Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Liver, Artificial”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1989

[Medical aspects of the artificial liver].

Artificial liver support may be indicated in cases of fulminant toxic or drug-induced liver failure, in fulminant viral hepatitis, after surgical procedures such as extended liver resections or liver transplantation with primary graft failure, and in some cases of chronic endstage liver disease. Neither artificial nor biological liver support systems have shown any convincing results, whereas plasma exchange combined with intensive medication is suitable for temporary liver failure or for providing support until a donor organ for liver transplantation becomes available.

Animals↗
PubMed1998

[Liver and artificial liver].

Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented.

Animals↗
PubMed1994

Is the biological artificial liver clinically applicable? A historic review of biological artificial liver support systems.

Hemoperfusion, hemodiafiltration, plasma exchange, and extracorporeal liver perfusion have already been adopted to treat patients with acute and chronic hepatic failure. However, the survival rate of patients with acute hepatic failure remains at approximately 30% and has not improved as expected. Current advances in biotechnology have opened the way for the development of a biological artificial liver, which is called the hybrid artificial liver because it consists of both biological and artificial materials. Isolated hepatocytes have been investigated for use in various types of hybrid artificial liver. In addition, the role of biomatrices, microcarriers, and the microencapsulation technique has been studied with respect to long-term maintenance of hepatocellular function and development of high-density culture systems for hepatocytes. Before clinical application of hybrid artificial liver support systems becomes possible, many problems have to be resolved, including large-scale preparation and long-term preservation of biomaterials, high-density and stable immobilization of biomaterials on artificial materials, control of immunological hazards, biocompatibility, safe transportation and sterilization of biomaterials, and the high cost. We review the history of biological artificial livers and discuss their future role.

Animals↗
PubMed1985

[Artificial liver].

An artificial liver should in fact be called an artificial liver assist device or system because at this point in its development it is unable to prolong the life of an ahepatic animal, whereas, an artificial heart or an artificial kidney enables the animal to live without a heart or kidneys for a long period of time. The hepatic assist devices are classified into three types: Artificial (charcoal hemoperfusion, PAN membrane dialysis or filtration); biological (baboon liver perfusion, cross dialysis between pig liver and patients systemic circulation); and hybrid (combined form of artificial and biological). Our hepatic support system is composed of a membrane plasma separator, blood and plasma pumps, hemodialyzer and controller. Using this system, the patients plasma is replaced with fresh donor plasma in amount of 5,000 ml daily. This procedure are taken place in the intensive care unit, until the patient recovers consciousness or his cerebral death is confirmed. A national survey of the patients with fulminant hepatic failure, revealed that the survival rate of the patients treated with plasma exchange was 34.1% (15/45), while that of the patient untreated with plasma exchange was 14.3% (5/35). The difference is statistically significant. However, plasma exchange requires a large amount of fresh plasma which occasionally induce hepatitis or allergy and its detoxication of the patients plasma was insufficient in severe cases. To overcome these problems, specific adsorpton of hepatic toxins and a combined therapy of blood purification with plasma exchange will be studied further.

Adult↗
PubMed2001

Artificial liver support devices for fulminant liver failure.

Artificial liver-support devices attempt to bridge patients with fulminant hepatic failure until either a suitable liver allograft is obtained for transplantation or the patient's own liver regenerates sufficiently to resume normal function. It is thought that toxins contribute to the clinical picture of fulminant hepatic failure. The earliest reports of successful toxin removal were blood- and plasma-exchange transfusions. Given these successful case reports, mechanical liver-support devices were designed to filter toxins. These mechanical devices used hemodialysis, charcoal hemoperfusion, hemoperfusion through cation-exchange resins, hemodiabsorption, and combinations of all of these techniques as in the MARS liver-support device. Despite promising case reports and small series, no controlled studies of mechanical devices have ever showed a long-term survival benefit. Thus, the removal of presumed toxins seems to be insufficient to support patients with fulminant hepatic failure, and the biologic function of the liver must also be replaced. Attempts at replacing the biologic function have included extracorporeal liver perfusion, cross-circulation, and hepatocyte transplantation. Current technologies have combined mechanical and biologic support systems in hybrid liver-support devices. The mechanical component of these hybrid devices serves both to remove toxins and to create a barrier between the patient's serum and the biologic component of the liver-support device. The biologic component of these hybrid liver support devices may consist of liver slices, granulated liver, or hepatocytes from low-grade tumor cells or porcine hepatocytes. These biologic components are housed within bioreactors. Currently the most clinically studied bioreactors are those that use capillary hollow-fiber systems. Both the bioartificial liver by Demetrious and the extracorporeal liver-assist device by Sussman and Kelly are in clinical trials. Although the trials seemed to have yielded good survival data when the devices are used as a bridge to transplantation, the type and degree of liver support provided by these devices remains uncertain. Thus, despite decades of great progress in the field of artificial liver support, no one technique alone yet provides sufficient liver support. A hybrid system seems to be the best option at present. Still to be determined is the best tissue to use, how much liver tissue should be used, and the optimal design of the bioreactor.

Cell Transplantation↗
PubMed1985

Use of artificial liver support.

Artificial liver support is used to remove toxic substances accumulating in the circulation of patients with fulminant hepatic failure. Charcoal haemoperfusion with infusion of prostacyclin (PGI2) to prevent platelet damage has become a routine treatment and has led to improved survival. In 76 patients treated 29 (38%) survived to leave hospital and of these 31 patients were treated when in Grade III coma and 20 (65%) survived. Charcoal haemoperfusion also reduced the incidence of cerebral oedema which is a major cause of death in fulminant hepatic failure. Most episodes (congruent to 80%) of cerebral oedema can be managed using the osmotic agent mannitol. In a complete liver support system both protein-bound and compounds of a middle relative molecular mass as well as water soluble compounds should be removed. An albumin-coated resin has been developed to remove these compounds and in preliminary clinical studies it has been shown to have good blood compatibility and satisfactory adsorption properties. The importance of combined systems has been confirmed in studies on the removal of inhibitors of brain Na+K+-ATPase, where both resin and charcoal columns removed significant amounts of the inhibitory activity.

Animals↗
PubMed2006

Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy.

AIM: To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT). METHODS: Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d) after OLT. RESULTS: In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30 d observation was: 28 kept alive and 6 patients died. CONCLUSION: Pre-operative SOFA, level of creatinine, INR, TNF-alpha, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantation can relieve these factors significantly.

Aged↗
PubMed2003

Study of severe hepatitis treated with a hybrid artificial liver support system.

Artificial liver support system (ALSS) has been used to treat hepatic failure and has significantly decreased the mortality. TECA hybrid artificial liver support system (TECA-HALSS), which combines the hollow fiber bioreactor with a plasma exchange circuit, was used to assess the efficacy, safety and feasibility in treating severe hepatitis patients. The hybrid artificial liver support system (HALSS) consists of a bioreactor containing more than 5 x10(9) porcine hepatocytes and plasma exchange device. Fifteen patients with severe hepatitis were treated with this hybrid system. All patients experienced a reduction in symptoms such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly while prothrombin activity increased. There were ten patients whose progress of hepatocyte necrosis was stopped after HALSS treatment, and finally they recovered completely. One patient received liver transplantation after HALSS therapy and survived. No serious adverse events were noted in the fifteen patients.

Adult↗
PubMed2004

Liver regeneration using a hybrid artificial liver support system.

We have developed two types of hybrid artificial liver support system (HALSS) that use hepatocyte organoid culture: (1) a PUF-HALSS comprising an artificial liver module using polyurethane foam (PUF), in which hepatocytes form spheroids in its pores, and maintained liver-specific functions for at least ten days in vitro; (2) an LLS-HALSS that uses a liver lobule-like structure (LLS) module containing hollow fibers with a microregular arrangement in which hepatocytes in the extra-fiber space of the module form the organoids by centrifugation that maintain liver-specific functions for at least two months in vitro. In preclinical experiments, a PUF-HALSS was applied to a pig having liver failure. To evaluate the effect of liver regeneration, a PUF- and an LLS-HALSS were applied to a rat having reversible hepatic failure. Each HALSS was effective in supporting liver function, stabilization of general conditions and recovery from liver failure state. These results indicate that these HALSS may be useful to treat liver failure patients until liver transplantation or until regeneration of the native liver.

Animals↗
PubMed1995

Influence of warm ischemia on isolation and primary culture of hepatocytes from rat liver for a hybrid artificial liver.

To assess the possibility of using hepatocytes from ischemic liver, as a bioreactor of a hybrid artificial liver, we investigated the influence of warm ischemia on the isolation and culture of hepatocytes in rats. Warm ischemia was induced by clamping the liver hilus and the animals were divided into 3 groups according to the duration of ischemia: group A (no ischemia), group B (10 minutes) and group C (20 minutes). Hepatocytes were isolated by the collagenase perfusion method and cultured for 5 days. The yield and viability of the isolated hepatocytes were lower in group C. Rate of attachment was decreased as the duration of ischemia increased. There was no significant difference observed in functions in culture. Sufficient hepatocytes, as a bioreactor, can be isolated and cultured from warm ischemic liver within 10 minutes. Though the number of available hepatocytes were diminished, hepatocytes procured from longer warm ischemic liver could be utilized as a bioreactor.

Analysis of Variance↗
PubMed1992

Artificial liver support based on artificial cells with emphasis on encapsulated hepatocytes.

Artificial liver support requires more than a detoxification system. We have investigated additional approaches. Microencapsulated hepatocytes increased the survival time of fulminant hepatic failure (FHF) rats. They also lowered the bilirubin in Gunn rats. Xenograft of microencapsulated rat hepatocytes into mice are immunoisolated. The viability of hepatocyte increased from 62 to 100% after 29 days. This is because of accumulation of a hepatic stimulatory factor (> 100,000 D) secreted by the hepatocytes in the artificial cells. A novel two-step method of cell encapsulation greatly improved immunoisolation and biocompatibility. Other metabolic approaches included a multienzyme system for conversion of ammonia to essential amino acid, and removal of bilirubin.

Animals↗
PubMedDate not supplied

Use of mammalian liver cells for artificial liver support.

Advances in orthotopic liver transplantation have improved the survival rate of both acute and chronic liver failure patients to nearly 70%. However, the success of this treatment modality has created an international organ shortage. Many patients die while awaiting transplantation in part due to the minimal capacity to store viable transplantable livers beyond 24 h. Additionally, for many areas of the world, routine use of whole liver transplantation to treat liver disease is impractical due to the demands on both financial and technical resources. Potentially, these issues may be alleviated, at least in part, by the use of liver cell transplantation or cellular-based liver assist devices. The well-documented regenerative capacity of the liver may obviate the need for whole organ transplantation in some instances of acute failure, if the patient may be provided temporary metabolic support. Although other patients ultimately may require transplantation, a longer period of time to find a suitable organ for transplantation may be gained by that supportive therapy. The field of liver cell transplantation may offer solutions to patients with inherited metabolic deficiencies or chronic liver disease. The potential to treat an hepatic disorder by using only a fraction of the whole liver would increase the number of whole organs available for orthotopic liver transplantation. Research in the fields of hepatocyte based intra- and extra-corporeal liver support is providing evidence that these therapeutic modalities may ultimately become routine in the treatment of severe liver disease. A historic overview of that technology along with its current status is discussed.

Animals↗
PubMedDate not supplied

[Acute hepatic insufficiency and the artificial liver].

The authors reviews some aspects related to hepatic encephalopathia and liver tissue regeneration, as well as criteria for prognosis of evolution and lethality of hepatic failure of the acute type. Methods of hepatic assistance include peritoneal dialysis, hemodialysis, exsanguinotransfusion, plasmapheresis, perfusion of isolated liver, crossed circulation, total washing of the organism, liver transplantation and artificial liver. The principles, the techniques and the materials used for the construction of an artificial liver are presented. Such materials include active charcoal, resins, enzymes, artificial cells of materials fixed upon active or passive supports presenting as plates, sheets, capillaries and dialysis membranes. The creation is suggested, of centers for hepatic depuration where prophylactic hepatic assistance could be provided, as well as the production of an artificial liver of the portable type for the treatment of chronic hepatic failure.

Acute Disease↗
PubMed2006

[Survival analysis on liver failure patients treated with an artificial liver support system].

OBJECTIVE: To evaluate the efficacy of artificial liver support system (ALSS) in the treatment of liver failure patients. METHODS: This is a prospective, multi-center, controlled, large sample clinic trial. 518 patients with liver failure from 5 hospitals were studied and followed. All the patients received similar pharmacological manipulation according to one and the same protocol but were divided into an ALSS treatment group and a control group without ALSS treatment. The ALSS treatment procedures included plasma exchange, molecular adsorbent recirculating system (MARS), plasma exchange plus hemofiltration and other combined nonbioartificial methods. The analysis of survival time was computed using the Kaplain-Maier method, and comparison among groups was done using Log-Rank, Breslow and/or the Tarone-Ware test. RESULTS: Survival time of acute liver failure patients was prolonged from 4.0+/-0.2 days to 8.0+/-0.4 days (P=0.004). ALSS was shown to be two times more effective. ALSS increased the survival time of acute on chronic (A on C) liver failure patients from 27.0+/-1.6 days to 39.0+/-4.0 days (P less than 0.01). In addition, it increased the survival time of the patients in the middle and end stage of subacute liver failure and A on C liver failure, but had no significant effects on early stage patients. The survival time of middle stage patients was 38.0+/-17.5 days in the control group vs 66.0+/-18.6 days in the ALSS group (P less than 0.05). The survival time of end stage patients of the control group and the ALSS group was 18.0+/-4.0 days vs 26.0+/-2.5 days (P less than 0.01). CONCLUSIONS: Multi ALSS treatment is more effective than the standard medicinal liver care treatment. Multi-ALSS treatment could increase survival time of patients suffering from acute liver failure or A on C liver failure, especially in their middle and end stages. It is important and necessary to treat these patients with ALSS.

Adolescent↗
PubMedDate not supplied

Extended liver resection and hepatic ischemia in pigs: a new, potentially reversible model to induce acute liver failure and study artificial liver support systems.

BACKGROUND: Extended hepatectomy is a valid model for the study of acute liver failure. Since the porcine liver is comparable in size, morphology and anatomy to the human liver, we describe a technique employing hepatic ischemia and extended liver resection to induce acute liver failure in a porcine model as a means of studying bioartificial liver support. METHOD: A subtotal (75-80% resection) extended left hepatectomy was performed in 7 pigs after 60 min warm ischemia of the future remnant liver. After resection, the animals were given the best supportive care and observed until death. RESULTS: All animals died within 18-48 h, none as a result of surgical complications. Gross appearance of the liver showed severe steatosis of the right lateral lobe, and histology revealed severe coagulative necrosis of the whole lobule. CONCLUSION: This technique of extended liver resection after hepatic ischemia in the porcine model may be useful for studies of potentially reversible acute liver failure and experimental bioartificial support.

Animals↗