Na+‐taurocholate cotransporting polypeptide inhibition has hepatoprotective effects in cholestasis in mice

Davor Slijepcevic, Reinout L.P. Roscam Abbing, Claudia D. Fuchs, Lizette C.M. Haazen, Ulrich Beuers, Michael Trauner, Ronald P.J. Oude Elferink, Stan F.J. van de Graaf – 24 March 2018 – Accumulation of bile salts (BSs) during cholestasis leads to hepatic and biliary injury, driving inflammatory and fibrotic processes. The Na+‐Taurocholate Cotransporting Polypeptide (NTCP) is the major hepatic uptake transporter of BSs, and can be specifically inhibited by myrcludex B. We hypothesized that inhibition of NTCP dampens cholestatic liver injury.

Ubiquitin‐Specific Protease 4 Is an Endogenous Negative Regulator of Metabolic Dysfunctions in Nonalcoholic Fatty Liver Disease in Mice

Yichao Zhao, Fang Wang, Lingchen Gao, Longwei Xu, Renyang Tong, Nan Lin, Yuanyuan Su, Yang Yan, Yu Gao, Jie He, Lingcong Kong, Ancai Yuan, Ying Zhuge, Jun Pu – 23 March 2018 – Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis (HS), insulin resistance (IR), and inflammation, poses a high risk of cardiometabolic disorders. Ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme, is pivotally involved in regulating multiple inflammatory pathways; however, the role of USP4 in NAFLD is unknown.

NI‐0801, an anti‐chemokine (C‐X‐C motif) ligand 10 antibody, in patients with primary biliary cholangitis and an incomplete response to ursodeoxycholic acid

Kathy L. de Graaf, Geneviève Lapeyre, Florence Guilhot, Walter Ferlin, Stuart M. Curbishley, Marco Carbone, Paul Richardson, Sulleman Moreea, C. Anne McCune, Stephen D. Ryder, Roger W. Chapman, Annarosa Floreani, David E. Jones, Cristina de Min, David H. Adams, Pietro Invernizzi – 23 March 2018 – NI‐0801 is a fully human monoclonal antibody against chemokine (C‐X‐C motif) ligand 10 (CXCL10), which is involved in the recruitment of inflammatory T cells into the liver. The safety and efficacy of NI‐0801 was assessed in patients with primary biliary cholangitis.

A real‐world observational cohort of patients with primary biliary cholangitis: TARGET‐primary biliary cholangitis study design and rationale

Cynthia Levy, Christopher L. Bowlus, Elizabeth Carey, Julie M. Crawford, Karen Deane, Marlyn J. Mayo, W. Ray Kim, Michael W. Fried – 23 March 2018 – Primary biliary cholangitis (PBC) is a rare chronic cholestatic liver disease that may progress to biliary cirrhosis if left untreated. The first‐line therapy for PBC is ursodeoxycholic acid (UDCA). Unfortunately, 1 of 3 patients does not respond to UDCA. These patients are at risk for developing clinical events, including cirrhosis, complications of portal hypertension, hepatocellular carcinoma, liver transplant, or death. Recently, the U.S.

Propensity‐Matched Analysis of Patients with Mixed Hepatocellular‐Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation

Keri E. Lunsford, Colin Court, Yong Seok Lee, David S. Lu, Bita V. Naini, Michael P. Harlander‐Locke, Ronald W. Busuttil, Vatche G. Agopian – 23 March 2018 – Mixed hepatocellular‐cholangiocarcinomas (HCC‐CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC‐CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC‐CCA and a matched cohort of HCC LT recipients.

Acute hepatitis B virus infection in humanized chimeric mice has multiphasic viral kinetics

Yuji Ishida, Tje Lin Chung, Michio Imamura, Nobuhiko Hiraga, Suranjana Sen, Hiroshi Yokomichi, Chise Tateno, Laetitia Canini, Alan S. Perelson, Susan L. Uprichard, Harel Dahari, Kazuaki Chayama – 23 March 2018 – Chimeric urokinase type plasminogen activator (uPA)/severely severe combined immunodeficiency (SCID) mice reconstituted with humanized livers are useful for studying hepatitis B virus (HBV) infection in the absence of an adaptive immune response.

Heterozygosity for the alpha‐1‐antitrypsin Z allele in cirrhosis is associated with more advanced disease

Benedikt Schaefer, Mattias Mandorfer, André Viveiros, Armin Finkenstedt, Peter Ferenci, Stefan Schneeberger, Herbert Tilg, Heinz Zoller – 23 March 2018 – Alpha‐1‐antitrypsin deficiency (A1ATD) due to homozygosity for the Z allele (ZZ) is an established risk factor for cirrhosis, but the liver disease risk in heterozygous Z allele carriers (MZ) is controversial. The aim of the present study was to determine the prevalence of the MZ genotype among patients with cirrhosis and the associated risk of decompensation and liver transplantation/mortality.

Achieving Sustained Virological Response in Liver Transplant Recipients With Hepatitis C Decreases Risk of Decline in Renal Function

Sanjaya K. Satapathy, Kiran Joglekar, Miklos Z. Molnar, Bilal Ali, Humberto C. Gonzalez, Jason M. Vanatta, James D. Eason, Satheesh P. Nair – 23 March 2018 – The effect of antiviral therapy (AVT) on kidney function in liver transplantation (LT) recipients has not been well described despite known association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD). We compared the incidence of CKD and end‐stage renal disease (ESRD) in 204 LT recipients with HCV based on treatment response to AVT.

Coding variants in PNPLA3 and TM6SF2 are risk factors for hepatic steatosis and elevated serum alanine aminotransferases caused by a glucagon receptor antagonist

Cristina B. Guzman, Suman Duvvuru, Anthony Akkari, Pallav Bhatnagar, Chakib Battioui, Wendra Foster, Xiaotian Michelle Zhang, Sudha S. Shankar, Mark A. Deeg, Naga Chalasani, Thomas A. Hardy, Christof M. Kazda, Sreekumar G. Pillai – 23 March 2018 – LY2409021 is a glucagon receptor antagonist that was associated with hepatic steatosis and elevated aminotransferases in phase 2 diabetes studies. We investigated the relationship between selected genetic variants and hepatic steatosis and elevated alanine aminotransferases (ALTs) associated with LY2409021.

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