Juhee Ahn, Moon Haeng Hur, Hyunjae Shin, Min Kyung Park, Sungho Won, Jeayeon Park, Yunmi Ko, Youngsu Park, Yun Bin Lee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
Clin Mol Hepatol 2026;32(1):339-352. Published online November 25, 2025
Background/Aims The association between aspirin use and hepatocellular carcinoma (HCC) risk in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study evaluated the effect of aspirin on HCC development in MASLD patients using Korean National Health Insurance Service (NHIS) and UK Biobank (UKB) databases.
Methods A retrospective cohort analysis was conducted using the NHIS database with a 3-year landmark design. Baseline characteristics were balanced using inverse probability of treatment weighting (IPTW) and 1:3 propensity score matching (PSM). Additionally, Mendelian randomization analysis was performed in the UKB cohort using a genomic risk score (GRS) for salicylic acid, based on genetic variants related to aspirin metabolism, as a proxy for aspirin use.
Result s: In the NHIS cohort, 6,584,155 eligible patients were included, of whom 1,723,435 had MASLD. After PSM, aspirin use was associated with a significantly lower risk of HCC compared to no aspirin use, in both the overall population (adjusted subdistribution hazard ratio [ASHR]=0.86; 95% confidence interval [CI] 0.78–0.95; P=0.002) and MASLD group (ASHR=0.86; 95% CI 0.75–0.99; P=0.036). Similar results were reproduced in the IPTW population and several sensitivity and subgroup analyses. In the UKB cohort, individuals in the top 95% of GRS had a significantly lower risk of HCC compared to those in the bottom 5%, in both the overall population (ASHR=0.61; 95% CI 0.39–0.95; P=0.028) and MASLD group (ASHR=0.47; 95% CI 0.29–0.76; P=0.002).
Conclusions Findings from both population-based and genetic analyses suggest a possible protective association between aspirin use and HCC in patients with MASLD, which warrants further validation.
Moon Haeng Hur, Dong Hyeon Lee, Jeong-Hoon Lee, Mi-Sook Kim, Jeayeon Park, Hyunjae Shin, Sung Won Chung, Hee Jin Cho, Min Kyung Park, Heejoon Jang, Yun Bin Lee, Su Jong Yu, Sang Hyub Lee, Yong Jin Jung, Yoon Jun Kim, Jung-Hwan Yoon
Clin Mol Hepatol 2024;30(3):500-514. Published online May 10, 2024
Background/Aims Chronic hepatitis B (CHB) is related to an increased risk of extrahepatic malignancy (EHM), and antiviral treatment is associated with an incidence of EHM comparable to controls. We compared the risks of EHM and intrahepatic malignancy (IHM) between entecavir (ETV) and tenofovir disoproxil fumarate (TDF) treatment.
Methods Using data from the National Health Insurance Service of Korea, this nationwide cohort study included treatment-naïve CHB patients who initiated ETV (n=24,287) or TDF (n=29,199) therapy between 2012 and 2014. The primary outcome was the development of any primary EHM. Secondary outcomes included overall IHM development. E-value was calculated to assess the robustness of results to unmeasured confounders.
Result s: The median follow-up duration was 5.9 years, and all baseline characteristics were well balanced after propensity score matching. EHM incidence rate differed significantly between within versus beyond 3 years in both groups (P<0.01, Davies test). During the first 3 years, EHM risk was comparable in the propensity score-matched cohort (5.88 versus 5.84/1,000 person-years; subdistribution hazard ratio [SHR]=1.01, 95% confidence interval [CI]=0.88–1.17, P=0.84). After year 3, however, TDF was associated with a significantly lower EHM incidence compared to ETV (4.92 versus 6.91/1,000 person-years; SHR=0.70, 95% CI=0.60–0.81, P<0.01; E-value for SHR=2.21). Regarding IHM, the superiority of TDF over ETV was maintained both within (17.58 versus 20.19/1,000 person-years; SHR=0.88, 95% CI=0.81–0.95, P<0.01) and after year 3 (11.45 versus 16.20/1,000 person-years; SHR=0.68, 95% CI=0.62–0.75, P<0.01; E-value for SHR=2.30).
Conclusions TDF was associated with approximately 30% lower risks of both EHM and IHM than ETV in CHB patients after 3 years of antiviral therapy.
Citations
Citations to this article as recorded by
Chronic hepatitis B, extrahepatic malignancies and the use of antiviral drugs Meng-Che Wu, Shih-Chi Yang, Shuo-Yan Gau Clinical and Molecular Hepatology.2025; 31(1): e19. CrossRef
The critical role of ferroptosis in virus-associated hematologic malignancies and its potential value in antiviral-antitumor therapy Miao Miao, Yuelei Chen, Xuehan Wang, Shengyang Li, Rong Hu Virulence.2025;[Epub] CrossRef
Antiviral Therapy Reduces Dyslipidemia and Cardiovascular Risk in Chronic Hepatitis B: TDF as the Most Effective Agent Hyuk Kim, Jae‐Young Kim, Hyun Bin Choi, Ji‐Soo Lee, Yoon E. Shin, Jeong‐Ju Yoo, Sang Gyune Kim, Young‐Seok Kim Journal of Medical Virology.2025;[Epub] CrossRef
Characteristics and outcomes in atorvastatin therapy for chronic subdural hematoma: a national, observational real-world study in China, 2019–2024 Tao Liu, Zhihao Zhao, Jiao Wang, Xiaoying Chen, Jinhao Huang, Weiwei Jiang, Yunhu Yu, Xide Zhu, Kaijie Wang, Kun Lin, Hu Qin, Baixiang Peng, Guohe Zhang, Zhiyong Liu, Weiliang Chen, Jun Shen, Baozhi Chen, Shengjie Li, Mingqi Liu, Wanqiang Su, Wanhai Ding, The Lancet Regional Health - Western Pacific.2025; 63: 101688. CrossRef
Association between atherogenic index of plasma and incident aortic disease: a population-based prospective analysis Cuihong Tian, Xiao Wang, Liang Tao, Wanyi Wei, Xuan Zhang, Haoxian Tang, Yequn Chen, Xuerui Tan Open Heart.2025; 12(2): e003511. CrossRef
Nucleos(t)ide analog therapy of chronic hepatitis B and extrahepatic cancer risk: Is tenofovir better than entecavir?: Editorial on “Extrahepatic malignancies and antiviral drugs for chronic hepatitis B: A nationwide cohort study” Yewan Park, Dong Hyun Sinn Clinical and Molecular Hepatology.2024; 30(4): 718. CrossRef
Effect of SARS-CoV-2 infection on liver function in patients with hepatitis B Tong Sun, Hongbo Chi, Jing Wang, Yufen Zheng, Hongguo Zhu, Jingxian Zhao, Kai Zhou, Mengyuan Chen, Donglian Wang, Tao-Hsin Tung, Jiaqin Xu, Bo Shen BMC Infectious Diseases.2024;[Epub] CrossRef
Jeayeon Park, Sung Won Chung, Yun Bin Lee, Hyunjae Shin, Moon Haeng Hur, Heejin Cho, Min Kyung Park, Jeonghwan Youk, Ji Yun Lee, Jeong-Ok Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Tae Min Kim, Jeong-Hoon Lee
Clin Mol Hepatol 2023;29(3):794-809. Published online May 17, 2023
Background/Aims Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients.
Methods This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively.
Result s: Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6–69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29–0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26–0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33–0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32–0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively.
Conclusions Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.
Citations
Citations to this article as recorded by
Chronic hepatitis b coinfection and survival in pediatric T-ALL: A propensity-matched analysis Yutong Zhang, Ruihong Wu, Yuan Zhang, Yufei Zhao, Xiaodan Zhong, Xianmei Jin, Chao Zhang, Jian Chang iScience.2026; 29(1): 114319. CrossRef
Letter regarding “Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma” Chi Hsiao, Yung-Po Liaw Clinical and Molecular Hepatology.2023; 30(1): 109. CrossRef
Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma Ye Rim Kim, Sung Won Chung, Min-Ju Kim, Won-Mook Choi, Jonggi Choi, Danbi Lee, Han Chu Lee, Ju Hyun Shim Journal of Hepatocellular Carcinoma.2024; Volume 11: 1235. CrossRef
First
Prev
