A Comparative Study Of Li-ALS And MARS In The Treatment Of Acute Liver Failure Pigs

Background:Non-bioartificial liver has become an effective and practical treatment method of liver failure. Complete replacement of the liver function is impossible using a single mode of blood purification technology because of the complexity of liver function. The optimal combination of blood purification technologies in order to maximize removal of hazardous substances and replace liver function is the key of the enhancement of efficacy. Molecular adsorbent recirculating system(MARS) is currently the most widely used non-bioartificial liver system in Europe and America, however, it is difficult to promote in our country because of the lack of support related liver synthetic function and its high cost.Recently, we have developed a novel blood purification system, named Li’s artificial liver system (Li-ALS), which couples low-volume plasma exchange with plasma filtration adsorption. Preliminary results of animal experiments show that, Li-ALS not only effectively remove the toxins and inflammatory cytokines, but also supplement coagulation factors to correct coagulopathy, which significantly prolong the survival time of liver failure animals.Aim:To carry out a comparative study of the efficacy of Li-ALS and MARS using acute liver failure pigs.Method: Twenty-four male Chinese experimental miniature pigs weighing23-30kg were used for the experiment. ALF was induced with D-galactosamine thorough the external jugular venous catheter without anesthesia. At36h after D-galactosamine injection, the experimental animals were randomly divided into three groups:the ALF control group (n=8), MARS treatment group (n=8), Li-ALS treatment group (n=8), beginning6hours therapeutic intervention. The efficacy of each treatment was assessed by survival time and improvement in hematological, biochemical, inflammatory, histological and immunohistological parameters.Result:All the Pigs in three groups tolerated the treatment procedure well and no significant side effects were observed. The mean survival time of three groups was61.6±2.1hours,73.5±2.2hours,89.1±3.8hours.Kaplan-Meier survival analysis shows: MARS and Li-ALS treatment both significantly prolong the survival time of acute liver failure animals; the Li-ALS treated animals live longer than the MARS treatment group.Li-ALS therapy significantly correct the coagulopathy of ALF animals by reducing the prothrombin time and increasing fibrinogen levels; MARS treatment did not improve the coagulation. Liver enzyme, bilirubin, bile acid and blood ammonia levels were both decreased significantly after Li-ALS and MARS treatment.Li-ALS can effectively remove the elevated TNF-a, TGF-βi,Ang-Ⅱ,while retaining HGF in the serum.. A higher hepatocyte regeneration index and less inflammation was also observed in the Li-ALS group.Conclusion:1. Li-ALS and MARS treatment,which significantly prolong the survival time of ALF animals, are both effective in the treatment of acute liver failure animals.2. Li-ALS are more effective than MARS in the treatment of acute liver failure animals..