在参与前瞻性对照试验的欧洲学术中心治疗慢性丙型肝炎基因型 1 患者：是否存在选择偏倚？

Treatment of chronic hepatitis C genotype 1 patients at an academic center in Europe involved in prospective, controlled trials: is there a selection bias?

机构信息

Internal Medicine III, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.

出版信息

Hepatology. 2012 Jan;55(1):30-8. doi: 10.1002/hep.24671. Epub 2011 Nov 30.

DOI:10.1002/hep.24671

PMID:21932410

Abstract

UNLABELLED

Pegylated interferon-alpha2/ribavirin (peg-IFN/RBV) is the standard of care (SOC) for patients with chronic hepatitis C (CHC) infection. Currently, direct-acting antiviral agents (DAAs) are evaluated in clinical trials. The aim of this study was to compare baseline characteristics and sustained virologic response (SVR) rates in patients included in clinical trials to those receiving SOC. Medical records of all 503 treatment-naïve patients with CHC, genotype (GT) 1, referred over a 4-year period (January 2006-December 2009) were reviewed. Only 310 of 503 (62%) patients received antiviral therapy, 141 were enrolled in randomized, controlled trials ("study patients"; 101 in DAA studies), and 169 received SOC. At baseline, viral load and platelet count were higher and bilirubin was lower in study patients than in SOC patients. History of psychiatric disorders was more common in SOC patients (43 [25%] versus study patients with 18 [13%]; P < 0.01). Liver biopsy was obtained in 98% of study patients, but only in 59% of SOC patients. Twenty-nine (21%) and 40 (40%) study and SOC patients, respectively, had advanced fibrosis (F3/4; P = 0.001). By intent-to-treat analysis, SVR rates were higher in DAAs (64%; 95% confidence interval [CI]: 53.4-74.4) than in SOC patients (46%; 95% CI: 37.9-53.7; P < 0.01), but not different when calculated on a treated-per-protocol (TPP) basis. Interleukin (IL)28B GT was equally distributed in both cohorts. By chance, more patients treated with IFN/RBV had rs12979860 C/C-GT (up to 44%) than DAA-treated patients. If analyzed according to the IL28B polymorphism, TPP SVR rates did not reach statistically significant differences among study and SOC patients.

CONCLUSIONS

Baseline characteristics slightly favored study patients, but IL28B GT and treatment adherence were the most important factors determining outcome. Thus, the applicability of the results of controlled studies has to be tested in a "real-world" setting.

摘要

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聚乙二醇干扰素-α2/利巴韦林（peg-IFN/RBV）是慢性丙型肝炎（CHC）感染患者的标准治疗方法（SOC）。目前，直接作用抗病毒药物（DAA）正在临床试验中进行评估。本研究的目的是比较纳入临床试验的患者与接受 SOC 治疗的患者的基线特征和持续病毒学应答（SVR）率。

回顾了在 4 年期间（2006 年 1 月至 2009 年 12 月）转诊的所有 503 例初治 CHC、基因型（GT）1 患者的病历。503 例患者中仅 310 例（62%）接受了抗病毒治疗，141 例入组了随机对照试验（“研究患者”；101 例在 DAA 研究中），169 例接受了 SOC。在基线时，研究患者的病毒载量和血小板计数较高，胆红素较低。SOC 患者中精神疾病史更为常见（43 [25%]比研究患者中 18 [13%]；P < 0.01）。98%的研究患者进行了肝活检，但只有 59%的 SOC 患者进行了肝活检。分别有 29（21%）和 40（40%）例研究患者和 SOC 患者存在晚期纤维化（F3/4；P = 0.001）。意向治疗分析显示，DAA 组（64%；95%置信区间[CI]：53.4-74.4）的 SVR 率高于 SOC 组（46%；95% CI：37.9-53.7；P < 0.01），但基于治疗方案（TPP）的计算结果并无差异。白细胞介素（IL）28B GT 在两个队列中分布均匀。偶然的是，与 DAA 治疗组相比，接受 IFN/RBV 治疗的患者 rs12979860 C/C-GT 比例更高（高达 44%）。如果根据 IL28B 多态性进行分析，研究患者和 SOC 患者的 TPP SVR 率并未达到统计学显著差异。