Clarification of the significance in purilying middle molewles in the blood of liver failure

Research Project

Project/Area Number	03670602
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Digestive surgery
Research Institution	TOHOKU UNIVERSITY
Principal Investigator	MATSUBARA Shuji TOHOKU UNIVERSITY SCHOOL of MEDICINE, LECTURER, 医学部附属病院, 講師 (20165856)
Co-Investigator(Kenkyū-buntansha)	OHCHI Kiyoaki TOHOKU UNIVERSITY SCHOOL OF MEDICINE,Associate Professor, 医学部, 助教授 (20124555) 斉藤善広東北大学, 医学部附属病院, 助手 (10215569)
Project Period (FY)	1991 – 1992
Project Status	Completed (Fiscal Year 1992)
Budget Amount *help	¥2,000,000 (Direct Cost: ¥2,000,000) Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywords	acute liver failure / middle molewles / coutinuous hemofiltration / 肝不全 / 血液浄化療法
Research Abstract	As a non-biological artificial liver support system, the technique of blood purification procedure has currently been applied widely in Japan. The main task of this method is to remove augmented noxious products in the patients blood and to supply essential substances which can not be procreated by the damaged liver. The first choice of the treatment should be massive plasma exchange with fresh frozen plasma since it can indiscriminately purify nondialyzable macromolecular substances such as protein-bound toxins and endotoxin, most of which are localized in the intravascular pool. Furthermore, plasma exchange substantially controls DIC by eliminating activated thrombin products in the blood and supplying all lacking coagulation factors. Moreover, we have reported the impaired host defense mechanism can be restored by plasma exchange because it increases the blood level of opsonic protein. However, plasma exchange alone can not prevent the progression of brain edema that is main cause o … More f death in fulminant hepatic failure. Recently accumulated attention has been focused on increased abnormal middle molecules, which can easily leak through the capillary wall and equilibrate between the intra-and extravascular spaces, as putative toxins promoting brain edema. To continuously wash out these middle molecules, continuous hemofiltration with high performance membrane, a hollow fiber hemofilter with polysulfone (PSP Filter, Kuraray) of which a nominal rejection rate (MW 10,000) of 43%, has been recently carried out in addition to daily plasma exchange. According to the HPLC study with gel-filtration method,the sera of patients with liver failure showed notched several peaks of abnormal middle molecules (MW<4,500). These abnormal peaks reduce in heights sequentially by continuous hemofiltration. And also the HPLC pattern of the filtrate showed a satisfactory sieving coefficients of these middle molecules (nearly 1.0). The improvement of the level of consciousness is shown to be well corresponds to such reduction of middle molecular peaks in the HPLC and the patients whose HPLC pattern almost normalized showed a compete awakening. Based upon these results, the combination of plasma exchange and continuous hemofiltration is found to be an useful modality of treatment as a non-biological artificial liver support system. However, even with this approach, the clinical response is still temporary and the most patients were finally exhausted to die by multi-system failure. Therefore, the efforts to find out the method to promote a sufficient regeneration of hepatic necrosis is now the most urgent problem to salvage the patients with acute liver failure. Less