直接作用抗病毒 HCV 治疗后肝细胞癌风险：系统评价、荟萃分析和荟萃回归。
Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: A systematic review, meta-analyses, and meta-regression.
机构信息
The Kirby Institute, UNSW Sydney, Sydney, Australia.
The Kirby Institute, UNSW Sydney, Sydney, Australia.
出版信息
J Hepatol. 2017 Dec;67(6):1204-1212. doi: 10.1016/j.jhep.2017.07.025. Epub 2017 Aug 9.
BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy remains unclear. The aims of this study were to compare the rate of HCC occurrence in patients with HCV-related cirrhosis, following DAA vs. interferon (IFN)-based cure, and to compare the rate of HCC recurrence in patients who received curative HCC treatment, following DAA vs. IFN-based cure.
METHODS
A search was conducted for reports published between January 2000 and February 2017. Studies were included if they assessed HCC outcomes by type and response to HCV therapy. Random-effects meta-analyses were undertaken to determine a combined estimate of HCC incidence rate per 100/person-years (py) among patients with a sustained virological response (SVR).
RESULTS
A total of 41 studies (n=13,875 patients), including 26 on HCC occurrence (IFN=17, DAA=9; prospective=19, retrospective=5, retrospective-prospective=2), and 17 on HCC recurrence (IFN=7, DAA=10; prospective=11, retrospective=5 and retrospective-prospective=1) were included. In studies assessing HCC occurrence, average follow-up was shorter (1.0 vs. 5.5years), and average age older (60 vs. 52years) in DAA studies. In studies assessing HCC recurrence, average follow-up was shorter (1.3 vs. 5.0years), but average age similar (64 vs. 66years) in DAA studies. HCC occurrence was 1.14/100 py (95% CI 0.86-1.52) and 2.96/100 py (95% CI 1.76-4.96) in IFN and DAA studies respectively. HCC recurrence was 9.21/100 py (95% CI 7.18-11.81) and 12.16/100 py (95% CI 5.00-29.58) in IFN and DAA studies respectively. In meta-regression adjusting for study follow-up and age, DAA therapy was not associated with higher HCC occurrence (RR 0.68; 95% CI 0.18-2.55; p=0.55) or recurrence (RR 0.62, 95% CI 0.11-3.45, p=0.56).
CONCLUSION
There is no evidence for differential HCC occurrence or recurrence risk following SVR from DAA and IFN-based therapy.
LAY SUMMARY
The risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy remains unclear. We conducted a meta-analysis to compare occurrence and recurrence of HCC in patients receiving either DAA or interferon (IFN) therapy. There is no evidence that HCC occurrence or recurrence is different between patients receiving DAA or IFN therapy.
背景与目的
直接作用抗病毒（DAA）丙型肝炎病毒（HCV）治疗后发生肝细胞癌（HCC）的风险仍不清楚。本研究旨在比较 DAA 与干扰素（IFN）治疗后 HCV 相关肝硬化患者 HCC 的发生率，并比较 DAA 与 IFN 治疗后接受根治性 HCC 治疗患者 HCC 的复发率。
方法
对 2000 年 1 月至 2017 年 2 月发表的报告进行了检索。如果研究评估了 HCC 结局与 HCV 治疗的类型和反应，则将其纳入。采用随机效应荟萃分析确定持续病毒学应答（SVR）患者每 100 人年（py） HCC 发生率的综合估计值。
结果
共纳入 41 项研究（n=13875 例患者），其中 26 项研究评估 HCC 发生（IFN=17，DAA=9；前瞻性=19，回顾性=5，回顾性前瞻性=2），17 项研究评估 HCC 复发（IFN=7，DAA=10；前瞻性=11，回顾性=5，回顾性前瞻性=1）。在评估 HCC 发生的研究中，DAA 研究的平均随访时间较短（1.0 年 vs. 5.5 年），平均年龄较大（60 岁 vs. 52 岁）。在评估 HCC 复发的研究中，DAA 研究的平均随访时间较短（1.3 年 vs. 5.0 年），但平均年龄相似（64 岁 vs. 66 岁）。IFN 和 DAA 研究中 HCC 的发生率分别为 1.14/100 py（95%CI 0.86-1.52）和 2.96/100 py（95%CI 1.76-4.96）。IFN 和 DAA 研究中 HCC 的复发率分别为 9.21/100 py（95%CI 7.18-11.81）和 12.16/100 py（95%CI 5.00-29.58）。在调整研究随访和年龄的荟萃回归中，DAA 治疗与 HCC 发生率（RR 0.68；95%CI 0.18-2.55；p=0.55）或复发（RR 0.62，95%CI 0.11-3.45，p=0.56）无关。
结论
无证据表明 DAA 和 IFN 治疗后 SVR 与 HCC 发生或复发风险的差异。
要点总结
DAA 丙型肝炎病毒（HCV）治疗后发生肝细胞癌（HCC）的风险仍不清楚。我们进行了一项荟萃分析，以比较接受直接作用抗病毒（DAA）或干扰素（IFN）治疗的患者 HCC 发生和复发的情况。没有证据表明 DAA 或 IFN 治疗的患者 HCC 发生或复发的风险不同。
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