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alpha-1 liver disease

María José Garcés Hernández, Miguel Klünder, Nayely Garibay Nieto, Juan Carlos López Alvarenga, Jenny Vilchis Gil, Samuel Flores Huerta, Rosa Quispe Siccha, Joselin Hernandez
OBJECTIVE: Visceral adiposity index (VAI) is a mathematical model associated with cardiometabolic risk in adults, but studies on children failed to support this association. Our group has proposed a pediatric VAI model using pediatric ranges, but it has not yet been evaluated and needs further adjustments. The objective of this study was to further adjust the proposed pediatric VAI by age, creating a new pediatric metabolic index (PMI), and assess the correlation of the PMI with insulin resistance indexes and hepatic enzymes...
March 2018: Endocrine Practice
Cristina Di Poto, Shisi He, Rency S Varghese, Yi Zhao, Alessia Ferrarini, Shan Su, Abdullah Karabala, Mesfin Redi, Hassen Mamo, Amol S Rangnekar, Thomas M Fishbein, Alexander H Kroemer, Mahlet G Tadesse, Rabindra Roy, Zaki A Sherif, Deepak Kumar, Habtom W Ressom
Disparities in hepatocellular carcinoma (HCC) incidence and survival have been observed between ethnic groups including African-Americans (AA) and European-Americans (EA). The evaluation of the changes in the levels of metabolites in samples stratified by race could provide a snapshot of ethnically diverse disease related pathways and identify reliable biomarkers. In this study, we considered AA and EA to investigate metabolites that may be associated with HCC in a race-specific manner. The levels of 46 metabolites in plasma samples, collected from patients recruited at MedStar Georgetown University Hospital, were analyzed by Agilent GC-qMS in selected ion monitoring (SIM) mode...
2018: PloS One
Maggie A Stanislawski, Catherine A Lozupone, Brandie D Wagner, Merete Eggesbø, Marci K Sontag, Nichole Nusbacher, Mercedes Martinez, Dana Dabelea
BACKGROUND: Recent evidence supports that the gut microbiota may be involved in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and may also offer avenues for treatment or prevention. METHODS: We investigated the associations among gut microbiota, diet and hepatic fat fraction (HFF) in 107 adolescents. Magnetic Resonance Imaging (MRI) was used to assess HFF, and 16S rRNA gene sequencing was performed on collected fecal samples. Dietary intake was assessed using Food Frequency Questionnaires...
March 14, 2018: Pediatric Research
Faiza Qayyum, Bo K Lauridsen, Ruth Frikke-Schmidt, Klaus F Kofoed, Børge G Nordestgaard, Anne Tybjærg-Hansen
Aims: Myocardial infarction (MI) and gallstone disease (GSD) are intrinsically linked via cholesterol metabolism. We tested the hypothesis that genetic variants in the gene encoding cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver, are associated with risk of MI and GSD in the general population. Methods and results: We performed tests of association between lipid levels and eight rare non-synonymous mutations and two common variants, rs2081687 and rs3808607, in CYP7A1 in 100 149 individuals from the general population...
February 23, 2018: European Heart Journal
Kung-Yen Chen, Jui-An Lin, Han-Yun Yao, An-Chih Hsu, Yu-Ting Tai, Jui-Tai Chen, Mao-Chih Hsieh, Tang-Long Shen, Ren-Yi Hsu, Hong-Tan Wu, Guey Horng Wang, Bing-Ying Ho, Yu-Pei Chen
Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays...
February 11, 2018: Nutrition Research
Saurabh Dhanda, Smriti Gupta, Avishek Halder, Aditya Sunkaria, Rajat Sandhir
Chronic liver disease per se induces neuroinflammation that contributes to cognitive deficits in hepatic encephalopathy (HE). However, the processes by which pro-inflammatory molecules result in cognitive impairment still remain unclear. In the present study, a significant increase in the activity of liver function enzymes viz. alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) was observed along with increase in plasma ammonia levels after four weeks of bile duct ligation (BDL) in rats suggesting hepatocellular damage...
March 5, 2018: Brain, Behavior, and Immunity
Adrien Guillot, Imène Gasmi, Arthur Brouillet, Yeni Ait-Ahmed, Julien Calderaro, Isaac Ruiz, Bin Gao, Sophie Lotersztajn, Jean-Michel Pawlotsky, Fouad Lafdil
Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases. In the current study, we found that diverse types of chronic liver diseases are associated with elevation of infiltrated interleukin (IL)-17-positive (+) cells and cytokeratin 19 (CK19)+ LPCs, and both cell types colocalized and their numbers positively correlated with each other...
March 2018: Hepatology Communications
Xiaojia Liu, Ning Tan, Hongtao Liao, Guangdong Pan, Qing Xu, Rong Zhu, Liping Zou, Songqing He, Hongguang Zhu
Glutathione S-transferase (GST) family members promote carcinogenesis and cancer progression. We assessed GST pi 1 (GSTP1) mRNA and protein levels in hepatocellular carcinoma (HCC) using genome databases and tissue microarray (TMA) technology. We found that in cancerous tissues, GSTP1 mRNA was down-regulated in genome databases, and immunohistochemical staining of GSTP1 in 237 HCC cases varied from negative to strongly positive. GSTP1 levels correlated negatively with tumor size and serum alpha-fetoprotein (AFP) in HCC patients, and higher GSTP1 levels associated with longer overall survival (OS) and disease-free survival (DFS)...
February 6, 2018: Oncotarget
Sanaa Kamal, Khaled K Aldossari, Dhalia Ghoraba, Sara Mahmoud Abdelhakam, Amgad H Kamal, Mohamad Bedewi, Leila Nabegh, Khaled Bahnasy, Tamer Hafez
Objective: Concomitant non-alcoholic fatty liver disease (NAFLD) and coeliac disease (CD) have not been adequately studied. This study investigated the frequency of CD among NAFLD patients and the clinicopathological and immunological patterns and outcome of concomitant NAFLD and CD. Design: This prospective longitudinal study screened patients with NAFLD for CD (tissue transglutaminase antibodies (TTGA); anti-TTGA and antiendomysial antibodies (EMA)). Patients with concomitant NAFLD and CD and patients with either NAFLD or CD were enrolled and followed...
2018: BMJ Open Gastroenterology
Norio Akuta, Joji Toyota, Yoshiyasu Karino, Fusao Ikeda, Akio Ido, Katsuaki Tanaka, Koichi Takaguchi, Atsushi Naganuma, Eiichi Tomita, Kazuaki Chayama, Shigetoshi Fujiyama, Yukiko Inada, Hitoshi Yoshiji, Hideaki Watanabe, Hiroki Ishikawa, Fiona McPhee, Stephanie Noviello, Hiromitsu Kumada
BACKGROUND: In the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3. METHODS: Treatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment...
March 2, 2018: Journal of Gastroenterology
Jong Man Kim, Choon Hyuck David Kwon, Jae-Won Joh, Sangbin Han, Jeejin Yoo, Kyunga Kim, Dong Hyun Sinn, Gyu-Seong Choi, David A Gerber, Hiroto Egawa, Suk-Koo Lee
BACKGROUND: ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. This study compares HCC recurrence in ABO-I LDLT with that in ABO-compatible (ABO-C) LDLT and explores the effects of rituximab prophylaxis and total plasma exchange (TPE) on HCC recurrence after LDLT. METHODS: Two-hundred forty patients with a diagnosis of HCC underwent LDLT between 2010 and 2015. Fifty-nine patients underwent ABO-I LDLT. RESULTS: Baseline, perioperative, and tumor characteristics did not vary between the two groups...
February 28, 2018: Transplantation
Jinsoo Rhu, Jong Man Kim, Gyu Seong Choi, Choon Hyuck David Kwon, Jae-Won Joh
BACKGROUND: This study was designed to validate the alpha-fetoprotein model for predicting recurrence after liver transplantation in Korean hepatocellular carcinoma patients. METHODS: Patients who underwent liver transplantation for hepatocellular carcinoma at Samsung Medical Center between 2007 and 2015 were included. Recurrence, overall survival, and disease-specific survival of patients divided by both the Milan criteria and the alpha-fetoprotein model were compared using Kaplan-Meier log-rank test...
February 20, 2018: Transplantation
A Perciaccante, P Charlier, C Negri, A Coralli, O Appenzeller, R Bianucci
A1AT deficiency- a genetically inherited autosomal codominant disease with more than 120 identified alleles- was first identified by Laurell and Eriksson in 1963. The most common hereditary disorder in adults, A1AT causes an increased risk of developing pulmonary emphysema and liver disease. In A1AT patients, lung disease generally presents at a younger age than "usual" chronic obstructive pulmonary disease (COPD) and it may be misdiagnosed as asthma. Because A1AT deficiency patients can show the same clinical features as non-deficient COPD (including increased evidence of bronchiectasis, frequent exacerbations, impaired health status and a degree of reversibility of airflow obstruction), the World Health Organization recommend to test every patient with a diagnosis of COPD or adult-onset asthma for A1AT deficiency...
February 2018: COPD
Zhen-Guo Pan, Xu-Sheng An
SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently identified TIR domain-containing cytosolic protein, which is involved in toll-like receptors (TLRs) signaling transduction. In the present study, the role of SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) progression was explored. We found that SARM1 was expressed highly in fatty liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in HFD-fed mice...
February 15, 2018: Biochemical and Biophysical Research Communications
Clerison Stelvio Garcia, Agnaldo Soares Lima, Ehideé Isabel Gómez La-Rotta, Ilka de Fátima Santana Ferreira Boin
BACKGROUND: Several diseases may lead to the need for liver transplantation due to progressive organ damage until the onset of cirrhosis, resulting in changes in interpersonal relationships. Social Support for transplant candidates is an important variable, providing them with psychological and social well-being. This study aims to assess social support in chronic hepatic patients, waiting for liver transplantation. METHODS: A cross-sectional study was conducted with 119 patients, for convenience sampling, from the liver transplant waiting list at a Brazilian University Hospital Outpatients...
February 17, 2018: Health and Quality of Life Outcomes
S A Townsend, R G Edgar, P R Ellis, D Kantas, P N Newsome, A M Turner
BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is estimated to affect three million people worldwide. It causes liver disease in a proportion of carriers of the PiS and PiZ allele due to the formation and retention of polymers within the endoplasmic reticulum of hepatocytes. The reason for this selective penetrance is not known. Although clinical trials are underway, liver transplantation is the only effective treatment for liver disease due to AATD. AIMS: To report the prevalence and natural history of liver disease among individuals with AATD, and assess the outcomes of liver transplantation through systematic review...
February 15, 2018: Alimentary Pharmacology & Therapeutics
Erika P Hamilton, Manish R Patel, Anne C Armstrong, Richard D Baird, Komal Jhaveri, Matthias Hoch, Teresa Klinowska, Justin P O Lindemann, Shethah Morgan, Gaia Schiavon, Hazel M Weir, Seock-Ah Im
PURPOSE: AZD9496 is an oral non-steroidal, small-molecule inhibitor of estrogen receptor alpha (ERα), and a potent and selective antagonist and degrader of ERα. This first in human Phase 1 study determined the safety and tolerability of ascending doses of oral AZD9496 in women with estrogen receptor (ER)+/HER2- advanced breast cancer, characterized its pharmacokinetic (PK) profile, and made preliminary assessment of antitumor activity. EXPERIMENTAL DESIGN: Forty-five patients received AZD9496 (20 mg once daily to 600 mg twice daily) in a dose-escalation, dose- expansion 'rolling 6' design...
February 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Junfeng Ma, Miloslav Sanda, Renhuizi Wei, Lihua Zhang, Radoslav Goldman
Aberrant core fucosylation of proteins has been linked to liver diseases. In this study, we carried out multiple reaction monitoring (MRM) quantification of core fucosylated N-glycopeptides of serum proteins partially deglycosylated by a combination of endoglycosidases (endoF1, endoF2, and endoF3). To minimize variability associated with the preparatory steps, the analysis was performed without enrichment of glycopeptides or fractionation of serum besides the nanoRP chromatography. Specifically, we quantified core fucosylation of 22 N-glycopeptides derived from 17 proteins together with protein abundance of these glycoproteins in a cohort of 45 participants (15 disease-free control, 15 fibrosis and 15 cirrhosis patients) using a multiplex nanoUPLC-MS-MRM workflow...
February 7, 2018: Journal of Proteomics
Maria Guido, Samantha Sarcognato, Francesco Paolo Russo, Romilda Cardin, Marika Piciocchi, Guido Colloredo, Fabio Farinati
BACKGROUND & AIMS: The histological intrahepatic microvasculature lesions have not been deeply investigated outside the setting of portal hypertension. The aim of this study was to analyze the type and the prevalence of microvasculature abnormalities and their correlation with inflammatory activity, fibrosis stage and tissue markers of fibrogenesis, angiogenesis and oxidative DNA damage in liver biopsies obtained from patients with chronic viral hepatitis. METHODS: Seventy- four liver biopsies from untreated patients affected by hepatitis B (22 cases) and C (52 cases) were included...
February 10, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Nicolai J Wewer Albrechtsen
Glucagon is a peptide hormone secreted from the pancreatic alpha cells in response to hypoglycemia but in some patients with type 2 diabetes a paradoxical hypersecretion results from the intake of glucose. In rodent, antagonizing the actions of glucagon have been shown to be effective for lowering blood glucose levels and this has recently have been solidified in patients with type 2 diabetes. Although the reported increases of liver enzymes, hyperglucagonemia, and alpha cell hyperplasia resulting from glucagon receptor antagonism may potentially limit the clinical applicability of glucagon receptor antagonists, they may serve as an instrumental toolbox for delineating the physiology of glucagon...
February 2018: Peptides
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