Department of Internal Medicine, Division of Gastroenterology and Hepatology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Department of Gastroenterology, International University of Health and Welfare, School of Medicine, 4Narita City, Chiba, Japan.
Hepatol Commun. 2024 Jan 29;8(2). doi: 10.1097/HC9.0000000000000371. eCollection 2024 Feb 1.
Patients with severe alcohol-associated hepatitis (SAH) have a high short-term mortality rate. Unmet needs exist in patients who are refractory to corticosteroids (CS) or are ineligible for early liver transplantation.
This was a prospective, open-label, nonrandomized pilot study conducted at a liver transplant center in Tokyo, Japan, starting in October 2015. Lille model and Model for End-stage Liver Disease (MELD) score-defined CS nonresponsive or CS-intolerant patients with SAH who fulfilled the inclusion criteria (leukocytosis over 10,000/μL, etc.) were considered for enrollment. The median duration from admission to enrollment was 23 days (IQR, 14-31 days), after standard of care. Granulocyte-monocyte/macrophage apheresis (GMA) performed with Adacolumn twice per week, up to 10 times per treatment course, was evaluated.
13 GMA treatments were conducted through December 2021. Maddrey Discriminant Function was 53.217.7 at admission. The overall survival rate was 90.9% at 90 and 180 days. MELD scores significantly improved, from median (IQRs) of 23 (20-25) to 15 (13-21) after GMA (p<0.0001). Estimated mortality risks using the Lille model and MELD scores significantly improved from 20.9%±16.5% to 7.4%±7.3% at 2 months and from 30.4%±21.3% to 11.6%±10.8% at 6 months, respectively (both p<0.01), and were internally validated. The cumulative rate of alcohol relapse was 35.9% per year. No severe adverse events were observed. In exploratory analysis, granulocyte colony-stimulating factor levels were significantly correlated with prognostic systems such as MELD-Sodium scores after GMA (correlation coefficient= -0.9943, p<0.0001) but not before GMA (p=0.62).
Compared to published studies, GMA is associated with a lower-than-expected 90- and 180-day mortality in patients with CS-nonresponsive or CS-intolerant SAH. GMA may meet the needs as a salvage anti-inflammatory therapy for SAH. (Trial registration: UMIN000019351 and jRCTs No.032180221) (274 words).
患有严重酒精性肝炎（SAH）的患者短期死亡率较高。对于皮质类固醇（CS）耐药或不适合早期肝移植的患者，存在未满足的需求。
这是一项在日本东京的肝移植中心进行的前瞻性、开放标签、非随机试点研究，始于 2015 年 10 月。符合纳入标准（白细胞计数超过 10,000/μL 等）的 CS 无反应或 CS 不耐受的 SAH 患者，根据 Lille 模型和终末期肝病模型（MELD）评分定义为 CS 无反应或 CS 不耐受，被考虑入组。中位入院至入组时间为 23 天（IQR，14-31 天），为标准治疗后。每周两次进行粒细胞-单核细胞/巨噬细胞吸附（GMA）治疗，每个疗程最多进行 10 次，评估 Adacolumn 的疗效。
2021 年 12 月前共进行了 13 次 GMA 治疗。入院时 Maddrey 判别函数为 53.217.7。90 天和 180 天的总生存率分别为 90.9%。MELD 评分显著改善，从 GMA 前的中位数（IQR）23（20-25）降至 15（13-21）（p<0.0001）。Lille 模型和 MELD 评分估计的死亡率风险在 2 个月时从 20.9%±16.5%显著改善至 7.4%±7.3%，在 6 个月时从 30.4%±21.3%改善至 11.6%±10.8%（均 p<0.01），且内部验证结果一致。酒精复发的累积率为每年 35.9%。未观察到严重不良事件。探索性分析显示，GMA 后粒细胞集落刺激因子水平与 MELD-Sodium 评分等预后系统显著相关（相关系数=-0.9943，p<0.0001），但在 GMA 前不相关（p=0.62）。
与已发表的研究相比，GMA 治疗 CS 无反应或 CS 不耐受的 SAH 患者的 90 天和 180 天死亡率较低。GMA 可能满足作为 SAH 挽救性抗炎治疗的需求。（试验注册：UMIN000019351 和 jRCTs No.032180221）（274 个单词）。
