Efficacy of Nafamostat Mesilate for improving the performance of a bioartificial liver using porcine hepatocytes

Our bioartificial liver (BAL) consists of porcine hepatocytes attached to b eads and plasma perfused through the system. The function of our BAL lasts for approximately 7 hours. The objective of the present study was to invest igate the efficacy of Nafamostat Mesilate (NM), a protease inhibitor and po tent complement inhibitor, for improving the performance of the BAL. The ex perimental groups were divided as follows; the NIM group (n=7) where the BA L had porcine hepatocytes with 3.8x10(-4) M, of NM, and the control group w here the BAL had no NM Plasma obtained from patients suffering from hepatic failure was perfused through the BAL for 10 hours. The viability of the po rcine hepatocytes and the levels of alanine aminotransferase (ALT) in the h uman plasma were measured during perfusion. After the 10-hour perfusion, an other human hepatic failure plasma was perfused for an additional I hour an d then the function of the BAL was evaluated. After the 10-hour perfusion, the viability of the hepatocytes in the NM group was 51+/-7 %, whereas that in the control group was rapidly reduced by 35 +/- 5 %. Although the level s of ALT in the human plasma in both groups increased with the perfusion ti me, those in the NM group were significantly lower than those in the contro l group (p < 0.05). These results suggest that NM prevented damage to the p orcine hepatocytes in human hepatic failure plasma as compared to the contr ol group. In the human hepatic failure plasma before perfusion, the partial thrombin time (PT) and the plasma ammonia (NH3) levels were 19.8 +/- 12 % and 288 +/- 102 mu g/dl, respectively. Fischer's ratios were 0.98 +/- 0.39. Even after the 10-hour perfusion, the BAL in the NM group significantly im proved the levels of PT (38 +/- 10 %; p < 0.05), NH3 (214 +/- 34 mu g/dl; p < 0.05) and Fischer's ratios (1.4 +/- 0.3; p < 0.05). On the other hand, t he BAL in the control group did not show any improvement in those parameter s. In conclusion, NM was found to help in maintaining the viability of porc ine hepatocytes in human hepatic failure plasma, thereby allowing the porci ne hepatocyte-based BAL to function much better.