基于猪肝细胞的肝脏支持系统的临床经验。

Clinical experience with a porcine hepatocyte-based liver support system.

作者信息

Chen S C, Hewitt W R, Watanabe F D, Eguchi S, Kahaku E, Middleton Y, Rozga J, Demetriou A A

机构信息

Department of Surgery, Cedars-Sinai Medical Center, UCLA School of Medicine, USA.

出版信息

Int J Artif Organs. 1996 Nov;19(11):664-9.

PMID:8970834

Abstract

UNLABELLED

The only clinically proven effective treatment of fulminant hepatic failure (FHF) is orthotopic liver transplant (OLT). However, many patients die before an organ becomes available. Thus, there is a need for development of an extracorporeal liver support system to "bridge" these patients either to OLT or spontaneous recovery. We developed a bioartificial liver (BAL) based on plasma perfusion through a circuit of a hollow-fiber cartridge seeded with matrix-anchored porcine hepatocytes to treat patients with severe acute liver failure. Two groups of patients were studied. Group 1 (n = 12): patients with FHF. All patients were successfully "bridged" to OLT. "Bridge" time to OLT was 21-96 hr (mean: 39.3 hr). All patients were discharged neurologically intact. Reversal of decerebration was noted in all 11 deep stage 4 coma patients. There was reduction in intracranial pressure (ICP mmHg, 18.2 +/- 2.2 to 8.5 +/- 1.2; p < 0.004) and increase in cerebral perfusion pressure (CPP mmHg, 71.1 +/- 4.0 to 84.7 +/- 2.6; p < 0.006). Laboratory values pre- and post-BAL treatment: glucose (mg/dl) 122 +/- 11 to 183 +/- 21, p < 0.002; ammonia (mumol/l) 155.6 +/- 13.2 to 121.6 +/- 9.5, p < 0.02; total bilirubin (mg/dl) 21.6 +/- 2.8 to 18.2 +/- 2.2, p < 0.001; PT (sec) 23.2 +/- 1.7 to 21.9 +/- 1.0, p < 0.3. Group II (n = 8): patients with chronic liver failure experiencing acute exacerbation. Two patients survived and later underwent OLT. Six patients (not OLT candidates) died 1-14 days after last BAL treatment. Laboratory values pre- and post-treatment: ammonia (mumol/l) 201 +/- 47 to 143 +/- 25, p < 0.06; total bilirubin (mg/dl) 22.8 +/- 5.2 to 19.5 +/- 4.4, p < 0.01; PT (sec) 22.5 +/- 2.0 to 21.8 +/- 1.1, p < 0.6.

CONCLUSION

our clinical experience with the BAL suggests that it may serve as "bridge" to OLT in patients with FHF primarily by reversing intracranial hypertension, but it is not a substitute for OLT in patients with end-stage liver disease who are non-transplant candidates.

摘要

未标记

暴发性肝衰竭（FHF）唯一经临床证实有效的治疗方法是原位肝移植（OLT）。然而，许多患者在获得可用器官之前就死亡了。因此，需要开发一种体外肝支持系统，将这些患者“过渡”到OLT或实现自发恢复。我们开发了一种基于血浆通过接种了基质固定猪肝细胞的中空纤维盒回路进行灌注的生物人工肝（BAL），用于治疗严重急性肝衰竭患者。研究了两组患者。第1组（n = 12）：FHF患者。所有患者均成功“过渡”到OLT。到OLT的“过渡”时间为21 - 96小时（平均：39.3小时）。所有患者出院时神经功能完好。所有11名深度4期昏迷患者的去大脑强直均得到逆转。颅内压（ICP mmHg，从18.2±2.2降至8.5±1.2；p < 0.004）降低，脑灌注压（CPP mmHg，从71.1±4.0升至84.7±2.6；p < 0.006）升高。BAL治疗前后的实验室值：葡萄糖（mg/dl）从122±11升至183±21，p < 0.002；氨（μmol/l）从155.6±13.2降至121.6±9.5，p < 0.02；总胆红素（mg/dl）从21.6±2.8降至18.2±2.2，p < 0.001；凝血酶原时间（PT，秒）从23.2±1.7降至21.9±1.0，p < 0.3。第II组（n = 8）：慢性肝衰竭急性加重患者。2名患者存活，后来接受了OLT。6名患者（非OLT候选者）在最后一次BAL治疗后1 - 14天死亡。治疗前后的实验室值：氨（μmol/l）从201±47降至143±25，p < 0.06；总胆红素（mg/dl）从22.8±5.2降至19.5±4.4，p < 0.01；凝血酶原时间（PT，秒）从22.5±2.0降至21.8±1.1，p < 0.6。