Efficacy Of A Newly Established Artificial Liver System In Treating Pigs With Acute Liver Failure

Aims:We developed a novel blood purification system, named Li’s artificial liver system (Li-ALS), which couples low-volume plasma exchange (low-volume PE) with plasma filtration adsorption (PFA). This study aims to evaluate the efficacy of our novel system in pigs with acute liver failure (ALF).Methods:Forty male Bama experimental miniature pigs weighing18-23kg were used for the experiment. ALF was induced with D-galactosamine thorough the external jugular venous catheter without anaesthesia. At36hours after D-galactosamine infusion,All animals were selected randomly according to sealed and pre-numbered envelopes and divided into five groups. Group I, the ALF control group (n=8), pigs only received intensive care and continuous anesthesia to establish the basic parameters of the ALF model, No further drug or treatment was administered. Group II, the PFA group (n=8), pigs underwent one-hour of extracorporeal blood circulation followed by five-hour of plasma recycling filtration and adsorption purification. Group III, the low-volume PE group (n=8), pigs received low-volume (approximately0.5L) plasma exchange for1h then followed by five-hour of extracorporeal blood circulation. Group IV, the Li-ALS group (n=8), included pigs that underwent low-volume PE for1h, followed by PFA for5h. Group V, the totally plasma exchange group (n=8), standard volume for plasma exchange was performed, and the pigs underwent plasma exchange for2h and followed by four-hour of extracorporeal blood circulation. The efficacy of each treatment was assessed by survival time and improvement in hematological, biochemical, inflammatory, histological and immunohistological parameters.Results:All the Pigs in groups Ⅱ-Ⅴ tolerated the treatment procedure well and no significant side effects were observed. Compared with the ALF control, the survival time was significantly prolonged in groups Ⅱ-Ⅴ (p<0.001; groups Ⅰ-Ⅳ were60±2,74±2,75±2,90±3,88±3hours, respectively). The survival times of the PFA and low-volume PE groups were similar (p>0.05) and shorter than that of the Li-ALS group (p<0.001). Liver enzyme, bilirubin, bile acid and blood ammonia levels were decreased significantly after Li-ALS treatment, and increases in inflammatory cytokines were ameliorated. A higher hepatocyte regeneration index was also observed in the Li-ALS group.Conclusion:1. PFA and low-volume PE could effectively reduce toxin-associated liver failure and prolong the survival time of FHF pigs.2. The proposed Li-ALS exhibited strong detoxification capacity, corrected coagulopathy, suppressed inflammation, and promoted liver regeneration. A longer survival time was achieved after Li-ALS therapy compared with using PFA or low-volume PE alone. Li-ALS is a promising, safe, and effective method to treat ALF.3. Compared with the totally plasma exchange group, Li-ALS significant reduced the exchange volume of plasma and achieved better therapeutic effects.