Department of Gastroenterology, GB Pant Hospital, New Delhi, India.
Aliment Pharmacol Ther. 2009 Jul;30(1):48-60. doi: 10.1111/j.1365-2036.2009.04015.x. Epub 2009 Apr 8.
A beta-blocker is recommended for primary prophylaxis of variceal bleeding; however, only one-third have hepatic venous pressure gradient (HVPG) response. The role of addition of isosorbide-5-mononitrate (ISMN) to beta-blocker and benefits of HVPG-guided 'a la carte' approach remain unclear.
To determine the benefits of HVPG-guided pharmacotherapy in primary prophylaxis of variceal bleeding using beta-blocker and ISMN.
Consecutive patients of cirrhosis, with high-risk varices, with no previous variceal bleeding were included. After baseline HVPG, patients received incremental propranolol to achieve HR of 55/min. After one-month, HVPG was repeated to determine response (<12 mmHg or >or=20% reduction). ISMN was added in nonresponders and HVPG repeated. Patients were followed up for 24 months.
Of 56 patients (age 47 +/- 13, males 79%) from 89 eligible patients, 21 (38%) responded to beta-blocker alone. Six additional patients responded to combination. Thus, overall 48% (27/56) patients responded. Variceal bleeding occurred in seven of 56 (13%) patients [one of 27 (4%) responder, five of 23 (22%) nonresponders and one of six (17%) with unknown response; P = N.S.]. The actuarial probability of variceal bleeding at median 24 months was 4% in responders and 22% in nonresponders (P < 0.05). Ten (18%) patients developed adverse effects to propranolol and six of 35 (17%) to nitrates requiring dose reduction. Risk factors of variceal bleed were grade IV varices and haemodynamic nonresponse.
For primary prophylaxis, a beta-blocker is effective in 38% and addition of ISMN raises the response rate to about half of patients. The HVPG-guided 'a la carte' approach may be considered for these patients.
推荐β受体阻滞剂用于预防静脉曲张出血;然而,只有三分之一的患者对肝静脉压力梯度(HVPG)有反应。添加单硝酸异山梨酯(ISMN)对β受体阻滞剂的作用和 HVPG 指导的“点菜式”方法的益处尚不清楚。
确定 HVPG 指导的药物治疗在使用β受体阻滞剂和 ISMN 预防静脉曲张出血中的益处。
连续纳入肝硬化、高危静脉曲张、无既往静脉曲张出血的患者。在基线 HVPG 后,患者接受递增普萘洛尔以达到 HR 为 55/min。一个月后,重复 HVPG 以确定反应(<12mmHg 或>或=20%减少)。在无反应者中添加 ISMN 并重复 HVPG。患者随访 24 个月。
在 89 例符合条件的患者中,56 例(年龄 47 +/- 13,男性 79%)患者中,21 例(38%)单独使用β受体阻滞剂有反应。另外 6 例患者联合用药有反应。因此,总共有 48%(27/56)的患者有反应。56 例患者中有 7 例(13%)发生静脉曲张出血[27 例中有 1 例(4%)反应者,23 例中有 5 例(22%)无反应者,6 例中有 1 例(17%)反应者未知;P=无统计学意义]。中位数 24 个月时,反应者静脉曲张出血的累积概率为 4%,无反应者为 22%(P<0.05)。10 例(18%)患者对普萘洛尔出现不良反应,35 例(17%)患者对硝酸盐出现不良反应,需要减少剂量。静脉曲张出血的危险因素是 IV 级静脉曲张和血流动力学无反应。
对于一级预防,β受体阻滞剂有效率为 38%,添加 ISMN 可将反应率提高到一半左右。对于这些患者,可以考虑 HVPG 指导的“点菜式”方法。