Liver[JOURNAL]
Sun
200 papers
Ubiquitin is a possible new predictive marker for the recurrence of human hepatocellular carcinoma.
Shirahashi H, Sakaida I, Terai S … +3 more , Hironaka K, Kusano N, Okita K
Liver · 2002 Oct · PMID 12458564 · Publisher ↗
BACKGROUND/AIM: Ubiquitin (Ub)-dependent degradation of regulatory proteins controls many cellular processes such as cell cycle progression, morphogenesis and signal transduction. In this study, we evaluated the meaning...
BACKGROUND/AIM: Ubiquitin (Ub)-dependent degradation of regulatory proteins controls many cellular processes such as cell cycle progression, morphogenesis and signal transduction. In this study, we evaluated the meaning of ubiquitination in chronic liver diseases, especially human hepatocellular carcinoma, with regard to recurrence. METHODS: A total 74 of liver tissues (8 of chronic hepatitis [CH], 9 of liver cirrhosis [LC], 7 of dysplastic nodule low grade (DSL), or dysplastic nodule high grade (DSH)and 50 of hepatocellular carcinoma [HCC]) were analyzed for ubiquitination by immunohistochemistry. Cell proliferation was also analyzed using Ki-67 staining. As a comparative marker for progression of HCC, PIVKA-II (protein induced by vitamin K absence-II) was employed to examine the recurrence rate of HCC. RESULTS: Ubiquitin (Ub) was positive in nuclei and cytoplasm of HCC in immunohistochemistry. The labeling index (L.I.) of ubiquitination was significantly higher with HCC than with other chronic liver diseases and tended to correlate with the lack of poorly-differentiated of HCC. The L.I. of Ki-67 staining was also correlated (P < 0.0001) with that of ubiquitination. The hepatocellular carcinoma (HCC) samples from potentially curatively operated patients having a ubiquitination L.I. of more than 20% suffered significantly higher recurrence of HCC than did patients with an L.I. of less than 20%. On the other hand, PIVA-II did not show such a difference. CONCLUSION: Ubiquitin (Ub) may reflect the growth activity of neoplasms and will be a possible new predictive marker for the recurrence of human hepatocellular carcinoma after potentially curative operation.
Hepatic graft-versus-host disease resembling acute hepatitis: additional treatment with ursodeoxycholic acid.
Chiba T, Yokosuka O, Kanda T … +5 more , Fukai K, Imazeki F, Saisho H, Nishimura M, Saito Y
Liver · 2002 Dec · PMID 12445178 · Publisher ↗
Hepatic graft-versus-host disease (GVHD) is a frequent complication after bone-marrow transplantation (BMT). The disease is often refractory to immunosuppressive therapy. We present a 30-year-old Japanese male, who devel...
Hepatic graft-versus-host disease (GVHD) is a frequent complication after bone-marrow transplantation (BMT). The disease is often refractory to immunosuppressive therapy. We present a 30-year-old Japanese male, who developed an abrupt elevation of aminotransferases, on day 135 after allogeneic BMT. A liver biopsy specimen revealed degeneration of the small bile ducts and portal fibrosis, and the diagnosis of chronic hepatic GVHD was confirmed. No manifestation of chronic GVHD was observed except liver dysfunction. The administration of prednisolone (PSL) and cyclosporin (CsA) ameliorated laboratory data to a degree, but they did not return to normal. Treatment with ursodeoxycholic acid (UDCA), subsequently added to the immunosuppressive therapy, apparently normalized the levels of biliary tract enzyme and total bilirubin. His liver function test completely returned to normal on day 260. We believe that it is worthwhile to administer UDCA as an additional treatment for not only common hepatic GVHD but also atypical cases presenting as acute hepatitis.
Allergic cholestatic hepatitis and exanthema induced by metamizole: verification by lymphocyte transformation test.
Herdeg C, Hilt F, Büchtemann A … +2 more , Bianchi L, Klein R
Liver · 2002 Dec · PMID 12445177 · Publisher ↗
We report about a 66-year-old-male patient who was hospitalized with generalized exanthema and increase of liver enzymes after intake of metamizole because of flue-like symptoms. Despite initial high dose steroids, disea...
We report about a 66-year-old-male patient who was hospitalized with generalized exanthema and increase of liver enzymes after intake of metamizole because of flue-like symptoms. Despite initial high dose steroids, disease activity persisted, and therefore liver biopsy was performed. Histology revealed acute hepatitis with perivenular non-bridging confluent necrosis and granuloma formation consistent with drug-induced hepatitis. A metamizole-induced process was suspected. Lymphocyte transformation test confirmed the sensitization of the patient's lymphocytes to metamizole and three of its four metabolites (4-methylaminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine). Other drugs could be excluded with high probability. In the follow-up, the general condition of the patient improved, and liver enzymes decreased under treatment with steroids. Thus, we conclude that in this patient metamizole has induced an allergic reaction not only of the skin but also of the liver. To our knowledge, an allergic cholestatic hepatitis caused by metamizole has been reported only once in literature.
Macro-aspartate aminotransferase in a female with antibodies to hepatitis C virus.
Collins J, Ritter D, Bacon BR … +2 more , Landt M, Creer MH
Liver · 2002 Dec · PMID 12445176 · Publisher ↗
Persistent elevation of aspartate aminotransferase (AST) activity in serum due to the presence of a macroenzyme form of AST (macro-AST) may lead to diagnostic confusion in many clinical conditions, particularly those ass...
Persistent elevation of aspartate aminotransferase (AST) activity in serum due to the presence of a macroenzyme form of AST (macro-AST) may lead to diagnostic confusion in many clinical conditions, particularly those associated with chronic liver disease. We describe a case of macro-AST arising in an adult female with a false-positive hepatitis C virus (HCV) RNA test result that was not accompanied by other biochemical or histologic evidence of liver disease. The presence of macro-AST in serum was confirmed utilizing size-exclusion, high performance liquid chromatography (HPLC) and Protein G-agarose beads to precipitate immune complexes of AST and immunoglobulin G followed by centrifugation and AST activity measurements in the supernatant. A brief review of the clinical enzymology of AST and methods used to quantify serum macro-AST activity is provided.
Cytotoxic response of sinusoidal endothelial cells to polymorphonuclear leukocytes and its potential implication in hypoxia-reoxygenation injury.
Lasnier E, Blanc MC, Housset C … +3 more , Rey C, Roch-Arveiller M, Vaubourdolle M
Liver · 2002 Dec · PMID 12445175 · Publisher ↗
AIMS: Interactions between polymorphonuclear leukocytes (PMN) and sinusoidal endothelial cells (SEC) may contribute to ischemia-reperfusion injury. The aim of the study was to determine the influence of PMN hypoxia-reoxy...
AIMS: Interactions between polymorphonuclear leukocytes (PMN) and sinusoidal endothelial cells (SEC) may contribute to ischemia-reperfusion injury. The aim of the study was to determine the influence of PMN hypoxia-reoxygenation and degranulation, on SEC toxic response. METHODS: PMNs collected from rat pleural cavity underwent hypoxia- reoxygenation or N-formyl-methionyl-leucyl-phenylalanine (fMLP) degranulation treatment, and were then separated from their conditioned medium. Rat SECs were incubated either with PMNs in coculture or with their conditioned medium, for 210 min. Oxidative metabolism in PMNs was measured by chemiluminescence. LDH release and elastase activity were measured in SEC supernatants. RESULTS: PMN-conditioned medium induced an increase in LDH release in SECs. Hypoxia-reoxygenation of PMNs induced an increase in their chemiluminescent response without increasing the cytotoxic effect of their conditioned medium. By contrast, the cytotoxic effect of conditioned medium was increased following PMN treatment with fMLP. In the latter case, cytotoxicity was combined with a rise in the elastase activity released in the supernatants, but was not reduced by inhibitors of elastase or of other proteases. CONCLUSIONS: The results indicate that toxic products are released, at least in part through degranulation, by PMNs, and induce cytotoxicity in SECs. This mechanism may contribute to SEC injury during hypoxia-reoxygenation.
Early gene expression of hepatocyte growth factor in mononuclear phagocytes of rat liver after administration of carbon tetrachloride.
Armbrust T, Batusic D, Xia L … +1 more , Ramadori G
Liver · 2002 Dec · PMID 12445174 · Publisher ↗
BACKGROUND: Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen supposed to be a main stimulant of hepatocyte replication during liver regeneration. During acute liver injury, HGF has been detected in nonparenc...
BACKGROUND: Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen supposed to be a main stimulant of hepatocyte replication during liver regeneration. During acute liver injury, HGF has been detected in nonparenchymal cells of the liver. METHODS: We performed in situ hybridization of HGF in rat livers after administration of carbon tetrachloride (CCl4). Mononuclear phagocytes (MNP) were isolated from normal and injured livers and HGF expression was analyzed by Northern blotting, in situ hybridization, and immunoprecipitation of 35S-labeled proteins. RESULTS: In situ hybridization of normal liver revealed few HGF positive cells within hepatic sinusoids. In injured livers, the number of cells containing HGF transcripts was increased at 6-24 h after CCl4. Hepatocyte growth factor transcripts in MNP from normal liver were detectable in trace amounts, but became clearly detectable at 6 h and persisted up to 24 h after CCl4 administration. In situ hybridization of MNP isolated from normal liver did not reveal positive cells. Mononuclear phagocytes became HGF-positive when isolated 6 h after CCl4. Hepatocyte growth factor protein was detected in MNP isolated 24 h after CCl4. CONCLUSIONS: Hepatocyte growth factor in MNP is not directly induced by interferon-alpha, interferon-gamma or tumour necrosis factor-alpha (TNF-alpha). Stimulated resident mononuclear phagocytes may play a significant role in the increase of HGF expression in liver regeneration after acute liver injury.
Cost-effectiveness of adjuvant interferon therapy after surgical resection of Hepatitis C-related hepatocellular carcinoma.
Hoshida Y, Shiratori Y, Omata M
Liver · 2002 Dec · PMID 12445173 · Publisher ↗
BACKGROUND: To evaluate cost-effectiveness of adjuvant interferon therapy used with surgical resection of hepatitis C-related primary hepatocellular carcinoma. DESIGN: We constructed a Markov model that simulated adjuvan...
BACKGROUND: To evaluate cost-effectiveness of adjuvant interferon therapy used with surgical resection of hepatitis C-related primary hepatocellular carcinoma. DESIGN: We constructed a Markov model that simulated adjuvant interferon therapy after resection of hepatitis C-related hepatocellular carcinoma, and evaluated life expectancy, costs, and cancer recurrence. The reference case is a 60-year-old man with hepatitis C-related compensated cirrhosis. RESULTS: At the baseline, adjuvant interferon therapy yielded 6.1 life years with a cost of dollars 77000, and an incremental cost-effectiveness ratios of dollars 15700/life year compared with no interferon therapy. The proportion of patients who experienced recurrence of hepatocellular carcinoma until death was reduced from 87.6% to 62.9% using adjuvant interferon therapy. The incidence of recurrent hepatocellular carcinoma after interferon influenced the cost-effectiveness of adjuvant interferon therapy. A threshold analysis showed that adjuvant interferon therapy was not cost-effective (ICER = dollars 27000/year) if the annual incidence of recurrent hepatocellular carcinoma after interferon is 16% (baseline 8.9%). The proportions of patients with recurrent hepatocellular carcinoma were 74.4% and 86.9% at the annual recurrence rates after interferon of 16% and 35%, respectively. CONCLUSIONS: Adjuvant interferon therapy after surgical resection of primary hepatitis C-related hepatocellular carcinoma improves life expectancy through suppression of recurrent cancer with acceptable cost-effectiveness.
HFE gene mutations and iron metabolism in Wilson's disease.
Erhardt A, Hoffmann A, Hefter H … +1 more , Häussinger D
Liver · 2002 Dec · PMID 12445172 · Publisher ↗
BACKGROUND: There is increasing evidence for an interaction between iron and copper metabolism. METHODS: Iron indices (ferritin, transferrin saturation [TS], serum iron), liver parameters, the prevalence and significance...
BACKGROUND: There is increasing evidence for an interaction between iron and copper metabolism. METHODS: Iron indices (ferritin, transferrin saturation [TS], serum iron), liver parameters, the prevalence and significance of C282Y and H63D HFE mutations were studied in 40 unrelated, Caucasian patients with Wilson's disease and 295 healthy controls. Due to specific treatment Wilson's disease was well controlled in all but one patient. RESULTS: The allele frequencies for the C282Y (11.3% vs. 6.2%) and the H63D (18.8% vs. 16.4%) mutation did not differ between patients with Wilson's disease and healthy controls. One patient with C282Y homozygous HH and Wilson's disease was identified showing progressive liver disease despite reasonable venesection and copper chelation therapy. No differences in iron indices and liver values were seen between HFE heterozygous and HFE wildtype patients with Wilson's disease. Higher serum ferritin levels were noticed in patients with Wilson's disease compared to healthy controls (149 +/- 26 microg/l vs. 87 +/- 8 microg/l; P < 0.03). CONCLUSIONS: It appears reasonable to assess iron indices in patients with Wilson's disease in order to detect iron overload. HFE mutations other than C282Y homozygosity seem to have no impact on iron indices and liver parameters as long as Wilson's disease is controlled.
Splenectomy ameliorates hepatic ischemia and reperfusion injury mediated by heme oxygenase-1 induction in the rat.
Ito K, Ozasa H, Yoneya R … +1 more , Horikawa S
Liver · 2002 Dec · PMID 12445171 · Publisher ↗
BACKGROUND/AIMS: Ischemia/reperfusion (I/R) induces severe organic injury. I/R injury seems to be mainly caused by oxidative stress. The aim of this study was to determine the role of the spleen in experimental hepatic I...
BACKGROUND/AIMS: Ischemia/reperfusion (I/R) induces severe organic injury. I/R injury seems to be mainly caused by oxidative stress. The aim of this study was to determine the role of the spleen in experimental hepatic I/R injury in the rat. Stress protein heme oxygenase (HO)-1 plays a protective role against the oxidative injury. In normal state, HO-1 is highly expressed in the spleen. METHODS: Liver HO-1 expression was assessed by Western blot before and after splenects. Liver injury was assessed by measurement of ALT and AST and by histopathology. RESULTS: Although HO-1 was not detected in normal liver, levels of HO-1 protein gradually increased and peaked on 3 days after splenectomy. When splenectomy was performed 3 days prior to the hepatic (45-min) ischemia followed by (2-h) reperfusion, the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT), as markers for hepatic injury, were improved compared to the rats with I/R alone. In addition, prior administration of zinc-protoporphyrin IX, a specific inhibitor of HO, suppressed the protective effect of the splenectomy on the subsequent hepatic I/R injury. Histopathological examination also confirmed these results. CONCLUSIONS: Our findings suggest that the elevated HO-1 levels by splenectomy play a protective role against hepatic I/R injury.
The effect of insulin and glucagon on splanchnic oxygen consumption.
Simonsen L, Coker R, A L Mulla N … +2 more , Kjaer M, Bülow J
Liver · 2002 Dec · PMID 12445170 · Publisher ↗
UNLABELLED: The purpose of these experiments was to measure the influence of insulin and glucagon on the splanchnic oxygen consumption. Two experiments were performed. METHODS: In one experiment, the influence of hyperin...
UNLABELLED: The purpose of these experiments was to measure the influence of insulin and glucagon on the splanchnic oxygen consumption. Two experiments were performed. METHODS: In one experiment, the influence of hyperinsulinaemia was investigated in six healthy subjects, who were studied during a euglycaemic hyperinsulinaemic clamp. In another experiment, the influence of glucagon was investigated in seven healthy subjects, who were studied twice during a pancreatic islet clamp with either supplementation of insulin and glucagon, or of insulin alone. In both situations the measurements were performed during euglycaemia. Splanchnic oxygen consumption and net substrate balances were studied by the arterio-hepatic venous catheterisation technique and measurement of splanchnic blood flow in all experiments. RESULTS: During the euglycaemic hyperinsulinaemic clamp, the splanchnic blood flow increased significantly and the splanchnic oxygen consumption decreased by about 20%, while the net splanchnic glucose output reversed to a net uptake. In the pancreatic islet clamp experiments there was a significant difference between the net splanchnic glucose outputs whether glucagon and insulin or only insulin was supplemented. In spite of this, the splanchnic oxygen consumption decreased by about 20% in both situations, i.e. independent of glucagon supplementation. In both experiments there was a pronounced inhibition of lipolysis, which led to decreased fatty acids availability to the liver. This resulted in a concomitant decrease in hepatic ketone body formation. This decrease could account for about 30% of the decrease in splanchnic oxygen consumption. CONCLUSION: The reduction in splanchnic oxygen consumption can be explained by decreased ketogenesis, decreased protein synthesis and changes in splanchnic fuel selection, while changes in the rate of gluconeogenesis does not seem to play a significant role.
Expression of uncoupling protein-2 in biliary epithelial cells in primary biliary cirrhosis.
Taniguchi E, Harada M, Kawaguchi T … +9 more , Koga H, Kumemura H, Hanada S, Shishido S, Baba S, Kumashiro R, Ueno T, Sakisaka S, Sata M
Liver · 2002 Dec · PMID 12445169 · Publisher ↗
BACKGROUND/AIMS: Uncoupling proteins are thought to protect cells from oxidative stresses. Because uncoupling protein-2 is expressed in liver and reactive oxygen species are involved in pathogenesis of various liver dise...
BACKGROUND/AIMS: Uncoupling proteins are thought to protect cells from oxidative stresses. Because uncoupling protein-2 is expressed in liver and reactive oxygen species are involved in pathogenesis of various liver diseases, this protein may protect liver cells from disease-associated oxidative stress. However, uncoupling protein-2 expression in human liver has not been examined. METHODS: We investigated hepatic uncoupling protein-2 distribution in various liver diseases including primary biliary cirrhosis, autoimmune hepatitis, chronic viral hepatitis, and histologically normal liver by immunohistochemistry. RESULTS: Uncoupling protein-2 was expressed in some hepatocytes, however, the degree of hepatocytic uncoupling protein-2 expression did not differ significantly among liver diseases and normal liver. Uncoupling protein-2 was abundant in biliary epithelial cells in primary biliary cirrhosis but not in other liver specimens. Enhanced uncoupling protein-2 expression in biliary epithelial cells was specific for primary biliary cirrhosis and did not result simply from cholestasis. The percentage of uncoupling protein-2 positive bile ducts in primary biliary cirrhosis patients treated with ursodeoxycholic acid was significantly lower than in untreated patients. CONCLUSIONS: These results suggest that uncoupling protein-2 is involved in the pathogenesis of primary biliary cirrhosis.
Endothelial, but not the inducible, nitric oxide synthase is detectable in normal and portal hypertensive rats.
Stumm MM, D'Orazio D, Sumanovski LT … +3 more , Martin PY, Reichen J, Sieber CC
Liver · 2002 Dec · PMID 12445168 · Publisher ↗
BACKGROUND: Chronic portal hypertension is accompanied by a nitric oxide (NO) dependent vasodilation. Three isoforms of NO producing synthases (NOS) are characterized: neuronal NOS (nNOS), endothelial NOS (eNOS) and indu...
BACKGROUND: Chronic portal hypertension is accompanied by a nitric oxide (NO) dependent vasodilation. Three isoforms of NO producing synthases (NOS) are characterized: neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Sources of increased NO levels in chronic hypertension is disputed. METHODS: To determine eNOS and iNOS expression in different organs of portal hypertensive and control rats, we divided Sprague-Dawley rats in 6 groups: (1). Partial portal vein ligated rats, (2). Bile duct ligated rats, (3). Carbon tetrachloride treated rats, (4). Sham operated rats, (5). Untreated control rats, and (6). LPS treated rats. Immunohistochemistry (IHC) and immunoblotting (IB) using antibodies against eNOS or iNOS were carried out on samples from thymus, aorta, heart, lung, oesophagus, liver, spleen, kidney, pancreas, small and large intestine. RESULTS: IHC revealed an even eNOS expression in all groups. Expression of iNOS was restricted to macrophages in organs of LPS treated and the thymus of rats. IB mirrored these results. CONCLUSION: In chronic portal hypertension, the main source for NO production depends on eNOS activity.
Artificial and bioartificial support systems for liver failure: a Cochrane Hepato-Biliary Group Protocol.
Liu J, Kjaergard LL, Als-Nielsen B … +1 more , Gluud C
Liver · 2002 Oct · PMID 12390479 · Publisher ↗
AIMS/BACKGROUND: Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support sy...
AIMS/BACKGROUND: Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure. DATA SOURCES: Randomized trials on any support system versus standard medical therapy will be included irrespective of publication status or language. Non-randomized studies are included in explorative analyses. Trials will be identified through bibliographies, correspondence with original investigators, and electronic searches (Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE, and The Chinese Biomedical Database). METHODS OF THE REVIEW: The extracted data will include characteristics of trials, patients, interventions, and all outcome measures. Methodological quality will be assessed by the randomization, follow up, and blinding. The RevMan and STATA will be used for statistical analyses. Sources of heterogeneity and methodological quality in the assessment of the primary outcome will be explored by sensitivity analyses and meta-regression.
Monitoring of transtubular potassium gradient in the diuretic management of patients with cirrhosis and ascites.
Lim YS, Han JS, Kim KA … +3 more , Yoon JH, Kim CY, Lee HS
Liver · 2002 Oct · PMID 12390478 · Publisher ↗
BACKGROUND/AIMS: Aldosterone antagonists are the diuretics of first choice in the treatment of cirrhotic ascites. However, there is still no reliable clinical parameter to evaluate their efficacy. Transtubular potassium...
BACKGROUND/AIMS: Aldosterone antagonists are the diuretics of first choice in the treatment of cirrhotic ascites. However, there is still no reliable clinical parameter to evaluate their efficacy. Transtubular potassium gradient (TTKG), the accurate indicator of aldosterone bioactivity, may serve as a guide for the proper use of the aldosterone antagonists. METHODS: In 23 patients with cirrhotic ascites, the daily administered initial dosage of 100 mg of spironolactone was increased by 100 mg/day at intervals of 5 days until either diuresis commenced or TTKG fell below 3.0, the value indicating complete blockade of aldosterone bioactivity. For the non-responders with TTKG lower than 3.0, furosemide was given in addition to spironolactone. RESULTS: Basal TTKG correlated significantly with plasma aldosterone concentration (r = 0.60, P = 0.002). Spironolactone induced the decrease of TTKG in 20 patients, from 5.3 +/- 0.5 to 2.9 +/- 0.2 (mean +/- SE, P < 0.001). A TTKG value of 3.0 could classify seven patients, who did not respond to low dose spironolactone, into two distinct groups at that time, indicating different further diuretic regimen. All patients achieved diuretic responses without complication by this TTKG-guided modification of diuretics. CONCLUSIONS: TTKG may be a suitable guide for the diuretic management of cirrhotic ascites by accurately reflecting the effect of aldosterone antagonists.
Cell proliferation and renewal of normal hepatocytes and bile duct cells in adult mouse liver.
Magami Y, Azuma T, Inokuchi H … +4 more , Kokuno S, Moriyasu F, Kawai K, Hattori T
Liver · 2002 Oct · PMID 12390477 · Publisher ↗
BACKGROUND/AIMS: The source of new cells in the normal adult liver has been controversial. Some investigators have hypothesized the streaming liver model. On the other hand, others reject this hypothesis. We examined hep...
BACKGROUND/AIMS: The source of new cells in the normal adult liver has been controversial. Some investigators have hypothesized the streaming liver model. On the other hand, others reject this hypothesis. We examined hepatic cell kinetics by a special labeling method with [3H]thymidine. METHODS: ICR mice received 112 repeated injections of [3H]thymidine at 6 h intervals for 28 days after birth and were killed immediately thereafter, or 100, 200 or 300 days after the last injection. Immediately after killing the animals, samples of the liver were taken and autoradiography was performed. RESULTS: After continuous labeling, more than 90% of the cells in the liver were labeled. Mean grain counts of hepatocytes decreased to half over approximately 100 days. Those of bile duct cells decreased at a slower rate (50%) than hepatocytes. Mean grain counts of hepatocytes decreased over the regions, although those in perivenular region decreased more rapidly in comparison to those in periportal region. CONCLUSIONS: The present study indicated that most cells in the liver arise postnatally. The changes in labeling of cells show that there is no special zone for proliferation of hepatocytes and they renew in all regions of the hepatic lobule, suggesting (i) that hepatocytes are supplied by postnatal replication and (ii) streaming of hepatocytes from periportal to pericentral regions does not occur in the adult mouse liver. The bile duct cells renewed more rapidly than hepatocytes.
Interleukin-1, interleukin-10 and tumour necrosis factor-alpha gene polymorphisms in hepatitis C virus infection: an investigation of the relationships with spontaneous viral clearance and response to alpha-interferon therapy.
Constantini PK, Wawrzynowicz-Syczewska M, Clare M … +4 more , Boron-Kaczmarska A, McFarlane IG, Cramp ME, Donaldson PT
Liver · 2002 Oct · PMID 12390476 · Publisher ↗
BACKGROUND/AIMS: Though there is a consensus that the HLA DQB1*0301 allele is important in untreated HCV clearance, this association is not universal and a number of genes outside the major histocompatibility complex may...
BACKGROUND/AIMS: Though there is a consensus that the HLA DQB1*0301 allele is important in untreated HCV clearance, this association is not universal and a number of genes outside the major histocompatibility complex may also play a role in host responses to HCV infection. Prime candidates, at present, are the genes encoding pro-inflammatory and immuno-regulatory cytokines. The aim of this study was to investigate the relationship between a number of these candidate genes and both spontaneous and treatment related clearance of hepatitis C virus infection. METHODS: Three members of the interleukin-1 gene family: IL-1A, IL-1B and IL-1RN, three polymorphic sites in the interleukin-10 gene promoter (- 1082, - 819, - 592) and two in the tumour necrosis factor-alpha promoter (- 308, - 238) were studied in two independent DNA banks, each with appropriate controls. Standard PCR-based genotyping techniques were used. RESULTS: No significant difference in the distribution of any of the polymorphisms was found in either study set. CONCLUSIONS: These findings in two large groups suggest that future investigations should focus on other candidate genes and may support the view that MHC-encoded susceptibility to chronic HCV infection may be determined by MHC class II rather than MHC class III genes.
Involvement of platelet-activating factor in hepatic apoptosis and necrosis in chronic ethanol-fed rats given endotoxin.
Murohisa G, Kobayashi Y, Kawasaki T … +2 more , Nakamura S, Nakamura H
Liver · 2002 Oct · PMID 12390475 · Publisher ↗
BACKGROUND/AIMS: Platelet-activating factor (PAF)-a potent activator of neutrophils-plays an important role in the pathogenesis of endotoxin-induced tissue injury. However, the role of PAF in hepatic damage during alcoho...
BACKGROUND/AIMS: Platelet-activating factor (PAF)-a potent activator of neutrophils-plays an important role in the pathogenesis of endotoxin-induced tissue injury. However, the role of PAF in hepatic damage during alcoholic hepatitis remains unclear. The aims of the present study were to test whether PAF contributes to hepatic injury in an animal model of alcoholic hepatitis and to investigate the involvement of the Fas-receptor/Fas-ligand system in this process. METHODS: Male Sprague-Dawley rats were pair-fed with Lieber-DeCarli ethanol liquid diet or isocaloric control diet for 6 weeks. Liver injury was induced by the intravenous (i.v.) injection of lipopolysaccharide (LPS) (1 mg/kg). Rats were pretreated with a specific PAF receptor antagonist (TCV-309; 100 mg/kg i.v.) or vehicle 1 h before LPS treatment. RESULTS: Chronic ethanol administration remarkably sensitized the rats to the effects of LPS, with resultant severe hepatocellular injury, accompanied by significant increases in serum levels of alanine aminotransferase (ALT), tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 (CINC/gro). Histological examination of the damaged livers showed hepatocyte apoptosis and necrosis with extensive infiltration by neutrophils, whereas immunohistochemical studies revealed enhanced Fas-receptor expression on hepatocytes and hepatic accumulation of neutrophils expressing Fas-ligand. Pretreatment with the PAF receptor antagonist protected against hepatic injury, suppressing hepatocyte apoptosis and necrosis, infiltration of neutrophils, expression of Fas-receptor and Fas-ligand, and serum TNF-alpha levels. CONCLUSIONS: Our study suggests that PAF is an important mediator of hepatic injury in the ethanol/endotoxin model of alcoholic hepatitis.
Incomplete septal cirrhosis associated with Wegener's granulomatosis.
Zen Y, Sunagozaka H, Tsuneyama K … +5 more , Masutomi K, Terasaki S, Kaneko S, Kobayashi K, Nakanuma Y
Liver · 2002 Oct · PMID 12390474 · Publisher ↗
Incomplete septal cirrhosis, which is included in the spectrum of hepatoportal sclerosis, is characterized by parenchymal nodularity, incomplete fibrous septa, clustered or dispersed portal tract remnants, and abnormal s...
Incomplete septal cirrhosis, which is included in the spectrum of hepatoportal sclerosis, is characterized by parenchymal nodularity, incomplete fibrous septa, clustered or dispersed portal tract remnants, and abnormal spacing of portal tracts and hepatic veins. Hepatoportal sclerosis is known to be associated with collagen vascular diseases. Here, we describe a 73 year-old-female with incomplete septal cirrhosis. At 57 years, she presented with respiratory symptoms, and lung biopsy disclosed active arteritis with granuloma. Perinuclear antineutrophilic cytoplasmic antibody was also positive. Immunosuppressive therapy was done under the diagnosis of Wegener's granulomatosis. At 63 years, liver dysfunction was noted, and laparoscopy revealed uneven surface of the liver and dilatation of the umbilical vein. Liver dysfunction progressed, and she developed encephalopathy and massive ascites. She died of sepsis at 73 years. At autopsy the liver (700 g) was macronodular with several deep depressions. The parenchyma showed fine and diffuse nodularity. Grossly visible portal and hepatic veins were patent. The above-mentioned histologic features characterizing incomplete septal cirrhosis were found. This is the first report of incomplete septal cirrhosis associated with Wegener's granulomatosis implying that vascular and extravascular lesions of Wegener's granulomatosis might have been related to the pathogenesis of incomplete septal cirrhosis.
Endotoxin and its binding proteins in chronic liver disease: the effect of transjugular intrahepatic portosystemic shunting.
Kaser A, Ludwiczek O, Waldenberger P … +3 more , Jaschke W, Vogel W, Tilg H
Liver · 2002 Oct · PMID 12390473 · Publisher ↗
BACKGROUND: Gut-derived endotoxin is insufficiently cleared by the diseased liver, and thus, is elevated in plasma of patients with chronic liver disease (CLD). Endotoxin action might be modified by binding to soluble CD...
BACKGROUND: Gut-derived endotoxin is insufficiently cleared by the diseased liver, and thus, is elevated in plasma of patients with chronic liver disease (CLD). Endotoxin action might be modified by binding to soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), both of which have not yet been sufficiently studied in CLD. METHODS: Endotoxin, sCD14 and LBP have been determined in peripheral blood of 72 patients and 39 control subjects, and in portal and hepatic venous blood of 12 patients during transjugular intrahepatic portosystemic shunt (TIPS) implantation. RESULTS: Peripheral endotoxin (average 3-fold increased compared to controls), LBP, and sCD14 plasma levels were elevated in chronic liver disease irrespective of Child stage m, preserve/absence of cirrhosis or aetiology. LBP, and sCD14. Furthermore, endotoxin levels in the portal vein (38.1 +/- 6.1 pg/ml) were only slightly elevated compared to the hepatic vein (29.2 +/- 4.4 pg/ml), and peripheral endotoxin levels did not increase after TIPS. CONCLUSIONS: Decreased hepatocellular function rather than hepatic blood shunting might be responsible for endotoxemia. The elevation in LBP and sCD14 levels may be a consequence of endotoxemia.
Correlation of clinical characteristics with detection of hepatitis B virus X gene in liver tissue in HBsAg-negative, and HCV-negative hepatocellular carcinoma patients.
Higashi Y, Tada S, Miyase S … +4 more , Hirota K, Imamura H, Kamio T, Suko H
Liver · 2002 Oct · PMID 12390472 · Publisher ↗
PURPOSE: We studied the clinical features and the etiology of hepatitis B virus surface antigen (HBsAg)-negative and antibody to hepatitis C virus (anti-HCV) negative patients with hepatocellular carcinoma. METHODS: A to...
PURPOSE: We studied the clinical features and the etiology of hepatitis B virus surface antigen (HBsAg)-negative and antibody to hepatitis C virus (anti-HCV) negative patients with hepatocellular carcinoma. METHODS: A total of 550 patients, hospitalized with an initial diagnosis of HCC were retrospectively studied. Eighty-one of these patients were HBsAg-positive (HB group), 404 patients were anti-HCV positive (HC group). The other 65 patients were negative for both HBsAg and for anti-HCV (NBNC group). We purified HBV-X gene from HCC or non-tumorous liver tissue of 23 NBNC patients using PCR. RESULTS: Clinical features of NBNC as compared with HB and HC patients were as follows, respectively: non-cirrhosis rate (%): 57,37,15 (P = 0.02 for HB, P < 0.00001 for HC), the proportion of patients with normal ALT concentrations (%): 59,28,10 (P = 0.0002 for HB, P < 0.00001 for HC). Forty of 59 NBNC patients (68%) had anti-HBs and/or anti-HBc (healthy controls: 29%, P < 0.00001) and two of 56 had serum HBV DNA. Twelve of 23 NBNC patients had HBV-X gene in HCC and/or non-cancerous liver tissues (52%). None of 52 had serum HCV RNA. CONCLUSIONS: The NBNC patients with HCC had a higher frequency of non-cirrhotic liver without liver injury. The presence of the HBV-X gene in HCC suggests a possible role of past HBV infection in the development of HCC. About half of NBNC HCC is associated with seronegativity for HBsAg and positivity for the HBV-X gene in liver tissue.
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