Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
Department of Critical Care Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
Hepatol Int. 2019 Nov;13(6):800-813. doi: 10.1007/s12072-019-09986-9. Epub 2019 Sep 20.
In addition to the portal pressure reducing effect, non-selective beta blockers (NSBBs) have possible immunomodulatory and effect in reducing bacterial translocation. Recently, it has been shown that patients who are already on NSBBs should be continued on them (if feasible), if acute-on-chronic liver failure (ACLF) develops. It, however, remains unknown if patients with ACLF and no or small esophageal varices at presentation will benefit from the use of NSBBs. We studied the efficacy and safety of carvedilol in patients with ACLF in reducing mortality, variceal bleeding and non-bleeding complications.
136 patients with ACLF (with no or small esophageal varices and HVPG ≥ 12 mmHg) were randomized to either carvedilol (n = 66) or placebo arms (n = 70).
Within 28 days, 7 (10.6%) of 66 patients in the carvedilol group and 17 (24.3%) of 70 in the placebo group died (p= 0.044). Fewer patients in the carvedilol compared to placebo group developed acute kidney injury (AKI) (13.6% vs 35.7%, p = 0.003 and spontaneous bacterial peritonitis (SBP) (6.1% vs 21.4%, p= 0.013). Significantly, more patients in the placebo group had increase in APASL ACLF Research Consortium-ACLF grade (22.9% vs 6.1%, p= 0.007). There was no significant difference in the 90-day transplant-free survival rate and development of AKI, SBP, non-SBP infections (including pneumonia) and variceal bleed within 90 days, between the two groups.
In ACLF patients with either no or small esophageal varices and HVPG ≥ 12 mmHg, carvedilol leads to improved survival and fewer AKI and SBP events up to 28 days. CLINICALTRIALS.
NCT02583698.
除了降低门静脉压力的作用外，非选择性β受体阻滞剂（NSBBs）还可能具有免疫调节作用，并能减少细菌易位。最近的研究表明，如果发生慢加急性肝衰竭（ACLF），已经在使用 NSBB 的患者（如果可行）应继续使用。然而，目前尚不清楚在 presentation 时无或小食管静脉曲张且 HVPG≥12mmHg 的 ACLF 患者是否会从 NSBB 的使用中获益。我们研究了卡维地洛在降低 ACLF 患者死亡率、静脉曲张出血和非出血并发症方面的疗效和安全性。
136 例 ACLF 患者（无或小食管静脉曲张且 HVPG≥12mmHg）被随机分为卡维地洛组（n=66）或安慰剂组（n=70）。
在 28 天内，卡维地洛组有 7（10.6%）例患者死亡，安慰剂组有 17（24.3%）例患者死亡（p=0.044）。与安慰剂组相比，卡维地洛组发生急性肾损伤（AKI）的患者更少（13.6%vs35.7%，p=0.003）和自发性细菌性腹膜炎（SBP）（6.1%vs21.4%，p=0.013）。显著的是，安慰剂组有更多的患者出现 APASL ACLF Research Consortium-ACLF 分级增加（22.9%vs6.1%，p=0.007）。两组间 90 天无移植生存率以及 AKI、SBP、非 SBP 感染（包括肺炎）和 90 天内静脉曲张出血的发生无显著差异。
在 presentation 时无或小食管静脉曲张且 HVPG≥12mmHg 的 ACLF 患者中，卡维地洛可提高生存率，并减少 AKI 和 SBP 事件，持续至 28 天。临床试验。
CLINICALTRIALS.GOV 标识符号：NCT02583698。
