Grandhe Sirisha, Frenette Catherine T
Dr Grandhe is a resident in the Department of Medicine at Scripps Green Hospital in La Jolla, California. Dr Frenette is the medical director of liver transplantation and director of the hepatocellular carcinoma program at the Scripps Center for Organ Transplant at Scripps Green Hospital.
Gastroenterol Hepatol (N Y). 2017 Jul;13(7):421-425.
Chronic hepatitis C virus (HCV) infection has generally been associated with a slightly increased risk of developing hepatocellular carcinoma (HCC). For the past several decades, most patients with chronic HCV cirrhosis have been treated with pegylated interferon and ribavirin therapies, which were known to achieve sustained virologic response (SVR) but also carried their own side effects and toxicities. The recent implementation of direct-acting antiviral (DAA) treatments revealed an increased efficacy in difficult-to-treat populations and higher adherence rates given the all-oral nature of the regimens. However, while these regimens are excellent in terms of improving the side-effect profile and achieving SVR at a higher rate and in a shorter time frame than interferon and ribavirin, some researchers are now discovering an increased rate of de novo and recurrent HCC in patients with HCV cirrhosis compared to interferon treatment protocols. Although other studies were not able to reproduce similar findings, the question as to the role of DAA therapy in HCC occurrence after achieving SVR in patients with HCV cirrhosis continues to persist. Possible theories as to the mechanisms behind tumor relapse after DAA therapy include alterations of immunosurveillance and gene expression, a protective and antineoplastic effect from inflammation secondary to chronic HCV infection that is then abolished with DAA therapy, and delay in radiographic identification of previously undetectable tumors. This article reviews the current literature regarding concern for the possible increase of HCC after DAA therapy.
慢性丙型肝炎病毒（HCV）感染通常与肝细胞癌（HCC）发生风险略有增加相关。在过去几十年中，大多数慢性HCV肝硬化患者接受聚乙二醇化干扰素和利巴韦林治疗，已知这些治疗可实现持续病毒学应答（SVR），但也有其自身的副作用和毒性。近期直接抗病毒药物（DAA）治疗的应用显示，在难治性人群中疗效有所提高，且由于治疗方案为全口服性质，依从率更高。然而，尽管这些方案在改善副作用方面表现出色，且比干扰素和利巴韦林能更快、更高比例地实现SVR，但一些研究人员现在发现，与干扰素治疗方案相比，HCV肝硬化患者中初发性和复发性HCC的发生率有所增加。尽管其他研究未能重现类似结果，但DAA治疗在HCV肝硬化患者实现SVR后对HCC发生的作用这一问题仍然存在。关于DAA治疗后肿瘤复发背后机制的可能理论包括免疫监视和基因表达的改变、慢性HCV感染继发炎症的保护和抗肿瘤作用因DAA治疗而消除，以及先前无法检测到的肿瘤在影像学上识别延迟。本文综述了当前关于DAA治疗后HCC可能增加的相关文献。
