Artificial liver support in pigs with acetaminophen-induced acute liver failure

Abstract

AIMTo establish a reversible porcine model of acute liver failure (ALF) and treat it with an artificial liver system.METHODSSixteen pigs weighing 30-35 kg were chosen and administered with acetaminophen (APAP) to induce ALF. ALF pigs were then randomly assigned to either an experimental group (n = 11), in which a treatment procedure was performed, or a control group (n = 5). Treatment was started 20 h after APAP administration and continued for 8 h. Clinical manifestations of all animals, including liver and kidney functions, serum biochemical parameters and survival times were analyzed.RESULTSTwenty hours after APAP administration, the levels of serum aspartate aminotransferase, total bilirubin, creatinine and ammonia were significantly increased, while albumin levels were decreased (P < 0.05). Prothrombin time was found to be extended with progression of ALF. After continuous treatment for 8 h (at 28 h), aspartate aminotransferase, total bilirubin, creatinine, and ammonia showed a decrease in comparison with the control group (P < 0.05). A cross-section of livers revealed signs of vacuolar degeneration, nuclear fragmentation and dissolution. Concerning survival, porcine models in the treatment group survived for longer times with artificial liver system treatment (P < 0.05).CONCLUSIONThis model is reproducible and allows for quantitative evaluation of new liver systems, such as a bioartificial liver. The artificial liver system (ZHJ-3) is safe and effective for the APAP-induced porcine ALF model.

Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure

“…Current literature reports of drugs that can induce ALF include those on D-gal, acetaminophen (APAP), and carbon tetrachloride, to name a few[ 12 - 14 ]. Yu et al[ 22 ] reported on the pharmacokinetics, drug metabolism, and hepatic toxicity of APAP in cynomolgus monkeys and found significant tolerance to APAP; therefore, APAP is not suitable to create a cynomolgus monkey model to study related hepatic injury.…”

“…There are current literature reports of many drugs that have been used to induce animal models of ALF[ 5 , 12 - 14 ]. D-galactosamine (D-gal) is a disruptor of uridine triphosphate of hepatocytes, causing diffuse hepatic necrosis and an inflammatory response, similar to the pathological changes of clinical viral hepatitis[ 15 , 16 ].…”

State of the art—Artificial liver in China

“…Yi Gao’s team established a BAL system consisting of a perfusion bioreactor and CL‐1 human hepatocytes line to treat D‐galactosamine (D‐GALN)‐induced ALF monkeys and acetaminophen (APAP)‐induced ALF animal models . The results supported a positive effect on prolonging survival time of ALF pigs.…”

Dynamic contrast enhanced MRI with clinical hepatospecific MRI contrast agents in pigs: initial experience

“…Pigs are a valuable translational biomedical tool, particularly for modeling human liver disease. Robust porcine models of cirrhosis [1][2][3][4] , non-alcoholic steatohepatitis 5,6 , hepatocellular carcinoma 7,8 , diabetes [9][10][11] , hereditary tyrosinemia type 1 [12][13][14][15] and acute liver failure 16,17 have all been reported and mimic many clinical manifestations of the human disease. Biomedical imaging can be used in conjunction with these porcine models in many ways.…”