直接作用抗病毒治疗慢性丙型肝炎和肝细胞癌患者的持续病毒学应答：系统评价和荟萃分析。
Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis.
机构信息
Department of Infectious Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA; National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Shaanxi Provincial Clinical Research Center for Hepatic & Splenic Diseases, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.
出版信息
J Hepatol. 2019 Sep;71(3):473-485. doi: 10.1016/j.jhep.2019.04.017. Epub 2019 May 13.
BACKGROUND & AIMS: The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC.
METHODS
PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models.
RESULTS
We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66).
CONCLUSION
Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates.
LAY SUMMARY
There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.
背景与目的
肝细胞癌（HCC）对慢性丙型肝炎（CHC）感染患者无干扰素直接作用抗病毒（DAA）治疗反应的影响尚不清楚。本研究采用系统评价和荟萃分析的方法，旨在研究 DAA 治疗对伴有活动、非活动或无 HCC 的 CHC 患者持续病毒学应答（SVR）的影响。
方法
从 2013 年 1 月 1 日至 2018 年 9 月 24 日，我们检索了 PubMed、Embase、Web of Science 和 Cochrane 对照试验中心注册库。采用 DerSimonian-Laird 随机效应模型计算汇总 SVR 率。
结果
我们纳入了来自 15 个国家的 49 项研究，共包括 3341 例 HCC 患者和 35701 例无 HCC 患者。总体而言，HCC 患者的 SVR 低于无 HCC 患者（89.6%，95%CI 86.8-92.1%，I²=79.1% vs. 93.3%，95%CI 91.9-94.7%，I²=95.0%，p=0.0012），meta 回归分析表明 SVR 降低了 4.8%（95%CI 0.2-7.4%）。最大的 SVR 降低（18.8%）发生在活动/残留 HCC 患者与非活动/消融 HCC 患者之间（SVR 分别为 73.1%和 92.6%，p=0.002）。同时，与未接受肝移植的 HCC 患者相比，接受过肝移植的 HCC 患者具有更高的 SVR 率（p<0.001）。关于特定的 DAA 方案，接受 ledipasvir/sofosbuvir 治疗的 HCC 患者的 SVR 率低于无 HCC 患者（92.6%，n=884 vs. 97.8%，n=13141，p=0.026），但异质性很高（I²=84.7%，p<0.001）。接受 ombitasvir/paritaprevir/ritonavir±dasabuvir（n=101）或 daclatasvir/asunaprevir（n=101）治疗的 HCC 患者和无 HCC 患者的 SVR 率相似（97.2% vs. 94.8%，p=0.79）和 91.7% vs. 89.8%，p=0.66）。
结论
总体而言，与无 HCC 患者相比，HCC 患者，尤其是活动型 HCC 患者，SVR 率较低，但异质性较高。需要继续努力积极筛查、诊断和治疗 HCC，以确保更高的 CHC 治愈率。
平铺直叙
现在有一些药物（直接作用抗病毒药或“DAA”）可以“治愈”丙型肝炎病毒，但患有丙型肝炎和肝癌的患者可能不如没有肝癌的患者容易治愈。然而，肝癌患者也更有可能患有晚期肝病和可能降低治愈率的风险因素，因此需要更好的对照研究来证实这些发现。
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