CAJ | 학술논문

目的评价新型多层平板型生物人工肝(BAL)体外支持系统治疗肝功能衰竭的临床效果及安全性.方法 2010年12月至2011年12月,有38例肝功能衰竭患者接受了新型多层平板型BAL治疗共计48例次,每次治疗时间为4h,于治疗前,治疗中,以及治疗后1、3、7和14d,抽取患者外周血监测肝功能和凝血功能等生化指标,并观察患者临床症状及体征的变化,以判定BAL的治疗效果.采用酶联免疫吸附试验法检测患者血浆及反应器中IgG、IgM及补体CH50的水平,采用聚合酶链反应检测外周血单个核细胞(PBMC)中猪内源性逆转录病毒(PERV) DNA、猪特异性细胞色素B(SsCytB)基因序列及逆转录酶的活性等,以评估BAL治疗的安全性.结果大部分患者接受BAL治疗后感觉良好,精神状态、临床症状、各项指标较治疗前均有所缓解或明显改善,未发生严重不良反应.38例患者中,临床治愈9例,好转25例,治愈好转率为89.5％(34/38),治疗无效4例；有7例患者经BAL治疗后病情好转,顺利等到供肝接受了肝移植.治疗期间,患者血浆IgG、IgM和CH50水平均未出现明显变化,仅补体CH50在治疗1h时出现一过性下降,随后很快恢复正常水平；反应器内未检测出IgG,仅治疗4h时检出极少量IgG,治疗4h内均未检测出IgM.各时间点患者PBMC均未检测到PERV DNA,且患者血浆中均未检测到猪特异性SsCytB基因序列和逆转录酶活性.结论新型多层平板型BAL体外支持系统对肝功能衰竭患者具有良好的临床治疗效果和安全性,其在患者等待供肝期间也可作为良好的过渡治疗手段.
목적 평개신형다층평판형생물인공간(BAL)체외지지계통치료간공능쇠갈적림상효과급안전성.방법 2010년12월지2011년12월,유38례간공능쇠갈환자접수료신형다층평판형BAL치료공계48례차,매차치료시간위4h,우치료전,치료중,이급치료후1、3、7화14d,추취환자외주혈감측간공능화응혈공능등생화지표,병관찰환자림상증상급체정적변화,이판정BAL적치료효과.채용매련면역흡부시험법검측환자혈장급반응기중IgG、IgM급보체CH50적수평,채용취합매련반응검측외주혈단개핵세포(PBMC)중저내원성역전록병독(PERV) DNA、저특이성세포색소B(SsCytB)기인서렬급역전록매적활성등,이평고BAL치료적안전성.결과 대부분환자접수BAL치료후감각량호,정신상태、림상증상、각항지표교치료전균유소완해혹명현개선,미발생엄중불량반응.38례환자중,림상치유9례,호전25례,치유호전솔위89.5％(34/38),치료무효4례；유7례환자경BAL치료후병정호전,순리등도공간접수료간이식.치료기간,환자혈장IgG、IgM화CH50수평균미출현명현변화,부보체CH50재치료1h시출현일과성하강,수후흔쾌회복정상수평；반응기내미검측출IgG,부치료4h시검출겁소량IgG,치료4h내균미검측출IgM.각시간점환자PBMC균미검측도PERV DNA,차환자혈장중균미검측도저특이성SsCytB기인서렬화역전록매활성.결론 신형다층평판형BAL체외지지계통대간공능쇠갈환자구유량호적림상치료효과화안전성,기재환자등대공간기간야가작위량호적과도치료수단.
Objective To investigate the safety and therapeutic effects ot a novel multi-layer flat-plate bioartificial liver (BAL) for patients with liver failure.Methods Thirty-eight patients with liver failure from Dec.2010 to Dec.2011 were treated with a novel BAL based on multi-layer flatplate bioreactor and the co-cultured cells of the porcine hepatocytes and mesenchymal stem cells.A total of 48 treatments was performed,4 h each time.The clinical signs and symptoms,liver function,ammonia,coagulation function and complete blood count were evaluated before,during and after the treatment.DNA in the collected PBMCs was extracted for PCR with PERV specific primers and the porcine specific primer Sus scrofa cytochrome B.The RT activity was detected as well.Levels of xenoantibodies (IgG,IgM) were determined by using ELISA kit. Titers of complement were quantified by CH50 kit.Results All treatment procedures were completed successfully without any adverse reaction. All samples presented negative PERV DNA and RT activity. The levels of antibodies were similar before and after treatment.Treatment was associated with a temporary decline in levels of complement,and then the levels were recovered quickly.The clinical symptoms such as acratia,anorexia and abdominal distension were improved.The stage of hepatic encephalopathy in 16 patients was decreased. The liver function and ammonia was reduced disproportionately. Seven patients in all were bridged to liver transplantation,2 patients died and 2 patients gave up the treatment,and the others were turned better.After the outcome judgment according to the standard developed by the Artificial Liver Group,and Chinese Association of Infectious and Parasitic Diseases,there were 9 patients with clinical healing,25 patients with improvement and 4 patients with no effect,and the cure-improvement rate was 89.5％.Conclusion The novel multi-layer flat-plate BAL could be used as a safe and effective therapy for patients with liver failure.