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Systematic review with meta-analysis: recurrence of hepatocellular carcinoma following direct-acting antiviral therapy.系统评价与荟萃分析:直接作用抗病毒治疗后肝细胞癌的复发。
Aliment Pharmacol Ther. 2018 Jul;48(2):127-137. doi: 10.1111/apt.14823. Epub 2018 May 30.
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Methods for time-varying exposure related problems in pharmacoepidemiology: An overview.药物流行病学中与时变暴露相关问题的方法:概述
Pharmacoepidemiol Drug Saf. 2018 Feb;27(2):148-160. doi: 10.1002/pds.4372. Epub 2017 Dec 28.
3
Short-term risk of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting anti-viral treatment.直接作用抗病毒治疗清除丙型肝炎病毒后肝细胞癌的短期风险。
Aliment Pharmacol Ther. 2018 Jan;47(1):104-113. doi: 10.1111/apt.14380. Epub 2017 Oct 16.
4
An unjustified benefit: immortal time bias in the analysis of time-dependent events.无正当理由的获益:在分析时依事件中存在不朽时间偏倚。
Transpl Int. 2018 Feb;31(2):125-130. doi: 10.1111/tri.13081. Epub 2017 Nov 9.
5
HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma.直接作用抗病毒药物诱导的丙型肝炎病毒清除可降低肝细胞癌的风险。
J Hepatol. 2017 Sep 5. doi: 10.1016/j.jhep.2017.08.030.
6
Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis.肝癌的影像学诊断:系统评价和荟萃分析。
Hepatology. 2018 Jan;67(1):401-421. doi: 10.1002/hep.29487. Epub 2017 Nov 29.
7
Statistical methods for elimination of guarantee-time bias in cohort studies: a simulation study.队列研究中消除保证时间偏倚的统计方法:一项模拟研究。
BMC Med Res Methodol. 2017 Aug 22;17(1):126. doi: 10.1186/s12874-017-0405-6.
8
Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: A systematic review, meta-analyses, and meta-regression.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。
J Hepatol. 2017 Dec;67(6):1204-1212. doi: 10.1016/j.jhep.2017.07.025. Epub 2017 Aug 9.
9
Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study.丙型肝炎病毒(HCV)肝硬化患者接受直接抗病毒药物治疗会影响肝细胞癌的早期复发吗?一项前瞻性多中心研究。
Aliment Pharmacol Ther. 2017 Oct;46(7):688-695. doi: 10.1111/apt.14256. Epub 2017 Aug 9.
10
Hepatocellular carcinoma recurrence after direct antiviral agent treatment: A European multicentre study.直接抗病毒药物治疗后肝细胞癌复发:一项欧洲多中心研究。
J Hepatol. 2017 Oct;67(4):876-878. doi: 10.1016/j.jhep.2017.07.007. Epub 2017 Jul 19.

直接作用抗病毒治疗与多中心北美队列研究中肝细胞癌的复发无关。

Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study.

机构信息

Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas.

Division of Digestive and Liver Disease, UT Southwestern Medical Center, Dallas, Texas.

出版信息

Gastroenterology. 2019 May;156(6):1683-1692.e1. doi: 10.1053/j.gastro.2019.01.027. Epub 2019 Jan 18.

DOI:10.1053/j.gastro.2019.01.027
PMID:30660729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6598433/
Abstract

BACKGROUND & AIMS: There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort.

METHODS

We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response).

RESULTS

Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70-1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70-1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P = .23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but this did not achieve statistical significance.

CONCLUSION

In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

摘要

背景与目的

直接作用抗病毒(DAA)疗法治疗丙型肝炎病毒(HCV)感染对肝细胞癌(HCC)复发和肿瘤侵袭性的影响存在争议。我们比较了在北美队列中,接受 DAA 治疗和未接受治疗的 HCV 感染患者在 HCC 治疗完全缓解后的 HCC 复发模式。

方法

我们对 2013 年 1 月至 2017 年 12 月期间,美国和加拿大 31 个卫生系统中接受过 HCC 切除术、局部消融术、经动脉化疗栓塞术或放射治疗的完全缓解的 HCV 相关 HCC 患者进行了一项回顾性队列研究。使用 Cox 回归分析 DAA 治疗与完全缓解后复发的时间之间的关联,DAA 治疗作为时变暴露进行分析。我们还估计了 DAA 治疗与 HCC 早期复发(定义为完全缓解后 365 天)之间的关联。

结果

在 793 例 HCV 相关 HCC 患者中,304 例(38.3%)接受了 DAA 治疗,489 例(61.7%)未接受治疗。128 例 DAA 治疗患者(42.1%;52 例早期复发)和 288 例未治疗患者(58.9%;227 例早期复发)发生 HCC 复发。在调整了研究地点、年龄、性别、Child-Pugh 评分、α-胎蛋白水平、肿瘤负担和 HCC 治疗方式后,DAA 治疗与 HCC 复发(风险比 0.90,95%置信区间 0.70-1.16)或 HCC 早期复发(风险比 0.96,95%置信区间 0.70-1.34)无关。在 DAA 治疗和未治疗的患者中,大多数复发均符合米兰标准(74.2% vs 78.8%;P=0.23)。与未治疗的患者相比,接受 DAA 治疗的患者接受潜在治愈性 HCC 治疗的比例更高(32.0% vs 24.6%),且获得完全或部分缓解的比例更高(45.3% vs 41.0%),但差异无统计学意义。

结论

在接受 HCC 治疗完全缓解的大型北美患者队列中,DAA 治疗与总体或 HCC 早期复发无关。DAA 治疗和未治疗的患者 HCC 复发模式(包括治疗反应)相似。