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Updated: May 23, 2026
Real-Time Polymerase Chain Reaction-Based Detection and Quantification of Hepatitis B Virus DNA
Published on: December 15, 2023
Relationship of HLA-DRB1 alleles with hepatocellular carcinoma development in chronic hepatitis B patients
Young-Joo Jin1, Ju Hyun Shim, Young-Hwa Chung
1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Insights
The HLA-DRB1*140101 allele may increase hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. This finding was independent of viral activity and treatment response in this study.
Area of Science:
- Immunogenetics
- Hepatology
- Oncology
Background:
- Chronic hepatitis B (CHB) is a major risk factor for hepatocellular carcinoma (HCC).
- Human leukocyte antigen (HLA) genes play a crucial role in immune response and disease susceptibility.
- Specific HLA-DRB1 alleles have been implicated in various immune-mediated diseases.
Purpose of the Study:
- To investigate the association between specific HLA-DRB1 alleles and the development of HCC in patients with CHB.
- To identify potential genetic markers for HCC risk stratification in CHB patients.
Main Methods:
- Retrospective analysis of 468 CHB patients treated with lamivudine for over 12 months.
- HLA-DRB1 genotyping using sequence-based typing.
- Regular surveillance for HCC using serum alpha fetoprotein and imaging studies.
Main Results:
- The HLA-DRB1*140101 allele was significantly more frequent in patients who developed HCC compared to those who did not (19.4% vs. 8.1%, P=0.014).
- Patients with the HLA-DRB1*140101 allele exhibited markedly higher cumulative rates of HCC development over 2, 4, and 6 years.
- No other HLA-DRB1 alleles showed a significant association with HCC development.
Conclusions:
- The HLA-DRB1*140101 allele may be a potential risk factor for HCC development in CHB patients.
- This association appears to be independent of hepatitis B virus replication and antiviral treatment response.
Goals:
We intended to analyze the relationship between specific human leukocyte antigen (HLA)-DRB1 alleles and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients.
Study:
A database of 468 consecutive CHB patients who received lamivudine for more than 12 months between July 1996 and February 2011 was retrospectively analyzed. Sera and buffy coats samples were obtained between April 2008 and April 2010. Six-digit HLA-DRB1 genotyping was performed with sequence-based typing. Serum α fetoprotein levels and ultrasonography or computed tomography image studies were assessed every 3 to 6 months for surveillance of HCC.
Results:
At baseline, median age was 43 years (range, 16 to 71) [male: 359 (76.7%); HBeAg positivity: 385 (82.3%)]. Among the 27 HLA-DRB1 alleles identified, HLA-DRB1*090102, *080302, and *070101 were the most frequent (>10%). HCC was diagnosed in 36 (7.7%) patients during the median follow-up of 69 months. The frequency of the HLA-DRB1*140101 allele was 9.0% and significantly higher in patients of the HCC group than those of the non-HCC group (19.4 vs. 8.1%, P=0.014). The 2-year, 4-year, and 6-year cumulative rates of HCC development were markedly higher in patients with HLA-DRB1*140101 than those without HLA-DRB1*140101 (2.4, 8.2, and 25.1% vs. 1.9, 4.7, and 7.4%, respectively, P=0.011). No other HLA-DRB1 alleles were associated with HCC development. Baseline clinical characteristics did not differ between patients with and without HLA-DRB1*140101.
Conclusions:
The HLA-DRB1*140101 allele may be potentially associated with increased risk of HCC development in CHB patients, irrespective of the replicative activity of hepatitis B virus and antiviral responsiveness.
