Afdhal N, Everson G T, Calleja J L, McCaughan G W, Bosch J, Brainard D M, McHutchison J G, De-Oertel S, An D, Charlton M, Reddy K R, Asselah T, Gane E, Curry M P, Forns X
Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
University of Colorado Denver, Aurora, Colorado, USA.
J Viral Hepat. 2017 Oct;24(10):823-831. doi: 10.1111/jvh.12706. Epub 2017 Apr 10.
Portal hypertension is a predictor of liver-related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon-free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child-Pugh-Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open-label sofosbuvir plus ribavirin at Day 1 or after a 24-week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by -1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow-up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long-term follow-up. (EudraCT 2012-002457-29).
门静脉高压是丙型肝炎和肝硬化患者肝脏相关临床事件及死亡率的一个预测指标。无干扰素的丙型肝炎治疗对门静脉压力的影响尚不清楚。50例Child-Pugh-Turcotte（CPT）A和B级肝硬化且伴有门静脉高压（肝静脉压力梯度[HVPG]＞6 mmHg）的患者被随机分为两组，一组在第1天接受48周的开放标签索磷布韦联合利巴韦林治疗，另一组在经过24周观察期后接受治疗。主要终点是接受≥1剂治疗的患者在治疗12周后的持续病毒学应答（SVR12）。次要终点包括HVPG、实验室参数以及终末期肝病模型（MELD）和CPT评分的变化。对一部分患者在治疗后48周进行随访，以确定HVPG的后期变化。46例患者中有72%（33/46）实现了SVR12。在37例在基线和治疗结束时进行了配对HVPG测量的患者中，平均HVPG下降了-1.0（标准差3.97）mmHg。9例患者（24%）在治疗期间HVPG下降≥20%。在39例治疗前HVPG≥12 mmHg的患者中，27例（69%）实现了SVR12。33例基线HVPG≥12 mmHg的患者中有4例（12%）在治疗结束时HVPG＜12 mmHg。在9例治疗前HVPG≥12 mmHg且实现SVR12并完成48周随访的患者中，8例（89%）的HVPG下降≥20%，3例患者的门静脉压力降至＜12 mmHg。实现SVR的慢性丙型肝炎合并代偿期或失代偿期肝硬化患者在长期随访中可出现具有临床意义的HVPG降低。（欧洲临床试验数据库编号：2012-002457-29）
