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

IF 26.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Journal of Hepatology Pub Date : 2024-10-03 DOI:10.1016/j.jhep.2024.09.038
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
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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 (SVR12) using direct-acting antivirals (DAAs) for hepatitis C virus (HCV).

Methods

1598 eligible patients received biannual alpha-fetoprotein (AFP) and liver imaging surveillance to detect de novo HCC beyond achieving SVR12. MASLD was defined as presence of controlled attenuation parameter (CAP) ≥ 248 dB/m and ≥ one 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 (PYFU) [95% confidence interval (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, LSM, platelet count, and AFP, MASLD (adjusted hazard ratio (aHR): 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 HR (sHR) 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 MASLD on HCC remain crucial for this population.

Impact and implications

The risk of de novo HCC among patients with MASLD, a novel nomenclature of steatotic liver disease (SLD), after the attaining of SVR12 using DAAs remains to be confirmed. In this study recruiting 1598 patients in Taiwan, individuals with MASLD exhibited approximately a two-fold increased risk of de novo HCC, compared to those without MASLD after achieving SVR12. MASLD significantly mediated CMRFs for HCC development. Our findings underscore the critical importance of pharmacological interventions and proactive lifestyle modifications to control CMRFs in patients with MASLD, as well as the need for vigilant HCC surveillance to ensure favorable outcomes following HCV eradication.

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直接作用抗病毒药物诱导治愈 HCV 感染后,MASLD 患者发生新发 HCC 的风险
方法1598名符合条件的患者接受一年两次的甲胎蛋白(AFP)和肝脏成像监测,以检测达到SVR12后的新生肝细胞癌(HCC)。MASLD的定义是受控衰减参数(CAP)≥ 248 dB/m且≥一个心脏代谢风险因素(CMRF)。比较了有/无 MASLD 患者的累积 HCC 发病率。我们建立了单变量和多变量 Cox 比例危险模型来评估与 HCC 相关的因素。使用Fine-Gray子分布危险度模型进行了敏感性分析。此外,我们还使用带引导的中介分析评估了MASLD对CMRFs以及CMRFs对MASLD对HCC的中介效应。结果每100人随访年(PYFU)的HCC发病率为1.44[95%置信区间(CI):1.19-1.74]。MASLD患者的累积HCC发病率高于非MASLD患者(log-rank检验,P <0.001)。多变量 Cox 回归分析显示,除年龄、性别、LSM、血小板计数和 AFP 外,MASLD(调整后危险比 (aHR): 2.07 [95% CI:1.36-3.16], p <0.001)也与 HCC 独立相关。Fine-Gray模型证实了这一发现,该模型显示MASLD的亚分布HR(sHR)为2.07(95% CI:1.34-3.19,p <0.001)。结论与没有MASLD的患者相比,在获得SVR12后,MASLD患者的HCC风险增加。影响和意义MASLD是脂肪性肝病(SLD)的一种新命名,使用DAAs获得SVR12后,MASLD患者发生新发HCC的风险仍有待证实。在这项招募了1598名台湾患者的研究中,与没有MASLD的患者相比,MASLD患者在达到SVR12后发生新发HCC的风险大约增加了两倍。MASLD在很大程度上介导了CMRFs对HCC发展的影响。我们的研究结果强调了药物干预和积极调整生活方式对控制 MASLD 患者的 CMRFs 的极端重要性,以及警惕 HCC 监测以确保根除 HCV 后取得良好疗效的必要性。
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来源期刊
Journal of Hepatology
Journal of Hepatology 医学-胃肠肝病学
CiteScore
46.10
自引率
4.30%
发文量
2325
审稿时长
30 days
期刊介绍: The Journal of Hepatology is the official publication of the European Association for the Study of the Liver (EASL). It is dedicated to presenting clinical and basic research in the field of hepatology through original papers, reviews, case reports, and letters to the Editor. The Journal is published in English and may consider supplements that pass an editorial review.
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