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Concept: Cirrhosis

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Wilson’s disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures.

Concepts: Central nervous system, Nervous system, Brain, Cirrhosis, Liver, Neurology, Basal ganglia, Copper

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To determine the accuracy of two-dimensional shear wave elastography (2D-SWE) for noninvasive staging of hepatic fibrosis in chronic hepatitis B (CHB).

Concepts: Cirrhosis, Hepatitis, Hepatitis C, Hepatitis B, Hepatitis A

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The aim of this study was to compare the efficacy of hepatic arterial infusion chemotherapy (HAIC) and sorafenib in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT).

Concepts: Cancer, Blood, Cirrhosis, Vein, Hepatic portal vein, Portal venous system, Hepatic portal system

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Plants are fantastic sources for present day life saving drugs. Monocrotaline a natural ligand exhibits dose-dependent cytotoxicity with potent antineoplastic activity. This study was intended to disclose the therapeutic potential of monocrotaline against hepatocellular carcinoma. The in silico predictions has high-light the antineoplastic potential, druglikeness and biodegradability of monocrotaline. The in silico docking study has provided an insight and evidence for the antineoplastic activity of monocrotaline against p53, HGF and TREM1 proteins which play a threatening role in causing hepatocellular carcinoma. The mode of action of monocrotaline was determined experimentally by in vitro techniques such as XTT assay, NRU assay and whole cell brine shrimp assay have further supported our in silico studies. The in vitro cytotoxicity of monocrotaline was proved at IC50 24.966 µg/mL and genotoxicity at 2 X IC50 against HepG2 cells. Further, the credible druglike properties with non-mutagenicity, non-toxic on mammalian fibroblast and the potential antineoplastic activity through in vitro experimental validations established monocrotaline as a novel scaffold for liver cancer with superior efficacy and lesser side effects.

Concepts: Cell, Cancer, Oncology, Arthropod, Cirrhosis, Crustacean, Experiment, In vitro

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A high prevalence of the rtI187V polymerase substitution of hepatitis B virus (HBV) was detected in nucleos(t)ide analogs-naïve and -treated chronic hepatitis B (CHB) patients. We aimed at assessing the replicative capacity and susceptibility of rtI187V alone or in conjunction with lamivudine (LAM) or adefovir (ADV) -resistant mutations to LAM and ADV in vitro. The reverse transcriptase region of HBV isolates was directly sequenced from a cohort of 300 CHB patients from China. Replication-competent HBV constructs containing rtI187V and combined with LAM-resistant (rtM204I, rtL180M/rtM204V) mutations were generated, and compared with wild-type (WT), LAM-resistant single (rtM204I) or double (rtL180M/rtM204V) and ADV-resistant (rtN236T) clones. In a Chinese cohort of 300 CHB patients, 8.7% (26/300) showed substitution in the rtI187 with V. Of note, the rtI187V prevalence in genotype B was significant higher than in genotype C (95.2 vs. 4.8%). In vitro phenotypic assays showed that the viruses bearing the rtI187V had impaired replication efficacy when compared to WT and the virus carrying the rtI187V combined with LAM-resistant single or double mutations showed even more significantly impaired replicative capacities. Furthermore, rtI187V remained susceptible towards treatment with LAM or ADV in vitro whereas the combination of rtI187V substitution with LAM-resistant mutations was resistant to LAM but still sensitive to ADV. Our study reveals that the rtI187V substitution in the HBV polymerase frequently occurred in CHB patients particular with genotype B. However, the emergence of rtI187V substitution significantly impair viral replication but without affecting drug sensitivity in vitro.

Concepts: DNA, Evolution, Virus, Cirrhosis, Hepatitis, Antiviral drug, Hepatitis B, Viruses

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Nonalcoholic fatty liver disease (NAFLD) is characterized by a massive accumulation of lipid droplets (LDs). The aim of this study was to determine the function of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), one of our newly identified LD-associated proteins in human subjects with normal liver histology and simple steatosis, in NAFLD development. LDs were isolated from 21 human liver biopsies, including 9 cases with normal liver histology (group 1) and 12 cases with simple steatosis (group 2). A complete set of LD-associated proteins from three liver samples of group 1 or group 2 were determined by 2D LC-MS/MS. By comparing the LD-associated protein profiles between subjects with or without NAFLD, 54 up-regulated and 35 down-regulated LD-associated proteins were found in NAFLD patients. Among them, 17β-HSD13 represents a previously unidentified LD-associated protein with a significant up-regulation in NAFLD. Because the 17β-HSD family plays an important role in lipid metabolism, 17β-HSD13 was selected for validating the proteomic findings and exploring its role in the pathogenesis of NAFLD. Increased hepatic 17β-HSD13 and its LD surface location were confirmed in db/db (diabetic) and high-fat diet-fed mice. Adenovirus-mediated hepatic overexpression of human 17β-HSD13 induced a fatty liver phenotype in C57BL/6 mice, with a significant increase in mature sterol regulatory element-binding protein 1 and fatty acid synthase levels. The present study reports an extensive set of human liver LD proteins and an array of proteins differentially expressed in human NAFLD. We also identified 17β-HSD13 as a pathogenic protein in the development of NAFLD.

Concepts: Cholesterol, Cancer, Metabolism, Nutrition, Cirrhosis, Non-alcoholic fatty liver disease, Fatty liver, Steatosis

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Purpose To evaluate the diagnostic performance of three-dimensional (3D) quantitative enhancement-based and diffusion-weighted volumetric magnetic resonance (MR) imaging assessment of hepatocellular carcinoma (HCC) lesions in determining the extent of pathologic tumor necrosis after transarterial chemoembolization (TACE). Materials and Methods This institutional review board-approved retrospective study included 17 patients with HCC who underwent TACE before surgery. Semiautomatic 3D volumetric segmentation of target lesions was performed at the last MR examination before orthotopic liver transplantation or surgical resection. The amount of necrotic tumor tissue on contrast material-enhanced arterial phase MR images and the amount of diffusion-restricted tumor tissue on apparent diffusion coefficient (ADC) maps were expressed as a percentage of the total tumor volume. Visual assessment of the extent of tumor necrosis and tumor response according to European Association for the Study of the Liver (EASL) criteria was performed. Pathologic tumor necrosis was quantified by using slide-by-slide segmentation. Correlation analysis was performed to evaluate the predictive values of the radiologic techniques. Results At histopathologic examination, the mean percentage of tumor necrosis was 70% (range, 10%-100%). Both 3D quantitative techniques demonstrated a strong correlation with tumor necrosis at pathologic examination (R(2) = 0.9657 and R(2) = 0.9662 for quantitative EASL and quantitative ADC, respectively) and a strong intermethod agreement (R(2) = 0.9585). Both methods showed a significantly lower discrepancy with pathologically measured necrosis (residual standard error [RSE] = 6.38 and 6.33 for quantitative EASL and quantitative ADC, respectively), when compared with non-3D techniques (RSE = 12.18 for visual assessment). Conclusion This radiologic-pathologic correlation study demonstrates the diagnostic accuracy of 3D quantitative MR imaging techniques in identifying pathologically measured tumor necrosis in HCC lesions treated with TACE. © RSNA, 2014 Online supplemental material is available for this article.

Concepts: Cancer, Pathology, Cirrhosis, Liver, Anatomical pathology, Hepatocellular carcinoma, Magnetic resonance imaging, Liver transplantation

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A growing body of evidence suggests that anti-complement-1q (anti-C1q) antibodies are elevated in a variety of autoimmune disease. Therefore, we investigated their prevalence and clinical significance in plasma of patients with hepatitis C virus (HCV) genotype IV in the presence and absence of autoimmune extra hepatic manifestations in comparison to normal healthy individuals. Plasma Anti-C1q Abs levels were assessed by an Enzyme Linked Immunosorbant Assay in 91 chronic HCV-infected patients (51 with and 40 without autoimmune rheumatic manifestations) and 40 healthy volunteers matched for age and gender. Epidemiological, clinical, immunochemical and virological data were prospectively collected. Positive Anti-C1q antibodies were more frequent among HCV patients with extra-hepatic autoimmune involvement, than those without and healthy control subjects. No significant correlations were found between Anti-C1q levels with either the liver activity or the fibrosis scores. In HCV-patients with autoimmune involvements, plasma Anti-C1q levels were significantly higher in patients with positive cryoglobulin, and in those with lymphoma than in those without. These results were confirmed by multivariate analysis. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies among HCV infected patients with positive cryoglobulinaemia and lymphoma.

Concepts: Medicine, Epidemiology, Cirrhosis, Hepatitis, Liver, Rheumatoid arthritis, Hepatitis C, Hepatitis A

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The role of liver transplantation (LT) in the management of cirrhotic patients with tumors exhibiting intrahepatic bile duct differentiation remains controversial. The objective of this study was to characterize the spectrum of these tumors and analyze post-LT outcomes.

Concepts: Cirrhosis, Liver, Hepatology, Bilirubin, Bile, Bile duct, Liver transplantation, Intrahepatic bile ducts

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L4F, an alpha helical peptide inspired by the lipid-binding domain of the ApoA1 protein, has potential applications in the reduction of inflammation involved with cardiovascular disease as well as liver fibrosis. In addition to its biological activity, amphipathic peptides such as L4F are likely candidates to direct the molecular assembly of peptide nanostructures. Here we describe the stabilization of the amphipathic L4F peptide through fusion to a high molecular weight protein polymer. Comprised of multiple pentameric repeats, elastin-like polypeptides (ELPs) are biodegradable protein polymers inspired from the human gene for tropoelastin. Dynamic light scattering confirmed that the fusion peptide forms nanoparticles with a hydrodynamic radius of approximately 50nm, which is unexpectedly above that observed for the free ELP (~5.1nm). To further investigate their morphology, negative and cryogenic transmission electron microscopy were used to reveal that they are unilamellar vesicles. On average, these vesicles are 49nm in radius with lamellae 8nm in thickness. To evaluate their therapeutic potential, the L4F nanoparticles were incubated with hepatic stellate cells. Stellate cell activation leads to hepatic fibrosis; furthermore, their activation is suppressed by ApoA1 mimetic peptides. Consistent with this observation, L4F nanoparticles were found to suppress hepatic stellate cell activation in vitro. To evaluate the in vivo potential for these nanostructures, their plasma pharmacokinetics were evaluated in rats. Despite the assembly of nanostructures, both free L4F and L4F nanoparticles exhibited similar half-lives of approximately 1hr in plasma. This is the first study reporting the stabilization of peptide-based vesicles using ApoA1 mimetic peptides fused to a protein polymer; furthermore, this platform for peptide-vesicle assembly may have utility in the design of biodegradable nanostructures.

Concepts: DNA, Protein, Gene, Amino acid, Cirrhosis, Peptide, Hepatic stellate cell, Stellate cell