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慢性丙型肝炎治愈后临床显著门静脉高压的非侵入性检测。

Non-invasive tests for clinically significant portal hypertension after HCV cure.

机构信息

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

Liver Unit, Hospital Clínic, Universitat de Barcelona, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain.

出版信息

J Hepatol. 2022 Dec;77(6):1573-1585. doi: 10.1016/j.jhep.2022.08.025. Epub 2022 Sep 5.

Abstract

BACKGROUND & AIMS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥10 mmHg) have predominantly been studied in patients with active HCV infection. Investigations after HCV cure are limited and have yielded conflicting results. We conducted a pooled analysis to determine the diagnostic/prognostic utility of liver stiffness measurement (LSM)/platelet count (PLT) in this setting.

METHODS

A total of 418 patients with pre-treatment HVPG ≥6 mmHg who achieved sustained virological response (SVR) and underwent post-treatment HVPG measurement were assessed, of whom 324 (HVPG/NIT-cohort) also had paired data on pre-/post-treatment LSM/PLT. The derived LSM/PLT criteria were then validated against the direct endpoint decompensation in 755 patients with compensated advanced chronic liver disease (cACLD) with SVR (cACLD-validation-cohort).

RESULTS

HVPG/NIT-cohort: Among patients with cACLD, the pre-/post-treatment prevalence of CSPH was 80%/54%. The correlation between LSM/HVPG increased from pre- to post-treatment (r = 0.45 vs. 0.60), while that of PLT/HVPG remained unchanged. For given LSM/PLT values, HVPG tended to be lower post- vs. pre-treatment, indicating the need for dedicated algorithms. Combining post-treatment LSM/PLT yielded a high diagnostic accuracy for post-treatment CSPH in cACLD (AUC 0.884; 95% CI 0.843-0.926). Post-treatment LSM <12 kPa & PLT >150 G/L excluded CSPH (sensitivity: 99.2%), while LSM ≥25 kPa was highly specific for CSPH (93.6%). cACLD-validation-cohort: the 3-year decompensation risk was 0% in the 42.5% of patients who met the LSM <12 kPa & PLT >150 G/L criteria. In patients with post-treatment LSM ≥25 kPa (prevalence: 16.8%), the 3-year decompensation risk was 9.6%, while it was 1.3% in those meeting none of the above criteria (prevalence: 40.7%).

CONCLUSIONS

NITs can estimate the probability of CSPH after HCV cure and predict clinical outcomes. Patients with cACLD but LSM <12 kPa & PLT>150 G/L may be discharged from portal hypertension surveillance if no co-factors are present, while patients with LSM ≥25 kPa require surveillance/treatment.

LAY SUMMARY

Measurement of liver stiffness by a specific ultrasound device and platelet count (a simple blood test) are broadly used for the non-invasive diagnosis of increased blood pressure in the veins leading to the liver, which drives the development of complications in patients with advanced liver disease. The results of our pooled analysis refute previous concerns that these tests are less accurate after the cure of hepatitis C virus (HCV) infection. We have developed diagnostic criteria that facilitate personalized management after HCV cure and allow for a de-escalation of care in a high proportion of patients, thereby decreasing disease burden.

摘要

背景与目的

用于诊断临床显著门静脉高压症(CSPH;肝静脉压力梯度[HVPG]≥10mmHg)的非侵入性检测(NIT)主要在慢性丙型肝炎病毒(HCV)感染患者中进行了研究。HCV 治愈后的调查研究有限,且结果相互矛盾。我们进行了一项汇总分析,以确定在这种情况下肝硬度测量(LSM)/血小板计数(PLT)的诊断/预后价值。

方法

共评估了 418 例治疗前 HVPG≥6mmHg 且获得持续病毒学应答(SVR)并接受治疗后 HVPG 测量的患者,其中 324 例(HVPG/NIT 队列)也具有治疗前/后 LSM/PLT 的配对数据。然后,根据衍生的 LSM/PLT 标准,对 755 例具有 SVR 的代偿性晚期慢性肝病(cACLD)患者(cACLD 验证队列)的直接终点失代偿进行验证。

结果

HVPG/NIT 队列:在 cACLD 患者中,治疗前/后 CSPH 的患病率分别为 80%和 54%。LSM/HVPG 的相关性从治疗前增加到治疗后(r=0.45 对 0.60),而 PLT/HVPG 的相关性保持不变。对于给定的 LSM/PLT 值,HVPG 倾向于在治疗后低于治疗前,表明需要专门的算法。联合治疗后 LSM/PLT 可提高 cACLD 治疗后 CSPH 的诊断准确性(AUC 0.884;95%CI 0.843-0.926)。治疗后 LSM<12kPa 和 PLT>150G/L 排除 CSPH(敏感性:99.2%),而 LSM≥25kPa 对 CSPH 具有高度特异性(93.6%)。cACLD 验证队列:符合 LSM<12kPa 和 PLT>150G/L 标准的患者中,3 年失代偿风险为 42.5%。在治疗后 LSM≥25kPa (患病率:16.8%)的患者中,3 年失代偿风险为 9.6%,而不符合上述任何标准的患者(患病率:40.7%)的失代偿风险为 1.3%。

结论

NIT 可估计 HCV 治愈后 CSPH 的概率,并预测临床结局。如果没有合并因素,具有 cACLD 但 LSM<12kPa 和 PLT>150G/L 的患者可以从门静脉高压监测中出院,而 LSM≥25kPa 的患者需要监测/治疗。

概要

一种特定的超声设备和血小板计数(一种简单的血液检查)用于广泛用于诊断导致肝脏并发症的静脉血压升高,这在晚期肝病患者中推动了并发症的发展。我们的汇总分析结果驳斥了之前的担忧,即这些检测在 HCV 感染治愈后准确性降低。我们已经开发出诊断标准,有助于 HCV 治愈后的个性化管理,并允许在很大一部分患者中降低护理级别,从而降低疾病负担。

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