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Liver[JOURNAL]

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Sclerosed hemangioma and sclerosing cavernous hemangioma of the liver: a comparative clinicopathologic and immunohistochemical study with emphasis on the role of mast cells in their histogenesis.

Makhlouf HR, Ishak KG

Liver · 2002 Feb · PMID 11906621 · Publisher ↗

BACKGROUND/AIMS: Sclerosed hemangiomas of the liver are rare. To date, their histopathology, immunohistochemistry, and the role of mast cells (MC) in their histogenesis have not been systematically studied. PATIENTS/METH... BACKGROUND/AIMS: Sclerosed hemangiomas of the liver are rare. To date, their histopathology, immunohistochemistry, and the role of mast cells (MC) in their histogenesis have not been systematically studied. PATIENTS/METHODS: Clinical, histopathologic and immunohistochemical features of 20 sclerosed hemangiomas were compared with those of 18 sclerosing cavernous hemangiomas. The number of MC was quantified and compared in all cases, using a tryptase immunostain. RESULTS: Compared to patients with sclerosed hemangiomas, those with sclerosing hemangiomas were younger (mean age, 63 versus 71 years); had larger tumors (mean 6 +/- 4.73 versus 3 +/- 2.2 cm); presented with a mass more frequently, and epigastric pain less frequently. Sclerosing hemangiomas, but not sclerosed hemangiomas, were more frequent in males than in females. Sclerosing hemangiomas occurred much more frequently in the right lobe than sclerosed hemangiomas. Sclerosing hemangiomas had less fibrosis, hyalinization, and elastic fibers than sclerosed hemangiomas (p = 0.00004). Numerous thick-walled blood vessels were a feature of sclerosed hemangiomas but not of sclerosing hemangiomas. Collagen IV, and laminin were more uniformly positive in sclerosing hemangiomas than in sclerosed hemangiomas. Increased immunoreactivity for smooth muscle actin was present in sclerosed hemangiomas more often than in sclerosing hemangiomas. FVIII-R Ag, CD34, and CD31 were more diffusely positive in sclerosing hemangiomas than in sclerosed hemangiomas. In sclerosing hemangiomas, the mean number of tryptase-positive MC per high power field (MC/HPF) varied from 8.25 +/- 6.23 in vascular areas to 1.6 +/- 4.01 in sclerotic areas. In comparison, the mean number of MC in sclerosed hemangiomas, was 4.3 +/- 5.01 in vascular areas, and 0.86 +/- 0.58 in sclerotic areas (p = 0.0095). The number of MC was significantly correlated with vascular proliferation and inversely related to the degree of fibrosis (p < 0.0001). CONCLUSIONS: This study demonstrates certain distinct clinical and histopathologic differences between sclerosing cavernous hemangiomas and sclerosed hemangiomas of the liver. We have established the presence of MC in those tumors, and suggest possible involvement of the MC in angiogenesis, and the regression process and development of fibrosis.

Expression of human telomerase reverse transcriptase in regenerative and precancerous lesions of cirrhotic livers.

Kotoula V, Hytiroglou P, Pyrpasopoulou A … +3 more , Saxena R, Thung SN, Papadimitriou CS

Liver · 2002 Feb · PMID 11906620 · Publisher ↗

BACKGROUND/AIMS: The catalytic subunit of human telomerase (hTERT) is known to be expressed in a variety of malignant tumours, including hepatocellular carcinoma (HCC). We studied hTERT expression in regenerative and pre... BACKGROUND/AIMS: The catalytic subunit of human telomerase (hTERT) is known to be expressed in a variety of malignant tumours, including hepatocellular carcinoma (HCC). We studied hTERT expression in regenerative and precancerous lesions arising in cirrhosis. METHODS/RESULTS: As shown by in situ hybridisation, hTERT mRNA was absent in normal liver, but present in varying numbers of hepatocytes and HCC cells of diseased livers, as well as in biliary epithelial cells, lymphocytes, sinusoidal-lining cells and tumour endothelial cells. RT-PCR for two hTERT transcript regions demonstrated hTERT expression in 11 out of 15 cirrhotic liver samples, in 20 out of 21 large regenerative nodules/low-grade dysplastic nodules, in 5 out of 5 high-grade dysplastic nodules, and in 4 out of 4 HCCs. The beta-splice variant was identified in all hTERT-positive cases, while the corresponding full-length transcript was found only in 13 out of 29 positive large nodular lesions and in 4 out of 11 positive cirrhotic samples. The full-length transcript was always found in the presence of the beta-splice variant, usually in low relative levels, and tended to correlate with telomerase activity in the samples, while the beta-splice variant did not. CONCLUSIONS: This study shows that hTERT re-expression takes place both in hepatic regeneration occurring in cirrhosis and in the early steps of hepatocarcinogenesis, and involves mainly the beta-splice variant of this molecule. Additional regulatory mechanisms may be required for the expression of the full-length hTERT transcript.

Fluorine-18 FDG imaging in hepatocellular carcinoma using positron coincidence detection and single photon emission computed tomography.

Verhoef C, Valkema R, de Man RA … +2 more , Krenning EP, Yzermans JN

Liver · 2002 Feb · PMID 11906619 · Publisher ↗

BACKGROUND/AIMS: We prospectively evaluated whether fluorine-18 deoxyglucose (FDG) positron coincidence detection (PCD) or FDG single-photon emission computed tomography (SPECT) provides additional benefits to our conven... BACKGROUND/AIMS: We prospectively evaluated whether fluorine-18 deoxyglucose (FDG) positron coincidence detection (PCD) or FDG single-photon emission computed tomography (SPECT) provides additional benefits to our conventional preoperative evaluation of lesion detection in patients suspected to have hepatocellular carcinoma (HCC). METHODS: Thirteen consecutive patients with a suspected HCC underwent conventional preoperative evaluation with ultrasonography (US), triple-phase helical computed tomography (CT), superparamagnetic iron oxides (SPIO) enhanced magnetic resonance imaging (MRI) and serum alpha-fetoprotein (AFP) level. All 13 patients had an FDG-PCD and SPECT. These results were evaluated to assess the value of FDG-PCD and SPECT in addition to US, SPIO-enhanced MRI and triple-phase helical CT. RESULTS: Ten of the 13 (77%) patients had at least one histologically confirmed HCC without extrahepatic abdominal spread. The tumors ranged in size from 1 to 8 cm and the serum AFP ranged from 3 to 30 000 microg/l. Of these 10 patients, two patients had an increased tumor F-FDG uptake (sensitivity of 20%); one patient with an AFP of 5 microg/l and a tumor size of maximum 4.5 cm and one patient with an AFP of 249 microg/l and a tumor size of maximum 2 cm. In three patients with a benign liver mass, FDG imaging with either PCD or SPECT was negative. There was no false positive finding. CONCLUSIONS: We found poor sensitivity of FDG-PCD and FDG-SPECT for the detection of HCC. There were no clear relations between AFP or tumor size and FDG uptake. Therefore, we conclude that FDG imaging with PCD or SPECT has no value in the preoperative work-up for HCC in patients with cirrhosis.

The mode of tumour progression in combined hepatocellular carcinoma and cholangiocarcinoma: an immunohistochemical analysis of E-cadherin, alpha-catenin and beta-catenin.

Asayama Y, Taguchi Ki K, Aishima Si S … +3 more , Nishi H, Masuda K, Tsuneyoshi M

Liver · 2002 Feb · PMID 11906618 · Publisher ↗

BACKGROUND/AIM: To investigate the mode of progression of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). METHODS: An immunohistochemical study for E-cadherin (ECD) and alpha- and beta-catenins was pe... BACKGROUND/AIM: To investigate the mode of progression of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). METHODS: An immunohistochemical study for E-cadherin (ECD) and alpha- and beta-catenins was performed on 29 cases of cHCC-CC. RESULTS: Reduced expression of ECD was significantly correlated with the tumour grade of the hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) components, intrahepatic metastasis (IM) of HCC, IM of CC, and vascular invasion of CC (p < 0.05, respectively). There was a significant relationship between the reduced expression of beta-catenin and the tumour grade of HCC components (p < 0.05). Cases showing concurrent intrahepatic metastasis composed of HCC, CC, or both, numbered 6, 5, and 2, respectively. The expression patterns of ECD and beta-catenin of IM were similar to those of primary lesion in most cases. On the other hand, expression of ECD and beta-catenin of IM of HCC component were preserved, even though those of the primary sites were reduced in two cases and one case, respectively. ECD and beta-catenin were significantly correlated with tumour differentiation and tumour progression. CONCLUSIONS: Preserved or recovered ECD and beta-catenin expression may be of beneficial effect for re-establishing the tissue architecture at the metastatic site.

Changes in distribution spaces and cell permeability caused by ATP in the rat liver.

Fernandes TR, Suzuki-Kemmelmeier F, de Oliveira DS … +1 more , Bracht A

Liver · 2002 Feb · PMID 11906617 · Publisher ↗

AIMS/BACKGROUND: Cellular and extracellular volume changes caused by ATP were investigated in the liver as well as the possible formation of diffusion barriers, which could be responsible for some of its metabolic effect... AIMS/BACKGROUND: Cellular and extracellular volume changes caused by ATP were investigated in the liver as well as the possible formation of diffusion barriers, which could be responsible for some of its metabolic effects. METHODS: The experimental system was the bivascularly perfused rat liver. [(14)C]Sucrose and [(3)H]water were simultaneously injected into either the portal vein or the hepatic artery. Mean transit times, distribution spaces, variances and linear superimpositions were calculated. RESULTS: In the portal system, ATP reduced the transit time in the great vessels, had little or no effect on sinusoidal and cellular spaces, but impaired the flow-limited distribution of both [(14)C]sucrose and [(3)H]water. In the arterial bed ATP infused into either the portal vein or the hepatic artery produced vasodilation and increased the aqueous extra-sucrose space. These effects were inhibited by Nomega-nitro-L-arginine methyl ester infused into the hepatic artery. CONCLUSIONS: Sucrose and extra-sucrose space changes caused in the arterial bed by portally infused ATP are most probably analogous to the transhepatic vasodilation effect already described for the rabbit liver. Impairment of flow-limited distribution of tracers in the sinusoidal bed indicates that ATP induces the formation of permeability barriers, which could be responsible for some of its metabolic effects.

Mannose-binding lectin and the prognosis of fulminant hepatic failure caused by HBV infection.

Hakozaki Y, Yoshiba M, Sekiyama K … +8 more , Seike E, Iwamoto J, Mitani K, Mine M, Morizane T, Ohtani K, Suzuki Y, Wakamiya N

Liver · 2002 Feb · PMID 11906616 · Publisher ↗

BACKGROUND/AIMS: The mannose-binding lectin (MBL) gene was reported to play an important role in determining the clinical outcome of persistent hepatitis B virus (HBV) infection. We investigated serum MBL concentrations... BACKGROUND/AIMS: The mannose-binding lectin (MBL) gene was reported to play an important role in determining the clinical outcome of persistent hepatitis B virus (HBV) infection. We investigated serum MBL concentrations and MBL gene mutations to determine whether they were related to the prognosis of patients with fulminant hepatic failure (FHF) caused by HBV infection. METHODS: We investigated serum MBL concentrations and MBL gene mutations in 43 HBV-infected Japanese patients with FHF and 260 HBsAg-negative healthy controls. Serum MBL concentrations were measured by an enzyme-linked immunosorbent assay, and mutations in the MBL gene were analysed by nested PCR and direct DNA sequencing. RESULTS: Only a mutation in codon 54 of the MBL gene was found. The frequency of this mutation in nonsurvivors (40%, 8/20) was higher than in survivors (13%, 3/23), and the difference was slightly significant (p = 0.043). The H allele frequency in survivors (70.5%, 31/44) was higher than in nonsurvivors (39.5%, 15/38) (p = 0.0048). Because of these factors the mean serum MBL concentration in survivors, 1.61 ,micro/ml (range 0.3-3.86), was significantly higher than in nonsurvivors, 0.79 microg/ml (range 0.04-1.51) (p < 0.0001). The likelihood ratio for nonsurvival was 0 for over 2.0 microg/ml, 0.67 for 1.0-2.0 microg/ml, and 2.24 for 0-1.0 microg/ml. CONCLUSIONS: The mutation in codon 54 of the MBL gene tended to be higher in nonsurvivors than in survivors. The H allele frequency (high producing allele in H/Y) in survivors was higher than that in nonsurvivors. High levels of serum MBL correlated with the survival of patients with FHF due to HBV infection. Serum MBL may be useful as a predictive factor for the survival of patients with FHF caused by HBV.

Prognosis of a large cohort of patients with hepatocellular carcinoma in a single European centre.

Herold C, Reck T, Fischler P … +6 more , Ott R, Radespiel-Troeger M, Ganslmayer M, Hohenberger W, Hahn EG, Schuppan D

Liver · 2002 Feb · PMID 11906615 · Publisher ↗

BACKGROUND/AIM: Only a few follow up data are available for patients with hepatocellular carcinoma (HCC) in Europe and the USA. Therefore, we analysed all HCC patients admitted to our hospital between 1988 and 1999. METH... BACKGROUND/AIM: Only a few follow up data are available for patients with hepatocellular carcinoma (HCC) in Europe and the USA. Therefore, we analysed all HCC patients admitted to our hospital between 1988 and 1999. METHODS: We documented aetiology, stage (HCC: Okuda and UICC classifications, liver cirrhosis: Child-Pugh score), and diagnostic and therapeutic measures of 281 consecutive HCC patients. Survival time was calculated as a function of staging and therapy. RESULTS: Cirrhosis was diagnosed in all patients. Seventy-two patients underwent liver resection, 28 liver transplantation, 31 transarterial chemoembolization and 14 percutaneous ethanol injection. One hundred and thirty-six patients received no treatment. The Okuda and the Child-Pugh classification predicted a significant decrease of median survival time, whereas the UICC classification was less powerful. CONCLUSIONS: HCC occurred only in patients with liver cirrhosis. Survival time correlated with therapy (or no therapy) and with the Child-Pugh Score. In European patients the Okuda classification is superior to the UICC classification and should be compared to novel classification systems.

High efficiency gene transfer into cultured primary rat and human hepatic stellate cells using baculovirus vectors.

Gao R, McCormick CJ, Arthur MJ … +6 more , Ruddell R, Oakley F, Smart DE, Murphy FR, Harris MP, Mann DA

Liver · 2002 Feb · PMID 11906614 · Publisher ↗

BACKGROUND/AIMS: Gene transfer into hepatic stellate cells (HSC) is inefficient when using plasmid-based transfection methods; viral-based systems are therefore being developed. A baculovirus system has recently been sho... BACKGROUND/AIMS: Gene transfer into hepatic stellate cells (HSC) is inefficient when using plasmid-based transfection methods; viral-based systems are therefore being developed. A baculovirus system has recently been shown to be useful for expressing genes in mammalian cells. The aim of this study was to determine if baculovirus vectors can infect and express target genes in rat and human HSC and to assess potential cytotoxic and modulatory effects of infection. METHODS: A recombinant baculovirus vector (AcCALacZ) carrying the LacZ gene was used to infect HSC. beta-Galactosidase assays and electron microscopy were used to determine efficiency of infection and gene expression. Counting of trypan blue negative cells was used to assess cytotoxic/cytostatic effects of infection. Measurement of protein content of cells and alpha-smooth muscle actin expression were performed to assess the effects of baculovirus on cell function/phenotype. RESULTS: Baculovirus infection of activated HSC was highly efficient (> 90%) and provided long-term LacZ gene expression (15 days) in the absence of cytotoxic, cytostatic or modulatory effects. Infection of freshly isolated cells was also observed but at lower levels (20%). CONCLUSIONS: Baculovirus vectors can therefore be used to deliver target genes to cultured rat and human HSC with high efficiency and longevity in the absence of detrimental effects on cell function.

A novel role of alkaline phosphatase in protection from immunological liver injury in mice.

Xu Q, Lu Z, Zhang X

Liver · 2002 Feb · PMID 11906613 · Publisher ↗

AIMS/BACKGROUND: Little is known about the role of alkaline phosphatase (AP) in liver diseases, except for its elevation in jaundice or cholestasis. Its substrate, endotoxin, is usually elevated in patients as well as an... AIMS/BACKGROUND: Little is known about the role of alkaline phosphatase (AP) in liver diseases, except for its elevation in jaundice or cholestasis. Its substrate, endotoxin, is usually elevated in patients as well as animals with liver damage. This study aimed to provide evidence for its new role as protection against immunological liver damage. METHODS: Liver injury was induced in mice by delayed-type hypersensitivity to picryl chloride. AP activity was measured using a commercial kit. RESULTS: In acute liver injury, a significant decrease in AP activity in serum was observed but there was an increase in liver tissue. Single administration of cyclophosphamide before sensitization with picryl chloride exacerbated the liver injury, with more serious AP changes, while consecutive use after the sensitization alleviated the injury with a recovery from the changes. When liver injury proceeded for 1 week, both serum and liver showed decreased AP activity. Lipopolysaccharide facilitated alanine transaminase release from levamisole-pretreated but not non-treated hepatocytes from naive mice. However, the release was confirmed from liver slices of mice with liver injury proceeding for 1 week, even without levamisole pretreatment. CONCLUSION: The development of liver injury may lead to a dysfunction in AP synthesis and release. Levamisole may make normal hepatocytes, like the hepatocytes from liver-injured mice, highly sensitive to lipopolysaccharide through inhibiting AP synthesis. The findings obtained in this study suggest that AP may contribute to protection from injury by a mechanism involving neutralization of endotoxin.

Transplantation for liver tumors: current status.

Ringe B

Liver · 2002 Feb · PMID 11906612 · Publisher ↗

The question of liver transplantation for hepatobiliary malignancy has continued to generate controversial discussion. As shown by single-center studies and large databases, there is a clear indication for total hepatect... The question of liver transplantation for hepatobiliary malignancy has continued to generate controversial discussion. As shown by single-center studies and large databases, there is a clear indication for total hepatectomy and liver replacement under the premises of appropriate selection of suitable patients as well as of favorable type and stage of tumors. Future improvement of tumor-free patient survival can be expected from better understanding of tumor biology, including prevention and earlier detection of cancer, and effective multimodality treatment strategies.

Sinusoidal endothelial cell injury by superoxide anion and iron in the Propionibacterium acnes-pretreated and lipopolysaccharide-stimulated rat liver.

Hasegawa T, Nakano M, Hashimoto T … +3 more , Hiraishi K, Suzuki K, Kuwano H

Liver · 2001 Dec · PMID 11903887 · Publisher ↗

AIMS/BACKGROUND: We attempted to measure the generation of superoxide anion, examine its site of release and determine its pathological role in Propionibacterium acnes-lipopolysaccharide-induced liver injury in the rat.... AIMS/BACKGROUND: We attempted to measure the generation of superoxide anion, examine its site of release and determine its pathological role in Propionibacterium acnes-lipopolysaccharide-induced liver injury in the rat. METHODS: The P. acnes-pretreated (16 mg/kg i.v.) rat liver was perfused with buffer containing lipopolysaccharide (2.5 microg/ml). Chemiluminescence enhanced with Cypridina luciferin analog, MCLA, and reduction of nitro blue tetrazolium were used for detecting superoxide anion. Leakage of enzymes and release of cytokines into the perfusate, and histological specimens were also examined. RESULTS: Superoxide dismutase-inhibitable chemiluminescence peaked at 30 min of lipopolysaccharide infusion and blue formazan precipitate was histochemically deposited mainly on hepatic macrophages. Purine nucleoside phosphorylase (PNP) activity in the perfusate, as a marker of sinusoidal endothelial cell injury, reached its maximum at 50 min and aspartate aminotransferase (AST) activity, as a marker of hepatocyte injury, reached a plateau at 90 min. Simultaneous treatment with superoxide dismutase and deferoxamine mesylate significantly suppressed the leakage of PNP and AST. Release of tumor necrosis factor-alpha and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 lagged behind PNP leakage. Light microscopy showed destruction of the sinusoids followed by hepatocyte necrosis. Electron microscopy revealed adherence of hepatic macrophages to sinusoidal endothelial cells. CONCLUSION: These results indicate that superoxide anion released from hepatic macrophages may induce sinusoidal endothelial cell injury via interaction with iron in the P. acnes-lipopolysaccharide-treated liver.

Minimal liver injury in chronic hepatitis C virus infection is associated with low levels of soluble TNF-alpha/Fas receptors and acquisition in childhood.

Macías J, Sánchez-Quijano A, Pineda JA … +5 more , Abad MA, Rubio A, Rosa R, Leal M, Lissen E

Liver · 2001 Dec · PMID 11903886 · Publisher ↗

BACKGROUND/AIMS: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF-alpha/Fas pathways. METHODS: The serum levels of soluble TNF-alpha type II receptor (sTNFr-II) and s... BACKGROUND/AIMS: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF-alpha/Fas pathways. METHODS: The serum levels of soluble TNF-alpha type II receptor (sTNFr-II) and soluble Fas antigen (sFas) were analyzed in patients with different histological outcomes of chronic parenterally acquired HCV infection of similar duration. RESULTS: One hundred and forty-five HCV-infected patients had a known duration of infection. Twelve (8.3%) patients had minimal changes and were assigned to the case group. The control group was selected from the 24 (17%) patients with cirrhosis and the 54 (37%) with chronic active hepatitis (CAH). Two controls, one with CAH and one with cirrhosis, were paired with the cases following these criteria: duration of infection, transmission route and sex. The proportions of genotype 1b and HCV RNA serum levels were similar among the groups. The median serum levels of sTNFr-II and sFas were significantly lower in the case group than in the control groups. The cases were significantly younger when they became infected than the control groups. Indeed, most cases were infected within the first 10 years of life. sTNFr-II and age at infection were independently associated with the minimal injury case group. When sTNFr-II was excluded from the logistic regression model, sFas and age at infection were independently associated with the case group. CONCLUSION: The rate of progression of parenterally acquired chronic hepatitis C to end-stage liver disease might be related to an upregulation of the TNF-alpha/Fas pathways and an age-dependent host response.

Insulin-like growth factor-I restores the reduced somatostatinergic tone controlling growth hormone secretion in cirrhotic rats.

Castilla-Cortázar I, Aliaga-Montilla MA, Salvador J … +5 more , García M, Delgado G, González-Barón S, Quiroga J, Prieto J

Liver · 2001 Dec · PMID 11903885 · Publisher ↗

BACKGROUND/AIMS: An altered growth hormone/insulin-like growth factor-I (GH/IGF-I) axis occurs in advanced liver cirrhosis, characterised by diminished serum levels of IGF-I and increased concentrations of GH. Under norm... BACKGROUND/AIMS: An altered growth hormone/insulin-like growth factor-I (GH/IGF-I) axis occurs in advanced liver cirrhosis, characterised by diminished serum levels of IGF-I and increased concentrations of GH. Under normal conditions, GH release is mediated by somatostatin (SS) inhibition. However, the influence of SS on GH release in cirrhosis is not well known. IGF-I supplementation has beneficial effects in experimental cirrhosis, and - under physiological conditions - IGF-I increases SS, inhibiting GH. The aims of this work were to study SS tone in cirrhotic animals and to evaluate whether IGF-I treatment influences SS tone, controlling GH secretion in cirrhosis. METHODS: We studied the influence of SS on GH secretion by assessing GH response to pyridostigmine (PD) in cirrhotic rats treated and untreated with IGF-I. Liver cirrhosis was induced with CCl4-inhalation for 11 weeks in male Wistar rats. The animals were randomly divided into two groups: CI+IGF (n=12), which received IGF-I treatment for 12 days (2 microg/100 g body wt-1 x d-1) and CI (n=12), which received saline. Healthy controls (CO, n=12) were studied at the same time. On day 13, animals from each group were subdivided into two groups (n=6) in order to explore the effect of a PD intrajugular bolus (10 microg x 100 gbw-1) on serum GH levels (at 0,10,20,30 and 60 min), which were assessed by RIA. RESULTS: PD bolus did not exert any effect on GH serum levels in the CI group, suggesting a low SS tone in cirrhotic rats. However, PD induced an increase in GH levels into CO and CI+IGF groups. In conclusion, as occurs under normal conditions, the cholinergic system is a significant modulator of GH secretion in experimental liver cirrhosis. CONCLUSION: Cirrhotic rats have a reduced somatostatinergic tone which can be restored by IGF-I supplementation, suggesting that somatostatin is the main factor involved in the feed-back regulation between GH and IGF-I in cirrhosis.

Meta-analysis of propylthiouracil for alcoholic liver disease--a Cochrane Hepato-Biliary Group Review.

Rambaldi A, Gluud C

Liver · 2001 Dec · PMID 11903884 · Publisher ↗

AIMS/BACKGROUND: The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease. METHODS: Systematic Cochrane Review of randomised clinical trials.... AIMS/BACKGROUND: The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease. METHODS: Systematic Cochrane Review of randomised clinical trials. The Cochrane Hepato-Biliary Controlled Clinical Trials Register, The Cochrane Library, MEDLINE, and full text searches were combined. All analyses were performed according to the intention-to-treat method. Only randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis and/or alcoholic cirrhosis were included. Interventions encompassed propylthiouracil at any dose versus placebo or no intervention. The trials could be double-blind, single-blind or unblinded. RESULTS: Six randomised clinical trials randomising 710 patients demonstrated no significant effects of propylthiouracil versus placebo on mortality (Peto odds ratio (OR) 0.91, 95% confidence interval (CI) 0.59 to 1.40), liver-related mortality (OR 0.78, CI 0.45 to 1.33), complications to the liver disease (OR 1.14, CI 0.58 to 2.24), and liver histology. Propylthiouracil was associated with a nonsignificant trend toward an increased risk of nonserious adverse events (OR 1.49, CI 0.74 to 2.99) and with the rare occurrence of serious adverse events (leukopenia). CONCLUSIONS: This systematic review could not demonstrate any significant effect of propylthiouracil on any clinically important outcomes (mortality, liver-related mortality, liver complications and liver histology) of patients with alcoholic liver disease.

Large-needle biopsy versus thin-needle biopsy in diagnostic pathology of liver diseases.

Röcken C, Meier H, Klauck S … +3 more , Wolff S, Malfertheiner P, Roessner A

Liver · 2001 Dec · PMID 11903883 · Publisher ↗

BACKGROUND/AIMS: A study was carried out to determine whether thin-needle biopsy (TNB) yields enough material to study diffuse liver diseases. METHODS: Using TNB (20G and 21G) and a conventional Menghini-type large-needl... BACKGROUND/AIMS: A study was carried out to determine whether thin-needle biopsy (TNB) yields enough material to study diffuse liver diseases. METHODS: Using TNB (20G and 21G) and a conventional Menghini-type large-needle biopsy (LNB; 17G), the amounts of tissue obtained and the histopathological diagnoses were compared. The biopsies were obtained by surgeons with a several-stroke method (17GS) and by physicians with a single-strike method (17GP, 20GP, 21GP). A total of 343 biopsy specimens from 258 patients were included in the study. RESULTS: A comparison of the mean values for the length of the core biopsy, as well as the mean numbers of portal tracts and terminal hepatic veins among the four groups showed significant differences (p<0.001): the mean number of portal tracts obtained with 17GS was 13.8+/-6.5, with 17GP it was 9.7+/-5.9, with 20GP it was 6.7+/-4.4, and with 21GP it was 4.0+/-3.1. A comparison of the histopathological diagnoses showed no major differences between 17GP and 20GP; the diversity and frequencies of the diagnoses were similar. CONCLUSION: We suggest that the use of TNB, particularly 20G-size needles, could be extended to the investigation of diffuse liver diseases in which LNB carries a high risk of complications or is contraindicated, and when the diagnosis is the primary reason for the biopsy rather than grading or staging of a known diffuse disease.

Effects of salviainolic acid A (SA-A) on liver injury: SA-A action on hepatic peroxidation.

Liu P, Hu Y, Liu C … +2 more , Liu C, Zhu D

Liver · 2001 Dec · PMID 11903882 · Publisher ↗

BACKGROUND/AIMS: This study aimed to investigate the actions of salviainolic acid A (SA-A), an antiperoxidative component of Salvia miltiorrhiza (Sm), on rat liver injury and fibrosis. METHODS: Acute and chronic rat live... BACKGROUND/AIMS: This study aimed to investigate the actions of salviainolic acid A (SA-A), an antiperoxidative component of Salvia miltiorrhiza (Sm), on rat liver injury and fibrosis. METHODS: Acute and chronic rat liver injury models were established using carbon tetrachloride (CCl4). After 48 h (acute) or during 6 weeks of CCl4 injection, rats were further divided and treated with biphenyl dimethyl-dicarboxylate (BDD) or colchicine, as a control antifibrotic treatment, with Sm, a herbal compound, or SA-A, a water-soluble extract of Sm. Liver function was investigated by assessing alanine transaminase (ALT) and aspartate transaminase (AST) activities, histological analysis, hydroxyproline (Hyp) and malondiadehyde (MDA) content. In vitro, isolated cultured hepatocytes were injured with CCl4 gas for 24 h, followed by treatment with either vitamin E or various concentrations of SA-A. The extent of hepatocyte injury was monitored by analyzing various lipid peroxidative parameters such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), lactase dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) levels in hepatocyte supernatants. RESULTS: SA-A significantly decreased abnormal serum ALT activity both in acutely and chronically injured rat livers, decreased abnormal serum AST activity, Hyp and MDA content and attenuated hepatic collagen deposition. After CCl4 incubation and injury, the activities of AST, ALT CAT, GSH-PX and LDH and MDA content in hepatocyte supernatants increased significantly, but GSH levels decreased significantly. SA-A markedly improved these pathological changes in a dose-dependent manner. 10(-4) mol/l SA-A had stronger inhibitory action than vitamin E. CONCLUSIONS: Our studies suggest that SA-A has antiperoxidative effects on injured hepatocytes in liver injury and fibrosis induced by CCl4.

Presence of low levels of anti-HBs antibody in so-called 'anti-HBc alone' subjects.

Greub G, Frei PC

Liver · 2001 Dec · PMID 11903881 · Publisher ↗

BACKGROUND/AIMS: The 'anti-Hbc alone' pattern could sometimes be that of subjects who produced anti-HBs after recovery, but at a lower level than that detectable using commercial assays. This study aimed to test this hyp... BACKGROUND/AIMS: The 'anti-Hbc alone' pattern could sometimes be that of subjects who produced anti-HBs after recovery, but at a lower level than that detectable using commercial assays. This study aimed to test this hypothesis. METHODS: A total of 104 'anti-HBc alone' serum samples, i.e.positive for the anti-HBc antibody but not for HBsAg nor for anti-HBs antibody, were recruited when routine testing a broad population of employees, patients and pregnant women from a university hospital. A possible subliminal anti-HBs production, that would have escaped detection by commercial EIAs, was investigated by comparing the optical densities (ODs) obtained in vaccinees (commercial anti-HBs EIA) to those of a control group of 100 nonimmunised and nonvaccinated subjects. RESULTS: The median OD was significantly higher (p<0.0001) in the 'anti-HBc alone' subjects (OD=0.035) than in the controls (OD=0.023). Thirty-six percent of the 'anti-HBc alone' subjects had an anti-HBs OD higher than the median OD of the controls+2SD. 'Anti-HBc alone' subjects with anti-HBe antibody had higher anti-HBs ODs (0.041) than had those without anti-HBe (0.029). In 'anti-HBc alone' subjects, the anti-HBs ODs, although under the cut-off value of the EIA, were found to be higher than in the controls. CONCLUSION: Our results show low anti-HBs production in some of the subjects studied.

Neuronal nitric oxide synthase immunoreactivity in the guinea-pig liver: distribution and colocalization with neuropeptide Y and calcitonin gene-related peptide.

Esteban FJ, Jiménez A, Fernández AP … +7 more , del Moral ML, Sánchez-López AM, Hernández R, Garrosa M, Pedrosa JA, Rodrigo J, Peinado MA

Liver · 2001 Dec · PMID 11903880 · Publisher ↗

AIMS/BACKGROUND: The innervation pattern of the guinea-pig liver is similar to that of the human liver. However, many aspects of the distribution of the neuronal isoform of the enzyme nitric oxide synthase (nNOS) in the... AIMS/BACKGROUND: The innervation pattern of the guinea-pig liver is similar to that of the human liver. However, many aspects of the distribution of the neuronal isoform of the enzyme nitric oxide synthase (nNOS) in the guinea-pig liver and its colocalization with neuropeptides remain to be elucidated. METHODS: The distribution of nNOS was studied in fixed guinea-pig liver by light microscopic immunohistochemistry. Confocal analysis was used to determine its colocalization with neuropeptide Y (NPY) or calcitonin gene-related peptide (CGRP). RESULTS: nNOS-immunoreactive (nNOS-IR) nerves were observed in relation to hilar and interlobar vessels and in Glisson's capsule. A few nNOS-IR ganglia were observed in the extrahepatic bile duct and close to the interlobar portal triads. In addition, nNOS-IR fibers were located in the interlobular portal triads and pervading the parenchyma. Moreover, nNOS-IR nerves were demonstrated for the first time in the larger central veins and in the hepatic vein. nNOS-NPY and nNOS-CGRP colocalizations were detected in the fibromuscular layer of the bile duct and periductal plexus, respectively. CONCLUSIONS: These results support the phylogenetic conservation of the nNOS-IR hepatic innervation and its possible contribution to the regulation of hepatic blood flow and certain hepatic functions.

Update on hepatic stem cells.

Alison MR, Poulsom R, Forbes SJ

Liver · 2001 Dec · PMID 11903879 · Publisher ↗

The liver, like most organs in an adult healthy body, maintains a perfect balance between cell gain and cell loss. Though normally proliferatively quiescent, simple hepatocyte loss such as that caused by partial hepatect... The liver, like most organs in an adult healthy body, maintains a perfect balance between cell gain and cell loss. Though normally proliferatively quiescent, simple hepatocyte loss such as that caused by partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response to restore liver mass. This restoration of moderate cell loss and 'wear and tear' renewal is largely achieved by hepatocyte self-replication. Furthermore, cell transplant models have shown that hepatocytes can undergo significant clonal expansion. Such observations indicate that hepatocytes are the functional stem cells of the liver. More severe liver injury activates a facultative stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of biliary epithelia within the lobules before these cells differentiate into hepatocytes. A third population of stem cells with hepatic potential resides in the bone marrow; these haematopoietic stem cells can contribute to the albeit low renewal rate of hepatocytes, make a more significant contribution to regeneration, and even completely restore normal function in a murine model of hereditary tyrosinaemia. How these three stem cell populations integrate to achieve a homeostatic balance is not understood. This review focuses on three aspects of liver stem cell biology: 1) the hepatic stem cell candidates; 2) models of cell transplantation into the liver; and 3) the therapeutic potential of hepatic stem cells.

Fatal liver infarction after transjugular intrahepatic portosystemic shunt procedure.

Mayan H, Kantor R, Rimon U … +5 more , Golubev N, Heyman Z, Goshen E, Shalmon B, Weiss P

Liver · 2001 Oct · PMID 11589774 · Publisher ↗

Hepatic infarction is a rare disease. We describe here a cirrhotic patient with end-stage renal failure and recurrent tense ascites with fatal hepatic infarction after transjugular intrahepatic portosystemic shunt (TIPS)... Hepatic infarction is a rare disease. We describe here a cirrhotic patient with end-stage renal failure and recurrent tense ascites with fatal hepatic infarction after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Abdominal ultrasound, radionuclide liver scan, abdominal computed tomography scan, and finally liver biopsy established the diagnosis. The mechanism causing the infarct is not clear. However, as the infarct appeared after the patient had an episode of shock and disseminated intravascular coagulation, it could well be that the concomitant hepatic arterial insufficiency contributed to the infarct. Physicians should be aware of this possible catastrophic complication.
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