Functional Evaluation of a Bioartificial Liver Support System Using Immobilized Hepatocyte Spheroids in a Porcine Model of Acute Liver Failure

Abstract

Bioartificial livers (BAL) may offer acute liver failure (ALF) patients an opportunity for cure without liver transplantation. We evaluated the efficacy of a spheroid-based BAL system, containing aggregates of porcine hepatocytes, in a porcine model of ALF. ALF pigs were divided into three groups. The control group consisted of treatment naïve pigs (n = 5), blank group consisted of pigs that were attached to the BAL system not containing hepatocytes for 12 hours (n = 5) and BAL group consisted of pigs that were attached to the BAL containing hepatocytes for 12 hours (n = 5). Increase in serum ammonia levels were significantly greater in the blank group (P < 0.01) and control group (P < 0.01), compared to the BAL group during the treatment period. Increase in ICP was significantly greater in the control group compared to the BAL group (P = 0.01). Survival was significantly prolonged in the BAL group compared to the blank group (P = 0.03). A BAL system with a bioreactor containing hepatocyte spheroids showed effective clearance of serum ammonia, preservation of renal function and delayed ICP increase in a porcine model of ALF.

Hollow fibre membrane bioreactor functionalized with GO‐cryogel 3D matrix promotes liver cell anchoring and their functional maintenance

“…Most of the BAL support systems consist of HFM cartridge packed with functional hepatocytes. However, in the recent in vitro study, it was found that hepatocyte spheroids exhibited higher liver‐specific metabolic activities than the monolayer hepatocytes (Lee et al, 2017).…”

Bioartificial liver support systems for acute liver failure: A systematic review and meta-analysis of the clinical and preclinical literature

“…Of 12 studies that performed preclinical experiments with pigs (8 studies, 160 animals), monkeys (2 studies, 45 animals), and canines (2 studies, 40 animals), the proportions of male and female animals were 45.3% (111/245) and 30.2% (74/245), respectively. Inducers included D-galactosamine in 7 studies (145 animals)[5,12,29-33], surgical operation in 3 studies (53 animals)[11,34,35], 85% hepatectomy in 1 study (18 animals)[36], and α-amanitin and lipopolysaccharide in 1 study (30 animals)[10] (Table 3).…”

HEV‐LFS: A novel scoring model for patients with hepatitis E virus‐related liver failure

“…In addition, there is no specific and effective treatment for liver failure. It primarily involves comprehensive treatment, including basic medical treatment, artificial liver support treatment and liver transplantation treatment . An important goal of clinical treatment for patients with liver failure is to select targeted prevention and treatment methods according to the causes, pathogenesis and clinical manifestations of various complications .…”