Higher incidence of hepatocellular carcinoma in suppressed hepatitis B cirrhosis compared to cured hepatitis C cirrhosis

Background /Aims : Direct-acting antiviral agents (DAA) effectively cure chronic hepatitis C (CHC) whereas curative therapy for chronic hepatitis B (CHB) is rare. We aimed to compare HCC incidence between suppressed CHB versus cured CHC patients with cirrhosis. Methods: We analyzed 5773 cirrhosis patients from 43 centers in 9 countries: 1877 with treated and suppressed CHB and 3896 with DAA-cured CHC using inverse probability treatment weight (IPTW) and competing risk analysis via Fine and Gray method. Results: After IPTW (on age, sex, ethnicity, study location, albumin, total bilirubin, creatinine, platelet, tobacco use, alcohol use, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease, steatotic liver disease, obesity, and follow-up years), two study groups became similar in relevant characteristics. The 5-year cumulative HCC incidence was significantly higher in suppressed CHB compared to cured CHC (18.1% vs. 7.4%, P <0.001) with consistent findings in subgroups by sex and MELD (all P <0.021), fast CHB responders (time from treatment to viral suppression <1 year) ( P <0.001), and CHB suppressed for <2 years ( P <0.001), but not among CHB suppressed for ≥2 years whose HCC incidence was similar to those of cured CHC ( P =0.954). On multivariable analysis, CHB suppression <2 years as compared to cured CHC (subdistribution hazard ratio (sHR) 20.92, P <0.001) and total bilirubin (sHR 0.71, P =0.04) were associated with higher HCC risk. Conclusion: HCC risk remains high in both treated and suppressed CHB cirrhosis and cured CHC cirrhosis. However, with prolonged CHB suppression, risk of HCC can be reduced, highlighting benefits of early treatment and viral suppression in patients with CHB.

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Publication Details

Journal
The American Journal of Gastroenterology
Published
2026-06-09
DOI
https://doi.org/10.14309/ajg.0000000000004071
Primary Topic
Hepatitis C virus research
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article
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article

Higher incidence of hepatocellular carcinoma in suppressed hepatitis B cirrhosis compared to cured hepatitis C cirrhosis

Seng Gee Lim, Norio Itokawa, Wan‐Long Chuang, Keigo Kawashima et al.
The American Journal of Gastroenterology
Hepatitis C virus research
article

Higher incidence of hepatocellular carcinoma in suppressed hepatitis B cirrhosis compared to cured hepatitis C cirrhosis

Seng Gee Lim, Norio Itokawa, Wan‐Long Chuang, Keigo Kawashima, Akira Asai, Adrian Carlos Gadano, Makoto Chuma, Jae‐Jun Shim, Eiichi Ogawa, Tomonori Senoh, Sally Tran, Eileen Laureal Yoon, Jiyoon Park, Xianhua Mao, Fanpu Ji, Hyunwoo Oh, Jihyun An, Philip Vutien, Wenqian Zang, Ming‐Lun Yeh, Sebastián Marciano, Yuichiro Eguchi, Chung‐Feng Huang, Sang Bong Ahn, Masatoshi Ishigami, Soung Won Jeong, Man‐Fung Yuen, Yoshiyuki Ueno, Sahith Kudaravalli, Kazuhiro Takahashi, Linda Henry, Doina Istrătescu, Takanori Ito, Akito Nozaki, Yu Li, J Li, Nicholas Chien, Wenjun Wang, Li Liu, Dong Hyun Lee, Jing Liang, Han Ah Lee, Joanne Kimiko Liu, Son Do, Charles Landis, Mi Jung Jun, Chengzheng Lu, Kaori Inoue, Mayumi Maeda, Ramsey Cheung, D Huang, Mindie Nguyen, V W Wong, Dae Won Jun, Yao-Chun Hsu, Rui Huang, CH Chen, Mei Carla Lam, Jee-Fu Huang, Koichi Takaguchi, Tsunamasa Watanabe, Qing Xie, Yasuhito Tanaka, Sung Eun Kim, Yong Kyun Cho, Hiroaki Haga, Ming-Lung Yu, Hiroshi Abe, Hidenori Toyoda, Hyoung Su Kim, Dang KH Vo, Grace LH Wong, Tomomi Okubo, Satoshi Yasuda, Haruki Uojima, Huy Trinh, Toru Ishikawa, Masaru Enomoto, Chia-Yen Dai, Carmen Preda, Cheng-Hao Tseng, Qing Ye, Masanori Atsukawa
article en

Abstract

Background /Aims : Direct-acting antiviral agents (DAA) effectively cure chronic hepatitis C (CHC) whereas curative therapy for chronic hepatitis B (CHB) is rare. We aimed to compare HCC incidence between suppressed CHB versus cured CHC patients with cirrhosis. Methods: We analyzed 5773 cirrhosis patients from 43 centers in 9 countries: 1877 with treated and suppressed CHB and 3896 with DAA-cured CHC using inverse probability treatment weight (IPTW) and competing risk analysis via Fine and Gray method. Results: After IPTW (on age, sex, ethnicity, study location, albumin, total bilirubin, creatinine, platelet, tobacco use, alcohol use, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease, steatotic liver disease, obesity, and follow-up years), two study groups became similar in relevant characteristics. The 5-year cumulative HCC incidence was significantly higher in suppressed CHB compared to cured CHC (18.1% vs. 7.4%, P <0.001) with consistent findings in subgroups by sex and MELD (all P <0.021), fast CHB responders (time from treatment to viral suppression <1 year) ( P <0.001), and CHB suppressed for <2 years ( P <0.001), but not among CHB suppressed for ≥2 years whose HCC incidence was similar to those of cured CHC ( P =0.954). On multivariable analysis, CHB suppression <2 years as compared to cured CHC (subdistribution hazard ratio (sHR) 20.92, P <0.001) and total bilirubin (sHR 0.71, P =0.04) were associated with higher HCC risk. Conclusion: HCC risk remains high in both treated and suppressed CHB cirrhosis and cured CHC cirrhosis. However, with prolonged CHB suppression, risk of HCC can be reduced, highlighting benefits of early treatment and viral suppression in patients with CHB.

The American Journal of Gastroenterology
Yamagata University (JP), Norwalk Hospital (US), Hallym University (KR), Kaohsiung Medical University (TW), St. Marianna University School of Medicine (JP), National University of Singapore (SG), Chang Gung University (TW), Saga University (JP), Shanxi Medical University (CN), Chinese University of Hong Kong (HK), University of Washington (US), VA Palo Alto Health Care System (US), Osaka Medical and Pharmaceutical University (JP), Eulji University (KR), Ruijin Hospital (CN), Soonchunhyang University Hospital Seoul (KR), Yokohama City University Medical Center (JP), Hospital Italiano de Buenos Aires (AR), Kaohsiung Medical University Chung-Ho Memorial Hospital (TW), Nagoya City University (JP), Kyung Hee University (KR), Tianjin Third Central Hospital (CN), Shaanxi Provincial People's Hospital (CN), E-Da Hospital (TW), Kaohsiung Chang Gung Memorial Hospital (TW), Kunming Third People's Hospital (CN), Kyushu University Hospital (JP), Kangbuk Samsung Hospital (KR), Saiseikai Niigata Daini Hospital (JP), Nanjing Drum Tower Hospital (CN), Tianjin People's Hospital (CN), Inje University Sanggye Paik Hospital (KR), Digestive Health Associates of Texas (US), Ogaki Municipal Hospital (JP), Hanyang University Guri Hospital (KR), Second Affiliated Hospital of Xi'an Jiaotong University (CN), Shinmatsudo Central General Hospital (JP), Stanford Medicine (US), Noguchi Hospital (JP), Hanyang University Seoul Hospital (KR), National University Hospital (SG), Kangdong Sacred Heart Hospital (KR), Kagawa Prefectural Central Hospital (JP), Osaka University Hospital (JP), Hallym University Sacred Heart Hospital (KR), Shanxi Provincial People’s Hospital (CN), Institutul Clinic Fundeni (RO), Eulji Medical Center (KR), Tianjin Medical University (CN), Nagoya University (JP), Kitasato University (JP), Chung-Ang University (KR), Nippon Medical School (JP), Sungkyunkwan University (KR), University of Hong Kong (HK), Yokohama City University (JP), Kumamoto University (JP), Stanford University (US)
Good health and well-being
Openalex Percentile: Top 7%
Hepatitis C virus research
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