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PubMed1990

Experimental colorectal liver metastases. Influence of sex, immunological status and liver regeneration.

The liver is the most frequent site of metastases from colon cancer. To improve our knowledge of liver metastases and to develop new adjuvant therapies, a good animal model is necessary. The aims of this study were to obtain a model of liver metastases with intraportal injection of colon adrenocarcinoma cell aggregates (DHDK12 cell line) and to study the effect of various factors, i.e., sex, liver regeneration and immunosuppression, on the development of liver metastasis. Cell aggregates were injected into the portal vein of 59 syngenic male and female BD IX rats following randomization into three groups. Group 1, (control 12 males and 10 females) received only cell aggregates; group 2 (12 males and 10 females) underwent a 70% hepatectomy before cell injection; group 3 (15 males and 10 females) received cyclosporin A injections at a dose of 10 mg/kg per day for 28 days following cell injection. Autopsy was performed at 10 weeks. Liver metastases were more frequent in the male rats in group 3 than in those in group 1 (80% vs. 30%, p less than 0.04). The rate of liver metastases in females was not increased by immunosuppression (22.2% vs. 12.5%, N.S.). Liver resection (group 2) did not significantly modify the incidence of liver metastasis. No female had liver metastases in this group. This relatively simple model rapidly produces liver metastasis with a high yield, but only in male rats. Besides sexual factors, immunosuppression also increased the rate of experimental liver metastasis, while liver regeneration failed to do so.

Adenocarcinoma↗
PubMed2005

Practice of adult liver transplantation in Italy. Recommendations of the Italian Association for the Study of the Liver (A.I.S.F.).

Liver transplantation is an efficient procedure as performed in Italy, yet major differences are present in terms of practice. In an effort to facilitate an homogeneous practice of liver transplantation in Italy, the Italian Association for the Study of Liver Disease has instituted a Commission aimed at providing recommendations on non-urgent liver transplantation in adults, based on current evidence. This nation-wide commission which included experienced hepatologists, surgeons and pathologists with major interest in liver transplantation has drafted a final document in October 2004, approved by the Italian Association for the Study of Liver Governing Board, whose key arguments and main conclusions are summarised in the present paper. The Commission has made specific recommendations on the following topics: the current needs of liver transplantation in Italy; the indications to liver transplantation and re-liver transplantation, with special reference to controversial issues and the minimal listing criteria; the use of marginal donors and the need to optimise donor/recipient matching; the use of living donor liver transplantation; the management of the waiting list and the introduction of Model for End-Stage Liver Disease to define priorities; the clinical management of liver transplantation recipients and disease recurrence; the implementation of audits and outcome monitoring; the training of transplant surgeons and hepatologists and the requirements for Centre accreditation; the pathology of liver transplantation.

Humans↗
PubMed2002

Preconditioning protects liver and lung damage in rat liver transplantation: role of xanthine/xanthine oxidase.

This study was designed to evaluate whether ischemic preconditioning could confer protection against liver and lung damage associated with liver transplantation. The effect of preconditioning on the xanthine/xanthine oxidase (XOD) system in liver grafts subjected to 8 and 16 hours of cold ischemia was also evaluated. Increased xanthine levels and marked conversion of xanthine dehydrogenase (XDH) to XOD were observed after hepatic cold ischemia. Xanthine/XOD could play a role in the liver and lung damage associated with liver transplantation. This assumption is based on the observation that inhibition of XOD reduced postischemic reactive oxygen species (ROS) generation and hepatic injury as well as ensuing lung inflammatory damage, including neutrophil accumulation, oxidative stress, and edema formation. Ischemic preconditioning reduced xanthine accumulation and conversion of XDH to XOD in liver grafts during cold ischemia. This could diminish liver and lung damage following liver transplantation. In the liver, preconditioning prevented postischemic ROS generation and hepatic injury as well as the injurious effects in the lung following liver transplantation. Administration of xanthine and XOD to preconditioned rats led to hepatic ROS and transaminase levels similar to those found after reperfusion and abolished the protective effect of preconditioning on the lung inflammatory damage. In conclusion, ischemic preconditioning reduces both liver and lung damage following liver transplantation. This endogenous protective mechanism is capable of blocking xanthine/XOD generation in liver grafts during cold ischemia.

Animals↗
PubMed2004

[CT-based liver volumetry in a porcine model: impact on clinical volumetry prior to living donated liver transplantation].

PURPOSE: Exact preoperative determination of the liver volume is of great importance prior to hepatobiliary surgery, especially in living donated liver transplantation (LDLT). In the current literature, a strong correlation between preoperatively calculated and intraoperatively measured liver volumes has been described. Such accuracy seems questionable, primarily due to a difference in the perfusion state of the liver in situ versus after explantation. Purpose of the study was to asses the influence of the perfusion state on liver volume and the validity of the preoperative liver volumetry prior to LDLT. METHODS: In an experimental study, 20 porcine livers were examined. The livers were weighted and their volumes were determined by water displacement prior and after fluid infusion to achieve a pressure physiologically found in the liver veins. The liver volumes in the different perfusion states were calculated based on CT-data. The calculated values were compared with the volume measured by water displacement and the weight of the livers. RESULTS: Assessment of calculated CT volumes and water displacements at identical perfusion states showed a tight correlation and differed on average by 4 +/- 5 %. However, livers before and after fluid infusion showed a 33 +/- 8 % (350 +/- 150 ml) difference in volume. CONCLUSION: CT-volumetry acquires highly accurate data as confirmed by water displacement studies. However, the perfusion state has major impact on liver volume, which has to be accounted for in clinical use.

Animals↗
PubMed2005

Detection of Helicobacter species in liver and stomach tissues of patients with chronic liver diseases using polymerase chain reaction-denaturing gradient gel electrophoresis and immunohistochemistry.

OBJECTIVE: Helicobacter DNA has been detected in the hepatobiliary tree of patients with chronic liver diseases (CLD). The presence of H. pylori in the stomach compared with in the liver of the same patients with CLD has not been studied, therefore to the aim of this study was to investigate the presence of Helicobacter DNA and antigens in the liver and stomach of Polish patients with chronic liver diseases using molecular and immunological methods. MATERIAL AND METHODS: Gastric mucosa and liver tissue samples and sera were collected from 97 Polish patients with CLD. Anti-H. pylori antibodies were detected by enzyme immunoassay (EIA), and H. pylori-like antigens detected by immunohistochemistry. Helicobacter DNA was detected in stomach and liver samples using a semi-nested Helicobacter genus-specific polymerase chain reaction (PCR) assay, and Helicobacter species identified by denaturing gradient gel electrophoresis (DGGE) and sequencing analysis of amplified PCR products. RESULTS: H. pylori was identified by DGGE and sequence analysis in 60/62 (97%) and 25/25 (100%) of the gastric and liver Helicobacter genus-positive samples, respectively, whereas DNA of H. heilmannii was detected in 2/62 (3%) of the Helicobacter genus-positive gastric samples. H. pylori cagA gene was detected in 23/62 (36%) and 3/25 (12%) gastric and liver tissue samples, respectively. H. pylori-like antigens were detected in 61/97 (63%) gastric mucosa and in 40/97 (41%) liver tissue samples. CONCLUSIONS: H. pylori-like organisms appeared to dominate the gastric mucosa and liver tissue of Polish patients with CLD. The prevalence of the cagA gene was higher in stomach compared with liver samples, which suggests a possible role of cagA negative H. pylori-like organisms in CLD. On the other hand, no significant correlation was found between the presence of H. pylori-like DNA and antigens in the liver and liver function tests.

Adolescent↗
PubMed2003

Assessment of prognosis in alcoholic liver disease: can serum hyaluronate replace liver biopsy?

1. Only 15-20% of chronic alcohol misusers ever develop cirrhosis. 2. Currently it is not possible to predict clinically who will develop progressive fibrotic alcoholic liver disease. 3. Liver biopsy is currently the gold standard diagnostic test in alcoholic liver disease, but it has associated morbidity and mortality. 4. Serum hyaluronic acid is a simple non-invasive test that may be able to give an estimate of the severity of fibrosis in alcoholic liver disease. The full clinical assessment of alcoholic liver disease includes liver biopsy, since accurate clinical prediction of the severity of liver damage is extremely difficult in all except very advanced cases. Unfortunately, liver biopsy has an associated complication rate and is contraindicated in, or unacceptable to, some patients. A reliable non-invasive test of the severity of fibrotic disease would be clinically useful at initial clinical assessment in some patients with alcoholic liver disease. Such a test would be more useful in subsequent monitoring of disease progression, and in particular may diminish the need for follow-up liver biopsy. Serum hyaluronic acid has been put forward as such a non-invasive test. Based on current evidence, serum hyaluronic acid may well be a useful adjunctive test in the assessment of certain categories of alcoholic liver disease patients, but at present it is unlikely to displace liver biopsy as the investigation of choice in alcoholic liver disease.

Biomarkers↗
PubMed1995

Hypothalamic-pituitary-testicular function in end-stage non-alcoholic liver disease before and after liver transplantation.

OBJECTIVE: Gonadal dysfunction is common in chronic liver disease, but most of the previous studies have been restricted to men with alcohol-induced liver disease. We have evaluated hypothalamic-pituitary-testicular function in patients with end-stage non-alcoholic liver disease before and at 6 and 12 months after hepatic transplantation. DESIGN: A prospective study of hypothalamic-pituitary-testicular endocrine function before and after cadaveric hepatic transplantation. PATIENTS: Fifty four consecutive patients with end-stage, non-alcoholic liver disease were evaluated before and after liver transplantation. MEASUREMENTS: Hypothalamic-pituitary-testicular (HPT) axis function was evaluated under basal conditions by single morning measurements of plasma total and free testosterone, sex hormone-binding globulin and by plasma LH and FSH responses to 100 micrograms i.v. GnRH. RESULTS: Men with chronic non-alcoholic liver disease had reduced levels of total and free testosterone and increased levels of SHBG compared with controls with normal liver function. Total and free testosterone were positively correlated with basal and stimulated LH (but not FSH) concentrations. Gonadotrophin responses to GnRH were preserved but delayed compared with healthy controls consistent with a predominantly hypothalamic defect in regulation of pituitary-testicular function. Increasing severity of underlying liver disease was associated with declining total and free testosterone as well as peak GnRH-stimulated LH concentrations. Spironolactone treatment was associated with decreased circulating testosterone levels only in men with liver disease of intermediate severity (Child-Pugh class B). Following hepatic transplantation, total and free testosterone and SHBG concentrations returned progressively towards eugonadal control levels over the first 12 months but total and free testosterone levels remained subnormal. CONCLUSIONS: Hypothalamic-pituitary regulation of testicular function is impaired in end-stage non-alcoholic liver disease in proportion to the severity of underlying liver disease. Spironolactone reduces circulating testosterone but only among men with Child-Pugh B liver cirrhosis. Gonadal function improves, but is not normalized, over the first year following successful liver transplantation.

Adolescent↗
PubMed2005

Neonatal hemochromatosis: fetal liver disease leading to liver failure in the fetus and newborn.

Acute liver failure in the newborn is relatively rare but often fatal. The broadest definition of acute liver failure is failure of the vital functions of the liver occurring within weeks or a few months of the onset of clinical liver disease. Therefore, by definition, any liver failure in the newborn can be construed to be acute liver failure. A second component of the general definition of acute liver failure is the lack of known preexisting liver disease. In the case of neonatal acute liver failure, preexisting disease would by definition be liver disease that affects the fetus. Almost nothing is known about fetal onset liver failure, and there is no literature addressing the subject. This review will address fetal liver disease that leads to liver failure in the fetus or newborn.

Female↗
PubMed2005

Outcome from molecular adsorbent recycling system (MARS) liver dialysis following drug-induced liver failure.

RATIONALE: Fulminant liver failure from drug ingestion is associated with a high mortality, and the introduction of liver transplantation has improved the mortality significantly if done in a timely fashion. Recently, molecular adsorbent recycling system (MARS) liver dialysis has been introduced as a support for liver failure with varying results. We review our experience with drug-induced liver failure and the impact of MARS liver dialysis on the outcome, in a setting where cadaveric liver transplantation is rarely available. RESULTS: A total of 13 patients were treated, and 40 sessions of MARS liver dialysis were conducted in the intensive care unit. The majority of cases were because of herbal medicine toxicity. Total bilirubin, conjugated bilirubin, and delta bilirubin were significantly reduced, with no change in unconjugated bilirubin. All patients satisfied the criteria for urgent liver transplantation with an average Model End Stage Liver Disease (MELD) score of 35. Only one patient received a liver transplantation from a live donor (right lobe). Overall mortality was 85%. Median time-to-death from the start of MARS was 8 days. CONCLUSIONS: MARS liver dialysis in a setting without timely liver transplantation is associated with a poor outcome. It does, however, provide a window of time for consideration of living donors in the setting of limited cadaveric donors.

Adult↗
PubMed1998

Serum IgA antibodies to human gut luminal aspirates and human liver in alcoholic liver disease.

BACKGROUND: Elevation of serum IgA is a characteristic feature of alcoholic liver disease. It has been proposed that this occurs partly as an antigenic response to gut-derived proteins or acetaldehyde-modified liver proteins, but the principal antigens responsible remain unknown. AIMS: The goal of this study was to determine if serum IgA antibodies were present against human gut luminal antigens or liver antigens in alcoholic liver disease. PATIENTS AND METHODS: Twenty-nine patients with alcoholic liver disease, 10 with primary biliary cirrhosis, 12 with "other" liver diseases, 8 alcoholics, and 20 healthy subjects were studied. Western blotting was used to examine the reactivity of sera from these groups against human small and large bowel aspirates and liver tissue from alcoholic liver disease patients. RESULTS: Serum IgA antibodies to a 140 kDa colonic luminal protein were found in 22 (76%) patients in the alcoholic liver disease group (p < 0.0001), and 7 (24%) patients had serum IgA antibodies to a 40 kDa colonic luminal protein (p = 0.04). These responses were confined to colonic aspirates and not observed in other disease groups, alcoholics or healthy subjects. There was no significant serum IgA response to human liver proteins in alcoholic liver disease. CONCLUSIONS: Serum IgA antibodies to a human 140 kDa colonic luminal protein are frequently found in alcoholic liver disease. This novel antigen may contribute to the increased levels of circulating IgA in alcoholic liver disease.

Adult↗
PubMed2001

Frequent detection of the human herpesvirus 6-specific genomes in the livers of children with various liver diseases.

This study was performed to investigate the frequency of human herpesvirus 6 (HHV-6) infection of the liver in children with a variety of liver diseases and to evaluate the role of HHV-6 infection in pediatric patients with prolonged non-B non-C hepatitis. Detection of the HHV-6 genomes in liver, in peripheral blood mononuclear cells (PBMC), and in plasma was performed by PCR or by in situ hybridization. Liver biopsy materials from 48 patients, in whom HHV-6 infection was serologically confirmed, were available for PCR analysis. Sequences of the HHV-6B genome were detectable in the livers of 36 of 48 patients (75%). The presence of the genome was not associated with serum transaminase activities. The genome was detectable in PBMC of 22 of 31 (71%) patients tested. In these 31 patients HHV-6 was detected in both the livers and PBMC of 20, was detected in PBMC but not in the livers of 2, was detected in the livers but not in PBMC of 3, and was detected in neither of samples of 6. In situ hybridization of the livers of six patients showed the presence of the HHV-6B genome in the nuclei of hepatocytes. The anti-HHV-6 immunoglobulin M antibody was detectable in 2 of 9 of the non-B non-C hepatitis patients, whereas none of the 22 patients with etiology-defined liver diseases tested positive. Cell-free viral DNA was not detectable in either group of patients. Our results showed that HHV-6B is frequently present in the livers of children with a variety of liver diseases but do not support the assumption that HHV-6B infection of the liver is associated with prolonged non-B non-C hepatitis.

Adolescent↗
PubMed2003

Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis.

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.

Animals↗
PubMed2006

Evaluation of ornithine carbamoyl transferase and other serum and liver-derived analytes in diagnosis of fatty liver and postsurgical outcome of left-displaced abomasum in dairy cows.

OBJECTIVE: To evaluate postsurgical outcome in dairy cows with left-displaced abomasum (LDA) with regard to severity of fatty liver and assess the usefulness of preoperative determination of serum ornithine carbamoyl transferase (OCT) activity, bile acids concentration, and other variables for evaluating liver function during the postsurgical convalescence period. DESIGN: Prospective study. ANIMALS: 68 Holstein cows. PROCEDURES: Blood and liver biopsy specimens were obtained during standing LDA surgery. Liver tissue was examined histologically and classified by severity of fatty change. Serum activities of liver-derived enzymes and concentrations of total lipids, triglycerides, bile acids, glucose, beta-hydroxybutyric acid, bilirubin, and nonesterified fatty acids were determined. RESULTS: Most cows with LDA and cows with severe fatty liver were detected within the first month after calving. Postsurgical outcome was related to severity of fatty liver. All cows that died had severe fatty liver. Serum activities of OCT, aspartate aminotransferase, and glutamate dehydrogenase and serum total bilirubin concentration were sensitive indicators of fatty liver. Serum bile acids concentration was not an accurate indicator of fatty liver. CONCLUSIONS AND CLINICAL RELEVANCE: Postsurgical outcome of cows undergoing surgery to correct LDA was related to fatty liver severity. Assessment of serum activities of OCT, aspartate aminotransferase, and glutamate dehydrogenase and serum total bilirubin concentration is recommended for diagnosis of fatty liver in dairy cows with LDA, whereas determination of bile acids concentration is not. The strong correlation between OCT activity and degree of hepatocellular damage supports use of this enzyme for assessing severity of fatty liver and predicting postsurgical outcome in cows with LDA.

Abomasum↗
PubMed1999

Total serum bile acid concentrations in dairy cows with fatty liver and liver failure.

In forty-five Holstein Frisian dairy cows (1-6 weeks post partum; mean age: 5.1 +/- 1.2 years) the serum total bile acid concentrations (SBA) were measured enzymatically. In all cows a left sided abomasal displacement was corrected surgically by right side laparotomy and omentopexy three days before investigation. The liver fat content was determined in all cows histologically. Liver failure was assumed if typical clinical signs (ataxia, general depression, recumbency or coma), an increased venous plasma ammonia level (> 35 mumol/l) and a decreased plasma amino acid index (< 4.0) were found. Cows without liver failure (N = 29) were grouped according to the liver fat content as cows with mild (N = 5), moderate (N = 19) or severe hepatosteatosis (N = 5). Histological examination of liver biopsies in cows with liver failure (N = 16) revealed in twelve cases a severe fatty liver and in four cases a hydropic degeneration of the liver tissue. Although in cows without liver failure mean SBA concentrations were higher in the group with moderate (47.3 +/- 30.9 mumol/l) or severe fatty liver (32.9 +/- 21.7 mumol/l) than in that with mild lipidosis (18.0 (16.8 mumol/l), differences were not significant. The mean SBA concentration in cows with liver failure (70.5 +/- 49.5 mumol/l) was only significantly (p < 0.05) increased compared to cows with uncomplicated mild hepatic lipidosis. In conclusion, the determination of SBA concentrations is of little value in the recognition of fatty liver or even liver failure due to the considerable variance of SBA concentrations in dairy cows.

Abomasum↗
PubMed2000

Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

Adult↗
PubMed2001

[Clinical significance of anti-liver-type arginase autoantibody in blood of recipients after partial liver transplantation].

Autoantibody against human liver-type arginase was detected in blood of patients treated with partial liver transplantation and consisted of all subclasses of IgG, i.e., IgG1, IgG2, IgG3 and IgG4, and IgM. We newly constructed an ELISA system for the antibodies by the aid of arginase protein immunopurified from extracts of human liver tissues. Addition of 2.0 mol/l urea in 0.1 mol/l citrate buffer(pH 4.5) was effective for elimination of immunoglobulins, such as IgG and IgM, and rheumatoid factors adsorped non-specifically to liver-type arginase-autoantibody complexes on the plate. We found that, during a short period of about two months after operation, in successful cases, liver-type arginase increased, remarkably and repeatedly, in blood of recipients followed by elevation of IgM level within a week and also IgG2 level two or three weeks later. Thus the change in IgG2 level seemed to depend on those of the arginase and/or IgM. However, in unsuccessful cases, such fluctuation was not so clear as the successful cases. To be noteworthy was production of autoantibodies directed to liver-type arginase in blood of patients with liver injury although the arginase, as well as AST and ALT, is an enzyme which leaks out of liver tissue. Appearance of the autoantibodies in blood supports occurrence of liver injury, in part, in graft liver because the enzyme exists exclusively in the liver. Among immunoglobulins to liver-type arginase, IgG2 seemed to be the most helpful index to know rightly postoperative conditions of recipients of liver transplantation, and its measurement could be useful for long-term follow-up of the patients.

Arginase↗
PubMed2003

[Effect of auxiliary heterotopic partial liver transplantation on the pig with acute ischemic liver failure].

OBJECTIVE: To study the effect of auxiliary heterotopic partial liver transplantation on the pig with acute ischemic liver failure. METHODS: When portal vein was shrinked more than 85 percent and artery was ligated or reserved, auxiliary heterotopic partial liver transplantation was performed in the pigs. The living condition, liver function, blood supply, pathological change and bile secretion of donor liver were observed, analysed and summarized. RESULTS: In the artery-ligated pigs, the volume of original liver reduced and the hepatocytes were necrotic evidently. While in the artery-reserved pigs, the colour and hepatocytes of original liver were normal. The volume of donor liver augmented, and the hepatocytes lived and proliferated well. CONCLUSIONS: Liver artery-ligated and portal vein-shrinker can result in acute ischemic liver failure, and auxiliary heterotopic partial liver transplantation is effective to treat this liver failure. reducing portal vein blood supply is little harmful to liver.

Animals↗
PubMed1996

Cell-based therapy of acute liver failure: the extracorporeal bioartificial liver.

The need for an alternative treatment to orthotopic liver transplantation for acute liver failure is a major issue, and systems capable of temporarily providing liver functions are being actively tested. Liver assist devices based on detoxication by dialysis or hemoperfusion through various membranes or cartridges proved to be inefficient because of their lack of metabolic function. An extracorporeal hybrid bioartificial liver might be an appropriate treatment, since it can provide liver-specific functions, maintain the patient alive, and allow spontaneous recovery of the patient's own liver or act as a bridge toward liver transplantation. Many devices have been proposed, including flat culture substrates, hollow-fiber bioreactors, or microcarriers, using xenogenic hepatocytes or hepatoma cell lines. Various drawbacks of these devices led us to attempt to develop a reliable extracorporeal bioartificial liver based on alginate bead-entrapped hepatocytes. This system was used successfully for the correction of the Gunn rat genetic defect, which results in lack of bilirubin conjugation. The development of this system for clinical purposes requires large yields of functional hepatocytes. We have isolated normal porcine hepatocytes by collagenase perfusion of the liver. Cells were immobilized in membrane-coated alginate gel beads, which were subsequently inoculated into a bioreactor. Porcine hepatocytes expressed liver-specific functions at high levels, particularly protein neosynthesis and enzymatic activities involved in detoxication and biotransformation processes. In addition, hepatocytes entrapped in coated alginate beads were isolated from immunoglobulins. This system represents a promising tool for the design of an extracorporeal bioartificial liver in human beings.

Animals↗