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Hepatology Communications

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https://www.readbyqxmd.com/read/30202827/advanced-hepatocellular-carcinoma-tumor-stage-at-diagnosis-in-the-1945-1965-birth-cohort-reflects-poor-use-of-hepatocellular-carcinoma-screening
#1
Ann Robinson, Hesam Tavakoli, Benny Liu, Taft Bhuket, Robert J Wong
Individuals from the 1945-1965 birth cohort account for the majority of hepatocellular carcinoma (HCC) cases in the United States. Understanding trends in HCC among this birth cohort is vital given the increasing burden of chronic liver disease among this group. We retrospectively evaluated trends and disparities in HCC tumor stage at the time of diagnosis among the 1945-1965 birth cohort in the United States using the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Tumor stage at the time of HCC diagnosis was assessed using Milan criteria and SEER HCC staging systems...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202826/preventing-hepatitis-b-reactivation-during-anti-cd20-antibody-treatment-in-the-veterans-health-administration
#2
A Jasmine Bullard, Francesca E Cunningham, Bryan D Volpp, Elliott Lowy, Lauren A Beste, Bernadette B Heron, Mark Geraci, Julia M Hammond, Kourtney LaPlant, Elise A Stave, Marsha J Turner, Meghan C O'Leary, Michael J Kelley, Christine M Hunt
Hepatitis B virus (HBV) reactivation may occur with high risk immunosuppression, such as anti-cluster of differentiation (CD)20 antibodies (Abs). Appropriate HBV prophylaxis during anti-CD20 Ab therapy averts hepatitis, chemotherapy disruption, and death. Serologic evidence of prior HBV exposure is present in one in nine veterans in the Veterans Health Administration (VHA). In 2014, most (61%-73%) patients in the VHA who were receiving anti-CD20 Ab treatment underwent HBV testing, yet <20% of eligible patients received HBV antiviral prophylaxis...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202825/discovery-of-the-novel-entecavir-resistant-hepatitis-b-virus-reverse-transcriptase-a181c-substitution-from-an-integrated-genotypic-analysis
#3
Ronald E Rose, Dennis Hernandez, Paul J Falk, Karen Ericson, Nannan Zhou, Alexandra Thiry, Fiona McPhee
Entecavir (ETV) is a first-line therapy for chronic hepatitis B virus (HBV), demonstrating potent suppression of HBV DNA and a high barrier to viral resistance. Previous studies revealed that ETV-resistant (ETVr) HBV DNA resulted from substitutions in the HBV reverse transcriptase (RT) at positions rtT184, rtS202, or rtM250 in combination with lamivudine resistance (LVDr) substitutions rtM204I/V±rtL180M. In vitro , viral variants exhibit varying degrees of ETV susceptibility and replication capacity depending on specific resistance substitutions...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202824/serum-autotaxin-concentrations-reflect-changes-in-liver-stiffness-and-fibrosis-after-antiviral-therapy-in-patients-with-chronic-hepatitis-c
#4
Wataru Ando, Hiroaki Yokomori, Fumihiko Kaneko, Mana Kaneko, Koji Igarashi, Hidekazu Suzuki
The purpose of this study was to determine whether serum autotaxin concentrations reflect liver stiffness in patients with chronic hepatitis C virus (HCV) treated with direct-acting antiviral agents. Adult patients with chronic HCV were enrolled from January 2016 to August 2017. Autotaxin concentrations in these patients were compared with those of a control group consisting of healthy individuals. Liver stiffness was determined by transient elastography. The relationship between fibrosis markers and fibrosis scores was evaluated before and after treatment...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202823/suboptimal-level-of-bone-forming-cells-in-advanced-cirrhosis-are-associated-with-hepatic-osteodystrophy
#5
Chhagan Bihari, Deepika Lal, Monika Thakur, Sukriti Sukriti, Dhananjay Mathur, Anupama G Patil, Lovkesh Anand, Guresh Kumar, Shvetank Sharma, Shalini Thapar, Apurba Rajbongshi, Archana Rastogi, Anupam Kumar, Shiv K Sarin
Bone loss is common in advanced cirrhosis, although the precise mechanisms underlying bone loss in cirrhosis are unknown. We studied the profile and functionality of bone-forming cells and bone-building proteins in bone marrow (BM) of individuals with cirrhosis (n = 61) and individuals without cirrhosis as normal controls (n = 50). We also performed dual energy X-ray absorptiometry for clinical correlation. BM mesenchymal cells (MSCs) were analyzed for colony-forming units-fibroblasts and their osteogenic (fibronectin-1 [ FN1 ] , insulin-like growth factor binding protein 3 [ IGFBP3 ] , collagen type 1 alpha 1 chain [ COL1A1 ] , runt-related transcription factor 2 [ RUNX2 ], and alkaline phosphatase, liver [ ALPL ]) and adipogenic ( adiponectin, C1Q, and collagen domain containing [ ADIPOQ ] , peroxisome proliferator-activated receptor gamma [ PPARγ ] , and fatty acid binding protein 4 [ FABP4 ]) potentials...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202822/dipeptidyl-peptidase-4-is-a-pro-recovery-mediator-during-acute-hepatotoxic-damage-and-mirrors-severe-shifts-in-kupffer-cells
#6
Nádia Duarte, Inês Coelho, Denys Holovanchuk, Joana Inês Almeida, Carlos Penha-Gonçalves, Maria Paula Macedo
Dipeptidyl peptidase-4 (DPP-4 or clusters of differentiation [CD]26) is a multifunctional molecule with established roles in metabolism. Pharmacologic inhibition of DPP-4 is widely used to improve glycemic control through regulation of the incretin effect. Colaterally, CD26/DPP-4 inhibition appears to be beneficial in many inflammatory conditions, namely in delaying progression of liver pathology. Nevertheless, the exact implications of CD26/DPP-4 enzymatic activity in liver dysfunction remain unclear. In this work, we investigated the involvement of CD26/DPP-4 in experimental mouse models of induced hepatocyte damage that severely impact Kupffer cell (KC) populations...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202821/abundance-of-cytochromes-in-hepatic-extracellular-vesicles-is-altered-by-drugs-related-with-drug-induced-liver-injury
#7
Laura Palomo, Justyna Emilia Mleczko, Mikel Azkargorta, Javier Conde-Vancells, Esperanza González, Felix Elortza, Félix Royo, Juan M Falcon-Perez
Drug-induced liver injury (DILI) is a serious worldwide health problem that accounts for more than 50% of acute liver failure. There is a great interest in clinical diagnosis and pharmaceutical industry to elucidate underlying molecular mechanisms and find noninvasive biomarkers for this pathology. Cell-secreted extracellular vesicles (EVs) have provided a new biological source to identify low disease invasive markers. Despite the intense research developed on these vesicles, there is currently a gap on their patho-physiological effects...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202820/follicular-t-helper-cell-signatures-in-primary-biliary-cholangitis-and-primary-sclerosing-cholangitis
#8
Leonie Adam, Katharina Zoldan, Maike Hofmann, Michael Schultheiss, Dominik Bettinger, Christoph Neumann-Haefelin, Robert Thimme, Tobias Böettler
Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common cholestatic liver diseases. While PBC is generally accepted to be an autoimmune disorder characterized by pathognomonic autoantibodies against mitochondrial antigens, the pathogenesis of PSC is less precisely defined; however, some degree of altered immunity toward autoantigens has been suggested. Follicular T helper (Tfh) cells, a distinct clusters of differentiation (CD)4 T-cell subset specialized in facilitating antibody responses, have been shown to contribute to humoral autoimmunity in various disorders; yet, there is only limited information on possible alterations of Tfh cells in the context of cholestatic liver diseases...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202819/ngm282-for-treatment-of-patients-with-primary-biliary-cholangitis-a-multicenter-randomized-double-blind-placebo-controlled-trial
#9
Marlyn J Mayo, Alan J Wigg, Barbara A Leggett, Hays Arnold, Alexander J Thompson, Martin Weltman, Elizabeth J Carey, Andrew J Muir, Lei Ling, Stephen J Rossi, Alex M DePaoli
Patients with primary biliary cholangitis (PBC) who had an inadequate response to ursodiol have few treatment options. Alkaline phosphatase (ALP) and bilirubin levels correlate with the risk of liver transplant or death in PBC patients. Fibroblast growth factor (FGF) 19 is a hormone that acts directly in the liver to regulate bile acid synthesis. We evaluated NGM282, an engineered analogue of FGF19, for the treatment of PBC. In this 28-day, double-blind, placebo-controlled phase 2 trial, 45 PBC patients who had an inadequate response to ursodiol were randomly assigned 1:1:1 to receive subcutaneous daily doses of either NGM282 at 0...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202818/a-rare-nonsense-mutation-in-the-glucokinase-regulator-gene-is-associated-with-a-rapidly-progressive-clinical-form-of-nonalcoholic-steatohepatitis
#10
Carlos J Pirola, Diego Flichman, Hernán Dopazo, Tomas Fernández Gianotti, Julio San Martino, Cristian Rohr, Martin Garaycoechea, Carla Gazzi, Gustavo O Castaño, Silvia Sookoian
We report on the presence of a rare nonsense mutation (rs149847328, p.Arg227Ter) in the glucokinase regulator ( GCKR ) gene in an adult patient with nonalcoholic fatty liver disease (NAFLD), morbid obesity, and type 2 diabetes; this patient developed a progressive histological form of the disease. Analysis of paired (5 years apart) liver biopsies (at baseline and follow-up) showed progression of simple steatosis to severe nonalcoholic steatohepatitis and cirrhosis. Study design involved an initial exploration that consisted of deep sequencing of 14 chromosomal regions in 96 individuals (64 of whom were patients with NAFLD who were diagnosed by liver biopsy that showed the full spectrum of histological severity)...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202817/whole-exome-sequencing-study-of-extreme-phenotypes-of-nafld
#11
Sarah E Kleinstein, Matthew Rein, Manal F Abdelmalek, Cynthia D Guy, David B Goldstein, Anna Mae Diehl, Cynthia A Moylan
Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease with highly variable outcomes. Patients with simple steatosis typically experience a benign course, whereas those with more advanced liver injury, nonalcoholic steatohepatitis (NASH), and advanced stage fibrosis suffer increased risk for complications such as cirrhosis, hepatic decompensation, and liver cancer. Genetic variants in patatin-like phospholipase domain-containing 3 ( PNPLA3 ) and transmembrane 6 superfamily member 2 ( TM6SF2 ) and clinical factors including diabetes, obesity, and older age increase a patient's risk for NASH, advanced fibrosis, and worse outcomes...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30202816/high-mobility-group-box-1-and-liver-disease
#12
REVIEW
Harriet Gaskell, Xiaodong Ge, Natalia Nieto
High-mobility group box-1 (HMGB1) is a ubiquitous protein. While initially thought to be simply an architectural protein due to its DNA-binding ability, evidence from the last decade suggests that HMGB1 is a key protein participating in the pathogenesis of acute liver injury and chronic liver disease. When it is passively released or actively secreted after injury, HMGB1 acts as a damage-associated molecular pattern that communicates injury and inflammation to neighboring cells by the receptor for advanced glycation end products or toll-like receptor 4, among others...
September 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30094408/-i-miss-my-liver-nonmedical-sources-in-the-history-of-hepatocentrism
#13
Riccardo Orlandi, Nicole Cianci, Pietro Invernizzi, Giancarlo Cesana, Michele Augusto Riva
Hepatocentrism was a medical doctrine that considered the liver the center of the whole human being. It originated in ancient populations (Mesopotamic civilization) and persisted in Western countries until the seventeenth century. Hidden references to hepatocentrism may be found in artistic representations and literary works, from the myth of Prometheus in the Greco-Roman world to the crucifixion iconography throughout the Middle Ages. In the mid-1600s, fundamental discoveries irrefutably demonstrated the central role of the heart in human physiology, which laid the foundations for creating cardiocentrism, shifting the life's center from the liver to the heart...
August 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30094407/immune-alterations-in-patients-with-type-1-autoimmune-hepatitis-persist-upon-standard-immunosuppressive-treatment
#14
Amédée Renand, Sarah Habes, Jean-François Mosnier, Hélène Aublé, Jean-Paul Judor, Nicolas Vince, Philippe Hulin, Steven Nedellec, Sylvie Métairie, Isabelle Archambeaud, Sophie Brouard, Jérôme Gournay, Sophie Conchon
Autoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new-onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis...
August 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30094406/gut-and-liver-b-cells-of-common-clonal-origin-in-primary-sclerosing-cholangitis-inflammatory-bowel-disease
#15
Brian K Chung, Eva Kristine Klemsdal Henriksen, Kristin Kaasen Jørgensen, Tom H Karlsen, Gideon M Hirschfield, Evaggelia Liaskou
B cells express an antigen-specific B-cell receptor (BCR) and may contribute to liver inflammation by recognizing shared antigens in the gut and liver. Herein, we used high-throughput BCR sequencing of the immunoglobulin heavy chain, specifically the complementarity-determining region 3 (CDR3), to characterize the B-cell repertoire of freshly-frozen paired gut and liver tissue samples from patients with primary sclerosing cholangitis (PSC) and concurrent inflammatory bowel disease (IBD) (PSC-IBD, n = 10) and paired formalin-fixed paraffin-embedded (FFPE) tumor-adjacent normal colon and liver tissue from patients with colorectal liver metastases (controls, n = 10)...
August 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30094405/a-survey-of-molecular-heterogeneity-in-hepatocellular-carcinoma
#16
Juan Jovel, Zhen Lin, Sandra O'keefe, Steven Willows, Weiwei Wang, Guangzhi Zhang, Jordan Patterson, Carlos Moctezuma-Velázquez, David J Kelvin, Gane Ka-Shu Wong, Andrew L Mason
Understanding the heterogeneity of dysregulated pathways associated with the development of hepatocellular carcinoma (HCC) may provide prognostic and therapeutic avenues for disease management. As HCC involves a complex process of genetic and epigenetic modifications, we evaluated expression of both polyadenylated transcripts and microRNAs from HCC and liver samples derived from two cohorts of patients undergoing either partial hepatic resection or liver transplantation. Copy number variants were inferred from whole genome low-pass sequencing data, and a set of 56 cancer-related genes were screened using an oncology panel assay...
August 2018: Hepatology Communications
https://www.readbyqxmd.com/read/30094404/prognostic-significance-of-controlled-attenuation-parameter-in-patients-with-compensated-advanced-chronic-liver-disease
#17
Cristina Margini, Giuseppe Murgia, Guido Stirnimann, Andrea De Gottardi, Nasser Semmo, Stefania Casu, Jaime Bosch, Jean-François Dufour, Annalisa Berzigotti
Obesity and steatosis have been associated with liver disease progression in patients with compensated advanced chronic liver disease (cACLD) (liver stiffness measurement [LSM] ≥ 10 kPa). The controlled attenuation parameter (CAP) estimates steatosis during LSM by transient elastography. We aimed to evaluate whether CAP is associated with the development of clinically relevant events in cACLD. Consecutive patients with cACLD and CAP measurements observed between September 2013 and September 2015 were retrospectively studied...
August 2018: Hepatology communications
https://www.readbyqxmd.com/read/30094403/spleen-and-liver-volumetrics-as-surrogate-markers-of-hepatic-venous-pressure-gradient-in-patients-with-noncirrhotic-portal-hypertension
#18
Ohad Etzion, Varun Takyar, Victor Novack, Ahmed M Gharib, Raissa Canales, Akeem Adebogun, Eric Matsumoto, Jason L Eccleston, David E Kleiner, Sergio D Rosenzweig, Meral Gunay-Aygun, Gulbu Uzel, Ivan Fuss, Richard Childs, Steven M Holland, Elliot B Levy, T Jake Liang, Theo Heller, Christopher Koh
Noncirrhotic portal hypertension (NCPH) is a rare disease that may lead to serious clinical consequences. Currently, noninvasive tools for the assessment of NCPH are absent. We investigated the utility of spleen and liver volumetrics as a marker of the presence and severity of portal hypertension in this population. A cohort of NCPH patients evaluated between 2003 and 2015 was retrospectively studied. The association of spleen and liver volumes with the hepatic venous pressure gradient (HVPG) level was evaluated using locally weighted scatterplot smoothing curves...
August 2018: Hepatology communications
https://www.readbyqxmd.com/read/30094402/l-carnitine-suppresses-loss-of-skeletal-muscle-mass-in-patients-with-liver-cirrhosis
#19
Masatsugu Ohara, Koji Ogawa, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Kazuharu Suzuki, Akihisa Nakamura, Machiko Umemura, Takaaki Izumi, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Shunsuke Ohnishi, Naoya Sakamoto
Liver cirrhosis (LC) is a major cause of secondary sarcopenia. Sarcopenia makes the prognosis worse; thus, novel therapeutic options for sarcopenia in patients with LC are urgently required as they are currently limited. In this retrospective study, 158 patients with LC were screened, and 35 of those patients who were treated with L-carnitine for more than 6 months and for whom skeletal muscle mass changes could be evaluated by computer tomography were enrolled. Of the 158 patients, 79 patients who did not receive L-carnitine supplementation served as controls...
August 2018: Hepatology communications
https://www.readbyqxmd.com/read/30094401/a-pragmatic-approach-identifies-a-high-rate-of-nonalcoholic-fatty-liver-disease-with-advanced-fibrosis-in-diabetes-clinics-and-at-risk-populations-in-primary-care
#20
PreyaJanubhai Patel, Fabrina Hossain, Leigh Ula Horsfall, Xuan Banh, Kelly Lee Hayward, Suzanne Williams, Tracey Johnson, Anne Bernard, Nigel Neil Brown, Guy Lampe, Lyndall Buck, Nivene Saad, Anthony William Russell, Patricia Casarolli Valery, Katharine Margaret Irvine, Andrew Donald Clouston, Katherine Anne Stuart, William Rosenberg, Elizabeth Ellen Powell
Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB-4], or enhanced liver fibrosis [ELF] test) are recommended as first-line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility. Anthropometric measurements, ELF test, ultrasound, and liver stiffness measurements (LSMs) were performed...
August 2018: Hepatology communications
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