Liver Unit, Hospital Clinic de Barcelona, Universidad de Barcelona, IDIBAPS, Barcelona, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
Gastroenterology. 2017 Nov;153(5):1273-1283.e1. doi: 10.1053/j.gastro.2017.07.016. Epub 2017 Jul 20.
BACKGROUND & AIMS: Patients with hepatitis C virus-associated cirrhosis and clinical significant portal hypertension (CSPH, hepatic venous pressure gradient [HVPG] 10 mmHg or greater), despite achieving sustained virological response (SVR) to therapy, remain at risk of liver decompensation. We investigated hemodynamic changes following SVR in patients with CSPH and whether liver stiffness measurements (LSMs) can rule out the presence of CSPH.
We performed a multicenter prospective study of 226 patients with hepatitis C virus-associated cirrhosis and CSPH who had SVR to interferon-free therapy at 6 Liver Units in Spain. The portal pressure gradient was determined based on HVPG at baseline and 24 weeks after therapy; patients also underwent right-heart catheterization and LSM at these time points. Primary outcomes were effects of SVR on the hepatic, pulmonary, and systemic hemodynamics; factors related to HVPG ≥10% reduction and to CSPH persistence; and whether LSMs can rule out the presence of CSPH after SVR.
Most patients (75%) had esophageal varices, 21% were Child-B, and 29% had at least 1 previous episode of liver decompensation. Overall, HVPG decreased from 15 (IQR: 12-18) before treatment to 13 (10-16) mmHg after SVR (reduction of 2.1 ± 3.2 mmHg; P < .01). However, CSPH persisted in 78% of patients. HVPG decreased by 10% or more from baseline in 140 patients (62%). Baseline level of albumin below 3.5 g/dL was the only negative factor associated with an HVPG reduction of 10% or more. LSM decreased from 27 (20-37) kPa before treatment to 18 (14-28) kPa after SVR (P < .05). One third of patients with a reduction in LSM to below 13.6 kPa after SVR still had CSPH. A higher baseline HVPG and a lower decrease in LSM after treatment were associated with persistence of CSPH after SVR. Systemic hemodynamics improved after SVR. Interestingly, pulmonary hypertension was present in 13 patients at baseline and 25 after SVR, although only 3 patients had increased pulmonary resistance.
In a multicenter prospective study of patients with hepatitis C virus-associated cirrhosis, an SVR to all-oral therapy significantly reduced HVPG, compared with before treatment. Nevertheless, CSPH persists in most patients despite SVR, indicating persistent risk of decompensation. In this population, changes in LSM do not correlate with HVPG and cut-off values are not reliable in ruling out CSPH after SVR.
尽管丙型肝炎病毒相关肝硬化和临床显著门静脉高压（CSPH，肝静脉压力梯度[HVPG]≥10mmHg）患者对治疗实现持续病毒学应答（SVR），但仍存在肝失代偿的风险。我们研究了 SVR 后 CSPH 患者的血流动力学变化，以及肝硬度测量（LSM）是否可以排除 CSPH 的存在。
我们在西班牙的 6 个肝脏单位对 226 例丙型肝炎病毒相关肝硬化和 CSPH 患者进行了一项多中心前瞻性研究，这些患者对无干扰素治疗实现了 SVR。门静脉压力梯度基于基线和治疗后 24 周的 HVPG 确定；患者还在这些时间点进行了右心导管检查和 LSM。主要结局为 SVR 对肝、肺和全身血流动力学的影响；与 HVPG 降低≥10%和 CSPH 持续相关的因素；以及 LSM 在 SVR 后是否可以排除 CSPH 的存在。
大多数患者（75%）有食管静脉曲张，21%为 Child-B 级，29%至少有 1 次肝失代偿发作。总体而言，HVPG 从治疗前的 15（IQR：12-18）mmHg 降至 SVR 后的 13（10-16）mmHg（降低 2.1±3.2mmHg；P<0.01）。然而，CSPH 在 78%的患者中持续存在。140 名患者（62%）的 HVPG 基线水平降低 10%或更多。基线白蛋白水平低于 3.5g/dL 是唯一与 HVPG 降低 10%或更多相关的负性因素。LSM 从治疗前的 27（20-37）kPa 降至 SVR 后的 18（14-28）kPa（P<0.05）。三分之一的 LSM 治疗后降至 13.6kPa 以下的患者仍有 CSPH。较高的基线 HVPG 和治疗后 LSM 降低幅度较小与 SVR 后 CSPH 的持续存在相关。SVR 后全身血流动力学改善。有趣的是，尽管只有 3 名患者的肺血管阻力增加，但基线时有 13 名患者存在肺动脉高压，而在 SVR 后有 25 名患者存在肺动脉高压。
在一项丙型肝炎病毒相关肝硬化患者的多中心前瞻性研究中，全口服治疗的 SVR 与治疗前相比显著降低了 HVPG。然而，尽管实现了 SVR，CSPH 在大多数患者中仍然持续存在，表明仍然存在失代偿的风险。在该人群中，LSM 的变化与 HVPG 不相关，且 SVR 后 LSM 的截断值不能可靠地排除 CSPH 的存在。
