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At least 811 records · Page 45Linked to original sources
PubMed2006

Variable degree of liver involvement in siblings with PiZZ alpha-1-antitrypsin deficiency-related liver disease.

PiZZ alpha-1-antitrypsin deficiency is the commonest genetic cause of chronic liver disease, but only 10-15% of PiZZ individuals develop liver disease in childhood. Studies have demonstrated varying patterns of disease progression within siblings with the PiZZ phenotype. We retrospectively analysed the case-notes of all patients diagnosed with PiZZ A1ATD between 1978-2002 and compared the pattern of liver disease between affected siblings. We identified 29 families with more than 1 child with the PiZZ phenotype. Twenty-one (72%) PiZZ siblings of the 29 probands had liver disease, which was concordant for severity in 6 (29%), while 8 (28%) had no liver involvement. Five of 7 children requiring liver transplantation had siblings with no persistent liver dysfunction. This study suggests that there is a variable degree of liver involvement in siblings with PiZZ A1ATD-related liver disease and environmental and/or other genetic factors must be involved in determining disease severity.

Aspartate Aminotransferases↗
PubMed2005

Ischemic preconditioning impairs liver regeneration in extended reduced-size livers.

OBJECTIVE: To evaluate the effect of ischemic preconditioning (IPC) in an experimental setting of extended liver resection with 30 minutes of inflow occlusion in rats. SUMMARY BACKGROUND DATA: IPC has been proven an effective strategy against hepatic ischemia-reperfusion injury in both animal and human studies. However, decreased protective effects in terms of transaminase levels were found in patients with larger resection volume, questioning the benefit of IPC in case of small liver remnants. METHODS: Rats undergoing 90% hepatectomy under strict inflow occlusion for 30 minutes were subjected to either receive or not receive an IPC period (5 minutes of ischemia followed by 30 minutes of reperfusion). In addition to 10-day survival rate, laser Doppler flowmetry of hepatic blood flow and fluorescence microscopic analysis of the hepatic microcirculation were performed to assess the effect of IPC on initial microvascular reperfusion of liver remnants after 90% resection. Moreover, regeneration capacity of livers undergoing IPC and 70% resection was studied over 7 days by means of histology and immunohistochemistry. RESULTS: Ten-day survival of rats which underwent IPC and 90% hepatectomy was 0 out of 10 animals versus 1 out of 10 animals without IPC. Hemodynamic and microcirculatory analysis revealed signs of hyperperfusion during initial reperfusion of preconditioned liver remnants in 90% hepatectomized animals. In addition to increased transaminase levels, IPC impaired hepatic proliferative response after 70% organ resection, as indicated by both a significant reduction in mitotic figures and Ki-67 nuclear staining of hepatocytes, as well as a decrease in restitution of liver mass. CONCLUSIONS: Though portal hypertension reflecting shear stress has been reported to trigger liver regeneration, remnant liver tissue after major hepatectomy may not benefit from hyperperfusion-induced trigger for cell cycle entry but is rather dominated from hyperperfusion-induced local organ injury. Further studies are required to finally judge on the harmfulness of IPC in extended liver resection.

Animals↗
PubMed2006

Laparoscopic liver resection for peripheral hepatocellular carcinoma in patients with chronic liver disease: midterm results and perspectives.

OBJECTIVE: Report the midterm results of laparoscopic resection for hepatocellular in chronic liver disease (CLD). SUMMARY BACKGROUND DATA: Surgical resection for hepatocellular carcinoma (HCC) in chronic liver disease (CLD) remains controversial because of high morbidity and recurrence rates. Laparoscopic resection of liver tumors has recently been developed and could reduce morbidity. METHODS: From 1998 to 2003, patients with HCC and CLD were considered for laparoscopic liver resection. Inclusion criteria were chronic hepatitis or Child's A cirrhosis, solitary tumor < or =5 cm in size, and location in peripheral segments of the liver. Mortality, morbidity, recurrence rates, and survival were analyzed. RESULTS: A total of 27 patients were included. Liver resections included anatomic resection in 17 cases and non anatomic resection in 10. Seven conversions to laparotomy (26%) occurred for moderate hemorrhage in 5 cases and technical difficulties in 2 cases. Mortality and morbidity rates were 0% and 33%, respectively. Postoperative ascites and encephalopathy occurred in 2 patients (7%) who both had undergone conversion to laparotomy. Mean surgical margin was 11 mm (range, 1-47 mm). After a mean follow-up of 2 years (range, 1.1-4.7), 8 patients (30%) developed intrahepatic tumor recurrence of which one died. Treatment of recurrence was possible in 4 patients (50%), including orthotopic liver transplantation, right hepatectomy, radiofrequency ablation, and chemoembolization in 1 case each. There were no adhesions in the 2 reoperated patients. Overall and disease-free 3-year survival rates were 93% and 64%, respectively. CONCLUSION: Our study shows that laparoscopic liver resection for HCC in selected patients is a safe procedure with very good midterm results. This approach could have an impact on the therapeutic strategy of HCC complicating CLD as a treatment with curative intent or as a bridge to liver transplantation.

Adult↗
PubMed2006

Pretransplant human herpesvirus 6 infection of patients with acute liver failure is a risk factor for posttransplant human herpesvirus 6 infection of the liver.

BACKGROUND: Acute liver failure (ALF) is a significant cause of liver transplantation. We have previously reported that human herpesvirus-6 (HHV-6) was found in most livers of patients with ALF of unknown origin ending up with liver transplantation. In this study, we investigated the posttransplant HHV-6 infection of the liver graft in these patients. METHODS: Thirty-two patients transplanted due to ALF were included in this retrospective study. Twelve of the 15 patients with unknown cause and four of 17 patients with a known cause of ALF had HHV-6 antigens in the explanted liver. Altogether, 18 patients had some pretransplant evidence of HHV-6. After transplantation, the patients were frequently monitored for the viruses, and biopsy histology was performed in every case of graft dysfunction. HHV-6 was demonstrated in liver tissue by immunohistochemistry. RESULTS: During the follow-up of 6 months, hepatic HHV-6 infection was demonstrated in 9 of the 18 patients, at a mean 19 days (6-38 days) after transplantation. All patients with posttransplant HHV-6 showed graft dysfunction. In biopsy histology, seven out of these nine patients demonstrated viral infection, one of them also having CMV antigens in the liver. None of those patients without evidence of pretransplant HHV-6 showed HHV-6 in the posttransplant biopsies. Posttransplant HHV-6 was not treated and the virus had no effect on 1-year patient or graft survivals. CONCLUSION: Pretransplant hepatic HHV-6 infection of patients with ALF is a risk factor for posttransplant HHV-6 infection and liver dysfunction, but has no effect on 1-year graft or patient survival.

Female↗
PubMed2006

Review article: non-biological liver support in liver failure.

Liver failure, whether acute or acute-on-chronic, remains an important cause of morbidity and mortality. The lack of liver detoxification, metabolic and regulatory functions of the liver leads to life-threatening complications, such as renal failure, altered immune response, hepatic coma and systemic haemodynamic dysfunction, eventually culminating in multiorgan failure. Current medical therapy involves the management of the precipitating event and treatment of complications until the liver eventually recovers, leaving us with no other treatment options than transplantation if these attempts fail. However, the shortage in cadaveric organs and other transplant-related problems, have prompted the need for alternative methods to provide liver support. As liver failure is often potentially reversible, considerable effort has been invested in the development of liver support systems. Currently, most of the experience is available for non-biological support systems. They represent the focus of this review, which aims to define the goals of liver support, to describe the design of the different existing devices and to analyse the available data to determine their current status in the management of patients with liver failure.

Albumins↗
PubMed2005

Value of computed tomography-derived estimated liver volume/standard liver volume ratio for predicting the prognosis of adult fulminant hepatic failure in Japan.

BACKGROUND AND AIMS: The prognosis of fulminant hepatic failure (FHF) has been improved but is still unsatisfactory, and liver atrophy has been reported as a poor prognostic factor for this disease. The aim of this study was to assess the clinical value of the estimated liver volume (ELV) compared to the standard liver volume (SLV) in patients with FHF. METHODS: Estimated liver volume of 24 adult patients with FHF receiving artificial liver support (ALS) was measured by using computed tomography. Actual liver weight (ALW) was measured if possible, and the calculated ELV/SLV ratio was compared to the ALW/SLV ratio and the ALW/BW (bodyweight) ratio. Sequential ELV/SLV ratios during the clinical course were analyzed in relation to the prognosis. RESULTS: The ELV/SLV ratio was significantly correlated with both the ALW/SLV and ALW/BW ratios. The mean ALW/SLV ratio of patients who underwent living donor liver transplantation (LDLT) was 0.59 +/- 0.17. The mean ELV/SLV ratio at the time of starting ALS (day 0) in the patients who survived (group 1) was 1.081 +/- 0.183, but that of cases who underwent LDLT or died without LDLT (group 2) was 0.764 +/- 0.255. The mean ELV/SLV ratios were 1.084 +/- 0.222 and 0.650 +/- 0.195 in groups 1 and 2, respectively, 5 days after starting ALS (day 5). Among the group 2 patients, those who had no liver atrophy on day 0 had a significantly decreased ELV/SLV ratio on day 5. CONCLUSIONS: These results suggest that the ELV/SLV ratio is a very useful objective marker to estimate liver atrophy and this marker reflects the prognosis of FHF patients very well.

Adult↗
PubMed1993

Atypical liver alcohol dehydrogenase in the Spanish population: its relation with the development of alcoholic liver disease.

The presence of atypical liver alcohol dehydrogenase (ADH) was determined in samples of liver tissue from 222 alcoholic and nonalcoholic subjects to determine its prevalence in the Spanish population, and to evaluate the possible relationship between the presence of this isoenzyme and the development of alcoholism and alcoholic liver disease. Alcoholic patients were classified into the following groups: control subjects, with normal liver pathology (group 1), patients with noncirrhotic liver disease (group 2), and patients with cirrhosis of the liver (group 3). Nonalcoholic subjects were also divided, following the same criteria, into groups 4, 5, and 6, respectively. The prevalence of atypical ADH in the population analyzed was 16.2%. Atypical ADH was present in 14.9% of alcoholics and in 17.4% of nonalcoholics (p = NS). There were no significant differences when the prevalence of atypical ADH of alcoholic and nonalcoholic patients with similar degrees of liver pathology was compared (group 1 vs. 4, group 2 vs. 5, and group 3 vs. 6). The prevalence of atypical ADH was also similar in cirrhotic patients with respect to those of noncirrhotic liver disease and control patients, either in alcoholic or nonalcoholic groups. Our findings indicate that the prevalence of atypical ADH in the Spanish population is similar to that reported for other Caucasian groups. Moreover, the presence of atypical ADH does not play a role in the development of alcoholism nor in the development of alcoholic liver disease in the population analyzed.

Adolescent↗
PubMed2006

Gene expression profiling of acute liver stress during living donor liver transplantation.

During liver transplantation, the donor graft is subjected to a number of acute stresses whose molecular basis is not well-understood. The effects of surgical stress, preservation and reperfusion injury were studied in 24 consecutive living donor liver transplant (LDLT) operations. Liver biopsies were taken early in the donor operation (OPENING), after transection of the donor liver (PRECLAMP) and following implantation of the graft (post hepatic artery, [PHA]); these were evaluated for histology, tissue glutathione content and gene expression using a 19K-human cDNA microarray. LDLT was associated with an ischemia/reperfusion injury, with accumulation of small numbers of neutrophils and decreased glutathione in the PHA biopsies. Following reperfusion, the expression of 129 genes increased and 106 genes decreased when compared to OPENING levels (> or <2-fold, p < 0.01). By real-time PCR a subset of 25 genes was verified (15 increased, 10 decreased). These genes were similarly altered in another condition of acute liver stress (the response to brain-death), but not in three chronic liver disease states (HCV, HBV and PBC). This study has identified a set of genes whose expression is altered in acute, but not chronic, liver stress, likely to play a central role in the pathogenesis of acute liver injury of liver transplantation.

Adult↗
PubMed1983

Liver membrane antibodies in alcoholic liver disease. II. Antibodies to ethanol-altered hepatocytes.

Using an indirect immunofluorescence technique, circulating liver membrane antibodies against normal rabbit hepatocytes and ethanol-altered rabbit hepatocytes have been sought in a series of patients with histologically confirmed alcoholic liver disease. Liver membrane antibodies against normal hepatocytes were found in 18 (28%) of the 65 sera examined, but with ethanol-altered hepatocytes as substrate liver membrane antibodies were found in 48 (74%) of the sera. Isolation of F(ab')2 fragments confirmed that the positive results were due to antibody binding. Liver membrane antibodies against ethanol-altered hepatocytes are peculiar to alcoholic liver disease, and there is a similar incidence in the various histological types of alcoholic liver disease. Absorption studies suggest that the liver membrane antibodies are directed against new or altered antigens which are not present in normal hepatocytes. These new or altered antigens may also appear after pretreatment with other primary alcohols and seem likely to be induced by a haptenic effect of the alcohol or a metabolic break-down product. These studies represent a novel approach to the further investigation of the possible role of immunological mechanisms in alcohol-induced liver injury.

Absorption↗
PubMed1999

Portal blood flow and liver regeneration in auxiliary partial orthotopic liver transplantation in a canine model.

Functional competition has been shown to lead to a detrimental outcome in auxiliary liver transplantation. We evaluated the interaction in auxiliary partial orthotopic liver transplantation between the native liver and the graft in terms of portal flow and regeneration. The need for diversion of the portal flow to the graft was also assessed. Reduced-size liver grafts were transplanted orthotopically after partial hepatectomy in beagles. There were two groups: the preserved group, where portal inflow to the native liver was preserved, and the ligated group, where it was interrupted. Portal flow was measured serially and liver regeneration was evaluated on postoperative day 5. Functional competition was not observed in the preserved group. On the other hand, ligation of the native liver portal vein had no obviously detrimental effects on the remnant native liver. This leads to the conclusion that the portal vein to the native liver can be safely ligated to prevent functional competition.

Animals↗
PubMed1986

[Effects of gomisin A, a lignan component of Schizandra fruits, on experimental liver injuries and liver microsomal drug-metabolizing enzymes].

Effects of oral administration of gomisin A, one of the components isolated from Schizandra fruits, on liver injuries induced by CCl4, d-galactosamine and dl-ethionine and on liver microsomal drug-metabolizing enzyme activities were investigated. Gomisin A suppressed the increase of serum transaminase activities and the appearances of histological changes such as degeneration and necrosis of hepatocyte, inflammatory cell infiltration and fatty deposition in each type of liver injury. The repeated administration of gomisin A (30 or 100 mg/kg, p.o., daily for 4 days) induced an apparent increase of liver weight in liver-injured and normal rats. Gomisin A decreased serum triglyceride and lipid contents of the liver in biochemical studies. Increases of microsomal cytochrome b5 and P-450, elevations of NADPH cytochrome C reductase, aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities and decrease of 3,4-benzo(a)pyrene hydroxylase activity per cytochrome P-450 were observed after the administration of gomisin A. In addition, gomisin A was found to enhance the incorporation of 14C-phenylalanine into liver protein and to shorten the hexobarbital-induced sleeping time. These changes caused by gomisin A were similar to those by phenobarbital. However, gomisin A is distinctly different from phenobarbital in the finding that phenobarbital lessened the survival ratio of CCl4-intoxicated mice, but gomisin A did not. Our observation suggest that gomisin A shows an antihepatotoxic action by oral application and also has hypolipidemic (mainly triglyceridemic) and liver protein synthesis-facilitating actions and that the enlargement of the liver seen with gomisin A is the adaptive hypertrophy which is due to the induction of drug-metabolizing enzymes.

Animals↗
PubMed2005

Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease.

AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease. However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type VI collagen 7S domain and hyaluronic acid. METHODS: One hundred and twelve patients with histologically proven NAFLD were studied. RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type VI collagen 7S domain > or =5.0 ng/mL, hyaluronic acid > or =43 ng/mL. Both markers had a high positive predictive value: type VI collagen 7S domain, 86% and hyaluronic acid, 92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type VI collagen 7S domain (> or =5.0 ng/mL), 84% and hyaluronic acid (> or =50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis. CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis.

Adult↗
PubMed2001

TECA hybrid artificial liver support system in treatment of acute liver failure.

AIM: To assess the efficacy and safety of TECA type hybrid artificial liver support system (TECA-HALSS) in providing liver function of detoxification, metabolism and physiology by treating the patients with acute liver failure (ALF). METHODS: The porcine liver cells (1-2) x 10(10) were separated from the Chinese small swine and cultured in the bioreactor of TECA-BALSS at 37.0 degrees C and circulated through the outer space of the hollow fiber tubes in BALSS. The six liver failure patients with various degree of hepatic coma were treated by TECA-HALSS and with conventional medicines. The venous plasma of the patients was separated by a plasma separator and treated by charcoal adsorbent or plasma exchange. The plasma circulated through the inner space of the hollow fiber tubes of BALSS and mixed with the patients' blood cells and flew back to their blood circulation. Some small molecular weight substances were exchanged between the plasma and porcine liver cells. Each treatment lasted 6.0-7.0 h. Physiological and biochemical parameters were measured before,during and after the treatment. RESULTS: The average of porcine liver cells was (1.0-3.0) x 10(10) obtained from each swine liver using our modified enzymatic digestion method. The survival rate of the cells was 85%-93% by trypan blue stain and AO/PI fluorescent stain. After cultured in TECA-BALSS bioreactor for 6 h, the survival rate of cells still remained 70%-85%. At the end of TECA-HALSS treatment, the levels of plasma NH(3), ALT, TB and DB were significantly decreased. The patients who were in the state of drowsiness or coma before the treatment improved their appetite significantly and regained consciousness, some patients resumed light physical work on a short period after the treatment. One to two days after the treatment, the ratio of PTA increased warkedly. During the treatment, the heart rates, blood pressure, respiration condition and serum electrolytes (K(+), Na(+) and Cl(-)) were stable without thrombosis and bleeding in all the six patients. CONCLUSION: TECA-HALSS treatment could be a rapid, safe and efficacious method to provide temporary liver support for patients with ALF.

Acute Disease↗
PubMedDate not supplied

Serum acute-phase protein level as indicator for liver failure after liver resection.

BACKGROUND/AIMS: We investigated the relationship between postoperative liver failure and serum acute-phase protein level before and after liver resection. METHODOLOGY: Thirty-four patients who underwent liver resection were prospectively included. Serum concentrations of negative (albumin, prealbumin and retinol-binding protein) and positive (orosomucoid, haptoglobin and C-reactive protein) acute-phase proteins were assayed prior to surgery (baseline) and on postoperative day 3, 12 and 45. Postoperative liver failure was defined as serum bilirubin more than 50 micromol/L or prothrombin time less than 50% on postoperative day 7. Univariate analysis was performed to compare patients who did and did not present postoperative liver failure. RESULTS: Postoperative liver failure occurred in 8 cases and was correlated with: 1) higher negative and lower positive acute-phase protein levels (p<0.04) at baseline, 2) lower negative and lower positive acute-phase protein levels on postoperative day 3, 12 or 45 (p< or =0.05). CONCLUSIONS: Early onset of inflammatory serum protein profile was correlated with absence of postoperative liver failure. Serum acute-phase protein could be used as predictor as well as early postoperative diagnosis marker of postoperative liver failure. Relationship between preoperative inflammation and postoperative liver failure warrants further investigations because of potential therapeutic consequences.

Acute-Phase Proteins↗
PubMed1979

[Effects of thiol compounds on experimental liver damage (II). Preventive and therapeutic effects of tiopronin (2-mercaptopropionylglycine) and glutathione on ethionine induced liver damage (author's transl)].

Preventive and therapeutic effects of tiopronin (2-mercaptopropionylglycine) and glutathione on ethionine induced liver damage were studied. Administration of 1 g/kg ethionine resulted in significant differences in the degree of liver damage, and such was dependent on the feeding conditions of the animals. The present experiment was performed under the conditions where the most serious liver damage was observed. In the experiment on the preventive effects, serum GOT and GPT were markedly elevated by ethionine, but such elevation could be suppressed by administering tiopronin or glutathione 10 min before ethionine administration. Liver nonprotein thiol (NPSH) content decreased by 40--60% of the normal level 16 hr after ethionine adminstration, but increased by 30--45% 24 hr later. Administration of tiopronin suppressed the initial fall of liver NPSH content caused by ethionine, but this tendency was not observed in the glutathione treatment. Both liver cholesterol and triglyceride increased in the ethionine treated rats, and triglycerides in particular decreased with administration of tiopronin or glutathione. In the experiment on the therapeutic effects, the maximal values of serum GOT and GPT brought by ethionine were suppressed by the thiol compounds given 16 hr after ethionine administration, but liver NPSH content and liver lipids were not influenced. Thus, tiopronin and glutathione are considered to have preventive and therapeutic effects on liver damage induced by ethionine.

Amino Acids, Sulfur↗
PubMed1984

Retinyl palmitate, retinyl phosphate, and dolichyl phosphate of postnuclear membrane fraction from hepatoma, host liver, and regenerating liver: marginal vitamin A status of hepatoma tissue.

The retinyl palmitate content of the postnuclear membrane fraction from 10 Morris hepatomas, their host rat livers, one acetylaminofluorene-induced rat liver hepatoma, and the host liver and of regenerating rat liver was measured by reverse-phase high-pressure liquid chromatography of the chloroform:methanol extracts. Membranes from the hepatoma tissue contained less than detectable levels of retinyl acyl esters, whereas membranes from host liver tissue and regenerating liver contained levels of retinyl palmitate within normal ranges. The amount of cellular retinol-binding protein was also decreased considerably in cytosols from 9618 and 7777 hepatomas. The ratio of endogenous retinyl phosphate to the polyisoprenoid dolichyl phosphate available for mannosylation in an assay containing postnuclear membranes and guanosine dephospho[14C] mannose was decreased by a factor of 3 to 10 in hepatoma tissue. Such change in ratio was not attributable to specific changes in retinyl phosphate mannose-synthesizing activity, but it appeared to be related to the vitamin A deficiency condition of the membrane from tumors. As for membranes from vitamin A-deficient liver tissue, postnuclear membranes from rat cystic hepatocarcinoma, Morris 7777, 3924A1-1, and 5123D-1-2 transplantable rat hepatomas and guinea pig line 10 hepatoma all synthesized a mannolipid with intermediate hydrophobic properties between retinyl phosphate mannose and dolichyl phosphate mannose and not normally found in liver tissue. These alterations in patterns of lipid intermediates may be responsible for altered glycosylation of glycoproteins in neoplastic cells. In conclusion, the present investigation establishes that hepatoma cell membrane is in a status of vitamin A and of retinyl phosphate depletion, while dolichyl phosphate contents appear similar to host liver membrane.

Animals↗
PubMed1993

Clearance by the liver in cirrhosis. I. Relationship between propranolol metabolism in vitro and its extraction by the perfused liver in the rat.

To delineate the factors responsible for impaired clearance in cirrhosis, we examined propranolol disposition in rats with carbon tetrachloride-induced cirrhosis and compared it with that in control animals, rats treated with chlorpromazine (an inhibitor of propranolol metabolism) and rats with acute liver injury. We measured the extraction ratio of propranolol by the isolated perfused liver and related it to estimates of propranolol drug-metabolizing enzyme activity in homogenates of the same livers. In control animals, drug-metabolizing enzyme activity (measured as the ratio Vmax/Km) averaged 5,319 +/- 1,193 ml/min; the extraction ratio in the perfused liver was close to 1.0 (0.97 +/- 0.01). Important decreases of microsomal enzyme activity were observed in rats treated with chlorpromazine (30 +/- 27 ml/min, p < 0.001) and in rats with acute liver injury (724 +/- 401 ml/min, p < 0.001), accounting for the decrease in the hepatic extraction ratio by the perfused liver (0.33 +/- 0.09 and 0.71 +/- 0.04, respectively, p < 0.01). In cirrhotic livers, enzyme activity was not significantly different from that of controls (3,592 +/- 1,857 ml/min) and could not account for the observed decrease in extraction (0.66 +/- 0.14, p < 0.01). The extraction of antipyrine by the isolated perfused liver was also measured as an index of microsomal enzyme activity and related to propranolol extraction. Antipyrine extraction was decreased by 90% in acute liver injury, compared with 33% in cirrhosis, suggesting a much greater reduction of microsomal enzyme activity in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Immunological consequences of the use of xenogeneic hepatocytes in a bioartificial liver for acute liver failure.

The use of cells from xenogeneic origin in a bioartificial liver can have a number of immunological consequences, not only for the cells in the bioartificial liver but also for the patient receiving the bioartificial liver treatment. The impact of these consequences will depend on the immune status of the patient receiving bioartificial liver treatment, the duration and frequency of the treatment and on the extent of interaction between the patients blood (or plasma) and the xenogeneic liver cells. In an experimental model we infused rats with a culture supernatant of pig hepatocytes and demonstrated using Western blots and immunohistological techniques that antibodies are raised against the very small amounts of the pig hepatocyte-derived proteins present in the culture medium. Potential problems of bioartificial liver destruction and the possibility of hypersensitivity reactions due to the secretion of xenogeneic proteins into the circulation of the patient are discussed. Because the liver has an important role in the clearance of immune complexes it is concluded that precautions should be taken when (repeated) application of a xenogeneic bioartificial liver in patients with liver failure is considered.

Animals↗