Risk of de novo HCC in patients with MASLD following direct-acting antiviral-induced cure of HCV infection

Chen-Hua Liu; Pin-Nan Cheng; Yu-Jen Fang; Chi-Yi Chen; Wei-Yu Kao; Chih-Lin Lin; Sheng-Shun Yang; Yu-Lueng Shih; Cheng-Yuan Peng; Yu-Ping Chang; Shang-Chin Huang; Tung-Hung Su; Tai-Chung Tseng; Chun-Jen Liu; Pei-Jer Chen; Jia-Horng Kao

doi:10.1016/j.jhep.2024.09.038

Risk of de novo HCC in patients with MASLD following direct-acting antiviral-induced cure of HCV infection

J Hepatol. 2024 Oct 3:S0168-8278(24)02578-9. doi: 10.1016/j.jhep.2024.09.038. Online ahead of print.

Authors

Chen-Hua Liu¹, Pin-Nan Cheng², Yu-Jen Fang³, Chi-Yi Chen⁴, Wei-Yu Kao⁵, Chih-Lin Lin⁶, Sheng-Shun Yang⁷, Yu-Lueng Shih⁸, Cheng-Yuan Peng⁹, Yu-Ping Chang¹⁰, Shang-Chin Huang¹¹, Tung-Hung Su¹², Tai-Chung Tseng¹³, Chun-Jen Liu¹⁴, Pei-Jer Chen¹⁴, Jia-Horng Kao¹⁵

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan.
² Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
³ Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan.
⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
⁶ Department of Gastroenterology, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan.
⁷ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
⁸ Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁹ Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan.
¹⁰ Department of Internal Medicine, National Taiwan University Biomedical Park Hospital, Hsin-Chu, Taiwan.
¹¹ Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan.
¹² Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
¹³ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
¹⁴ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
¹⁵ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: kaojh@ntu.edu.tw.

PMID: 39368711
DOI: 10.1016/j.jhep.2024.09.038

Abstract

Background & aims: Data are limited on the risk of de novo hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) after achieving sustained virologic response at off-treatment week 12 (SVR12) using direct-acting antivirals (DAAs) for HCV.

Methods: A total of 1,598 eligible patients received biannual alpha-fetoprotein (AFP) and liver imaging surveillance to detect de novo HCC after achieving SVR12. MASLD was defined as presence of controlled attenuation parameter (CAP) ≥248 dB/m and ≥1 cardiometabolic risk factor (CMRF). Cumulative HCC incidence was compared between patients with/without MASLD. We built univariable and multivariable Cox proportional hazards models to evaluate factors associated with HCC. Sensitivity analysis was performed using the Fine-Gray subdistribution hazards model. Additionally, we evaluated the mediation effect of MASLD on CMRFs and of CMRFs on MASLD for HCC using mediation analysis with bootstrapping.

Results: The incidence rate of HCC was 1.44 per 100 person-years of follow-up (95% CI 1.19-1.74). Patients with MASLD had a higher cumulative HCC incidence than those without MASLD (log-rank test, p <0.001). Multivariable Cox regression analysis revealed that in addition to age, sex, liver stiffness measurement, platelet count, and AFP, MASLD (adjusted hazard ratio 2.07; 95% CI 1.36-3.16; p <0.001) was independently associated with HCC. This finding was confirmed by the Fine-Gray model, which showed a subdistribution hazard ratio of 2.07 (95% CI 1.34-3.19, p <0.001) for MASLD. MASLD significantly mediated CMRFs for HCC development.

Conclusion: After achieving SVR12, patients with MASLD exhibited an increased HCC risk compared to those without MASLD. Vigilant HCC surveillance and control of CMRFs to mitigate the effect of MASLD on HCC remain crucial for this population.

Impact and implications: The risk of de novo hepatocellular carcinoma (HCC) among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) after attaining a sustained virologic response to direct-acting antivirals remains to be confirmed. In this study, recruiting 1,598 patients in Taiwan, individuals with MASLD had an approximately two-fold increased risk of de novo HCC compared to those without MASLD after achieving a sustained virologic response. MASLD significantly mediated cardiometabolic risk factors for HCC development. Our findings underscore the critical importance of pharmacological interventions and proactive lifestyle modifications to control cardiometabolic risk factors in patients with MASLD, as well as the need for vigilant HCC surveillance to ensure favorable outcomes following HCV eradication.

Keywords: direct-acting antiviral; hepatitis C virus; hepatocellular carcinoma; metabolic dysfunction-associated steatotic liver disease; sustained virologic response; type 2 diabetes.