bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eight‐week regimen of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C with hepatitis C virus genotype 2 and a rapid virological response
Authors: Toyoda Hidenori , Kumada Takashi , Kiriyama Seiki , Sone Yasuhiro , Tanikawa Makoto , Hisanaga Yasuhiro , Kanamori Akira , Atsumi Hiroyuki , Nakano Satoshi , Arakawa Takahiro 
Published: March 2010

AbstractBackground: It remains unclear how we can shorten the treatment duration of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C virus (HCV) genotype 2 infection who achieved a rapid virological response (RVR).Aim: We compared the efficacy of antiviral combination therapy with peginterferon and ribavirin for 8 vs. 24 weeks for the treatment of patients with HCV genotype 2 infection and with RVR.Methods: Sixty‐one patients were enrolled. Serum HCV RNA was not detected at 4 weeks after the start of treatment in 32 patients with an RVR. These 32 patients were randomly assigned to 8‐week (n=15) or 24‐week (n=17) treatment regimens. Patients in the 8‐week group who relapsed underwent a 24‐week retreatment.Results: No significant difference in patient characteristics was observed between the 8‐ and the 24‐week treatment groups. A sustained virological response (SVR) was seen in five of 15 patients (33.3%) in the 8‐week treatment group and 14 of 17 (82.4%) in the 24‐week treatment group; the rate was significantly higher in the 24‐week treatment group (P=0.0140). Nine of 10 relapsed patients in the 8‐week treatment group underwent a 24‐week retreatment, and seven achieved an SVR.Conclusion: An 8‐week regimen of combination antiviral therapy with peginterferon and ribavirin yielded an increase in the relapse rate, indicating the limitation of a reduction of treatment below 12 weeks in patients with genotype 2, after RVR.
Enhanced actions of insulin‐like growth factor‐I and interferon‐α co‐administration in experimental cirrhosis
Authors: Tutau Federico , Rodríguez‐Ortigosa Carlos , Puche Juan Enrique , Juanarena Nerea , Monreal Iñigo , García Fernández María , Clavijo Encarna , Castilla Alberto , Castilla ‐ Cortázar Inma 
Published: March 2010

AbstractBackground: Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin‐like growth factor‐I (IGF‐I) whose plasma levels are diminished in cirrhosis. IGF‐I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon‐α (IFN‐α) therapy seems to suppress the progression of hepatic fibrosis.Aims: The aim of this study was to investigate the effect of the co‐administration of IGF‐I+IFN‐α to Wistar rats with CCl4‐induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology.Methods: The mechanisms underlying the effects of these agents were studied by reverse transcription‐polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor‐β (TGF‐β), α‐smooth muscle actin, collagen, tissular inhibitor of metalloproteinases‐1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection.Results: Both IGF‐I and IFN‐α exerted significant effects on fibrogenesis. IGF‐I significantly increased serum albumin and HGF whereas IFN‐α‐therapy did not. The inhibition of TGF‐β expression was only observed by the effect of IFN‐α‐therapy. In addition, only the co‐administration of IGF‐I and IFN‐α was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture.Conclusion: The co‐administration IGF‐I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.
Differences in molecular alterations of hepatocellular carcinoma between patients with a sustained virological response and those with hepatitis C virus infection
Authors: Hayashi Takehiro , Tamori Akihiro , Nishikawa Manabu , Morikawa Hiroyasu , Enomoto Masaru , Sakaguchi Hiroki , Habu Daiki , Kawada Norifumi , Kubo Shoji , Nishiguchi Shuhei , Shiomi Susumu 
Published: March 2010

AbstractBackground/Aims: The mechanism of hepatocarcinogenesis remains unclear in patients in whom hepatitis C virus (HCV) disappears after interferon (IFN) therapy. We compared molecular alterations in hepatocellular carcinoma (HCC) between patients with a sustained virological response (SVR) to IFN and patients with HCV.Methods: The study group comprised 44 patients with HCV and 13 patients with SVR. One patient in the SVR group had two tumour nodules, both of which were examined. Mitochondrial DNA (mtDNA) mutations in displacement‐loop lesions were directly sequenced. Mutation of the TP53 gene was examined by direct sequencing. The methylation status of p16, p15, p14, RB and PTEN genes was evaluated by a methylation‐specific polymerase chain reaction.Results: The average number of mtDNA mutations was 4.2 in 44 HCCs with HCV and 2.0 in 14 HCCs with SVR (P=0.0021). mtDNA mutation was less frequently detected in HCCs from patients with SVR than in patients with HCV. TP53 mutations were detected in 12 (27%) of 44 HCCs with HCV and 2 (14%) of 14 SVR‐HCCs. Hypermethylation of the p16, p15, p14, RB and PTEN promoters was, respectively, detected in 34, 13, 8, 12 and 11 of 44 HCCs from patients with HCV and 14, 0, 0, 2 and 2 of 14 HCCs from patients with SVR (P=0.049, 0.021, 0.085, 0.322 and 0.402). Hypermethylation of p16 was one of the most important alterations in SVR‐HCC.Conclusions: Molecular alterations in hepatocarcinogenesis of patients with SVR‐HCC were different from those of patients with continuous HCV infection.
Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver
Authors: Nagatsuma Keisuke , Hayashi Yoshihiro , Hano Hiroshi , Sagara Hiroshi , Murakami Kazuhiro , Saito Masaya , Masaki Takahiro , Lu Tomoe , Tanaka Mitsugu , Enzan Hideaki , Aizawa Yoshio , Tajiri Hisao , Matsuura Tomokazu 
Published: March 2010

AbstractBackground: To determine the extent to which hepatic stellate cell (HSC) activation contributes to liver fibrosis, it was found necessary to develop an alternative structural and functional stellate cell marker for in situ studies. Although several HSC markers have been reported, none of those are associated with particular HSC functions.Aim: The present study was undertaken to examine whether lecithin:retinol acyltransferase (LRAT), the physiological retinol esterification enzyme of the liver, is a potential and relevant tissue marker for HSC.Methods: An antibody specific to mouse and human LRAT was prepared based on the amino acid sequences. Antibodies to LRAT were used for immunohistochemical studies to assess the distribution of LRAT‐positive cells in the liver with the aid of fluorescence and immunogold electron microscopy.Results: LRAT‐positive cells were found to be confined in the space of Disse, corresponding with the location of desmin‐positive HSC in rodent liver, also in human liver. Interestingly, LRAT‐positive staining was also observed along the liver sinusoidal endothelial lining. Furthermore, immune electron microscopic studies revealed that LRAT was mainly distributed in HSC within the rough‐endoplasmic reticulum (RER) and multivesicular bodies, whereas LRAT staining within the endothelial cells was largely confined to the perinuclear area and to some extent to the RER.Conclusion: Evidence has been accumulated that LRAT might serve as an excellent alternative HSC marker for future structural and functional studies. Furthermore, the presence of LRAT in endothelial cells might suggest a currently unknown function of this enzyme in liver endothelial biology.
Effect of steatosis and inflammation on liver fibrosis in chronic hepatitis C
Authors: Nieminen Urpo , Arkkila Perttu E. T. , Kärkkäinen Päivi , Färkkilä Martti A. 
Published: March 2010

AbstractBackground/Aims:The role of liver biopsy has been questioned in the management of patients with hepatitis C viral (HCV) infection. The aims of this study were to determine the impact of clinical parameters and degree of inflammation and steatosis on liver fibrosis.Patients/Methods:Clinical data and liver histology findings in 510 HCV patients were analysed.Results:Hepatitis C virus genotype 1 (GT‐1) was found in 38%, GT‐2 in 15% and GT‐3 in 45% of patients. In liver biopsy specimens, inflammation activity was present in 68%, increased fibrosis in 19% and marked steatosis in 17% of patients. Independent clinical risk factors for the increased fibrosis were patients' age at biopsy, body mass index (BMI) and duration of HCV. Steatosis and inflammation activity were independent histological risk factors for fibrosis only in GT‐1; in GT‐3, only inflammation correlated independently with fibrosis.Conclusions:Age at liver biopsy, BMI and duration of HCV were independent risk factors for increased fibrosis in HCV patients. Steatosis as a risk factor for fibrosis is evident in GT‐1. When scoring liver biopsies of HCV patients, the degree of steatosis should be included in addition to fibrosis and inflammation activity.
Curcumin reduces the toxic effects of iron loading in rat liver epithelial cells
Authors: Messner Donald J. , Sivam Gowsala , Kowdley Kris V. 
Published: March 2010

AbstractBackground/Aims: Iron overload can cause liver toxicity and increase the risk of liver failure or hepatocellular carcinoma in humans. Curcumin (diferuloylmethane), a component of the food spice turmeric, has antioxidant, iron binding and hepatoprotective properties. The aim of this study was to quantify its effects on iron overload and the resulting downstream toxic effects in cultured T51B rat liver epithelial cells.Methods: T51B cells were loaded with ferric ammonium citrate (FAC) with or without the iron delivery agent 8‐hydroxyquinoline. Cytotoxicity was measured by methylthiazolyldiphenyl‐tetrazolium bromide assay. Iron uptake and iron bioavailability were documented by chemical assay, quench of calcein fluorescence and ferritin induction. Reactive oxygen species (ROS) were measured by a fluorescence assay using 2′,7′‐dichlorodihydrofluorescein diacetate. Oxidative stress signalling to jnk, c‐jun and p38 was measured by a Western blot with phospho‐specific antibodies.Results: Curcumin bound iron, but did not block iron uptake or bioavailability in T51B cells given FAC. However, it reduced cytotoxicity, blocked the generation of ROS and eliminated signalling to cellular stress pathways caused by iron. Inhibition was observed over a wide range of FAC concentrations (50–500 μM), with an apparent IC50 in all cases between 5 and 10 μM curcumin. In contrast, desferoxamine blocked both iron uptake and toxic effects of iron at concentrations that depended on the FAC concentration. The effects of curcumin also differed from those of α‐tocopherol, which did not bind iron and was less effective at blocking iron‐stimulated ROS generation.Conclusions: Curcumin reduced iron‐dependent oxidative stress and iron toxicity in T51B cells without blocking iron uptake.
Model for end‐stage liver disease, model for end‐stage liver disease‐sodium and Child–Turcotte–Pugh scores over time for the prediction of complications of liver cirrhosis
Authors: Choi Pil Cho , Kim Hong Joo , Choi Woo Hyuk , Park Dong Il , Park Jung Ho , Cho Yong Kyun , Sohn Chong Il , Jeon Woo Kyu , Kim Byung Ik 
Published: March 2010

AbstractBackground/Aims: There has been no report concerning the predictive capability of each scoring system in determining the development of complications of liver cirrhosis such as variceal bleeding and/or hepatic encephalopathy.Methods: We retrospectively studied 128 patients with liver cirrhosis [92 males; mean (standard deviation) 54.2 (11.2) years] admitted to our institution from March 2004 to April 2006. Seventy‐three patients (57.0%, group 1) were admitted because of complications of cirrhosis and 55 patients (43.0%, group 2) were admitted for causes unrelated to complications of cirrhosis. We calculated values for model for end‐stage liver disease (MELD), MELD‐sodium (MELD‐Na) and Child–Turcotte–Pugh (CTP) scores on admission and at 3 and 6 months before admission. Each delta score was defined as the difference in the scores of 3 and 6 months before admission.Results: The relative risk for complications in the patients with ΔMELD/3 months ≥1.35, ΔMELD‐Na/3 months ≥1.35 and ΔCTP/3 months ≥1 was 2.05 [95% confidence intervals (CI) 1.47–2.85, P<0.01], 2.04 (95% CI 1.45–2.88, P<0.01) and 1.98 (95% CI 1.39–2.81, P<0.01) respectively. The area under the receiver‐operating characteristic curves of ΔMELD/3 months, ΔMELD‐Na/3 months and ΔCTP/3 months for the occurrence of cirrhotic complications were 0.691, 0.694 and 0.722 respectively. A higher ΔMELD/3 months (≥1.35), ΔMELD‐Na/3 months (≥1.35) and ΔCTP/3 months (≥1) was associated with decreased survival.Conclusions: Delta model for end‐stage liver disease/3 months, ΔMELD‐Na/3 months and ΔCTP/3 months were clinically useful parameters for predicting the occurrence of cirrhotic complications.
Antifibrogenic effects of tamoxifen in a rat model of periportal hepatic fibrosis
Authors: Ryu Soo Hyung , Chung Young‐Hwa , Lee Jae Kyun , Kim Jeong A. , Shin Jung Woo , Jang Myoung Kuk , Park Neung Hwa , Lee Han Chu , Lee Yung Sang , Suh Dong Jin 
Published: March 2010

AbstractBackgrounds/Aims: It has been reported that tamoxifen may affect hepatoma cell growth in vitro by suppressing transforming growth factor β‐1 (TGF‐β1) expression, suggesting that tamoxifen might also retard fibrogenesis. Thus, we examined whether tamoxifen might suppress TGF‐β1 expression and consequently inhibit the process of hepatic fibrosis in vivo.Methods: To induce periportal hepatic fibrosis, 50 male adult Sprague–Dawley rats were injected with 0.62 mmol/kg of allyl alcohol, intraperitoneally, twice a week for 8 weeks. Hepatic fibrosis scores, intrahepatic collagen levels and plasma TGF‐β1 expression levels were evaluated in three groups of 10 rats orally administered tamoxifen at 1, 5 and 10 mg/kg, respectively, and in 20 controls. Messenger RNAs (mRNAs) encoding TGF‐β1 and TGF‐β receptors in liver tissue were semiquantified using reverse transcriptase polymerase chain reaction.Results: Hepatic fibrosis scores decreased progressively as the dose of tamoxifen increased, resulting in a significant change in rats treated with tamoxifen at 10 mg/kg compared with controls (P=0.018). Intrahepatic collagen content was significantly less in the group treated with tamoxifen at 10 mg/kg compared with the control (P=0.045). Plasma TGF‐β1 levels were also significantly lower in rats treated with tamoxifen at 10 mg/kg compared with controls (P=0.007). All three concentrations of tamoxifen tested decreased the expression levels of hepatic TGF‐β1 mRNA and type I TGF‐β receptor (TGF‐β RI) mRNA to similar extents.Conclusions: Tamoxifen seems to inhibit the process of hepatic fibrosis dose‐dependently by suppressing the transcription of TGF‐β1 and TGF‐β RI in an experimental model of periportal hepatic fibrosis.
Gender‐incompatible liver transplantation is not a risk factor for patient survival
Authors: Lehner Frank , Becker Thomas , Klempnauer Jürgen , Borlak Jürgen 
Published: March 2010

AbstractBackground/Aims: Clinical data may be suggestive for differences in patient survival in gender‐incompatible orthotopic liver transplantation (OLT), but findings are inconsistent and are putatively linked to circulating hormones. We therefore investigated patient survival as well as metabolism of steroids to identify possible causes of improved graft survival in gender‐mismatched OLT.Methods: We examined our single‐centre database of 1355 recipients of first liver transplants for overall patient survival by non‐parametric and parametric analysis of multivariance taking the age of recipient and donor, ischaemia time, underlying liver disease and the time period of transplantation into account. Furthermore, the metabolism of androgens in gender‐incompatible OLT was studied in cultures of primary human hepatocytes obtained from male and female patients.Results: Unlike previous studies we were unable to determine overall significant differences in patient survival in gender‐incompatible OLT, even though a statistically significant improved patient survival was observed when male donor livers were transplanted into female recipients in univariant analysis (P=0.047). However, when the overall patient management was taken into account no difference in survival was determined in multivariant analysis. Importantly, the metabolism of testosterone did not differ between male and female hepatocyte cultures, except for the production of 6‐α‐hydroxy‐testosterone (P<0.001).Conclusions: Taken collectively, clinical observations may tend to suggest a slightly improved patient survival in gender‐incompatible OLT but this cannot be explained on the bases of androgen metabolism. Overall, we view gender‐incompatible liver transplantation not to be a confounder in patient survival after OLT.
Efficacy of lamivudine on hepatitis B viral status and liver function in patients with hepatitis B virus‐related hepatocellular carcinoma
Authors: Kim Ji Hoon , Park Joong‐Won , Koh Dong Wook , Lee Woo Jin , Kim Chang‐Min 
Published: March 2010

AbstractBackground/Aims: Treatment of patients with hepatocellular carcinoma (HCC) depends on the tumour extent and underlying liver function. Antiviral therapy with nucleoside/nucleotide analogues has been shown to be effective in improving the liver function of chronic hepatitis B (CHB) patients. We assessed whether lamivudine could induce biochemical and virological improvements in patients with hepatitis B virus‐related HCC.Patients/Methods: Of 148 CHB patients treated with 100 mg/day lamivudine for at least 6 months, 80 had HCC (CHB/HCC group) and 68 did not (CHB group). Biochemical and virological parameters were serially monitored.Results: Compared with the CHB group, the CHB/HCC group was older, had higher male predominance, bilirubin levels and liver cirrhosis rate, and lower albumin and hepatitis B virus (HBV) DNA levels and hepatitis B e antigen (HBeAg) positivity (P<0.05 each). The two groups showed similar cumulative rates of alanine aminotransferase normalization, HBV DNA seroconversion, HBeAg loss and viral breakthrough during 12 months of lamivudine treatment. After 12 months, the CHB/HCC group showed, relative to baseline, increased albumin levels (3.51±0.5 vs. 3.72±0.5 mg/ml) and decreased ascites scores (1.63±0.7 vs. 1.45±0.6) and Child–Pugh scores (6.92±1.9 vs. 6.02±1.38) (P<0.05 each).Conclusion: Lamivudine had comparable antiviral effects both in patients with CHB and CHB/HCC, and improved underlying liver function in the latter group. Treatment of HBV may increase the chance of curative treatments in patients with HBV‐related HCC.
Syndecan 1 (CD138) serum levels: a novel biomarker in predicting liver fibrosis stage in patients with hepatitis C
Authors: Zvibel Isabel , Halfon Phillipe , Fishman Sigal , Penaranda Guillaume , Leshno Moshe , Or Anat Bet , Halpern Zamir , Oren Ran 
Published: March 2010

AbstractBackground and Aims: Syndecan 1 (CD 138) is a cell surface proteoglycan shed by cells in several pathological conditions, including wound healing. The aim of this study was to test whether CD138 could serve as a non‐invasive marker for detection of liver fibrosis and thereby reduce the need for liver biopsy.Patients and Methods: An estimation set of 134 patients and a validation set of 67 patients with chronic hepatitis C were studied. There were 80 normal healthy volunteers. Patients were staged according to liver biopsies (Metavir fibrosis staging, stage F0, n=35; F1, n=40; F2, n=37, F3, n=39; F4, n=51). Serum CD138 levels were retrospectively measured by enzyme‐linked immunoabsorbent assay the same day of the liver biopsy. The primary endpoints were the diagnostic values of CD138 for F2–F4, F3–F4 and F4.Results: Respective areas under receiver operating characteristic curve of CD138 for F2–F4, F3–F4 and F4 diagnosis were 0.82, 0.76 and 0.81. CD138 had a positive predictive value of 82% for F2–F4 diagnosis and a high negative predictive value (86%) and specificity (84%) for exclusion of F4.Conclusion: CD138 is a new simple non‐invasive marker for predicting liver fibrosis in patients with chronic hepatitis C. The relevance of this marker in combination with other fibrosis markers should be explored.
New aspects of liver abnormalities as part of the systemic mast cell activation syndrome
Authors: Alfter Kirsten , Von Kügelgen Ivar , Haenisch Britta , Frieling Thomas , Hülsdonk Alexandra , Haars Ulrike , Rolfs Arndt , Noe Gerhard , Kolck Ulrich W. , Homann Jürgen , Molderings Gerhard J. 
Published: March 2010

AbstractBackground/Aims: This study was aimed at investigating the form and prevalence of liver involvement in patients with systemic mast cell activation syndrome, a possibly common subvariant of systemic mastocytosis. An attempt was made to shed light on potential mechanisms responsible for mast cell mediator‐related liver abnormalities.Methods: The methods used were clinical investigation, biochemical determination of cholesterol, transaminases and bilirubin in blood, determination of chitotriosidase by enzyme‐linked immunosorbent assay technique, and quantitative reverse transcribed‐polymerase chain reaction to determine chitotriosidase expression.Results: An elevation of plasma cholesterol was detected in 75% of the patients; elevations of transaminases and bilirubin were determined in 40 and 36% of the patients respectively; hepatomegaly or morphological hepatic alterations were observed in 34%. Chitotriosidase level in blood as a surrogate parameter for Kupffer cell activation in the liver was unchanged. However, chitotriosidase expression in isolated mast cells was downregulated at the mRNA level.Conclusions: Hypercholesterolaemia and liver abnormalities are frequently found in patients with the mast cell activation syndrome. Hence, the mast cell activation syndrome should be considered at an early stage as a possible cause of hypercholesterolaemia and of hepatic abnormalities of unknown reason. Mast cell activation may be indicated by a reduced expression of the enzyme chitotriosidase in blood‐derived mast cells as well as by an increased plasma cholesterol level.