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Hepatology Communications

Sarah T K Sin, Yan Li, Ming Liu, Yun-Fei Yuan, Stephanie Ma, Xin-Yuan Guan
Hepatocellular carcinoma (HCC) is one of the most common and lethal cancer types worldwide, especially in Asian countries. Genetic alterations, including hyperactivation of oncogenes and loss of expression of tumor suppressor genes, greatly contribute to the initiation and progression of HCC. Here we report that down-regulation of trophoblast cell surface antigen 2 ( TROP-2 ) was frequently detected in HCC. Transcriptome sequencing of non-tumor and HCC patient samples revealed down-regulation of TROP-2 in tumor tissues...
November 2018: Hepatology Communications
Chih-Li Chen, Yu-Shuen Tsai, Yen-Hua Huang, Yuh-Jin Liang, Ya-Yun Sun, Chien-Wei Su, Gar-Yang Chau, Yi-Chen Yeh, Yung-Sheng Chang, Jui-Ting Hu, Jaw-Ching Wu
Lymphoid enhancer factor 1 (LEF1) activity is associated with progression of several types of cancers. The role of LEF1 in progression of hepatocellular carcinoma (HCC) remains poorly known. We investigated LEF1 expression in HCC and its interactions with epithelial-mesenchymal transition (EMT) regulators (e.g., Snail, Slug, Twist) and stemness genes (e.g., octamer-binding transcription factor 4 [ Oct4 ], sex determining region Y-box 2 [ Sox2 ], Nanog homeobox [ Nanog ]). Microarray analysis was performed on resected tumor samples from patients with HCC with or without postoperative recurrence...
November 2018: Hepatology Communications
Arvin Iracheta-Vellve, Charles D Calenda, Jan Petrasek, Aditya Ambade, Karen Kodys, Luciano Adorini, Gyongyi Szabo
Bile acids (BAs) activate various dedicated receptors, including the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). The FXR agonist obeticholic acid (OCA) is licensed for the treatment of primary biliary cholangitis and has shown promising results in NASH patients, whereas TGR5 agonists target inflammation and metabolism. We hypothesized that FXR and/or TGR5 agonists may be therapeutic in early alcoholic liver disease (ALD) in mice, in which hepatic inflammation plays a major role...
November 2018: Hepatology Communications
Mark R Deneau, Cara Mack, Reham Abdou, Mansi Amin, Achiya Amir, Marcus Auth, Fateh Bazerbachi, Anne Marie Broderick, Albert Chan, Matthew DiGuglielmo, Wael El-Matary, Mounif El-Youssef, Federica Ferrari, Katryn N Furuya, Frederic Gottrand, Nitika Gupta, Matjaž Homan, M K Jensen, Binita M Kamath, Kyung Mo Kim, Kaija-Leena Kolho, Anastasia Konidari, Bart Koot, Raffaele Iorio, Mercedes Martinez, Parvathi Mohan, Sirish Palle, Alexandra Papadopoulou, Amanda Ricciuto, Lawrence Saubermann, Pushpa Sathya, Eyal Shteyer, Vratislav Smolka, Atsushi Tanaka, Pamela L Valentino, Raghu Varier, Veena Venkat, Bernadette Vitola, Miriam B Vos, Marek Woynarowski, Jason Yap, Tamir Miloh
Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA)...
November 2018: Hepatology Communications
YanChao Jiang, Yi Huang, ShiYing Cai, YongFeng Song, James L Boyer, KeZhong Zhang, Ling Gao, JiaJun Zhao, WenDong Huang, Guang Liang, Suthat Liangpunsakul, Li Wang
Long noncoding RNA (lncRNA) H19 is abundantly expressed in fetal liver. Its expression is significantly diminished in adult healthy liver but is re-induced in chronic liver diseases, including cholestasis. In this study, we developed a new method with combined in situ hybridization (ISH) and immunofluorescence (IF) colabeling to establish an H19 expression profile with both parenchymal and nonparenchymal cell-specific markers in the livers of cholestatic mouse models and patients with cholestasis. H19 RNA+ cells showed no colocalization with biliary epithelial cell marker cytokeratin 19 (CK19)+ cholangiocytes but were immediately adjacent to biliary structures in bile duct ligation (BDL), 3,5-diethoxycarbony1-1,4-dihydrocollidine (DDC), and multidrug-resistant gene 2 knockout ( Mdr2 -/- ) mouse models and in human primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) liver specimens...
November 2018: Hepatology Communications
Oliver Glass, Ricardo Henao, Keyur Patel, Cynthia D Guy, Hans J Gruss, Wing-Kin Syn, Cynthia A Moylan, Robert Streilein, Russell Hall, Anna Mae Diehl, Manal F Abdelmalek
The severity of hepatic fibrosis is the primary predictor of liver-related morbidity and mortality in patients with nonalcoholic fatty liver disease (NAFLD). Unfortunately, noninvasive serum biomarkers for NAFLD-associated fibrosis are limited. We analyzed baseline serum samples for 24 cytokines of 97 patients with biopsy-proven NAFLD. These patients were prospectively enrolled in a clinical study ( NCT00794716) to identify cytokines associated with liver fibrosis in patients with nonalcoholic steatohepatitis...
November 2018: Hepatology communications
Aya Ugamura, Po-Sung Chu, Nobuhiro Nakamoto, Nobuhito Taniki, Keisuke Ojiro, Taizo Hibi, Masahiro Shinoda, Hideaki Obara, Yohei Masugi, Akihiro Yamaguchi, Shunsuke Shiba, Rei Morikawa, Shingo Usui, Hirotoshi Ebinuma, Yuko Kitagawa, Hidetsugu Saito, Takanori Kanai
A prognostic system for acute liver failure (ALF) with a higher predictive value is urgently needed. The role of extracellular matrix (ECM) remodeling in ALF has not been fully elucidated. We hypothesized that serologic fibrosis markers, which reflect ECM remodeling, are predictive of ALF outcome at first presentation. This observational study included 110 patients with acute liver dysfunction, of which 73 had non-acetaminophen-associated ALF (NAA-ALF). We evaluated serum levels of hyaluronic acid, 7S domain of type IV collagen (4COL7S), and Wisteria floribunda agglutinin-positive Mac-2-binding protein at first presentation to a tertiary center...
November 2018: Hepatology Communications
Jason J Pan, Fei Bao, Emma Du, Chase Skillin, Catherine T Frenette, Jill Waalen, Lakshmi Alaparthi, Zachary D Goodman, Paul J Pockros
Sustained virologic response (SVR) after direct-acting antiviral (DAA) therapy for chronic hepatitis C results in significant decreases in liver stiffness measured by transient elastography (TE). The aim of this study was to clarify if TE can guide post-SVR management in patients with advanced fibrosis or cirrhosis prior to treatment as current guidelines are unclear on the role of TE after SVR. In total, 84 patients with hepatitis C virus and advanced fibrosis or cirrhosis and from a single center underwent DAA treatment and achieved SVR...
November 2018: Hepatology communications
Daniel H Leung, Stefan Wirth, Betty B Yao, Rolando M Viani, Regino P Gonzalez-Peralta, Maureen M Jonas, Steven J Lobritto, Michael R Narkewicz, Etienne Sokal, Clàudia Fortuny, Evelyn K Hsu, Antonio Del Valle-Segarra, Jiuhong Zha, Lois Larsen, Li Liu, Diana L Shuster, Daniel E Cohen, Philip Rosenthal
In adults, treatment of hepatitis C virus (HCV) infection with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) with or without dasabuvir (DSV) and ±ribavirin (RBV) results in high rates of sustained virologic response (SVR). However, these regimens have not been investigated in adolescents. This ongoing, open-label, phase 2/3 study evaluated the pharmacokinetics, safety, and efficacy of OBV/PTV/r+DSV±RBV treatment for 12 weeks in adolescents infected with HCV genotype (GT) 1 without cirrhosis (part 1) and the safety and efficacy of OBV/PTV/r±DSV±RBV treatment for 12 or 24 weeks in adolescents infected with GT1 or GT4 without cirrhosis or with compensated cirrhosis (parts 1 and 2)...
November 2018: Hepatology Communications
Tatyana Kushner, Jennifer Cohen, Phyllis C Tien, Norah A Terrault
There is a rising prevalence of hepatitis C (HCV) among women of child-bearing age nationally, which prompted a recommendation by national guidelines to screen all women for HCV during pregnancy. Women with HCV during pregnancy are at risk of perinatal transmission of HCV. Directly acting antiviral (DAA) therapy during pregnancy can potentially reduce the risk of perinatal transmission as well as cure women while they are engaged in antenatal care. However, data on the safety and efficacy of DAAs during pregnancy are limited...
November 2018: Hepatology Communications
Hannes Hagström, Jonas Höijer, Hanns-Ulrich Marschall, Catherine Williamson, Michael A Heneghan, Rachel H Westbrook, Jonas F Ludvigsson, Olof Stephansson
There are limited data on pregnancy outcomes in women with cirrhosis. To address this gap, we examined the records of singleton births from Sweden's National Patient Register (NPR), Cause of Death Register (CDR), and Medical Birth Register (MBR) between 1997 and 2011 to assess exposure and pregnancy-related and liver-related outcomes of pregnant women with cirrhosis. Exposure status was defined as having an International Classification of Diseases (ICD) code for cirrhosis obtained prior to or during pregnancy...
November 2018: Hepatology Communications
Kenneth Leung, Michael Quezada, Zhengshan Chen, Gary Kanel, Neil Kaplowitz
Niacin (vitamin B3) is available as a prescription medication and over-the-counter supplement. Although it is well known for its vasodilatory effect, it has also been associated with mild hepatotoxicity and, rarely, acute liver failure. We present the case of a 74-year-old Hispanic woman who developed acute liver failure (anicteric encephalopathy and coagulopathy) after her home dose of immediate-release niacin was replaced with an extended-release formulation during an inpatient hospital stay. This is the first reported case of niacin toxicity associated with a histopathologic finding of diffuse microvesicular steatosis...
November 2018: Hepatology Communications
Giuseppe Indolfi, Silvia Ricci
Editorial to Leung et al. "Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4".
November 2018: Hepatology Communications
Christopher B O'Brien, Eytan R Barnea, Paul Martin, Cynthia Levy, Eden Sharabi, Kalyan R Bhamidimarri, Eric Martin, Leopold Arosemena, Eugene R Schiff
Preimplantation factor (PIF) is an evolutionary conserved peptide secreted by viable embryos which promotes maternal tolerance without immune suppression. Synthetic PIF (sPIF) replicates native peptide activity. The aim of this study was to conduct the first-in-human trial of the safety, tolerability, and pharmacokinetics of sPIF in patients with autoimmune hepatitis (AIH). We performed a randomized, double-blind, placebo-controlled, prospective phase I clinical trial. Patients were adults with documented AIH with compensated chronic liver disease...
October 2018: Hepatology Communications
Nicole J Kim, Catherine Magee, Cassie Cummings, Helen Park, Mandana Khalili
Recent hepatitis C virus (HCV) guidelines recommend disease monitoring and hepatocellular carcinoma (HCC) screening in patients with advanced fibrosis after a sustained virologic response (SVR) with direct-acting antiviral (DAA) therapy. However, data on practice patterns in this setting is lacking. We aimed to characterize disease monitoring and HCC screening practices post-SVR in an underserved HCV-infected cohort. Records of 192 patients who received DAA therapy at the San Francisco safety-net health care system between January 2014 and January 2016 with ≥12 months of follow-up post-SVR were reviewed...
October 2018: Hepatology Communications
Tian-Qi Zhang, Qun-Qing Su, Xiao-Ying Huang, Jin-Guang Yao, Chao Wang, Qiang Xia, Xi-Dai Long, Yun Ma
Our previous reports have shown that microRNA-4651 is a potential early diagnostic and prognostic marker for hepatocellular carcinoma. We aimed to investigate whether microRNA-4651 modified postoperative adjuvant transarterial chemoembolization (pa-TACE) to improve the prognosis of hepatocellular carcinoma. A hospital-based retrospective study, including 302 patients with advanced-stage hepatocellular carcinoma who received tumor resection or tumor resection plus pa-TACE as an initial therapy, was conducted to assess the effects of microRNA-4651 on pa-TACE treatment...
October 2018: Hepatology Communications
Takahiro Suda, Tomohide Tatsumi, Akira Nishio, Tadashi Kegasawa, Teppei Yoshioka, Ryoko Yamada, Kunimaro Furuta, Takahiro Kodama, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Takasuke Fukuhara, Yoshiharu Matsuura, Tetsuo Takehara
Natural killer cells (NK cells) play an essential role in the immunological mechanism underlying chronic hepatitis C (CHC). Impairment of NK cell function facilitates persistent infection with hepatitis C virus (HCV) and hepatocellular carcinogenesis. However, the mechanism by which NK cell activity is suppressed in CHC is not completely understood. In this study, we focused on carcinoembryonic antigen-related cell-adhesion molecule 1 (CEACAM1). CEACAM1 is thought to suppress NK cell function. We examined the effect of CEACAM1 on NK cell function in CHC...
October 2018: Hepatology Communications
Omer Shahab, Rakesh Biswas, James Paik, Haley Bush, Pegah Golabi, Zobair M Younossi
Dyslipidemia is one of the common risk factors for NAFLD and is associated with cardiovascular (CV) mortality, which is the most common cause of death in NAFLD. Lipid-lowering agents (LLAs) are used to reduce CV events in the general population. Our aim was to assess whether the use of LLAs in patients with NAFLD can reduce the risk of CV mortality. We used the third National Health and Nutrition Examination Survey mortality linked files. Mortality was determined from the National Death Index records through 2011...
October 2018: Hepatology communications
Erin E Elbel, Joel E Lavine, Michael Downes, Mark Van Natta, Ruth Yu, Jeffrey B Schwimmer, Cynthia Behling, Elizabeth M Brunt, James Tonascia, Ronald Evans
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adults. This study examined the relationship between hepatic nuclear receptor (NR) expression and histologic features of NAFLD. Drugs targeting a variety of NRs for nonalcoholic steatohepatitis (NASH) are in clinical trials. Liver messenger RNA was isolated from 40 children (10-19 years) undergoing end-of-treatment biopsy in the Treatment of NAFLD in Children (TONIC) trial. High-throughput quantitative polymerase chain reaction assayed NR messenger RNA...
October 2018: Hepatology Communications
Sanghoon Lee, Ping Zhou, Anita Gupta, Soona Shin
While reactive ductules (RDs) have been observed in viral hepatitis, biliary atresia, nonalcoholic fatty liver disease, and adult hepatocellular carcinoma (HCC), RDs in pediatric liver cancer remain uncharacterized. This study investigated the relationship of RDs with angiogenic paracrine factors, the extent of angiogenesis, and tumor cell proliferation in pediatric hepatoblastoma (HBL)/HCC livers. We quantified the extent of RDs and their expression of paracrine factors that include vascular endothelial growth factor (VEGF), vascular endothelial growth factor D (VEGFD), platelet-derived growth factor C, and angiopoietin 1 (ANGPT1)...
October 2018: Hepatology communications
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