Services des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Lille, Lille, France.
Department of Biostatistics, Centre Hospitalier Universitaire de Lille, Lille, France.
Lancet Gastroenterol Hepatol. 2022 May;7(5):416-425. doi: 10.1016/S2468-1253(21)00430-1. Epub 2022 Feb 23.
Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence.
We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794.
Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]).
We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis.
The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.
早期肝移植治疗严重酒精性肝炎是一种新兴的治疗选择。我们旨在评估与酒精相关肝硬化患者至少戒酒 6 个月后进行肝移植相比，严重酒精性肝炎患者在早期肝移植后 2 年内酒精复发的风险。
我们在法国和比利时的 19 家医院进行了一项多中心、非随机、非劣效性、对照研究。所有参与者年龄均在 18 岁或以上。前瞻性招募了三组患者：未对药物治疗有反应且根据新的基于社会和成瘾项目的选择评分系统符合早期肝移植标准的严重酒精性肝炎患者（早期移植组）；至少戒酒 6 个月后等待肝移植的酒精性肝硬化患者（标准移植组）；未对药物治疗无反应且不符合选择评分的早期肝移植标准的严重酒精性肝炎患者（无资格进行早期移植组），该组未进入任何进一步的肝移植过程。我们还定义了一组严重酒精性肝炎患者的历史对照组，这些患者对药物治疗无反应且未进行移植。主要结局是使用酒精时间线回溯（TLFB）方法，通过预先指定的非劣效性边界 10%，比较早期移植组和标准移植组在移植后 2 年内的酒精复发率。次要结局是早期移植组的酒精复发模式、2 年移植后生存率，以及早期移植组与无资格进行早期移植组和历史对照组患者的 2 年总生存率。这项试验在 ClinicalTrials.gov 注册，NCT01756794。
2012 年 12 月 5 日至 2016 年 6 月 30 日期间，我们纳入了 149 例严重酒精性肝炎患者：102 例在早期移植组，47 例在无资格进行早期移植组。129 例患者纳入标准移植组。早期移植组 68 例和标准移植组 93 例患者接受了肝移植。早期移植组 23 例（34%）患者复发，标准移植组 23 例（25%）患者复发；因此，早期移植与标准移植的非劣效性未得到证明（绝对差异 9.1%[95%CI-∞至 21.1%]；p=0.45）。早期移植组的高酒精摄入率高于标准移植组（绝对差异 16.7%[95%CI5.8-27.6%]）。两组的饮酒时间无差异（标准化差异 0.24[95%CI0.07-0.55]），但早期移植组大量饮酒的时间高于标准移植组（标准化差异 0.50[95%CI0.17-0.82]）。早期移植组和标准移植组的 2 年移植后生存率相似（风险比[HR]0.87[95%CI0.33-2.26]）；早期移植组的 2 年总生存率高于无资格进行早期移植组和历史对照组（HR0.27[95%CI0.16-0.47]和 0.21[0.13-0.32]）。
我们不能得出早期肝移植和标准肝移植在移植后酒精复发率方面的非劣效性结论。早期肝移植后高酒精摄入更为频繁。这项前瞻性对照研究证实了早期肝移植治疗严重酒精性肝炎的重要生存获益；并且该研究为严重酒精性肝炎患者的管理提供了有关生存和酒精复发的客观数据。
本研究得到了法国卫生部 2010 年临床研究计划的资助。
