Radu Pompilia, Becchetti Chiara, Schropp Jonas, Schmid Patrick, Künzler-Heule Patrizia, Mertens Joachim, Moradpour Darius, Müllaupt Beat, Semela David, Negro Francesco, Heim Markus, Clerc Olivier, Roelens Maroussia, Keiser Olivia, Berzigotti Annalisa
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse, 3010 Bern, Switzerland.
Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, 9000 St. Gallen, Switzerland.
Cancers (Basel). 2024 Jul 18;16(14):2573. doi: 10.3390/cancers16142573.
The use of direct-acting antivirals (DAAs) has drastically changed the management of HCV-infected patients by achieving a 95-98% sustained virologic response (SVR) and reducing morbidity and mortality in this population. However, despite their effectiveness, controversy exists concerning the occurrence of oncologic events following DAA therapy. A retrospective analysis was conducted on data from the Swiss Hepatitis C Cohort Study, a prospective cohort involving patients with positive HCV viremia upon inclusion, enrolled in various Swiss centers from September 2000 to November 2021. To examine potential differences in the risk of intrahepatic tumor (IHT) occurrence and death among patients treated with direct-acting antivirals (DAAs), untreated patients, and those receiving interferon (IFN)-based therapy, a semiparametric competing risk proportional hazards regression model was used. Among 4082 patients (63.1% male, median age 45 years; genotype 1: 54.1%; cirrhosis: 16.1%), 1026 received exclusive treatment with IFN-based regimens, and 1180 were treated solely with DAAs. Over a median follow-up of 7.8 years (range: 3.8-11.9), 179 patients (4.4%) developed intrahepatic tumors (IHT), and 168 (4.1%) experienced extrahepatic tumors (EHT). The 5-year cumulative incidence of IHT was 1.55% (95% CI 0.96-2.48) for IFN-based therapy, 4.27% (95% CI 2.93-6.2) for DAA and 0.89% (95% CI 0.4-1.99) for untreated patients. There was no statistically significant difference in the risk of developing IHT (HR = 1.34; 95% CI = [0.70; 2.58]; = 0.380) or death (HR = 0.66; 95% CI = [0.43; 1.03]; = 0.066) between patients treated with DAAs and those treated with IFN. The DAAs reduced the risk of death and were not associated with an increased risk of extrahepatic tumors (EHT). In the adjusted model, accounting for cirrhosis and high liver stiffness, the DAA treatment was associated with a higher risk of IHT occurrence compared with untreated patients, emphasizing the relevance of implementing standardized hepatocellular carcinoma (HCC) screening post-DAA treatment.
直接作用抗病毒药物（DAAs）的使用通过实现95%-98%的持续病毒学应答（SVR）以及降低该人群的发病率和死亡率，极大地改变了丙型肝炎病毒（HCV）感染患者的治疗管理。然而，尽管其疗效显著，但关于DAAs治疗后肿瘤事件的发生仍存在争议。对瑞士丙型肝炎队列研究的数据进行了回顾性分析，该前瞻性队列研究纳入了2000年9月至2021年11月期间在瑞士各中心登记的、纳入时HCV病毒血症呈阳性的患者。为了研究接受直接作用抗病毒药物（DAAs）治疗的患者、未治疗患者以及接受基于干扰素（IFN）治疗的患者发生肝内肿瘤（IHT）和死亡风险的潜在差异，使用了半参数竞争风险比例风险回归模型。在4082例患者中（男性占63.1%，中位年龄45岁；基因1型：54.1%；肝硬化：16.1%），1026例接受了单纯基于IFN方案的治疗，1180例仅接受了DAAs治疗。在中位随访7.8年（范围：3.8 - 11.9年）期间，179例患者（4.4%）发生了肝内肿瘤（IHT），168例（4.1%）发生了肝外肿瘤（EHT）。基于IFN治疗的患者IHT的5年累积发病率为1.55%（95%CI 0.96 - 2.48），DAAs治疗的患者为4.27%（95%CI 2.93 - 6.2），未治疗患者为0.89%（95%CI 0.4 - 1.99）。接受DAAs治疗的患者与接受IFN治疗的患者发生IHT的风险（HR = 1.34；95%CI = [0.70；2.58]；P = 0.380）或死亡风险（HR = 0.66；95%CI = [0.43；1.03]；P = 0.066）无统计学显著差异。DAAs降低了死亡风险，且与肝外肿瘤（EHT）风险增加无关。在调整模型中，考虑到肝硬化和高肝硬度，与未治疗患者相比，DAAs治疗与发生IHT的风险更高相关，这强调了在DAAs治疗后实施标准化肝细胞癌（HCC）筛查的重要性。
