Inevitability of disease recurrence after liver transplantation for NAFLD cirrhosis

非酒精性脂肪肝肝硬化肝移植术后疾病复发的必然性

Abstract

摘要

Background & aims: Liver transplantation (LT) is the only available treatment for end-stage non-alcoholic fatty liver disease (NAFLD) (related decompensated cirrhosis and/or hepatocellular carcinoma). The aim of our study was to evaluate the risk of disease recurrence after LT and the factors influencing it.

背景和目标：肝移植（LT）是终末期非酒精性脂肪性肝病（NAFLD）（相关失代偿性肝硬化和/或肝细胞癌）的唯一可用治疗方法。本研究的目的是评估LT后疾病复发的风险及其影响因素。

Method: This retrospective multicenter study included adults transplanted for NAFLD cirrhosis between 2000 and 2019 in 20 participating French-speaking centers. Disease recurrence (steatosis, steatohepatitis and fibrosis) was diagnosed from liver graft biopsies.

方法：这项回顾性多中心研究纳入了2000年至2019年在20个法语中心接受NAFLD肝硬化移植的成人患者。通过移植肝活检诊断疾病复发（脂肪变性、脂肪性肝炎和纤维化）。

Results: We analyzed 150 patients with at least one graft liver biopsy available ≥6 months after transplantation, among 361 patients transplanted for NAFLD. The median (IQR) age at LT was 61.3 (54.4-64.6) years. The median follow-up after LT was 4.7 (2.8-8.1) years. The cumulative recurrence rates of steatosis and steatohepatitis at 5 years were 80.0% and 60.3%, respectively. Significant risk factors for steatohepatitis recurrence in multivariate analysis were recipient age at LT <65 years (odds ratio [OR] 4.214; p = 0.044), high-density lipoprotein-cholesterol <1.15 mmol/L after LT (OR 3.463; p = 0.013) and grade ≥2 steatosis on the graft at 1 year after LT (OR 10.196; p = 0.001). The cumulative incidence of advanced fibrosis (F3-F4) was 20.0% at 5 years after LT and significant risk factors from multivariate analysis were metabolic syndrome before LT (OR 8.550; p = 0.038), long-term use of cyclosporine (OR 11.388; p = 0.031) and grade ≥2 steatosis at 1 year after LT (OR 10.720; p = 0.049). No re-LT was performed for NAFLD cirrhosis recurrence.

结果：在361例因NAFLD接受移植的患者中，我们分析了150例在移植后≥6个月至少有一次移植肝活检的患者。LT时的中位（IQR）年龄为61.3（54.4-64.6）岁。LT后的中位随访时间为4.7（2.8-8.1）年。5年时脂肪变性和脂肪性肝炎的累积复发率分别为80.0%和60.3%。多变量分析中脂肪性肝炎复发的重要危险因素是LT时受者年龄〈65岁（比值比[OR] 4.214;p = 0.044），肝移植后高密度脂蛋白胆固醇〈1.15mmol/L（OR值3.463;p = 0.013）和LT后1年移植物上≥2级脂肪变性（OR 10.196;p = 0.001）。晚期肝纤维化（F3-F4）在肝移植后5年的累积发生率为20.0%，多变量分析的显著危险因素为肝移植前代谢综合征（OR 8.550;p = 0.038），长期使用环孢素（OR 11.388;p = 0.031）和LT后1年≥2级脂肪变性（OR 10.720;p = 0.049）。未对NAFLD肝硬化复发进行再次LT。

Conclusion: Our results strongly suggest that recurrence of initial disease after LT for NAFLD is inevitable and progressive in a large proportion of patients; the means to prevent it remain to be further evaluated.

结论：我们的研究结果强烈表明，在大部分患者中，LT治疗NAFLD后初始疾病的复发是不可避免的和进行性的;防止这种情况的手段有待进一步评估。

Impact and implications: Non-alcoholic fatty liver disease (NAFLD) is a growing indication for liver transplantation, but the analysis of disease recurrence, based on graft liver biopsies, has been poorly studied. Cumulative incidences of steatosis, steatohepatitis and NAFLD-related significant fibrosis recurrence at 5 years were 85.0%, 60.3% and 48.0%, respectively. Grade ≥2 steatosis on graft biopsy at 1 year (present in 25% of patients) is highly predictive of recurrence of steatohepatitis and advanced fibrosis: bariatric surgery should be discussed in these patients specifically.

影响和含义：非酒精性脂肪性肝病（NAFLD）是肝移植的一个日益增长的适应症，基于移植肝活检判断疾病复发的分析研究很少。5年时脂肪变性、脂肪性肝炎和NAFLD相关显著纤维化复发的累积发生率分别为85.0%、60.3%和48.0%。1年时移植物活检时≥2级脂肪变性（25%的患者存在）高度预测脂肪性肝炎和晚期纤维化复发：应特别讨论这些患者的减肥手术。

Keywords: ABM, Agence de la Biomédecine; BS, bariatric surgery; Bariatric surgery; CNI, calcineurin inhibitor; CST, corticosteroid; CV, cardiovascular; CYA, cyclosporine; ESLD, end-stage liver disease; HCC, hepatocellular carcinoma; LT, liver transplantation; MS, metabolic syndrome; NAFLD recurrence; NAFLD, non-alcoholic fatty liver disease; NASH; NASH, non-alcoholic steatohepatitis; liver transplantation; mTOR-i, mTOR inhibitor; metabolic syndrome.

关键词：ABM;生物医学机构;BS，减肥手术;减肥手术;CNI，钙调磷酸酶抑制剂;CST，皮质类固醇;CV，心血管;CYA，环孢菌素;ESLD，终末期肝病;HCC，肝细胞癌;LT，肝移植;MS，代谢综合征;NAFLD复发;NAFLD，非酒精性脂肪性肝病;NASH，非酒精性脂肪性肝炎;肝移植;mTOR-i，mTOR抑制剂;代谢综合症。