Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, VasantKunj, New Delhi, 110070, India.
Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India.
Hepatol Int. 2020 Jul;14(4):577-586. doi: 10.1007/s12072-020-10013-5. Epub 2020 Feb 11.
Ischemic hepatitis (IH) following acute variceal bleed (AVB) carries an ominous prognosis. N-Acetylcysteine (NAC), a potent anti-oxidant, may prevent IH by improving tissue oxygen delivery and improving hepatic hypoxia.
Consecutive cirrhotics with AVB were prospectively randomized to receive either standard of care (SOC) plus NAC intravenously for 72 h(at 150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h, followed by 6.25 mg/kg for 67 h) (Group A, n = 107) or SOC alone (Group B, n = 107).
Baseline characteristics were comparable. IH developed more frequently in Gr.B 25(23%) than A-15(14%); p = 0.08). Incidence of IH increased with severity of liver disease. Binary logistic regression analysis showed reduced incidence of IH in Gr.A than B [odds ratio (OR) 0.33, 0.11-0.93] patients after controlling for other significant factors. The incidence of acute kidney injury (AKI) was also reduced in Gr.A [OR 0.34, 0.15-0.75]. Development of IH was significantly associated with increased deaths due to liver failure at 6 weeks [subdistribution hazard ratio (SHR) 21.6, 7.4-62.8]. On multivariate competing risk analysis, significantly lower deaths due to liver failure (SHR 0.33, 0.11-0.97) were noted in Gr.A than B.
One in five patients with acute variceal bleed develops ischemic hepatitis which is associated with worse outcomes. NAC therapy averts deaths due to liver failure by preventing IH and reduces AKI and is, therefore, recommended for cirrhotics with acute variceal bleed.
Clinicaltrials.gov no: NCT02015403.
急性静脉曲张出血（AVB）后发生的缺血性肝炎（IH）预后不良。N-乙酰半胱氨酸（NAC）是一种有效的抗氧化剂，通过改善组织氧输送和改善肝缺氧，可能预防 IH。
连续前瞻性随机分配肝硬化伴 AVB 的患者接受标准治疗（SOC）加静脉内 NAC 治疗 72 小时（150mg/kg/h 持续 1 小时，随后 12.5mg/kg/h 持续 4 小时，随后 62.5mg/kg 持续 67 小时）（A 组，n=107）或单独 SOC（B 组，n=107）。
基线特征无差异。B 组 IH 发生率为 25（23%）高于 A 组的 15（14%）；p=0.08）。IH 的发生率随着肝病的严重程度增加而增加。二元逻辑回归分析显示，在控制其他重要因素后，A 组 IH 的发生率低于 B 组[比值比（OR）0.33，0.11-0.93]。A 组急性肾损伤（AKI）的发生率也降低[OR 0.34，0.15-0.75]。IH 的发生与 6 周时因肝功能衰竭导致的死亡增加显著相关[亚分布风险比（SHR）21.6，7.4-62.8]。多变量竞争风险分析显示，A 组因肝功能衰竭导致的死亡明显较低[SHR 0.33，0.11-0.97]。
急性静脉曲张出血患者中有五分之一发生缺血性肝炎，其预后更差。NAC 治疗通过预防 IH 降低肝功能衰竭相关死亡，减少 AKI，因此建议急性静脉曲张出血的肝硬化患者使用。
Clinicaltrials.gov 编号：NCT02015403。
