = 26) with small HCC (<3 cm).ConclusionsUsing pathway-based analysis, we successfully identified the pathways involved in recurrence of HBV-positive HCC that may be effectively used as prognostic markers.

Dataset Information

HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Background

Methods

Results

Conclusions

Publications

HLA Zygosity Increases Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Similar Datasets

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