Hepatocyte culture systems for artificial liver support: Implications for critical care medicine (bioartificial liver support)

OBJECTIVEThe primary purpose of this review article is to familiarize critical care practitioners with newly developing techniques of hybrid artificial liver support. Implantable and extra-corporeal hepatocyte culture systems are emphasized based on their current experimental and clinical status. DATA SOURCESData used to prepare this document were obtained from the authorsʼ personal files, as well as the computerized MEDLINE database. Medical headings used includeliver, artificial organs, cell culture, growth hormones, extracellular matrix, and transplantation. Only articles published in English have been cited. STUDY SELECTIONAll studies are discussed in which hepatocyte culture systems have been used to support human patients with liver failure. All studies reported the patientʼs condition before therapy, duration of therapy, and outcome after therapy in order to be included in this review. Since the number of clinical trials is small at this time, animal studies were used to demonstrate application of other systems in the treatment of experimentally induced liver failure. Similar selection criteria were used to select animal studies for review. All initially identified human studies met these selection criteria. DATA EXTRACTIONIndependent extraction by multiple observers. DATA SYNTHESISLiver failure, resulting from infection, drugs, or as a part of the multiple organ failure syndrome, remains a major cause of morbidity, mortality, and resource allocation. Current therapy is limited to supportive care, along with liver transplantation. Because of these therapeutic limitations, hybrid artificial liver systems have been proposed for temporary and long-term hepatic support. Several animal studies and a small number of preliminary human studies indicate that hepatocyte culture systems are capable of supporting nearly all essential hepatic functions and may supply biologically active substances that promote regeneration and repair of the damaged liver being supported. Hybrid systems may be constructed from materials that serve as immunoprotective barriers against host defenses. CONCLUSIONSDuring the past decade, important progress has been made with hybrid artificial liver support systems. Cell culture technology has progressed sufficiently so that an artificial liver, composed of metabolically active hepatocytes, may be a potential reality in the foreseeable future. Both implantable and extra-corporeal artificial liver support systems have been developed to