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应用分子吸附再循环系统治疗肝衰竭的体外解毒:长期随访中的清除效率和临床结果。

Extracorporeal detoxification for hepatic failure using molecular adsorbent recirculating system: depurative efficiency and clinical results in a long-term follow-up.

机构信息

Department of Nephrology, Dialysis and Renal Transplantation Unit, S. Orsola Hospital, University of Bologna, Bologna, Italy.

出版信息

Artif Organs. 2014 Feb;38(2):125-34. doi: 10.1111/aor.12106. Epub 2013 Jul 3.

Abstract

Acute liver failure and acute-on-chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty-four patients with life-threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23-82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32-62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36-54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1-year follow-up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17-29); direct bilirubin RRs was 28% (21-35), and indirect bilirubin RRs was 8% (3-21). Ammonia RRs was 34% (12-86). Conjugated cholic acid RRs was 58% (48-61); chenodeoxycholic acid RRs was 34% (18-48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9-7.9) versus 7.9 ng/mL (3.2-14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End-stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan-Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In conclusion, MARS was clinically well tolerated by all patients and significantly reduced hepatic toxins. Better survival rates were linked to an OLT program, but patients' clinical characteristics on starting MARS therapy were the main factors predicting survival. The role of HGF should be evaluated in larger clinical trials.

摘要

急性肝衰竭和慢加急性肝衰竭仍然预后不良。分子吸附再循环系统(MARS)已被广泛用作这些疾病患者最有前途的解毒治疗方法。选择了 64 名生命垂危的肝衰竭患者,进行了 269 次 MARS 治疗,作为原位肝移植(OLT)或肝功能恢复的桥梁。所有患者均根据 MARS 治疗的目的进行分组。A 组包括 47 名接受肝功能恢复治疗的患者(中位年龄 59 岁,范围 23-82 岁)。B 组包括 11 名在等待名单上接受 OLT 的患者(中位年龄 47 岁,范围 32-62 岁)。C 组包括 6 名未接受 OLT 的等待名单上的患者(中位年龄 45.5 岁,范围 36-54 岁,P=0.001)。在 1 年的随访期间,评估了 MARS 在清除肝毒素、细胞因子和生长因子方面的清除效率,并评估了患者的临床结果。每次 MARS 治疗的总胆红素降低率(RRs)为 23%(范围 17-29);直接胆红素 RRs 为 28%(21-35),间接胆红素 RRs 为 8%(3-21)。氨 RRs 为 34%(12-86)。结合胆酸 RRs 为 58%(48-61);鹅脱氧胆酸 RRs 为 34%(18-48)。各组之间无差异。MARS 开始时肝细胞生长因子(HGF)值为 4.1ng/ml(1.9-7.9),而 MARS 结束时为 7.9ng/ml(3.2-14.1)(P<0.01)。为确定预测患者结局的危险因素,进行了 Cox 回归分析,结果显示年龄、性别和序贯器官衰竭评估评分(而非终末期肝病模型评分)是预测死亡的因素,而 MARS 治疗次数和 ΔHGF 是保护性因素。Kaplan-Meier 生存分析也被使用;12 个月后,A 组 21.3%的患者存活,B 组 90.9%的患者存活,C 组 16.7%的患者存活(对数秩=0.002)。总之,所有患者均耐受良好,MARS 显著降低了肝毒素。更好的生存率与 OLT 方案有关,但患者在开始 MARS 治疗时的临床特征是预测生存率的主要因素。HGF 的作用应在更大的临床试验中进行评估。

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