Association Between Hepatitis B Virus Serological Patterns and Hepatocellular Carcinoma: A Case-Control Study

Quansong XIA; Chuanqiong WANG; Lihong DUAN; Juan XU; Yu’e JIANG

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Quansong XIA, Chuanqiong WANG, Lihong DUAN, Juan XU, Yu’e JIANG. Association Between Hepatitis B Virus Serological Patterns and Hepatocellular Carcinoma: A Case-Control Study[J]. Journal of Kunming Medical University.

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Association Between Hepatitis B Virus Serological Patterns and Hepatocellular Carcinoma: A Case-Control Study

1.
Department of Clinical Laboratory，The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital/ Yunnan Cancer Hospital Affiliated to Peking University Cancer Hospital，Kunming Yunnan 650118
2.
Department of Endocrinology，Guandu District People’s Hospital of Kunming，Kunming Yunnan 650200，China

Received Date: 2026-05-29

Abstract

Abstract

Objective To examine the association between hepatitis B virus （HBV） serological patterns and hepatocellular carcinoma （ HCC）, and to compare the discriminative ability of serological patterns, individual markers, and a combined analysis of five markers in distinguishing HCC cases from healthy controls. Methods A retrospective case-control study was conducted, including 2, 532 HCC patients hospitalized at Yunnan Cancer Hospital and confirmed by histopathological examination from April 8, 2022 to April 9, 2026, and 6, 970 healthy physical examination controls during the same period. After defining serological patterns, the fully negative pattern was used as the reference. Firth logistic regression was applied to analyze the association between each pattern and case-control status, and odds ratios （ORs） and 95% confidence intervals （CIs） adjusted for non-linear age effects, sex, and region were estimated. A demographic baseline model, a single-marker model, a five-marker combined model, and a full-pattern model were constructed separately to evaluate discrimination, prediction error, and the 95% CIs of differences between models. Results A total of 19 serological observed, the most common being 2+ （HBsAb positive only, 47.51%）, all-negative （26.27%）, and 145+ （HBsAg, HBeAb, and HBcAb positive, 11.42%）. Compared with the all-negative pattern, 2+ was negatively associated with HCC （OR 0.55, 95% CI: 0.45～0.68）; 145+, 15+, and 135+ were positively associated with HCC, with adjusted ORs of 56.70 （95% CI: 41.91～76.72）, 241.81 （95% CI: 124.17～470.87）, and 195.63 （95% CI: 73.94～517.61）, respectively. The cross-validated area under the curve （AUC） for the demographic baseline model, the best single-marker model （HBsAg）, the five-marker combined model, and the full-pattern model was 0.9165 （95% CI: 0.9110～0.9226）, 0.9649 （95% CI: 0.9610～0.9685）, 0.9693 （95% CI: 0.9657～0.9728）, and 0.9702 （95% CI: 0.9666～0.9736）, respectively; the AUC of the full-pattern model increased by 0.00088 （95% CI: 0.00039～0.00139） compared with the five-marker combined model. Conclusion The association between HBV serological patterns and HCC showed marked heterogeneity. The five-marker combined model had better discriminative ability for distinguishing cases from physical examination controls than a single marker, but the full-pattern model provided only a very small performance gain over the five-marker combined model; its main value lies in retaining and presenting specific combined serological phenotypes.
- Hepatocellular carcinoma,
- Hepatitis B virus,
- Serology,
- Case-control studies,
- Logistic models

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References(24)

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