The HepatAssist® Bioartificial Liver Support System: clinical study and pig hepatocyte process

Mullon, Claudy; Pitkin, Zorina

doi:10.1517/13543784.8.3.229

Cited by 43 publications

(18 citation statements)

References 10 publications

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“…Thirty-two patients were successfully bridged to liver transplantation and six recovered without requiring a graft. Survival rate at 1 month was 90% 53. Based on these results, a multicentre phase II/III prospective randomised controlled trial was initiated in which HepatAssist therapy was compared to standard medial therapy in patients with ALF or primary non-function 29.…”

Section: Future Treatment Of Liver Failure: Bioartificial Liver Systemsmentioning

confidence: 99%

Artificial and bioartificial liver devices: present and future

Carpentier

Gautier

Legallais

2009

Gut

178

155

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Liver failure is associated with high morbidity and mortality without transplantation. There are two types of device for temporary support: artificial and bioartificial livers. Artificial livers essentially use non-living components to remove the toxins accumulated during liver failure. Bioartificial livers have bioreactors containing hepatocytes to provide both biotransformation and synthetic liver functions. We review here the operating principles, chemical effects, clinical effects and complications of both types, with specific attention paid to bioartificial systems. Several artificial support systems have FDA marketing authorisation or are CE labelled, but the improvement they provide in terms of patient clinical outcome has not yet been fully demonstrated. At present, different bioartifical systems are being investigated clinically on the basis of their promises and capacity to provide and replace most liver functions. However, important issues such as cost, cell availability, maintenance of cell viability and functionality throughout treatment, and regulatory issues, as well as difficult challenges, including implementing cell-housing devices at the patient's bedside on an emergency basis, have delayed their appearance in intensive care units and on the market. Bioreactors are, nevertheless, when combined with artificial components, a pragmatic approach for future treatment of liver failure.

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Section: Future Treatment Of Liver Failure: Bioartificial Liver Systemsmentioning

confidence: 99%

Artificial and bioartificial liver devices: present and future

Carpentier

Gautier

Legallais

2009

Gut

178

155

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“…On the basis of a total of 405 control DNA samples, the false positive rate for this assay was 9.88%. The samples nere therefore retested up to two additional times to confirm a pos-2) Extracorporeal perfusion for liver failure with the HepatAssist device (Circe Biomedical) (n = 28), which contains pig hepatocytes enclosed in a semipermeable membrane (19). After the procedure.…”

mentioning

confidence: 99%

Search for Cross-Species Transmission of Porcine Endogenous Retrovirus in Patients Treated with Living Pig Tissue

Paradis

Langford

Zhang

et al. 1999

Science

691

403

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Pig organs may offer a solution to the shortage of human donor organs for transplantation, but concerns remain about possible cross-species transmission of porcine endogenous retrovirus (PERV). Samples were collected from 160 patients who had been treated with various living pig tissues up to 12 years earlier. Reverse transcription-polymerase chain reaction (RT-PCR) and protein immunoblot analyses were performed on serum from all 160 patients. No viremia was detected in any patient. Peripheral blood mononuclear cells from 159 of the patients were analyzed by PCR using PERV-specific primers. No PERV infection was detected in any of the patients from whom sufficient DNA was extracted to allow complete PCR analysis (97 percent of the patients). Persistent microchimerism (presence of donor cells in the recipient) was observed in 23 patients for up to 8.5 years.

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“…1). Like others 30,31 we use microcarriers for cell growth. Thus, the provided anchorage and the free flow conditions resulting from rotation ensure an adequate supply of nutrients even in very high cell densities.…”

Section: Discussionmentioning

confidence: 99%

Challenging Small Human Hepatocytes with Opiates: Further Characterization of a Novel Prototype Bioartificial Liver

Wurm

Woess

Libiseller

et al. 2010

Tissue Engineering Part A

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Bioartificial liver (BAL) systems can take over liver functions in patients undergoing liver failure until transplantation. Recently, a novel prototype rotary BAL has been developed using small human hepatocytes (SH). This study investigated the metabolism of opiates morphine and methadone in the BAL and their influence on the basic cell culture parameters, viability, and growth of SH. Opiates may be present in patients due to pain therapy, anticancer treatment, or drug abuse. Cells were cultivated in the BAL for a total of 12 days and exposed twice to 100 microg/L of morphine or methadone. Morphine and methadone concentrations were analyzed using gas chromatography with a mass spectrometry detector. Further, the production of albumin, lactate dehydrogenase release, lactate release, urea production, and glucose consumption were measured. Cell viability and growth were determined by confocal microscopy. Cytochrome P 3A4 and uridindiphosphat (UDP) glucuronosyl transferase 2B7 in SH were analyzed by western blot. The mean cell density during treatment was 5.5 +/- 0.7 x 10(6) cells/mL (n = 6) and was not altered significantly by the opiates. Cell viability stayed above 90%. Morphine was not reduced by SH and was a stress factor as determined by decreased metabolic activity. On the other hand, SH metabolized methadone showing first-order kinetics: the first-order rate constant k = 0,019, half-life t(1/2) = 36 h. Methadone metabolism led to decreased urea and albumin production. The expression of cytochrome P 3A4, mainly responsible for methadone metabolism, was proved in SH. The prototype BAL is basically suited to support liver functions, provided patients receive therapy with methadone.

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The HepatAssist® Bioartificial Liver Support System: clinical study and pig hepatocyte process

Cited by 43 publications

References 10 publications

Artificial and bioartificial liver devices: present and future

Artificial and bioartificial liver devices: present and future

Search for Cross-Species Transmission of Porcine Endogenous Retrovirus in Patients Treated with Living Pig Tissue

Challenging Small Human Hepatocytes with Opiates: Further Characterization of a Novel Prototype Bioartificial Liver

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