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Disruption of the middle hepatic vein is not crucial for liver regeneration of the remnant liver after right hemihepatectomy for hepatic tumors.

BACKGROUND: To clarify the role of the middle hepatic vein (MHV) in liver regeneration of the remnant liver after right hemihepatectomy for hepatic tumors, we reviewed 29 patients to evaluate liver regeneration for up to 12 postoperative months. METHODS: Volume regeneration of the remnant liver was investigated by computed tomography at 3, 6, and 12 postoperative months. The remnant liver was divided into the following three areas: the medial section (segment IV), the lateral section (segments II and III), and segment I. The patients were divided into two groups: group A (n = 17), in which the MHV was preserved in the remnant liver, and group B (n = 12), in which the MHV was removed. RESULTS: Volume regeneration of each area continued until 6 postoperative months but did not increase thereafter. On univariate analysis, differences in the volume regeneration of each area between the groups were not significant at any measured time point. Furthermore, disruption of the MHV was determined to not be crucial to the volume regeneration of any liver area on multivariate analysis. Only the resection volume (percentage) significantly affected liver regeneration of the remnant liver. CONCLUSIONS: Disruption of the MHV does not decisively affect liver regeneration of remnant liver after right hemihepatectomy for hepatic tumors.

Female↗

Liver cirrhosis and oestrogen metabolism--perfusion studies with cirrhotic rat livers.

1. Radioactive oestrone and oestradiol-17 beta were perfused through normal and cirrhotic livers of rats. Liver cirrhosis had been induced by a combined application of carbon tetrachloride and azathioprine. 2. The hepatic uptake of both oestrogens by cirrhotic livers was reduced; the uptake of oestrone was more affected than that of oestradiol-17 beta. 3. The pattern of oestrogen metabolites indicated a reduction of the sulphotransferase activity in cirrhotic livers. The activity of other enzymes of oestrogen metabolism were similar in normal and cirrhotic livers. 4. The amount of oestrogen glucuronides excreted into the bile was significantly less in cirrhotic livers although the bile volume was larger in cirrhotic than normal livers. 5. The release of oestrogen metabolites into the circulating medium was considerably higher during perfusion of cirrhotic livers. From the findings presented here it is concluded that the turnover of oestrogens is slower in cirrhotic than in normal livers. Moreover, it may be speculated that the distribution volume of the oestrogen metabolites is smaller in rats with liver cirrhosis, due to a disturbed enterohepatic circulation. This results in higher oestrogen concentrations in extracellular fluids, thus supporting the concept of hyper-oestrogenism in liver cirrhosis.

Animals↗

Genes for interleukin-1, interleukin-6, and tumor necrosis factor are expressed at markedly reduced levels in the livers of patients with severe liver disease.

The genes for interferon (IFN) alpha, IFN gamma, IL-1 beta, IL-6, and TNF alpha were transcribed at readily detectable levels both in liver biopsies from individuals with normal liver function and in samples of normal viable liver taken for transplantation. These results provided evidence for the concept that such multifunctional cytokines play a role in homeostasis in normal human tissues. In normal human liver, in situ hybridization studies showed that, in the absence of a detectable inflammatory response, both hepatocytes and mononuclear cells exhibited a similar degree of expression of IL-6 mRNA in keeping with the finding that IL-6 is produced by cells of different lineages. The levels of IL-1, IL-6, and TNF mRNA were found to be markedly reduced in extracts of the livers of patients with primary biliary cirrhosis and other forms of autoimmune liver disease at a time when extensive liver lesions were apparent, compared to the levels of expression of these cytokines in the livers of normal individuals. The reduced expression of IL-1, IL-6, and TNF mRNAs appeared to be a specific effect and not due to a general reduction in RNA synthesis as the IFN alpha, IFN gamma and actin mRNAs were expressed at similar levels in both normal and diseased livers. The levels of IL-1 beta, IL-6, and TNF mRNAs were also reduced in samples of liver from a patient with a drug induced fulminant hepatitis suggesting that this specific pattern of altered cytokine gene expression was characteristic of the advanced stage of severe liver disease.

Autoimmune Diseases↗

Expression of interferon-alpha/beta receptor protein in liver of patients with hepatitis C virus-related chronic liver disease.

AIM: To study the expression of interferon-alpha/beta (IFN-alpha/beta) receptor protein in liver of patients with hepatitis C virus (HCV)-related chronic liver disease and its clinical significance. METHODS: A total of 181 patients with HCV-related chronic liver disease included 56 with HCV-related liver cirrhosis (LC) and 125 with chronic hepatitis C (CHC). CHC patients were treated with five megaunits of interferon-?1b six times weekly for the first 2 weeks and then every other day for 22 wk. The patients were divided into interferon (IFN) treatment-responsive and non-responsive groups, but 36 patients lost follow-up shortly after receiving the treatment. The expression of IFN-alpha/beta receptor (IFN-alpha/betaR) protein in liver of all patients was determined with immunofluorescence. RESULTS: In liver of patients with HCV-related chronic liver disease, the expression of IFN-alpha/betaR protein in liver cell membrane was stronger than that in cytoplasm and more obvious in the surroundings of portal vein than in the surroundings of central vein. Moreover, it was poorly distributed in hepatic lobules. The weak positive, positive and strong positive expression of IFN-alpha/betaR were 40% (50/125), 28% (35/125), 32% (40/125), respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56), respectively in LC group. The positive and strong positive rates were higher in CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8% (10/36) showed weak positive expression; 72.2% (26/36) showed positive or strong positive expression. In the non-responsive group, 71.7% (38/53) showed weak positive expression; 28.3% (15/53) showed positive or strong positive expression. The expression of IFN-alpha/betaR protein in liver was more obvious in IFN treatment responsive group than in non-responsive group. CONCLUSION: Expression of IFN-alpha/betaR protein in liver of patients with HCV-related chronic liver disease is likely involved in the response to IFN treatment.

Antiviral Agents↗

Transplantation of fetal liver epithelial progenitor cells ameliorates experimental liver fibrosis in mice.

AIM: To investigate the effect of transplanted fetal liver epithelial progenitor (FLEP) cells on liver fibrosis in mice. METHODS: FLEP cells were isolated from embryonal day (ED) 14 BALB/c mice and transplanted into female syngenic BALB/c mice (n = 60). After partial hepatectomy (PH), diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received FLEP cells and non-supplemented drinking water, the model group received DEN-spiked water, and the experimental group received FLEP cells and DEN. Mice were killed after 1, 2, and 3 mo, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), and laminin (LN) in serum, and hydroxyproline (Hyp) content in liver were assessed. Alpha-smooth muscle actin (alpha-SMA) of liver was tested by immunohistochemistry. Transplanted male mice FLEP cells were identified by immunocytochemistry for sry (sex determination region for Y chromosome) protein. RESULTS: Serum ALT, AST, HA, and LN were markedly reduced by transplanted FLEP cells. Liver Hyp content and alpha-SMA staining in mice receiving FLEP cells were lower than that of the model group, which was consistent with altered liver pathology. Transplanted cells proliferated and differentiated into hepatocytes and bile duct epithelial cells with 30%-50% repopulation in the liver fibrosis induced by DEN after 3 mo. CONCLUSION: Transplanted FLEP cells proliferate and differentiate into hepatocytes and bile duct epithelial cells with high repopulation capacity in the fiberized liver induced by DEN, which restores liver function and reduces liver fibrosis.

Alanine Transaminase↗

Fatty liver suppressed the angiogenesis in liver metastatic lesions.

BACKGROUND/AIMS: We have demonstrated that colorectal cancer with fatty liver had few liver metastases clinically as well as experimentally. In this study, to clarify why colorectal cancer with fatty liver had few liver metastases, we focused on the angiogenesis of carcinomas. METHODOLOGY: The rat colon cancer cells (RCN-9) were injected into 40 rats (the fatty liver group = FL group includes 20 rats, the non-fatty liver group = NFL group includes 20 rats). In each group, the PyNPase (pyrimidine nucleoside phosphorylase) activity in the metastatic lesion of the liver was examined using the high-performance liquid chromatographic method. In addition, the microvessel density in the metastatic lesion of the liver was assessed by Von Willebrand factor-related antigen immunostaining. RESULTS: 1) The PyNPase activity in the FL group was 33.34 +/- 6.27 (microgram FU/mg protein/hr), which was significantly lower than that of the NFL group (49.30 +/- 14.82) (P = 0.0021). 2) Microvessel density in the FL group was 1.845 +/- 0.357 (%), while that in the NFL group was 2.777 +/- 1.371 (%). The microvessel density of the FL group was significantly lower than that of the NFL group (P = 0.0365). 3) The regression coefficient between PyNPase activity and microvessel density was 0.480, which indicated a significant correlation (P = 0.0098). CONCLUSIONS: We think that, in colorectal carcinomas with fatty liver, the decreased activity of PyNPase and the decreased neovascularization in the metastatic lesion are closely related to fewer liver metastasis compared with colorectal cancer patients without fatty liver.

Animals↗

[Correlation between liver fibrosis stage and serum liver fibrosis markers in patients with chronic hepatitis B].

OBJECTIVE: To evaluate the diagnostic value of serum liver fibrosis markers by analyzing the correlation between liver fibrosis stage in patients with chronic hepatitis B and serum liver fibrosis markers, such as hyaluronate, type III procollagen, laminin, and type IV collagen. METHODS: There were 278 patients with chronic hepatitis B in this series. Before liver biopsy, the serum was collected to test hyaluronate, type III procollagen, laminin, and type IV collagen. Data were analyzed statistically. RESULTS: Liver fibrosis stage was correlated to inflammation degree. In patients with moderate or serious liver inflammation and fibrosis, serum hyaluronate was above normal level, and correlated to liver inflammation and fibrosis. For patients with chronic hepatitis B, serum type III procollagen, laminin, and type IV collagen increased apparently. While laminin was correlated to liver fibrosis, type III procollagen and type IV collagen correlated to liver inflammation. CONCLUSIONS: Serum hyaluronate, type III procollagen, laminin, and type IV collagen could reflect the state of liver fibrosis. Hyaluronate may be a useful marker for liver cirrhosis.

Adolescent↗

[Treatment of severe hepatitis with artificial liver support system and liver transplantation].

OBJECTIVE: To observe and investigate the efficacy of the hybrid artificial liver support system plus liver transplantation in the treatments of patients with severe viral hepatitis. METHODS: Eight severe viral hepatitis patients with metaphase and advanced stage liver failure received the artificial liver support using a self-command extracorporeal hybrid artificial liver support system and orthotopic liver transplantation after the artificial support for 3-14 days. RESULTS: The liver failure of the 8 patients was controlled by the hybrid artificial liver support effectively. All patients were successfully bridged to orthotopic liver transplantation. Four out of the eight patients survived after transplantation. Four patients died of pulmonary infection or hepatorenal syndrome. CONCLUSIONS: Artificial liver support system combined with liver transplantation can be regarded as an efficient measure for the treatment of metaphase and advanced stage patients of severe viral hepatitis.

Adult↗

Quantitation of liver and spleen uptake of (99m)Tc-phytate colloid using SPECT: detection of liver cirrhosis.

UNLABELLED: The purpose of this study was to assess the diagnostic performance of quantitative SPECT of (99m)Tc-phytate colloid in detecting liver cirrhosis and to assess the correlation between the SPECT results and the severity of disease. METHODS: Quantitative SPECT was performed on 60 patients (38 men, 22 women; mean age, 62.4 y) with liver cirrhosis and 36 control patients (21 men, 15 women; mean age, 58.7 y) without liver cirrhosis, and the results for the 2 groups were compared. Correlation with Child--Pugh classification and receiver operating characteristic methodology was used to analyze the results. RESULTS: Cirrhotic livers had a lower total uptake than did control livers (35.6% plus minus 13.5% vs. 61.6% +/- 10.2%, P < 0.0001). This reduced uptake was associated with a significantly reduced percentage injected dose per cubic centimeter (%ID/cm(3)) (0.024 +/- 0.01 vs. 0.044 +/- 0.01, P < 0.0001). The volume, 1,467 +/- 348 cm(3), was similar to that of control livers (1,487 +/- 397 cm(3), P = 0.80). Total uptake in the spleen was significantly greater in patients with cirrhosis than in control patients (24.9% +/- 12% vs. 7.6% +/- 3.2%, P < 0.0001) because of an increased volume (833 +/- 460 cm(3) vs. 239 +/- 90 cm(3), P < 0.0001). The %ID/cm(3) of spleen tissue was 0.033 +/- 0.01, which was similar to the value in control patients (0.032 +/- 0.01, P = 0.88). Spleen volume showed the best performance in detecting liver cirrhosis, with a mean area under the curve of 0.97 (95% CI = 0.91--0.99). The severity of liver disease correlated better with total liver uptake (r = -0.68, 95% CI = -0.80 to -0.52, P < 0.0001). CONCLUSION: Individual SPECT quantitation of (99m)Tc-phytate colloid uptake in the liver and spleen could be used as a noninvasive method to separate normal from cirrhotic livers and to evaluate the severity of disease.

Adolescent↗

Longitudinal measurement of methotrexate liver concentrations does not correlate with liver damage, clinical efficacy, or toxicity during a 3.5 year double blind study in rheumatoid arthritis.

OBJECTIVES: In patients with rheumatoid arthritis (RA), we examined whether methotrexate (MTX) and MTX polyglutamate accumulation in the liver correlated with clinical efficacy or clinical/laboratory toxicity. We also began preliminary examination of a new histologic index of liver histology (the Iowa Score) relative to the Roenigk grading system. METHODS: Forty patients with RA participated in a prospective, double blind, 3.5 year study of MTX treatment. Liver biopsies, liver MTX and MTX polyglutamate concentrations, laboratory tests, evaluation of disease activity, and evaluation of adverse events were done prospectively at baseline and at 1, 2, and 3.5 years. Biopsies were examined using the Roenigk grading system and an additional histological scoring system. Radiochemical ligand binding assays and HPLC methods were used to measure MTX and MTX polyglutamates. Statistical analysis included ANOVA, linear regression, and logistic regression modeling. RESULTS: No significant changes in the mean values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, albumin, or hemoglobin occurred. A significant percentage of patients had at least one abnormal alkaline phosphatase, AST, or ALT (25 to 52%), although most abnormalities were small and transient. Histological abnormalities did not progress using either the Roenigk or the Iowa score. The last abnormal AST, the number of abnormal AST and ALT, and female sex correlated with histological liver abnormalities (r2 = 0.41) using a new preliminary histologic scoring system (the Iowa Score). Amount of alcohol use correlated with fatty change, and the MTX dose at biopsy was associated with liver histological abnormalities (p = 0.03 and 0.049, respectively). Total liver MTX concentrations were stable from Year 1 to Year 3.5 and the percentage of higher order polyglutamates was relatively high (38 to 56%) relative to monoglutamates. No correlation of these concentrations with clinical response or toxicity, histology, or liver function tests could be documented. CONCLUSION: This analysis describes the accumulation and stabilization of MTX concentrations in the liver and examined correlations between MTX liver concentrations, patient demographics, liver histology, concomitant medications, and disease activity. No such correlations were found, decreasing the likelihood that MTX concentrations in serum would be useful measures to predict significant hepatotoxicity.

Antirheumatic Agents↗

[Computerized tomography in the diagnosis of nonalcoholic fatty liver--comparison with liver biopsy].

The frequency of nonalcoholic fatty liver disease (NAFLD) is high, an estimated 10-25% of the population in different countries. Due to the lack of specific symptoms or irregularities in laboratory examinations the major role in diagnosis is played by, apart form liver biopsy, the imaging examinations. AIM: The assessment of the correlation between intensity of fatty liver in computed tomography (CT) and in liver biopsy. INVESTING GROUP AND METHOD: The initial group comprised of 147 patients who had undergone CT of the abdomen. Within this group the range of attenuation coefficient in Hansfield units was measured in certain areas of liver and spleen. Density of the tissues being given (in Hansfield units) the increase of the fat content in the liver above the norm (tKT) was calculated, according to the formula: tKT = [(spleen density in OH units + 4 OH units) - liver density in OH units] x 0.8 = fat above norm in mg/l g of the liver tissue. Out of this group 12 patients (8 men and 4 women, average age 45.9 +/- 14.5 years) with clinical features of NAFLD on clinical indications for liver biopsy were selected. RESULTS: 3 patients the received value of tKT was found to be correct, that is tKT < 0. In these patients the estimated percentage of hepatocytes affected by steatosis (%TB) reached 5-20%. In the subgroup that comprised if the folio wing 6 patients %TB ranged from 30 to 70% and tKT--from 3.2 to 10. In the group of patients with the highest %TB, reaching 100%, the tKT value reached respectively 5, 10.8 and 13.6. The analysis of the relation between %TB and tKT showed a linear correlation of these two parameters. Following the increase of the intensity of the fatty liver in the biopsy the value of tKT rises. CT of the liver with the range of attenuation coefficient marked (in Hansfield units) is a useful tool for quantitative assessment of the fatty pulp.

Adult↗

Immediate-early gene expression differs between regenerating liver, insulin-stimulated H-35 cells, and mitogen-stimulated Balb/c 3T3 cells. Liver-specific induction patterns of gene 33, phosphoenolpyruvate carboxykinase, and the jun, fos, and egr families.

Immediate-early genes, whose expression increases independent of de novo protein synthesis during the transition from quiescence to proliferation, are postulated to play important regulatory roles in the growth response. The complement of immediate-early genes expressed must depend on the milieu of preexisting transcription factors in the quiescent cell as well as the type of mitogenic stimulation and, thus, may differ between cell types. We have begun characterizing the immediate-early response in regenerating liver and insulin-stimulated Reuber H-35 hepatoma cells in comparison with previously published results from mitogen-stimulated Balb/c 3T3 fibroblasts. The proliferating H-35 and regenerating liver cells maintain their similarity to quiescent liver as demonstrated by their continued production of the liver-specific albumin, CCAAT/enhancer binding protein, and phosphoenolpyruvate carboxykinase messenger RNAs (mRNA). Surprisingly, the phosphoenolpyruvate carboxykinase gene, which undergoes down-regulation in insulin-treated H-35 cells, was cloned by differential screening of a subtraction-enriched regenerating liver cDNA library and is an immediate-early gene in regenerating liver. H-35 cells treated with either insulin or phorbol 12-myristate 13-acetate express elevated levels of the jun genes, and phorbol 12-myristate 13-acetate pretreatment fails to abolish the insulin response, indicating that it does not depend on protein kinase C. jun family gene expression in regenerating liver differs from that in mitogen-treated fibroblasts in that the time course of expression of c-jun and junB is prolonged, and junD mRNA levels distinctly increase. Additionally, although c-fos and egr-1 mRNAs are expressed at elevated levels in stimulated liver cells, fos-B, fra-1, and egr-2 are not, which suggests that factors in addition to the serum response factor participate in the regulation of immediate-early gene induction. Interestingly, gene 33, which was cloned from a regenerating liver cDNA library by differential screening and lacks a recognizable serum response element, functions as an immediate-early gene in regenerating liver and in mitogen-treated H-35 and Balb/c 3T3 cells. These results suggest that gene 33 participates in the transition from quiescence to proliferation in many mitogen-treated cells in addition to its previously reported involvement in hormone responses. Overall, the results presented here suggest that the immediate-early response varies considerably between regenerating liver and mitogen-stimulated fibroblasts and could involve multiple, preexisting, tissue-specific, transcription-activating proteins.

Animals↗

Structurally and immunologically distinct poly(A) polymerases in rat liver. Occurrence of a tumor-type enzyme in normal liver.

Poly(A) polymerases purified from rat liver nuclei consisted of two distinct species, a predominant enzyme of Mr = 38,000 and a minor one of Mr = 48,000. Prior to extensive purification, the minor enzyme constituted approximately 1% of the total liver poly(A) polymerase. Poly(A) polymerase purified from a rat tumor, Morris hepatoma 3924A, was comprised of a single species of Mr = 48,000 which was identical to the minor liver enzyme with respect to chromatographic and immunological characteristics. Gel filtration on Sephacryl S-200 using 0.3 M NaCl for elution showed that the major liver poly(A) polymerase had a molecular weight of 156,000, which corresponded to a tetramer of the 38-kDa polypeptide, whereas the hepatoma and minor liver 48-kDa species existed as dimers with a molecular weight of 96,000. Fractionation by Sephacryl S-200 resulted in complete loss of both liver poly(A) polymerase activities which could be restored by exogenous N1-type protein kinase. Following CNBr cleavage, the 48-kDa poly(A) polymerase from liver and hepatoma exhibited nearly identical peptide maps which were distinct from that of the major liver enzyme (38 kDa). Antibodies raised against tumor poly(A) polymerase reacted with the 48-kDa polypeptide but not with the 38-kDa liver enzyme. Immune complex formation was observed between seven of the eight CNBr cleavage products derived from the 48-kDa polypeptide of both liver and hepatoma. It is concluded that distinct genes in rat liver code for two structurally and immunologically unique nuclear poly(A) polymerases, one of which is identical to the enzyme from the hepatoma.

Animals↗

Detection of antibodies to Chang liver cell in sera from patients with chronic liver diseases by 125I-labelled protein A binding assay and the effect of prednisolone and 6-mercaptopurine treatment on the level of the antibodies.

Antibody binding to living Chang liver cell was measured in sera from 71 patients with various chronic liver diseases using 125I-labelled protein A binding assay. The level of antibody binding to Chang liver cell was significantly elevated in sera from patients with chronic active hepatitis (CAH), chronic persistent hepatitis (CPH) and liver cirrhosis as compared to those from healthy donors, but not in sera from patients with fatty liver. There was no detectable antibody binding to HeLa cells in those sera. The antibody binding to Chang liver cell was blocked by a human liver specific protein (LSP) preparation. The levels of antibody binding to Chang liver cell were significantly higher in patients with CAH than patients with CPH. On the other hand, the level of antibody binding to Chang liver cell was significantly decreased in sera from patients with CAH after a treatment with prednisolone (PSL) for 2 months and a subsequent combined administration of 6MP and a maintenance dose of PSL for 1 month. These results suggest that antibodies to Chang liver cell are closely correlated with the activity of chronic liver disease and that PSL and 6MP treatment can reduce the level of the antibodies.

Antibodies↗

Choline deficiency, lipotrope deficiency and the development of liver disease including liver cancer: a new perspective.

Thus, the pathologic consequences of feeding a CD diet are fatty liver, liver cell death, liver cell proliferation, and liver cell cancer. The fatty liver with CD is similar to that with other types of fatty liver in that the most attractive current hypothesis is based on some interference with the production and output of VLDL by the liver. The induction of cell death appears to be consistent with quite a different hypothesis, genesis and/or increase in liver free radicals leading to both acute necrosis and initiation of carcinogenesis. Especially noteworthy is the low incidence of liver cirrhosis, even after 2 years of exposure to the CD diet. The feeding of the CD diet reproducibly induces severe and persistent fatty liver coupled with extensive cell death, a combination that is frequently considered to be appropriate for the induction of "micronodular" (fatty) cirrhosis in humans. The findings with the LD diet, the high incidence of cirrhosis, with severe persistent fatty liver without significant cell death, together with the low incidence of cirrhosis with the CD diet, stand out as unpredictable and strange, according to current concepts of the pathogenesis of human cirrhosis. The CD model offers an unusual opportunity to explore in increasing detail the possible roles of free radicals in two important problems in pathology and medicine-acute cell injury and neoplasia. The challenges include mechanistic studies on how the free radicals are generated and how they relate to the biological consequences. The relatively slow sequential changes in the induction of cell injury and neoplasia makes the CD model one of the best for mechanistic studies relating to free radicals.

Carcinoma, Hepatocellular↗

[Criteria for and results of liver transplantation in patients with acute liver insufficiency].

OBJECTIVE: Evaluation of the results of emergency liver transplantation in patients with acute liver failure. DESIGN: Analysis of 25 patients with acute liver failure. SETTING: University Hospital Rotterdam Dijkzigt. METHOD: Twenty-five patients with acute liver failure were admitted to the Intensive Care Unit in January 1989-May 1993. Patients were selected for emergency liver transplantation according to the Clichy criteria (presence of confusion or coma and factor V activity less than 20-30%). RESULTS: Liver transplantation was indicated in 17 patients and performed in 13. The 1-year survival rate in patients with a liver transplant was 85%. Four patients with an indication for liver transplantation, but who could not be transplanted died. All 8 patients without an indication for emergency liver transplantation survived. CONCLUSION: Survival after liver transplantation for acute hepatic failure is now about 80%; the Clichy criteria appear to be helpful in selecting patients with acute hepatic failure for liver transplantation.

Adolescent↗

Serum transforming growth factor-alpha level can be a parameter for evaluating liver regeneration after partial hepatectomy in patients with liver cancer.

Sensitive and reliable laboratory parameters are necessary to evaluate the degree of liver regeneration serially in patients after partial hepatectomy for liver cancer. We evaluated the serum levels of transforming growth factor-alpha (TGF-alpha) and hepatocyte growth factor (HGF), both of which are potent mitogens for hepatocytes, in 22 hepatectomized patients with liver cancer: 10 patients with hepatocellular carcinoma and 12 patients with metastatic liver tumors. Ten patients who underwent laparotomy for nonhepatic surgery were also studied as surgical controls. The serum TGF-alpha and HGF levels were measured by sandwich enzyme-linked immunosorbent assay techniques. Both the serum TGF-alpha and HGF levels increased after partial hepatectomy. However, there was no correlation between the levels of TGF-alpha and HGF. The maximal level of TGF-alpha achieved in each case correlated significantly with the resected liver volume and the increased volume of the remaining liver. Hepatocyte growth factor showed no such correlations. After nonhepatic surgery, the HGF level also increased significantly, while the TGF-alpha level did not. These results suggest that the serum TGF-alpha level varies depending on the regenerative stimulus to the liver, and that its increase corresponds with the degree of liver regeneration that occurs in patients after partial hepatectomy for liver cancer. In contrast, it is unlikely that the serum HGF level reflects liver regeneration. In conclusion, the serum TGF-alpha level can be used as a parameter for evaluating liver regeneration in patients who have undergone partial hepatectomy.

Carcinoma, Hepatocellular↗

High density culture of immortalized liver endothelial cells in the radial-flow bioreactor in the development of an artificial liver.

Liver endothelial cells are important components of the tissue along the hepatic sinusoid. They are responsible for microcirculation in the liver and scavenger functions. It would therefore be important to include these cells in any hybrid type of artificial liver in addition to hepatocytes. However, it is difficult to culture these cells in vitro. The development of a liver endothelial cell line, which maintains the characteristics of the primary culture, would thus be of great benefit in the development of an artificial liver. In the present study we established immortalized liver endothelial cells from the liver of an H-2Kb-tsA58 transgenic mouse, which harbors the SV40 TAg gene. Hepatic sinusoidal cells isolated from H-2Kb-tsA58 mouse proliferated in the presence of gamma-interferon at 33 degrees C. Four clones were established, out of which clone M1 had the highest amounts of PGI2 production, as well as plasminogen activator activity and internalized acetylated low density lipoprotein. On culture dishes the M1 cells grew individually and spread. Sieve plates on the cell surface were not readily visible, but small pores were detected under electron microscopic observation. These results suggest that M1 clone cells originated from liver endothelial cells. Moreover it was possible to culture the immortalized liver endothelial cells in a radial-flow bioreactor for 5 days, with a maximum 6-keto prostaglandin F1alpha production of 25 microg per day. This suggests that immortalized liver endothelial cells and a radial-flow bioreactor can prove useful tools in the development an artificial liver.

Animals↗