BACKGROUND:Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES:Five English-language medical databases,MEDLINE,ScienceDirect,OVID,Springer Link and Wiley Interscience were searched for articles on 'acute liver failure',' prognosis',and related topics. RESULTS:Multi-variable prognostic models including the King’s College Hospital criteria and the model for end-stage liver disease score have been widely used in determination of the prognosis of ALF,but the results are far from satisfactory. Other prognostic indicators including serum Gc-globulin,arterial blood lactate,serum phosphate,arterial blood ammonia,and serum alpha-fetoprotein are promising but await further assessement. CONCLUSIONS:A reliable prognostic model to be developed in the future should not only have predictive value for poor outcome but also help to predict the survival of patients without a liver transplantation. Further studies are necessary to assess the prognostic accuracy of any new models.
BACKGROUND:The bioartificial liver is anticipated to be a promising alternative choice for patients with liver failure. Toxic substances which accumulate in the patients'plasma exert deleterious effects on hepatocytes in the bioreactor,and potentially reduce the efficacy of bioartificial liver devices. This study was designed to investigate the effects of plasma from patients with acute on chronic liver failure(AoCLF)on immortalized human hepatocytes in terms of cytochrome P450 gene expression,drug metabolism activity and detoxification capability. METHODS:Immortalized human hepatocytes(HepLi-2 cells)were cultured in medium containing fetal calf serum or human plasma from three patients with AoCLF.The cytochrome P450(CYP3A5,CYP2E1,CYP3A4)expression, drug metabolism activity and detoxification capability of HepLi-2 cells were assessed by RT-PCR,lidocaine clearance and ammonia elimination assay. RESULTS:After incubation in medium containing AoCLF plasma for 24 hours,the cytochrome P450 mRNA expression of HepLi-2 cells was not significantly decreased compared with control culture.Ammonia elimination and lidocaine clearance assay showed that the ability of ammonia removal and drug metabolism remained stable. CONCLUSIONS:Immortalized human hepatocytes can be exposed to AoCLF plasma for at least 24 hours with no significant reduction in the function of cytochrome P450. HepLi-2 cells appear to be effective in metabolism and detoxification and can be potentially used in the development of bioartificial liver.
Du, Wei-BoPan, Xiao-PingYu, Xiao-PengYu, Cheng-BoLv, Guo-LiangChen, YuLi, Lan-Juan
目的观察慢性重型乙型肝炎人工肝支持系统（artificial liver support system，ALSS）-血浆置换（plasma exchange，PE）治疗前后临床症状、肝功能、凝血功能及IL-10的变化。方法将151例慢性重型乙型肝炎患者分成治疗组和对照组，治疗组在综合药物治疗的基础上加用ALSS-PE，而对照组仅采用药物治疗。治疗前后常规观察两组患者临床症状、肝功能、凝血酶原时间（PT）、凝血酶原活动度（PTA）及用ELISA法检测IL-10的变化。结果治疗组在临床症状、肝功能、PT、PTA等指标的改善上明显优于对照组（P〈0．05）；IL-10有上升趋势（P〈0．05）。结论ALSS-PE能明显提高药物治疗慢性重型乙型肝炎的疗效，升高IL-10，减轻肝脏炎症反应。
BACKGROUND:Bioartificial liver support systems are becoming an effective therapy for hepatic failure.Bioreactors,as key devices in these systems,can provide a favorable growth and metabolic environment,mass exchange,and immunological isolation as a platform.Currently,stagnancy in bioreactor research is the main factor restricting the development of bioartificial liver support systems.DATA SOURCES:A PubMed database search of English-language literature was performed to identify relevant articles using the Keywords "bioreactor","bioartificial liver","hepatocyte",and"liver failure".More than 40 articles related to the bioreactors of bioartificial livers were reviewed.RESULTS:Some progress has been made in the improvement of structures,functions,and modified macromolecular materials related to bioreactors in recent years.The current data on the improvement of bioreactor configurations for bioartificial livers or on the potential of the use of certain scaffold materials in bioreactors,combined with the clinical efficacy and safety evaluation of cultured hepatocytes in vitro,indicate that the AMC(Academic Medical Center)BAL bioreactor and MELS(modular extracorporeal liver support) BAL bioreactor system can partly replace the synthetic and metabolic functions of the liver in phaseⅠclinical studies.In addition,it has been indicated that the microfluidic PDMS(polydimethylsiloxane)bioreactor,or SlideBioreactor,and the microfabricated grooved bioreactor are appropriate for hepatocyte culture,which is also promising for bioartificial livers.Similarly,modified scaffolds can promote the adhesion,growth,and function of hepatocytes,and provide reliable materials for bioreactors.CONCLUSIONS:Bioreactors,as key devices in bioartificial livers,play an important role in the therapy for liver failure both now and in the future.Bioreactor configurations are indispensable for the development of bioartificial livers used for liver failure,just as the modified scaffold materials available for bioreactors are favorable to the constructio
