Randomized Trial of Spheroid Reservoir Bioartificial Liver in Porcine Model of Posthepatectomy Liver Failure.
Randomized Trial of Spheroid Reservoir Bioartificial Liver in Porcine Model of Posthepatectomy Liver Failure.
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DOI：
10.1002/hep.30184
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Nyberg SL
中科院分区：
文献类型：
--
作者：
Chen HS;Joo DJ;Shaheen M;Li Y;Wang Y;Yang J;Nicolas CT;Predmore K;Amiot B;Michalak G;Mounajjed T;Fidler J;Kremers WK;Nyberg SL
急性肝衰竭（ALF）是肝脏大切除后可能发生的灾难性疾病。本研究的目的是确定球形储层生物人工肝（SRBAL）对肝切除后ALF猪的生存、血清化学和肝脏再生的影响。野生型大白猪（20公斤-30公斤）行颅内压（ICP）探头置入，并行85%肝切除术。采用计算机断层扫描（CT）测量体积来测量切除的程度，并在肝切除术后48小时评估残肝的再生。根据肝切除术后24-48小时的治疗情况，将动物随机分为三组：第一组：标准药物治疗（SMT, n = 6）；第2组- smt +不使用肝细胞的生物人工肝治疗（0 g, n = 6）；组3 - smt加SRBAL治疗，使用200 g原代猪肝细胞球体（200 g, n = 6）。主要终点是肝切除术后存活至90小时。等效死亡定义为无反应性4级肝性脑病或ICP大于20mmhg，临床证据为脑疝。两组（SMT和0 g）对照组的所有动物在肝切除术后51小时内均达到等效死亡。200 g组6只动物中有5只存活至90 h （P < 0.01）。在200 g组中，平均氨、ICP和国际标准化比值值显著降低。CT体积测量显示，与SMT组和0-g组相比，200-g组肝切除术后48小时的体积再生增加（P < 0.01）。Ki-67染色显示肝切除术后48 h阳性染色增加（P < 0.01）。SRBAL改善了肝切除后ALF患者的生存，减少了氨，并加速了肝脏再生。生存率的提高与SRBAL治疗的神经保护益处相关。这些有利的结果为SRBAL的进一步临床试验提供了依据。
Acute liver failure (ALF) is a catastrophic condition that can occur after major liver resection. The aim of this study was to determine the effects of the spheroid reservoir bio-artificial liver (SRBAL) on survival, serum chemistry, and liver regeneration in posthepatectomy ALF pigs. Wild-type large white swine (20 kg-30 kg) underwent intracranial pressure (ICP) probe placement followed by 85% hepatectomy. Computed tomography (CT) volumetrics were performed to measure the extent of resection, and at 48 hours following hepatectomy to assess regeneration of the remnant liver. Animals were randomized into three groups based on treatment delivered 24–48 hours after hepatectomy: Group1—standard medical therapy (SMT, n = 6); Group2—SMT plus bio-artificial liver treatment using no hepatocytes (0 g, n = 6); and Group3—SMT plus SRBAL treatment using 200 g of primary porcine hepatocyte spheroids (200 g, n = 6). The primary endpoint was survival to 90 hours following hepatectomy. Death equivalent was defined as unresponsive grade 4 hepatic encephalopathy or ICP greater than 20 mmHg with clinical evidence of brain herniation. All animals in both (SMT and 0 g) control groups met the death equivalent before 51 hours following hepatectomy. Five of 6 animals in the 200-g group survived to 90 hours (P < 0.01). The mean ammonia, ICP, and international normalized ratio values were significantly lower in the 200-g group. CT volumetrics demonstrated increased volume regeneration at 48 hours following hepatectomy in the 200-g group compared with the SMT (P < 0.01) and 0-g (P < 0.01) groups. Ki-67 staining showed increased positive staining at 48 hours following hepatectomy (P < 0.01). The SRBAL improved survival, reduced ammonia, and accelerated liver regeneration in posthepatectomy ALF. Improved survival was associated with a neuroprotective benefit of SRBAL therapy. These favorable results warrant further clinical testing of the SRBAL.
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