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Randomized Trial of Spheroid Reservoir Bioartificial Liver in Porcine Model of Posthepatectomy Liver Failure

 Harvey S. Chen  ;  Dong Jin Joo  ;  Mohammed Shaheen  ;  Yi Li  ;  Yujia Wang  ;  Jian Yang  ;  Clara T. Nicolas  ;  Kelly Predmore  ;  Bruce Amiot  ;  Gregory Michalak  ;  Taofic Mounajjed  ;  Jeff Fidler  ;  Walter K. Kremers  ;  Scott L. Nyberg 
 HEPATOLOGY, Vol.69(1) : 329-342, 2019 
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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). Conclusion: 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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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Joo, Dong Jin(주동진) ORCID logo https://orcid.org/0000-0001-8405-1531
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