Sapena Victor, Enea Marco, Torres Ferran, Celsa Ciro, Rios Jose, Rizzo Giacomo Emanuele Maria, Nahon Pierre, Mariño Zoe, Tateishi Ryosuke, Minami Tatsuya, Sangiovanni Angelo, Forns Xavier, Toyoda Hidenori, Brillanti Stefano, Conti Fabio, Degasperi Elisabetta, Yu Ming-Lung, Tsai Pei-Chien, Jean Kevin, El Kassas Mohamed, Shousha Hend Ibrahim, Omar Ashraf, Zavaglia Claudio, Nagata Hiroko, Nakagawa Mina, Asahina Yasuhiro, Singal Amit G, Murphy Caitlin, Kohla Mohamed, Masetti Chiara, Dufour Jean-François, Merchante Nicolas, Cavalletto Luisa, Chemello Liliana Lc, Pol Stanislas, Crespo Javier, Calleja Jose Luis, Villani Rosanna, Serviddio Gaetano, Zanetto Alberto, Shalaby Sarah, Russo Francesco Paolo, Bielen Rob, Trevisani Franco, Cammà Calogero, Bruix Jordi, Cabibbo Giuseppe, Reig Maria
Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, CIBEREHD, Hospital Clinic de Barcelona, Barcelona, Spain.
Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Sicilia, Italy.
Gut. 2022 Mar;71(3):593-604. doi: 10.1136/gutjnl-2020-323663. Epub 2021 Mar 19.
The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.
We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.
Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I=74.6%) and 5.7 (2.5 to 15.3, I=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1).
Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.
在肝细胞癌（HCC）成功治疗后，直接作用抗病毒药物（DAA）治疗丙型肝炎病毒（HCV）的益处仍存在争议。本项对个体患者数据的荟萃分析评估了给予DAA后的HCC复发风险。
我们汇总了来自21项HCV相关肝硬化和HCC研究的977例连续患者的数据，这些患者在手术/局部区域治疗后实现了完全放射学缓解并接受了DAA治疗（DAA组）。复发或死亡风险表示为每100人年（100PY）的HCC复发或死亡情况。来自ITA.LI.CA.队列的倾向评分匹配患者（n = 328）作为未接受DAA的对照（非DAA组）。使用随机效应泊松模型确定HCC复发的危险因素。
接受DAA治疗的患者每100PY的复发率和死亡风险分别为20（95%CI 13.9至29.8，I = 74.6%）和5.7（2.5至15.3，I = 54.3）。复发的预测因素为甲胎蛋白对数（相对风险（RR）= 1.11，95%CI 1.03至1.19；p = 0.01，每增加1 log ng/mL）、DAA开始前的HCC复发史（RR = 1.11，95%CI 1.07至1.16；p < 0.001）、体能状态（2级与0级相比，RR = 4.35，95%CI 1.54至11.11；2级与1级相比，RR = 3.7，95%CI 1.3至11.11；p = 0.01）以及HCC治疗前的肿瘤负荷（多灶性与孤立性结节相比，RR = 1.75，95%CI 1.25至2.43；p < 0.001）。在倾向评分匹配患者中，接受DAA组和未接受DAA组之间的RR未观察到显著差异（RR = 0.64，95%CI 0.37至1.1；p = 0.1）。
DAA暴露对HCC复发风险的影响仍不明确。对接受DAA根除HCV后的HCC患者进行积极的临床和放射学随访是合理的。
