Evidence map›Paper›PMID 40084945›Full record

ArticleHepatology (Baltimore, Md.)2026

HLA-DQB1*03:01 and risk of HBV-related HCC.

Ting Zhang, Chih-Jen Huang, Hai-Tao Chen, Yu-Han Huang, Mei-Hung Pan, Mei-Hsuan Lee, Mathias Viard, Allan Hildesheim, Ruth M Pfeiffer, Mary Carrington and 6 more

Abstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ting ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0002-9862-9434
Chih-Jen HuangGenomics Research Center, Academia Sinica, Taipei, Taiwan.ORCID 0000-0001-7791-6656
Hai-Tao ChenState Key Laboratory of Organ Failure Research, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, Mainland China.ORCID 0000-0002-8490-5039
Yu-Han HuangInstitute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.ORCID 0000-0002-4276-3060
Mei-Hung PanGenomics Research Center, Academia Sinica, Taipei, Taiwan.ORCID 0000-0002-0121-8242
Mei-Hsuan LeeInstitute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.ORCID 0000-0002-0222-2251
Mathias ViardBasic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland, USA.ORCID 0000-0002-1737-8021
Allan HildesheimDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0003-0257-2363
Ruth M PfeifferDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0001-7791-2698
Mary CarringtonBasic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland, USA.ORCID 0000-0002-2692-2180
Chien-Jen ChenGenomics Research Center, Academia Sinica, Taipei, Taiwan.ORCID 0000-0002-6996-9069
Bin ZhuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0003-0172-5516
Tobias L LenzResearch Unit for Evolutionary Immunogenomics, Department of Biology, University of Hamburg, Hamburg, Germany.ORCID 0000-0002-7203-0044
Deke JiangState Key Laboratory of Organ Failure Research, MOE Key Laboratory of Infectious Diseases Research in South China, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangdong Institute of Liver Diseases, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, Mainland China.ORCID 0000-0002-7888-2344
Hwai-I YangGenomics Research Center, Academia Sinica, Taipei, Taiwan.ORCID 0000-0002-3433-942
Zhiwei LiuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA.ORCID 0000-0002-0136-651

Funding

CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z99 CA999999NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

BACKGROUND AND

aimsThe human leukocyte antigen (HLA) locus is implicated in HCC among chronic HBV carriers. We investigated associations of HLA variants, amino acid polymorphisms, zygosity, and evolutionary divergence with HBV-related HCC in Han Chinese and explored biological mechanisms. APPROACH AND

resultsWe examined the associations of HLA variants (imputed 4-digit classical alleles and amino acid polymorphisms), zygosity, and evolutionary divergence with HBV-related HCC in a discovery set (706 HBV-related HCC cases, 6197 chronic HBV carriers in Taiwan). Significant signals were validated in an independent set (636 cases, 560 controls in Qidong, Mainland China). We used logistic regression adjusted for sex, age, and top 10 genetic principal components, with a Bonferroni correction for multiple testing ( p <1.6×10 -4 ). We evaluated predicted peptide-binding affinities and control of viral load, viral population diversity, and inflammatory markers for significant signals. HLA-DQB1*03:01 was most significantly associated with HBV-related HCC in discovery and validation sets (OR meta-analysis =1.33, pmeta-analysis =2.6×10 -8 ). Three amino acids within the DQβ1 peptide-binding region, HLA-DQβ1Ala13, HLA-DQβ1Tyr26, and HLA-DQβ1Glu45, were positively associated with HCC. HLA-DQB1*03:01 was associated with lower binding affinity of HBV nucleocapsid antigen and higher HBV DNA load and serum soluble programmed cell death 1 (sPD-1) ( p <0.05). HLA-DQB1 heterozygosity was inversely associated with HCC independent of HLA-DQB1*03:01 ( pmeta-analysis =3.3×10 -3 ).

conclusionsHLA-DQB1*03:01 and its 3 key amino acids are associated with an increased HBV-related HCC risk. This association may be explained by the low binding affinity to HBV antigen, resulting in poor control of viral load and increased inflammation, as evidenced by sPD-1 levels.

Indexed as

Carcinoma, HepatocellularHepatitis B, ChronicHLA-DQ beta-ChainsLiver NeoplasmsAdultCase-Control StudiesChinaEast Asian PeopleFemaleGenetic Predisposition to DiseaseHepatitis B virusHumansMaleMiddle AgedTaiwanHLA-DQB1 antigenHLA-DQ beta-Chainsevolutionary divergenceHBVHCChuman leukocyte antigenzygosity

Identifiers

PMID40084945
PMCPMC12353533

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.