Department of Internal Medicine, Postgraduate Institute of Medical Education and Research Chandigarh, Chandigarh, India.
Department of Hepatology, Postgraduate Institute of Medical Education and Research Chandigarh, Chandigarh, India.
Hepatol Int. 2022 Apr;16(2):433-446. doi: 10.1007/s12072-022-10312-z. Epub 2022 Mar 28.
Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF.
Thirty-three patients [13 in the FMT arm; 20 in the standard of care arm (SOC)] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days 7, 28, and 90.
Survival at 28 and 90 days was significantly better in the FMT arm (100% versus 60%, p = 0.01; 53.84% versus 25%, p = 0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, p = 0.11) patients, while ascites resolved in 100% versus 40% survivors (p = 0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (p = 0.77; p = 0.70). Median IL1beta decreased by 21.39% (IQR - 73.67 to 7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR - 0.88 to 128.11) (p = 0.01). Percentage changes in bilirubin and ALT between baseline and day 7 emerged as predictors of 90-day mortality.
FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF.
NCT03827772 available from http://clinicaltrials.gov/ct2/show/NCT03827772 CTRI Reference number: CTRI/2019/02/017538 dated 7 February 2019.
以急性肝衰竭（ALF）为表现的重症酒精性肝炎（SAH）具有很高的短期死亡率。肠道微生物群的改变是其发病机制中的一个关键组成部分，其调节被认为是一种潜在的治疗手段。我们评估了粪便微生物群移植（FMT）的安全性及其在改善 SAH-ACLF 患者短期生存率和临床严重程度评分方面的疗效。
这项开放标签研究纳入了 33 名 SAH-ACLF 患者[FMT 组 13 名；标准治疗组（SOC）20 名]。通过鼻空肠管给予单次 FMT 治疗，即由预先确定的健康家庭成员粪便供体制备的新鲜粪便混悬液。患者在第 7、28 和 90 天进行随访。
FMT 组 28 天和 90 天的生存率明显更高（100%比 60%，p=0.01；53.84%比 25%，p=0.02）。100%的患者肝性脑病得到缓解（FMT 组比 SOC 组，p=0.11），而腹水缓解的患者为 100%（FMT 组比 SOC 组，p=0.04）。两组自发性细菌性腹膜炎和胃肠道出血等主要不良事件发生率相似（p=0.77；p=0.70）。FMT 组白细胞介素 1β中位数下降 21.39%（IQR-73.67 至 7.63），而 SOC 组增加 27.44%（IQR-0.88 至 128.11）（p=0.01）。基线至第 7 天胆红素和 ALT 的百分比变化是 90 天死亡率的预测因素。
FMT 安全，可提高 SAH-ACLF 患者的短期和中期生存率，并改善临床严重程度评分。
可从 http://clinicaltrials.gov/ct2/show/NCT03827772 获得，临床研究登记号：CTRI/2019/02/017538，日期为 2019 年 2 月 7 日。
