bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transjugular intrahepatic portosystemic shunts in liver transplant recipients
Authors: Kim John J. , Dasika Narasimham L. , Yu Esther , Fontana Robert J. 
Published: August 2010

AbstractBackground: The aim of this study was to determine the efficacy and safety of transjugular intrahepatic portosystemic shunts (TIPS) in liver transplant (LT) recipients with refractory ascites/variceal bleeding and to compare the observed outcomes with those obtained in cirrhotic controls.Methods: Clinical features of 14 LT recipients referred for TIPS placement between August 1985 and September 2006 were reviewed and compared with published series and 28 cirrhotic control patients undergoing TIPS.Results: The median age of the 14 LT recipients was 52 years, 57% had chronic hepatitis C virus and the median time from LT to TIPS placement was 46 months. Portal vein thromboses in two patients and a procedural complication in another patient precluded TIPS deployment. Among the 11 patients who completed TIPS, the mean hepatic venous pressure gradient was significantly reduced post‐TIPS (18.3 ± 6.1 to 9.0 ± 3.5 mmHg, P<0.01). However, only 50% of the patients with varices had no further bleeding and 57% of the refractory ascites patients required no further paracentesis. In addition to a single peri‐procedural death and renal failure in three others, four patients (29%) developed infection and nine (82%) developed new onset or worsening encephalopathy at a median of 11 days post‐TIPS. The 1‐year patient survival of 14% was substantially lower than that observed in other series of LT recipients (57–67%) as well as the matched cirrhotic control group undergoing TIPS (58%).Conclusion: The frequent morbidity noted in LT recipients undergoing TIPS, coupled with the low 1‐year patient survival, demonstrates that portal decompression provides only marginal short‐term benefit in the absence of retransplantation.
Treatment of bile duct‐ligated rats with the nitric oxide synthase transcription enhancer AVE 9488 ameliorates portal hypertension
Authors: Biecker Erwin , Trebicka Jonel , Kang Alice , Hennenberg Martin , Sauerbruch Tilman , Heller Jörg 
Published: August 2010

AbstractAim: Nitric oxide levels are decreased in the cirrhotic liver and increased in the systemic vasculature. We investigated whether the nitric oxide synthase (NOS) transcription enhancer AVE 9488 ameliorates portal hypertension in cirrhotic rats.Methods: Rats with secondary biliary cirrhosis [bile duct ligation (BDL)] were treated with AVE 9488. BDL animals without treatment served as controls. Blood flow was determined with the microsphere technique. Intrahepatic resistance was measured by in situ perfusion. NOS‐3 mRNA and protein levels in the liver, aorta and superior mesenteric artery (SMA) were measured.Results: Arterial pressure did not differ between treated and non‐treated animals. Portal pressure, hepatic portal‐vascular resistance and perfusion pressure of the in situ perfused liver were lower in the AVE 9488‐treated animals. Arterial splanchnic resistance, portal venous inflow and shunt volume were increased by AVE 9488. N (G)‐nitro‐l‐arginine methyl ester abolished the effect of AVE 9488. AVE 9488‐treated rats had higher liver NOS‐3 mRNA and protein levels, whereas NOS‐3 mRNA and protein in the aorta and the SMA did not vary between groups. Phosphorylation of liver vasodilator‐stimulated phosphoprotein (VASP) and NOS‐3 as well as hepatic nitrite/nitrate was increased by AVE 9488.Conclusions: Treatment of BDL rats with the NOS transcription enhancer AVE 9488 induces an increase in NOS‐3 mRNA and protein in the liver. This is associated with an amelioration of portal hypertension.
Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver cirrhosis in Turkey: a meta‐analysis
Authors: Değertekin Halil , Yalçιn Kendal , Yakut Mustafa , Yurdaydin Cihan 
Published: August 2010

AbstractBackground: Recent reports suggest a decline of delta hepatitis (DH) in the West as well as in the Far East.Aim: To study the DH seroepidemiology in Turkey.Methods: Statistical power analysis was utilized based on data available in a recent article using prevalence figure estimates. Binominal distribution was applied in order to assess the number of samples required to estimate the prevalence with a given precision.Results: Out of 62 studies in the original study, 32 were eliminated because of insufficient power. A total of 6734 patients (5231 with chronic hepatitis and 1503 with cirrhosis) were analysed. Anti‐HDV seropositivity among patients with chronic hepatitis B (CHB) and hepatitis B‐induced cirrhosis was lowest in the west of the country and highest in the southeast (5 vs. 27%, P<0.0001 and 20 vs. 46%, P<0.0001) respectively. Compared with data obtained before 1995, after 1995, DH prevalence in patients with CHB and cirrhosis decreased from 29 to 12% (P<0.0001) and from 38 to 27% (P=0.03) in central and southeast Turkey and from 38 to 20% (P<0.0001) and from 66 to 46% (P<0.002) in west and southeast Turkey respectively.Conclusion: Despite the decrease of its prevalence in Turkey, DH remains a significant health problem in parts of the country with low socio‐economic level.
Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation
Authors: Rubio‐Tapia Alberto , Abdulkarim Ahmad S. , Wiesner Russell H. , Moore S. Breanndan , Krause Patricia K. , Murray Joseph A. 
Published: August 2010

AbstractBackground/aims: Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end‐stage autoimmune liver disease (ESALD), (ii) the correlation among auto‐antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics.Methods: Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non‐autoimmune disease) were tested for tTGAs. Positive samples were also tested for EMAs, and retested 6–12 and ≥24 months post‐transplantation. Results were correlated with the HLA type of the recipient.Results: Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non‐autoimmune) of the patients (five‐fold increased risk in ESALD). The prevalence of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was significantly higher in patients with the HLA‐DQ2 or HLA‐DQ8 haplotypes. tTGAs and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post‐transplantation. Post‐transplantation, of the five patients with symptoms of ‘classical’ CD, three improved. Intestinal lymphoma was diagnosed in another two cases with clinically ‘silent’ CD.Conclusions: Patients with ESALD, especially those who are HLA‐DQ2 or HLA‐DQ8 positive had a high prevalence of CD‐associated antibodies. Both tTGAs and EMAs decreased post‐transplantation without gluten withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent progression to intestinal lymphoma.
Nuclear factor‐κB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy
Authors: Liu Hongqun , Lee Samuel S. 
Published: August 2010

AbstractBackground/Aims:Cytokines such as tumour necrosis factor (TNF‐α) contribute to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor‐κB (NF‐κB) is crucial for cytokine regulation, and induces cardiac dysfunction in several heart disease models. We aimed to elucidate possible NF‐κB involvement in cirrhotic cardiomyopathy.Methods:Rats were bile duct ligated (BDL) to produce cirrhosis; controls received sham operation. Animals were studied 4 weeks later. Two NF‐κB inhibitors were used: pyrrolidine dithiocarbamate (PDTC) and Bay 11‐7082. Four groups were studied in most protocols: sham control, sham+PDTC, BDL and BDL+PDTC. Additional contractility studies were performed with Bay 11‐7082. Myocardial NF‐κB and TNF‐α expression was measured by Western blot and ELISA. The contractility of isolated cardiomyocytes was observed under direct microscopy.Results:Nuclear factor‐κB and TNF‐α levels were increased in cirrhotic hearts compared with controls. PDTC significantly reduced NF‐κB activity and TNF‐α expression in cirrhotic hearts; controls were unaffected. Cirrhotic cardiomyocytes showed decreased systolic and diatolic velocity compared with sham controls. Both PDTC and Bay 11‐7082 restored contractile function in cirrhotic cardiomyocytes, but did not affect controls.Conclusions:Inhibition of the increased NF‐κB activity in cirrhotic hearts was associated with improvement of attenuated cardiomyocyte contractility. NF‐κB, via effects on cytokine expression, may contribute to the pathogenesis of cirrhotic cardiomyopathy.
Mitochondrial electron transport inhibition in full genomic hepatitis C virus replicon cells is restored by reducing viral replication
Authors: Ando Mie , Korenaga Masaaki , Hino Keisuke , Ikeda Masanori , Kato Nobuyuki , Nishina Sohji , Hidaka Isao , Sakaida Isao 
Published: August 2010

AbstractBackground/Aim:Hepatitis C virus (HCV) core protein has been shown to inhibit mitochondrial electron transport and to increase reactive oxygen species (ROS)in vitroandin vivo. The aim of this study was to investigate whether inhibiting HCV replication could restore the mitochondrial redox state and electron transport activity.Methods:We measured ROS, mitochondrial reduced glutathione content, and mitochondrial complex I, II, III and IV activities and protein expression in full genomic HCV replicon cells and cured cells that had been prepared by eliminating HCV RNA from replicon cells by interferon (IFN)‐α treatment.Results:Cured cells had significantly lower ROS production and greater mitochondrial glutathione content than replicon cells. Complete inhibition of HCV replication by IFN‐α restored complex I and IV activities by 20–30% (P<0.01) and complex I expression (P<0.05). Treatment with fluvastatin, one of the 3‐hydroxy‐3‐methylglutaryl co‐enzyme A reductase inhibitors, which is known to have anti‐HCV activity, partially inhibited core protein expression and restored complex I activity in full genomic HCV replicon cells to a lesser degree (P<0.05).Conclusions:Our results show that the mitochondrial redox state and electron transport activity can be restored by reducing HCV replication.
Serological markers for monitoring disease progression in noncirrhotic primary biliary cirrhosis on ursodeoxycholic acid therapy
Authors: Färkkilä Martti , Rautiainen Henna , Kärkkäinen Päivi , Karvonen Anna‐L. , Nurmi Heimo , Niemelä Onni 
Published: August 2010

AbstractBackground/Aim: Liver biopsy has so far been the only method to accurately follow the progression of primary biliary cirrhosis (PBC). The stage and the severity of lymphocytic piecemeal necrosis (LPN) have been shown to be an independent factor for the development of cirrhosis. In this 3‐year prospective study, we evaluated the diagnostic value of several liver function tests, surrogate markers of fibrogenesis, hyaluronic acid (HA), procollagen III N‐terminal peptide (S‐PIIINP), cholestanol and plant sterols in noncirrhotic PBC patients treated with ursodeoxycholic acid (UDCA) or with UDCA and budesonide to assess the stage, inflammation and fibrosis.Methods: Seventy‐seven stage I–III PBC patients were included into the study, with control biopsy at 36 months. Serum liver enzymes, bile acids (BA), HA, PIIINP, immunoglobulins, lipids and cholesterol precursors and plant sterols were measured at baseline and at 36 months.Results: Aspartate aminotransferase (AST), HA, BA and PIINP were significantly different between stages I to III and differentiated mild (F0F1) from moderate (F2F3) fibrosis. The combination of these variables (PBC score) exhibited best sensitivity and specificity, compared with AST/platelet ratio, Forns' score and fibrosis index. Using a cut‐off value of 66 for the PBC score, the sensitivity was 81.4% and specificity was 65.2% for classifying the stage of PBC, regarding the stage the and fibrosis in noncirrhotic PBC.Conclusions: Serum HA, BA, PIIINP and AST may serve as valuable simple tools to monitor the treatment response to UDCA in early stages of PBC. Combinations of these biomarkers into a single index further potentiate the diagnostic value of such measurements.
Association of interferon regulatory factor ‐7 gene polymorphism with liver cirrhosis in chronic hepatitis C patients
Authors: Sermasathanasawadi Radsamee , Kato Naoya , Muroyama Ryosuke , Dharel Narayan , Shao Run‐Xuan , Chang Jin‐Hai , Li Chang‐Zheng , Kawabe Takao , Omata Masao 
Published: August 2010

AbstractBackground and aims:Interferon (IFN) regulatory factor 7 (IRF‐7) has been shown to play an essential role in the transcriptional activation of virus‐inducible cellular genes, especially IFN genes. Polymorphisms of the IRF‐7 gene may probably affect both the quality and the quantity of IRF‐7. We investigated the role of IRF‐7 polymorphisms in Japanese patients with chronic hepatitis C virus (HCV) infection.Methods:We studied a total of nine polymorphisms of the IRF‐7 gene including SNP1047A/G (Lys/Glu) and SNP2157A/G (Gln/Arg) using the Taqman allelic discrimination and sequencing techniques in 406 Japanese patients with chronic HCV infection. We further performed functional analysis of SNP1047 and SNP2157 by transcriptional activation of the IFNA promoter.Results:We found that SNP1047AG and SNP2157AG genotypes were in complete linkage disequilibrium and were present in a significantly higher proportion in HCV‐infected patients with cirrhosis (5.6%) than in those without cirrhosis (1.7%) (P=0.03). Multivariate analysis also revealed that SNP1047 and SNP2157 were independently associated with cirrhosis at an odds ratio of 2.5. Functional analysis revealed that SNP1047G and SNP2157G alleles increased IFNA expression.Conclusion:SNP1047AG and SNP2157AG genotypes were strongly associated with cirrhosis. SNP1047G and SNP2157G alleles might be used as markers of host factors associated with a higher risk of cirrhosis in Japanese patients with chronic HCV infection.
Outcome and prognostic factors of 391 Japanese patients with primary sclerosing cholangitis
Authors: Tanaka Atsushi , Takamori Yoriyuki , Toda Gotaro , Ohnishi Saburo , Takikawa Hajime 
Published: August 2010

AbstractObjectives: We performed a national survey in 2003, and demonstrated characteristic features of primary sclerosing cholangitis (PSC) patients in Japan. In this study, we aimed to clarify the outcome and prognostic factors of Japanese PSC patients.Methods: Questionnaires were sent to gastroenterologists in Japan, and 391 patients with PSC were registered and enrolled in the current study. The median follow‐up was 5.3 years (range 0.1–20.8 years). The cumulative incidence for survival was analysed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox‐proportional hazards regression model for determining prognostic variables.Results: The estimated median survival of all patients was 13.1 years, with a 5‐year survival rate of 74.5%. Thirty‐eight patients (9.7%) who underwent liver transplantation (LT) had a 5‐year survival rate of 92.0%. Both univariate and multivariate analysis demonstrated that younger age [below 49 years old; odds ratio (OR)=1.76, 1.12–2.76, P=0.0136] and lower total bilirubin (below 3.0 mg/dl; OR=2.50, 1.60–3.89, P≤0.0001) were independent prognostic factors for LT‐free survival of PSC patients in Japan. Cholangiocarcinoma (CCA) was found in 14 (3.6%) patients, and only two out of 125 PSC patients exhibited a history of inflammatory bowel diseases.Conclusions: Although several characteristic features existed, the outcome as well as prognostic factors of Japanese PSC patients appeared to be similar to those from the United States and European countries. In contrast, the incidence of CCA in PSC appeared to be lower in Japan.
Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow‐up study
Authors: Catalano Daniela , Trovato Guglielmo M. , Martines Giuseppe F. , Randazzo Marianna , Tonzuso Antonia 
Published: August 2010

AbstractBackground: Nonalcoholic fatty liver disease (NAFLD) because of its association with obesity, diabetes and insulin resistance (IR), is the hepatic expression of metabolic syndrome. Exercise and nutritional intervention can improve and prevent these inter‐related conditions; the relationships between the degree of IR and ultrasound (US) morphological post‐interventional changes are not defined.Aims: The aim of our study was to assess the relationship, if any, in NAFLD patients, among IR, BMI and degree of bright liver, before and after 6 months of a moderately hypocaloric/balanced dietary/lifestyle treatment. Fifty outpatients with a clinical and US diagnosis of NAFLD were studied.Methods: Liver echogenicity [Bright Liver Score (BLS)] was scored on a four‐graded scale. IR was assessed by homoeostasis model‐insulin resistance (HOMA‐IR). Body composition was assessed by bioimpedance assessment and skinfold measurements.Results: A significant decrease of BLS was observed, with a concurrent decrease of body weight, body mass index (BMI) and HOMA‐IR. Bright liver decrease has a trend parallel to IR, much less steep than the trend of bright liver reduction against US liver dimensions, body weight and BMI decrease. HOMA‐IR is the only baseline variable that enters significantly in the multiple regression and, alone, explains 21.4% of variance in predicting bright liver degree. After dietary interventions, both HOMA‐IR and BMI are significantly involved in the multiple regression and explain, together, 42.3% of variance in predicting bright liver degree; variation in BLS can be predicted by variation of body weight and of US longitudinal measurement of the liver.Conclusions: Liver US BLS appears to be a useful tool, both alone and along with other US measurements and body weight changes, for the assessment of clinical‐metabolic amelioration in patients treated with dietetic interventions. The clinical‐diagnostic role, if any, of other assessed laboratory analyses, in the subset of NAFLD, does not appear to be definite.
A higher alanine aminotransferase level correlates with earlier hepatitis B e antigen seroconversion in lamivudine‐treated chronic hepatitis B patients
Authors: Tseng Tai‐Chung , Liu Chun‐Jen , Wang Chia‐Chi , Chen Pei‐Jer , Lai Ming‐Yang , Kao Jia‐Horng , Chen Ding‐Shinn 
Published: August 2010

AbstractBackground/Aims: A pretherapy serum alanine aminotransferase (ALT) level above five times the upper limit of normal (ULN) is known to predict hepatitis B e antigen (HBeAg) seroconversion during lamivudine therapy for chronic hepatitis B patients. However, whether an even higher pretherapy serum ALT value or other viral factors could affect treatment responses remains unclear.Patients and methods: A total of 253 HBeAg‐positive chronic hepatitis B patients who had a pretherapy serum ALT level over five times ULN and received lamivudine for 12–18 months were retrospectively collected. Among these patients, 38% had received prior lamivudine treatment. HBeAg seroconversion was the primary endpoint of treatment. Baseline clinical and viral features were compared between responders and non‐responders at the end of treatment and 6 months post‐treatment.Results: At the end of therapy, the overall HBeAg seroconversion rate was 33.6%. For lamivudine‐naïve patients, the HBeAg seroconversion rate was 37.8%. Subgroup analysis showed that patients with pretherapy ALT levels over 10 times ULN had a significantly higher HBeAg seroconversion rate than those with a pretherapy ALT level between five and 10 times ULN at 3 months (P=0.045) and 6 months (P=0.037) of lamivudine treatment. No significant difference was found in terms of pretherapy serum ALT values, viral load and genotypes between seroconverters and non‐seroconverters.Conclusions: For lamivudine‐treated HBeAg‐positive patients with pretherapy ALT levels over five times ULN, an even higher ALT level could predict earlier HBeAg seroconversion; however, neither ALT levels nor viral factors correlate with higher response rates after 12–18 months of treatment.
Contribution of hepatic stellate cells and matrix metalloproteinase 9 in acute liver failure
Authors: Yan Chunli , Zhou Ling , Han Yuan‐Ping 
Published: August 2010

AbstractBackground/Aims: Fulminant hepatitis or acute liver failure (ALF), initiated by viral infection or hepatic toxin, is a devastating medical complication without effective therapeutic treatment. In this study, we addressed the potential roles of hepatic stellate cells (HSCs) and their produced matrix metalloproteinases (MMPs) in development of ALF.Methods: Mice were given lipopolysaccharide (LPS) and beta‐galactosamine (GA) or carbon tetrachloride to create ALF and establish the association of IL‐1, MMP‐9, and caspase‐3 in acute liver failure.Results: In response to the hepatic toxin, IL‐1 and MMP‐9 were promptly induced within 1 hour, followed by caspase‐3 activation at 2 hours, and dehiscence of sinusoids at 4 hours, and consequent lethality. In contrast, MMP‐9 knockout mice were resistant to lethality and absent of caspase‐3 activation, demonstrating an MMP‐9‐dependent activation of caspase in vivo. Further, IL‐1‐receptor knockout mice were resistant to lethality in MMP‐9 dependent manner, indicating a causative relationship. Although many hepatic cells are capable to produce MMP‐9 in vitro, HSCs were demonstrated here as the major hepatic cells to express MMP‐9 in liver injury. To recapitulate the sinusoidal microenvironment we cultured primary HSCs in 3‐dimensional ECM. In response to IL‐1, massive MMP‐9 was produced by the 3D culture concomitantly with degradation of type‐IV collagen.Conclusions: Based on these evidences, we propose a novel model to highlight the initiation of acute liver failure: IL‐1‐induced MMPs by HSCs within the space of Disse and thereafter ECM degradation may provoke the collapse of sinusoids, leading parenchymal cell death and loss of liver functions.
Green tea consumption and liver disease: a systematic review
Authors: Jin Xi , Zheng Ruo‐heng , Li You‐ming 
Published: August 2010

AbstractObjectives: To present the effect of green tea consumption against liver disease.Data sources: Interventional and observational studies both in Western countries and in China and published between the years 1989 and December 2007.Review Methods: The articles were retrieved from Medline, Embase database, Chinese biomedicine web database and Chinese scientific journal's database using proper MESH headings and assessed by two independent investigators according to established inclusion criteria. The characteristics and outcomes of the chosen articles were displayed for further analysis and the quality of each study was also evaluated according to the widely acknowledged criteria. P<0.05 was defined as statistically significant in all enrolled trials.Results: Ten qualified studies (eight from China, one from Japan and the other from the USA) with various outcomes such as liver cancer, cirrhosis and fatty liver disease were finally chosen. Among them, study designs differed in that there were four randomized‐controlled clinical trials, two cohort, one case–control and three cross‐sectional studies. The heterogeneity in the study design, outcomes, cofounders and amount of tea consumption precluded further meta‐analysis. Nevertheless, eight studies showed a significant protective role of green tea against various liver diseases as determined by relative risk/odds ratio or P‐value and among them, four studies showed a positive correlation between green tea intake and attenuation of liver disease. Moreover, the other two studies also presented the protective tendency of green tea against liver disease.Conclusions: An increased consumption of green tea may reduce the risk of liver disease.