Clinical Experience With a Bioartificial Liver in the Treatment of Severe Liver Failure

Watanabe, F.; Mullon, Claudy; Hewitt, Winston R.; Arkadopoulos, N.; Kahaku, E; Eguchi, Susumu; Khalili, Theodore M.; Arnaout, Walid S.; Shackleton, Christopher R.; Rózga, Jacek; Solomon, Barry A.; Demetriou, Achilles A.

doi:10.1097/00000658-199705000-00005

Cited by 432 publications

(238 citation statements)

References 17 publications

Supporting

Mentioning

228

Contrasting

Unclassified

Order By: Relevance

“…46 Of the 3 BAL support systems for which clinical data are available (Table 2), significant differences exist in the number of cells used to load the bioreactor (6 ϫ 10 9 to 1 ϫ 10 11 ), which corresponds to 2% to 33% of normal liver mass. 47 Specifically, the BAL device, HepatAssist, contains approximately 6 ϫ 10 9 cryopreserved porcine hepatocytes (30 g; 2% of normal hepatocyte mass), 48 whereas the ELAD contains 4 ϫ 10 10 transformed C3A cells (200 g; 15% of normal hepatocyte mass). 49 A more complex device, Gerlach's device contains 1 ϫ 10 11 porcine hepatocytes (500 g; 33% of normal hepatocyte mass).…”

Section: Critical Cell Massmentioning

confidence: 99%

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Tsiaoussis

Newsome

Nelson

et al. 2001

Liver Transplantation

View full text Add to dashboard Cite

Liver failure, notwithstanding advances in medical management, remains a cause of considerable morbidity and mortality in the developed world. Although bioartificial liver (BAL) support systems offer the potential of significant therapeutic benefit for such patients, many issues relating to their use are still to be resolved. In this review, these issues are examined in terms of the functions required, the cells of choice in such a system, and the most appropriate environment to optimize the function of such cells T he development of nonbiological systems to support critically ill patients with acute liver failure (ALF) that incorporate plasmapheresis, 1 charcoal hemoperfusion, 2 and ultrafiltration techniques 3 has not had a significant impact on survival. Consequently, hepatocytebased biological systems have attracted intense interest worldwide but have also generated most of the controversy. Uncertainty exists about the most suitable biological component and the risk for zoonoses and immune rejection in the host. In addition, the optimization of culture conditions and thus metabolic function of the biological component have not been systematically studied, although continuing improvements in these areas have rendered this therapeutic avenue in ALF more promising. To compound matters, the question of which aspects of hepatocyte metabolism in an artificial liver are required to sustain life and promote recovery remains largely unanswered, further limiting development. In this review, the biological substrate of such systems is critically examined and insights are provided into the ideal system.

show abstract

Section: Critical Cell Massmentioning

confidence: 99%

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Tsiaoussis

Newsome

Nelson

et al. 2001

Liver Transplantation

View full text Add to dashboard Cite

show abstract

“…1 At least one BAL containing porcine hepatocytes (porcine BAL) has completed preliminary (phase I) testing. 2 However, concern still exists regarding the possibility of infectious transmission (pig to human) during porcine BAL therapy. Of particular interest are retroviruses found endogenously in all pig tissues.…”

confidence: 99%

Influence of human fulminant hepatic failure sera on endogenous retroviral expression in pig hepatocytes

et al. 2000

View full text Add to dashboard Cite

A porcine endogenous retrovirus (PERV) has been shown to infect human embryonic kidney 293 (HEK293) cells in vitro. The PERV proviral sequence exists in the genome of all porcine cells, including hepatocytes used in a bioartificial liver (BAL). We examined the possibility of PERV infection in HEK293 cells during exposure to supernatant from cultured pig hepatocytes. Pig hepatocytes were cultured in media supplemented with serum from patients in fulminant hepatic failure (FHF) to simulate conditions of an extracorporeal BAL. Pig hepatocytes were cultured in serum-free media for 24 hours and then exposed to fresh medium containing serum from a patient with FHF (22 patients tested). Twenty-four hours later, supernatant was collected and analyzed by polymerase chain reaction (PCR), with and without reverse transcriptase. Primers targeting the pol gene of PERV were used for PCR. Products of amplification were detected by an enzyme-linked immunosorbent assay-based technique using an internal capture probe also targeting the pol gene. Levels of PERV sequences were estimated by serial dilution. All positive samples were tested for infectivity in HEK293 cells. Porcine kidney 15 cell supernatant and fresh culture media were studied as positive and negative controls, respectively. Pig hepatocytes were also studied in the absence of FHF sera and in the presence of mitogenic stimulation with phytohemagglutinin (PHA) and phorbol 12-myristate-13-acetate (PMA). PERV DNA and PERV RNA were detected in all supernatants of cultured pig hepatocytes. The level of PERV RNA in the supernatant of pig hepatocytes was not altered by exposure to human FHF serum or stimulation with PHA and PMA. In addition, PERV RNA was undetectable in the supernatant of HEK293 cells for up to 50 days after exposure to pig hepatocyte supernatant (with or without FHF sera). These findings show that production of PERV by cultured pig hepatocytes was unaffected by exposure to growth factors and cytokines present in human FHF sera.

show abstract

“…5 Patients could be successfully bridged until a transplant was available for HU transplantation. However, mortality in acute or chronic hepatic failure remains high because of less availability of urgent transplants for these patients and thus, the needed bridging time is much longer.…”

mentioning

confidence: 99%

Liver Support by Extracorporeal Blood Purification: A Clinical Observation

Stange

Mitzner

Klammt

et al. 2000

Liver Transplantation

131

View full text Add to dashboard Cite

Liver failure associated with excretory insufficiency and jaundice results in an endogenous accumulation of toxins involved in the impairment of cardiovascular, kidney, and cerebral function. Moreover, these toxins have been shown to damage the liver itself by inducing hepatocellular apoptosis and necrosis, thus creating a vicious cycle of the disease. We report a retrospective cohort study of 26 patients with acute or chronic liver failure with intrahepatic cholestasis (bilirubin level > 20 mg/dL) who underwent a new extracorporeal blood purification treatment. A synthetic hydrophilic/hydrophobic domain-presenting semipermeable membrane (pore size < albumin size, 100-nm thick) was used for extracorporeal blood detoxification using dialysis equipment. The opposite side was rinsed with ligandin-like proteins as molecular adsorbents that were regenerated online using a chromatography-like recycling system (molecular adsorbent recirculating system [MARS]). Bile acid and bilirubin levels, representing the previously described toxins, were reduced by 16% to 53% and 10% to 90% of the initial concentration by a single treatment of 6 to 8 hours, respectively. Toxicity testing of patient plasma onto primary rat hepatocytes by live/dead fluorescence microscopy showed cell-damaging effects of jaundiced plasma that were not observed after treatment. Patients with a worsening of Child-TurcottePugh (CTP) index before the treatments showed a significant improvement of this index during a period of 2 to 14 single treatments with an average of 14 days. After withdrawal of MARS treatment, this improvement was sustained in all long-term survivors. Ten patients represented a clinical status equivalent to the United Network for Organ Sharing (UNOS) status 2b (group A1), and all survived. Sixteen patients represented a clinical status equivalent to UNOS status 2a, and 7 of these patients survived (group A2), whereas 9 patients (group B) died. We conclude that in acute excretory failure caused by a chronic liver disease, this treatment provides a therapy option to remove toxins involved in multiorgan dysfunction secondary to liver failure. (Liver Transpl 2000;6: 603-613.)

show abstract

Clinical Experience With a Bioartificial Liver in the Treatment of Severe Liver Failure

Abstract: The authors' clinical experience with the BAL has yielded encouraging results. A randomized, controlled, prospective trial (phase II-III) is being initiated to determine the efficacy of the system.

Cited by 432 publications

References 17 publications

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Which hepatocyte will it be? Hepatocyte choice for bioartificial liver support systems

Influence of human fulminant hepatic failure sera on endogenous retroviral expression in pig hepatocytes

Liver Support by Extracorporeal Blood Purification: A Clinical Observation

Contact Info

Product

Resources

About