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人类免疫缺陷病毒(HIV)-丙型肝炎病毒(HCV)合并感染患者持续病毒学应答前后的肝纤维化:哪种非侵入性标志物最适合用于监测纤维化消退?

Liver Fibrosis in Human Immunodeficiency Virus (HIV)-Hepatitis C Virus (HCV) Coinfection Before and After Sustained Virologic Response: What Is the Best Noninvasive Marker for Monitoring Regression?

机构信息

Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada.

Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.

出版信息

Clin Infect Dis. 2021 Aug 2;73(3):468-477. doi: 10.1093/cid/ciaa702.

Abstract

BACKGROUND

Noninvasive markers of liver fibrosis such as aspartate aminotransferase-to-platelet ratio (APRI) and transient elastography (TE) have largely replaced liver biopsy for staging hepatitis C virus (HCV). As there is little longitudinal data, we compared changes in these markers before and after sustained virologic response (SVR) in human immunodeficiency virus (HIV)-HCV coinfected patients.

METHODS

Participants from the Canadian Coinfection Cohort study who achieved SVR after a first treatment with either interferon/ribavirin or direct acting antivirals (DAAs), with at least 1 pre- and posttreatment fibrosis measure were selected. Changes in APRI or TE (DAA era only) were modeled using a generalized additive mixed model, assuming a gamma distribution and adjusting for sex, age at HCV acquisition, duration of HCV infection, and time-dependent body mass index, binge drinking, and detectable HIV RNA.

RESULTS

Of 1981 patients, 151 achieved SVR with interferon and 553 with DAAs; 94 and 382 met inclusion criteria, respectively. In the DAA era, APRI increased (0.03 units/year; 95% credible interval (CrI): -.05, .12) before, declined dramatically during, and then changed minimally (-0.03 units/year; 95% CrI: -.06, .01) after treatment. TE values, however, increased (0.74 kPa/year; 95% CrI: .36, 1.14) before treatment, changed little by the end of treatment, and then declined (-0.55 kPa/year; 95% CrI: -.80, -.31) after SVR.

CONCLUSIONS

TE should be the preferred noninvasive tool for monitoring fibrosis regression following cure. Future studies should assess the risk of liver-related outcomes such as hepatocellular carcinoma according to trajectories of fibrosis regression measured using TE to determine if and when it will become safe to discontinue screening.

摘要

背景

非侵入性肝纤维化标志物如天门冬氨酸氨基转移酶与血小板比值(APRI)和瞬时弹性成像(TE)在很大程度上已取代肝活检用于丙型肝炎病毒(HCV)分期。由于纵向数据较少,我们比较了人类免疫缺陷病毒(HIV)-HCV 合并感染患者在获得持续病毒学应答(SVR)前后这些标志物的变化。

方法

从加拿大合并感染队列研究中选择了接受首次干扰素/利巴韦林或直接作用抗病毒药物(DAA)治疗后获得 SVR 的患者,且至少有 1 次治疗前后纤维化指标。采用广义加性混合模型对 APRI 或 TE(仅 DAA 时代)的变化进行建模,假设为伽马分布,并调整性别、HCV 感染时的年龄、HCV 感染持续时间以及时间依赖性体重指数、 binge drinking 和可检测到的 HIV RNA。

结果

在 1981 例患者中,151 例患者接受干扰素治疗获得 SVR,553 例患者接受 DAA 治疗获得 SVR;94 例和 382 例分别符合纳入标准。在 DAA 时代,APRI 在治疗前增加(0.03 单位/年;95%可信区间(CrI):-.05,.12),在治疗期间急剧下降,然后在治疗后变化很小(-0.03 单位/年;95% CrI:-.06,.01)。然而,TE 值在治疗前增加(0.74 kPa/年;95% CrI:.36,1.14),在治疗结束时变化不大,然后在 SVR 后下降(-0.55 kPa/年;95% CrI:-.80,-.31)。

结论

TE 应该是监测治疗后纤维化消退的首选非侵入性工具。未来的研究应该根据 TE 测量的纤维化消退轨迹评估与肝脏相关的结局(如肝细胞癌)的风险,以确定何时以及是否可以安全停止筛查。

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