Rutledge Stephanie M, Zheng Hui, Li Darrick K, Chung Raymond T
Department of Medicine, Massachusetts General Hospital, Gastroenterology Unit/Warren 10, Boston, MA02114, USA.
Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Hepatoma Res. 2019;5. doi: 10.20517/2394-5079.2019.19. Epub 2019 Aug 7.
Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC) in the United States. Achieving sustained viral response with interferon (IFN) treatment reduces the risk from 3%-5% to 0.5%-1% annually. Several studies reported unexpectedly high rates of HCC after treatment with direct-acting antivirals (DAAs). The aim of our study was to compare HCC rates in DAA-, IFN-treated and untreated populations.
A literature search was conducted using ScienceDirect, Ovid®, Web of Science and MEDLINE through January 2019. Studies were included if they measured rates of or recurrent HCC (following curative treatment) in HCV-infected persons. We included 138 studies ( = 177,512). Simple pooling of data and meta-analysis were performed, using the random effects method.
Mean age was higher in the DAA-treated IFN-treated group (58.4 years 52.6 years; = 0.0073), as were diabetes prevalence (34.5% 11.7%; ≤ 0.001) and incident cirrhosis (47.8% 34.2%, = 0.0017). The incidence rate of HCC was 2.01/100 person-years (py) (95%CI: 1.38, 2.67) in the DAA group and 1.45/100py (95%CI: 0.98, 1.94) in the IFN-treated group. HCC recurred at 16.76/100py (95%CI: 10.75, 22.91) in the DAA-treated group 20.04/100py (95%CI: 2.58, 45.21) after IFN. After adjusting for factors such as age and cirrhosis, the hazard ratio was 0.58 (95%CI: 0.20, 1.07) for HCC occurrence and 0.59 (95%CI: 0.24, 1.03) for HCC recurrence after DAA treatment compared to IFN-based treatment.
We did not find evidence for increased rates of HCC in DAA-treated compared with IFN-treated patients. Compared to those treated with IFN, older patients with additional risk factors for HCC were treated with DAAs. This imbalance appears to explain the higher numerical incidence of HCC among DAA-treated patients.
丙型肝炎病毒（HCV）是美国肝细胞癌（HCC）的主要病因。通过干扰素（IFN）治疗实现持续病毒学应答可将每年的风险从3%-5%降至0.5%-1%。多项研究报告称，直接抗病毒药物（DAA）治疗后HCC发生率意外地高。我们研究的目的是比较接受DAA治疗、IFN治疗和未治疗人群中的HCC发生率。
通过ScienceDirect、Ovid®、Web of Science和MEDLINE进行文献检索，截至2019年1月。纳入的研究需测量HCV感染者中HCC的发生率或复发率（根治性治疗后）。我们纳入了138项研究（n = 177,512）。使用随机效应方法进行简单的数据合并和荟萃分析。
接受DAA治疗的组比接受IFN治疗的组平均年龄更高（58.4岁对52.6岁；P = 0.0073），糖尿病患病率（34.5%对11.7%；P≤0.001）和新发肝硬化发生率（47.8%对34.2%，P = 0.0017）也是如此。DAA组HCC的发生率为2.01/100人年（py）（95%CI：1.38，2.67），IFN治疗组为1.45/100py（95%CI：0.98，1.94）。DAA治疗组HCC复发率为16.76/100py（95%CI：10.75，22.91），IFN治疗后为20.04/100py（95%CI：2.58，45.21）。在调整年龄和肝硬化等因素后，与基于IFN的治疗相比，DAA治疗后HCC发生的风险比为0.58（95%CI：0.20，1.07），HCC复发的风险比为0.59（95%CI：0.24，1.03）。
我们没有发现证据表明接受DAA治疗的患者与接受IFN治疗的患者相比HCC发生率增加。与接受IFN治疗的患者相比，有更多HCC危险因素的老年患者接受了DAA治疗。这种不平衡似乎解释了接受DAA治疗的患者中HCC在数值上较高的发生率。
