Yew Kuo Chao, Tan Quan Rui, Lim Phei Ching, Low Wei Yang, Lee Chong Yew
Department of Gastroenterology and Hepatology, Tan Tock Seng Hospital, Singapore, Singapore.
Imperial College London-Nanyang Technological University Lee Kong Chian School of Medicine, Singapore, Singapore.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Mar;397(3):1421-1431. doi: 10.1007/s00210-023-02716-x. Epub 2023 Sep 20.
Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.
直接抗病毒药物（DAA）已成为丙型肝炎的首选治疗方法。然而，DAA在预防丙型肝炎并发症方面的疗效仍不确定。我们评估了与未接受DAA治疗的丙型肝炎患者相比，DAA对肝细胞癌（HCC）发生和复发、全因死亡率、肝失代偿和肝移植的影响，以及与基线肝脏状态的关联。使用三个电子数据库对1993年3月至2022年3月的文章进行了系统检索。纳入了与未接受DAA治疗进行比较并报告至少一项结局的随机、病例对照和队列研究。进行了基于基线肝脏状态的荟萃分析和亚组荟萃分析。在检索到的1497篇文章中，纳入了19项研究，包括266,310名患者（56.07%为男性）。DAA在非肝硬化（RR 0.80，95%CI 0.69 - 0.92）和肝硬化（RR 0.39，95%CI 0.24 - 0.64）患者中显著降低了HCC的发生，但在失代偿期肝硬化患者中未降低。DAA治疗降低了HCC复发率（RR 0.71，95%CI 0.55 - 0.92），尤其是在基线时有HCC且等待肝移植的患者中。DAA还显著降低了全因死亡率（RR 0.43，95%CI 0.23 - 0.78）和肝失代偿率（RR 0.52，95%CI 0.33 - 0.83）。然而，DAA并不能预防肝移植。该研究强调了在丙型肝炎治疗中尽早开始使用DAA的重要性，其益处不仅仅在于持续病毒学应答。DAA治疗尤其在非肝硬化和代偿期肝硬化组中预防了HCC，表明在预防肝脏状态进一步恶化方面有益处。尽早开始使用DAA还降低了HCC复发、肝失代偿和全因死亡率。
