bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptin stimulates α1(I) collagen expression in human hepatic stellate cells via the phosphatidylinositol 3‐kinase/Akt signalling pathway
Authors: Niu Liwen , Wang Xiaohong , Li Jun , Huang Yan , Yang Zhen , Chen Feihu , Ni Hongchang , Jin Yong , Lu Xiongwen , Cao Qi 
Published: August 2010

AbstractBackground/Aims: Leptin has been recognized as a profibrogenic hormone in the liver and is involved in collagen type I formation by activated hepatic stellate cells (HSCs) in response to fibrogenic substances, but the molecular signal mechanisms by which leptin promotes liver fibrogenesis through upregulation of collagen type I expression is not clear. We investigated whether leptin‐induced collagen type I is mediated by the Janus kinase–phosphatidylinositol 3‐kinase–Akt (JAKs–PI3K–Akt) pathway in a human HSC cell line, LX‐2.Methods: LX‐2 cells were treated with or without various inhibitors in the presence of leptin.Results: Leptin increased α1(I) collagen mRNA and protein. JAK1, PI3K and Akt were activated after leptin stimulation. AG490, a JAK inhibitor, blocked JAK1 phosphorylation accompanied by inhibition of PI3K and Akt activation as well as α1(I) collagen mRNA expression, indicating a JAK1‐dependent mechanism. Wortmannin, a PI3K inhibitor, prevented PI3K and Akt activation and resulted in suppression of α1(I) collagen mRNA expression, suggesting a PI3K‐mediated process. These changes were reproduced by overexpression of the dominant‐negative p85α mutant. A443654.3, an Akt inhibitor, opposed Akt activation, leading to downregulation of α1(I) collagen mRNA. Overexpression of the dominant‐negative Akt mutant led to similar alterations.Conclusion: Leptin has a direct action on liver fibrogenesis by stimulating α1(I) collagen production in activated HSC. The process appears to be mediated by the PI3K/Akt pathway through activated JAK1.
Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis
Authors: Rigopoulou Eirini I. , Davies Edward T. , Bogdanos Dimitrios‐Petrou , Liaskos Christos , Mytilinaiou Maria , Koukoulis George K. , Dalekos George N. , Vergani Diego 
Published: August 2010

AbstractBackground/Aims: Primary biliary cirrhosis (PBC) is characterised by the presence of immunoglobulin (Ig) G antimitochondrial antibodies (AMA), which are routinely detected by indirect immunofluorescence (IFL) using composite rodent tissue substrate. The IgG subclass distribution and clinical significance of IFL‐detected AMA in patients with PBC have not been previously studied in detail.Methods: We have examined IgG subclass‐specific AMA detected by IFL on rodent liver, kidney and stomach tissue substrate using affinity‐purified IgG subclass monospecific antisera as revealing reagents in 95 AMA‐positive PBC patients from Greece.Results: AMA of any of the IgG1, IgG2 or IgG3 subclasses were present in 89/95 (93.7%) patients. Among those 89, 55 (61.8%) had IgG1, 2, 3 AMA positivity; eight (9%) had IgG1, 2; seven (7.9%) had IgG2, 3; eight (9%) had IgG1, 3; nine (10.1%) had IgG1 subclass and two (2.2%) single IgG3 AMA reactivity. IgG4 AMA was absent. IgG3 titres were higher than IgG2 and IgG1 (P<0.001) and IgG1 higher than IgG2 (P<0.001). IgG3 AMA‐positive patients had a histologically more advanced disease (P<0.01) and were more frequently cirrhotic compared with those who were negative (P<0.01). There was a positive correlation between AMA IgG3 titre and Mayo risk score (r=0.55, P=0.009, Spearman's correlation).Conclusions: Our findings suggest that AMA are not restricted to a specific IgG subclass. AMA of the IgG3 subclass are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.
Methylenetetrahydrofolate reductase C677T polymorphism and liver fibrosis progression in patients with recurrent hepatitis C
Authors: Toniutto Pierluigi , Fabris Carlo , Falleti Edmondo , Cussigh Annarosa , Fontanini Elisabetta , Bitetto Davide , Fornasiere Ezio , Minisini Rosalba , De Feo Tullia , Marangoni Francesca , Pirisi Mario 
Published: August 2010

AbstractBackground/Aims: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, being a putative steatogenic factor, may promote liver fibrosis progression in patients with chronic hepatitis C. This study aimed to verify the role of recipient MTHFR polymorphism in favouring graft fibrosis progression in patients with recurrent HCV after orthotopic liver transplantation (OLT).Methods: We studied 63 such patients, followed for >1 year. MTHFR allelic variants were determined by a polymerase chain reaction/restriction fragment length polymorphism method.Results: Recipients carrying the TT genotype had more frequently, 1‐year post‐OLT, homocysteine serum levels >23 μmol/L (P<0.05), serum triglycerides >180 mg/dL (P<0.02) and de novo diabetes mellitus (P<0.05) but not a higher frequency of graft steatosis. Time‐to‐event analysis in reaching an Ishak staging score >2 was performed by stratifying the recipients as follows: (a) patients with donor age ≤45 years, (b) patients with donor age >45 and C/* genotype, and (c) patients with donor age >45 years and TT genotype. A significant linear trend was observed, with increasing frequencies as follows: (a) 8/37, (b) 10/19 and (c) 6/7 (P=0.0005).Conclusion: The MTHFR C677T polymorphism may play a role in influencing liver fibrosis progression in patients with recurrent hepatitis C, in conjunction with donor age, but not via steatosis promotion.
Treatment of chronic portosystemic encephalopathy in cirrhotic patients by embolization of portosystemic shunts
Authors: Zidi Sémia H. , Zanditenas David , Gelu‐Siméon Moana , Rangheard Anne‐Sophie , Valla Dominique C. , Vilgrain Valérie , Pelletier Gilles M. 
Published: August 2010

AbstractAims/Backgrounds: Large spontaneous portal‐systemic shunts can occasionally be the cause of chronic and disabling encephalopathy in cirrhotic patients. Shunt embolization has been proposed, however the clinical relevance of this technique remains uncertain.Methods/Results: We report our results in seven patients treated by shunt embolization. Although the procedure was achieved and technically successful in all patients, the clinical results were poor as long‐term improvement was obtained in only one patient. Three patients died within 3 months after the procedure from cirrhoses' end stage complications.Conclusion: We believe that optimal management of these patients with chronic spontaneous encephalopathy is liver transplantation.
Lentivirus‐mediated superoxide dismutase1 gene delivery protects against oxidative stress‐induced liver injury in mice
Authors: Venugopal Senthil Kumar , Wu Jian , Catana Andreea M. , Eisenbud Lauren , He Song‐Qing , Duan Yu‐You , Follenzi Antonia , Zern Mark A. 
Published: August 2010

AbstractBackground: The exposure of liver to hepatotoxins, and their subsequent metabolism, results in increased reactive oxygen species (ROS), one of the major culprits in causing both acute liver cell injury and chronic liver diseases. The aim of this present study is to investigate the protective effects of lentiviral vector‐mediated copper–zinc superoxide dismutase (LV‐SOD1) gene transfer against ROS‐induced cytotoxicity in Hep G2 cells and liver injury in mice.Methods: In vitro SOD1 efficacy was tested against two ROS‐generating systems: hypoxanthine/xanthine oxidase (HX/XO) and hydroxyethyl radicals (HER), whereas in vivo SOD1 efficacy was evaluated in carbon tetrachloride (CCl4)‐induced liver injury in C57BL/6 mice.Results: LV‐SOD1 transduction in Hep G2 cells resulted in a significant increase in SOD activity in cell lysates, and it significantly decreased the toxicity induced by HX/XO and HER. High SOD1 expression in the liver was achieved via portal vein injection of LV‐SOD1 in mice and these high levels were observed for 30 days, the length of the experiment to date. SOD1 overexpression significantly decreased the toxicity and restored liver function in the CCl4‐treated mice.Conclusions: These findings demonstrate for the first time that LV transduction led to the long‐term expression of fully functional transgene expression in both in vitro and in vivo systems.
Managing chronic hepatitis C in the difficult‐to‐treat patient
Authors: Kemmer Nyingi , Neff Guy W. 
Published: August 2010

AbstractPatients with chronic hepatitis C virus (HCV) infection and disease‐related complications – among them cirrhosis and liver failure – pose a particular management challenge. Some of these patients may fail to respond to current therapy (non‐responders), and some are affected so severely that treatment puts them at an unacceptable risk for complications. Treatment with pegylated interferon (peg‐IFN) plus ribavirin improves hepatic enzyme levels and eradicates the virus in ≈50% of patients; however, a significant number of patients do not respond to therapy or relapse following treatment discontinuation. Several viral, hepatic and patient‐related factors influence response to IFN therapy; many of these factors cannot be modified to improve long‐term outcomes. Identifying risk factors and measuring viral load early in the treatment can help to predict response to IFN therapy and determine the need to modify or discontinue treatment. Retreatment options for patients who have failed therapy are limited. Retreatment with peg‐IFN has been successful in some patients who exhibit an inadequate response to conventional IFN treatment, particularly those who have relapsed. Consensus IFN, another option in treatment‐resistant patients, has demonstrated efficacy in the retreatment of non‐responders and relapsers. Although the optimal duration of retreatment and the benefits and safety of maintenance therapy have not been determined, an extended duration is likely needed. This article reviews the risk factors for HCV treatment resistance and discusses the assessment and management of difficult‐to‐treat patients.
Lamivudine prophylaxis is effective in reducing hepatitis B reactivation and reactivation‐related mortality in chemotherapy patients: a meta‐analysis
Authors: Martyak Lenna A. , Taqavi Ehsan , Saab Sammy 
Published: August 2010

AbstractBackground: Hepatitis B viral (HBV) reactivation in patients undergoing chemotherapy is associated with significant morbidity and mortality. Lamivudine has been suggested to be useful as a prophylaxis for HBV reactivation; however, its impact on overall survival and HBV reactivation‐related liver disease survival is unclear.Objective: To determine the effect of lamivudine prophylaxis on the rate of HBV reactivation, overall survival and HBV reactivation‐related survival in patients with HBV undergoing chemotherapy.Methods: A comprehensive search of MEDLINE, Cochrane Collaboration Database, reference lists and abstracts from national meetings. Statistical analysis was performed using revman.Results: Eleven studies met the defined inclusion criteria and were included in the analysis. Two‐hundred and twenty patients received lamivudine prophylaxis and 400 did not receive prophylaxis. Patients given lamivudine prophylaxis had an 87% decrease in HBV reactivation [risk ratio (RR) 0.13, 95% confidence interval (CI), 0.07–0.24] than patients not given prophylaxis [absolute risk reduction (ARR) −0.46, 95% CI, −0.61 to −0.31]. The number needed to treat to prevent one reactivation was 3. The Lamivudine prophylaxis group was also associated with a 70% reduction in reactivation‐related mortality (RR 0.30, 95% CI, 0.1–0.94) compared with controls (ARR −0.03, 95% CI, 0.07–0.00). There was a reduction in treatment delays and premature termination of chemotherapy in the lamivudine prophylaxis arm (RR 0.41, 95% CI, 0.27–0.63; ARR −0.33, 95% CI, −0.33 to −0.15). There was no significant heterogeneity in the comparisons.Conclusion: Lamivudine prophylaxis during chemotherapy is effective in reducing the rate of HBV reactivation, and reactivation‐related liver mortality. Patients with lamivudine prophylaxis had less chemotherapy treatment delays and premature termination of their chemotherapy. Few patients need to be treated to prevent reactivation. Patients with HBV undergoing chemotherapy should be started on lamivudine prophylaxis.
Epigenetic DNA hypermethylation in cholangiocarcinoma: potential roles in pathogenesis, diagnosis and identification of treatment targets
Authors: Sandhu Dalbir S. , Shire Abdirashid M. , Roberts Lewis R. 
Published: August 2010

AbstractCholangiocarcinomas (CCs) are highly lethal malignant tumours arising from the biliary tract epithelium. The disease is notoriously difficult to diagnose and is usually fatal because of its typically late clinical presentation and the lack of effective non‐surgical therapeutic modalities. The overall survival rate, including resected patients is poor, with less than 5% of patients surviving 5 years, a rate which has not changed significantly over the past 30 years. Although CC is a relatively uncommon tumor, interest in this disease is rising as incidence and mortality rates for intrahepatic cholangiocarcinoma are increasing markedly worldwide. A variety of risk factors, including primary sclerosing cholangitis, liver fluke infestation, and hepatolithiasis have been described. However, for most CCs the cause is unknown, and affected individuals have no history of exposure to, or association with, known risk factors. Recent advances in molecular pathogenesis have highlighted the importance of epigenetic alterations in the form of promoter region hypermethylation and histone deacetylation in addition to genetic changes in the process of cholangiocarcinogenesis. This review provides a comprehensive overview of the genes reported to be methylated in CC to date and their putative roles in cholangiocarcinogenesis. Future directions in the study of methylated genes and their potential roles as diagnostic and prognostic markers are also discussed.
Gallstones are associated with carotid atherosclerosis
Authors: Méndez‐Sánchez Nahum , Zamora‐Valdés Daniel , Flores‐Rangel José A. , Pérez‐Sosa Julio A. , Vásquez‐Fernández Francisco , Lezama‐Mora Jezer I. , Vázquez‐Elizondo Genaro , Ponciano‐Rodríguez Guadalupe , Ramos Martha H. , Uribe Misael 
Published: August 2010

AbstractBackground/Aims: Gallstone disease (GD) and cardiovascular disease (CD) are common diseases worldwide with considerable economical impact and they are strongly associated. Carotid atherosclerosis is an excellent marker of risk for CD like stroke and myocardial infarction. The aim of this study was to assess the association between gallstones and carotid atherosclerosis.Methods: A cross‐sectional study was conducted. We evaluated subjects with ultrasonographical evidence of GD and asymptomatic subjects without such evidence. Anthropometric, clinical and biochemical variables were collected. The Metabolic syndrome was evaluated using adult treatment panel III criteria. Carotid artery intima–media thickness (CIMT) was determined by a standard ultrasound protocol. Insulin‐like growth factor‐1 (IGF‐1) serum levels were measured in all subjects.Results: We studied 191 subjects: 62 subjects with GD (53.2% males) and 129 asymptomatic subjects without GD (65.9% males). Subjects with GD exhibited a higher body mass index, body fat percent, insulin serum levels and CIMT (P<0.05 for all). The prevalence of GD was higher in subjects with a CIMT>0.75 independently of other factors [odds ratio (OR) 2.12, 95% confidence interval (CI) 1.04–4.34; P=0.039], and for every 0.1 mm increase in CIMT the independent probability to be a case of GD increased by a factor of 1.25 (95% CI 1.02–1.53; P=0.027). IGF‐1 levels did not differ among groups.Conclusions: Subjects with GD exhibit greater carotid atherosclerosis, and therefore have a higher risk for stroke and myocardial infarction.
Molecular characterization of hepatitis A virus in children with fulminant hepatic failure in Argentina
Authors: Munné María Silvina , Vladimirsky Sara , Moreiro Rita , Ciocca Mirta , Cuarterolo Miriam , Otegui Lucio , Soto Sonia , Brajterman Leonardo , Castro Raúl , Sasbón Jorge , Gianivelli Silvina , Buamscha Daniel , Quarleri Jorge , González Jorge E. 
Published: August 2010

AbstractBackground: Hepatitis A infection, a vaccine‐preventable disease, is an important cause of fulminant hepatic failure (FHF) in children in Argentina. Universal vaccination in 1‐year‐old children was implemented in June 2005. The limited studies about the correlation between the characteristics of the hepatitis A virus (HAV) and FHF have been carried out in adults.Methods: Samples from 41 children with FHF were studied from September 2003 to January 2006 and HAV RNA was detected, sequenced and analysed in the 5′ non‐coding region and VP1/2A region.Results: Eighteen HAV strains were characterized and found to be different at the nucleotide level from the self‐limited acute infection strains that have been circulating in Argentina with no temporal or geographical pattern. They did not form a genetic cluster, but some of them were identical in the largest fragment characterized and some of them seemed to be more closely related in time and/or geographically.Conclusion: Our results suggest that viral factors could be involved in the severity of the clinical presentation of HAV infection in children in Argentina.
Physiological variations of stem cell factor and stromal‐derived factor‐1 in murine models of liver injury and regeneration
Authors: Swenson E. Scott , Kuwahara Reiichiro , Krause Diane S. , Theise Neil D. 
Published: August 2010

AbstractBackground/Aims: Stem cell factor (SCF) and stromal‐derived factor‐1 (SDF‐1) regulate the regenerative response to liver injury, possibly through activation of liver progenitor ‘oval’ cells and recruitment of circulating, marrow‐derived progenitors.Methods: We performed a detailed analysis of SCF, SDF‐1 and oval cell proliferation induced by tyrosinaemia, 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) or liver irradiation in mice by ELISA and immunofluorescence.Results: Liver injury in the tyrosinaemia mouse is characterized by a dramatic decline in plasma SCF and absence of oval cell proliferation. In contrast, DDC induces bile duct (BD) and oval cell proliferation, and a modest decline in plasma SCF. Focal liver irradiation increases plasma SCF, but not oval cell density. In normal mouse liver, SCF is localized primarily to Kupffer cells, cholangiocytes and arterial smooth muscle, with little or no expression in hepatocytes. However, SCF appears in hepatocyte nuclei after injury, where its function is unknown. In all three models, SDF‐1 is expressed exclusively in BD epithelium, indicating that tissue SDF‐1 levels are proportional to the total mass of oval cells and cholangiocytes. However, increased plasma levels of SDF‐1 in fumaryl acetoacetate hydroxylase‐null mice were not accompanied by oval cell proliferation.Conclusion: Changes in SCF and SDF‐1 varied with the nature of liver injury and were not directly related to oval cell proliferation.
Asymptomatic individuals at genetic risk of haemochromatosis take appropriate steps to prevent disease related to iron overload
Authors: Allen Katrina J. , Nisselle Amy E. , Collins Veronica R. , Williamson Robert , Delatycki Martin B. 
Published: August 2010

AbstractBackground/Aims: If community screening for hereditary haemochromatosis is to be considered, compliance with preventative measures and absence of significant psychological morbidity must be demonstrated.Methods: Workplace screening for the HFE C282Y mutation and then clinical care for C282Y homozygotes was instituted. Data were collected on understanding of test results, perceived health status and anxiety for C282Y homozygotes compared with controls. Uptake of clinical care, compliance and response to treatment and changes in diet were monitored for up to 4 years for C282Y homozygotes.Results: After 11 307 individuals were screened, 40/47 (85%) newly identified C282Y homozygotes completed questionnaires 12 months after diagnosis compared with 79/126 (63%) of controls. Significantly more C282Y homozygotes correctly remembered their test result compared with controls (95 vs 51%, P<0.0001). No significant difference in perceived health status was observed within or between the two groups at 12 months compared with baseline. Anxiety levels decreased significantly for C282Y homozygotes at 12 months compared with before testing (P<0.05). Forty‐five of the 47 (95.8%) C282Y homozygotes accessed clinical care for at least 12 months. All 22 participants requiring therapeutic venesection complied with treatment for at least 12 months (range 12–47 months).Conclusion: Individuals at a high genetic risk of developing haemochromatosis use clinical services appropriately, maintain their health and are not ‘worried well’. Population genetic screening for haemochromatosis can be conducted in the work place in a way that is acceptable and beneficial to participants.
Liver adenomatosis: re‐evaluation of aetiology and management
Authors: Veteläinen Reeta , Erdogan Deha , De Graaf Wilmar , Ten Kate Fiebo , Jansen Peter L. M. , Gouma Dirk J. , Van Gulik Thomas M. 
Published: August 2010

AbstractBackground: Liver adenomatosis (LA) is a rare benign parenchymal liver disease with unknown aetiology. In recent reports, LA has been associated with hepatic steatosis, with potential implications for the management of this disease. The aim of this study was to determine prognosis and optimal management of patients with LA.Methods: Clinical presentation, diagnostic studies and management of patients with LA were analysed in our centre. Furthermore, a Medline search of all published case reports and series of LA patients was performed.Results: Ninety‐four patients with LA have been reported in the literature. Fifty‐two per cent of females had a history of oral contraceptive use. Eighteen per cent of patients had steatosis in nontumoral tissue. In our own series, five of six patients had histologically confirmed steatosis. Forty‐three per cent of patients presented with acute pain, of whom 46% had a haemorrhagical complication, in contrast to 2% of nonsymptomatic patients. Tumours <5 cm tended to increase in size during follow‐up and only in four patients tumour regression was observed.Conclusion: Liver adenomatosis is a progressive, benign parenchymal disease mainly occurring in females. There is a potential link with hepatic steatosis with implications for the management of patients with LA. Noninvasive diagnosis is difficult because of the variety of tumoral and nontumoral components. Management should primarily be conservative.