NLRP3 inflammasome driven liver injury and fibrosis: Roles of IL‐17 and TNF in mice

Alexander Wree, Matthew D. McGeough, Maria Eugenia Inzaugarat, Akiko Eguchi, Susanne Schuster, Casey D. Johnson, Carla A. Peña, Lukas J. Geisler, Bettina G. Papouchado, Hal M. Hoffman, Ariel E. Feldstein – 13 September 2017 – The NLRP3 inflammasome, a caspase‐1 activation platform, plays a key role in the modulation of liver inflammation and fibrosis. Here, we tested the hypothesis that interleukin 17 (IL‐17) and tumor necrosis factor (TNF) are key cytokines involved in amplifying and perpetuating the liver damage and fibrosis resulting from NLRP3 activation.

Reassessing the safety concerns of utilizing blood donations from patients with hemochromatosis

Adam C. Winters, Douglas Tremblay, Suzanne Arinsburg, John Mascarenhas, Thomas D. Schiano – 13 September 2017 – Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism that may lead to iron overload. Clinical penetrance is low, however those afflicted may develop cirrhosis, hepatocellular carcinoma, diabetes mellitus, and cardiomyopathy. Treatment of HH involves regular phlebotomy to reduce the systemic iron burden.

LiverLearning®: 2017 Webinar: Surrogate Endpoints in Primary Sclerosing Cholangitis (PSC)

This webinar, presented by the Cholestatic and Biliary Diseases SIG, will focus on the complex topic of Surrogate Endpoints in PSC. The webinar will discuss the Natural History of PSC and the resulting difficulty in identifying relevant endpoints for prognostication and for use in clinical trials. Promising candidate endpoints will be specifically addressed based on the latest clinical research.David Assis (Moderator) Dr. David Assis is an assistant professor of medicine in the section of Digestive Diseases at Yale University School of Medicine.

Contradictory effects of mitochondria‐ and non‐mitochondria‐targeted antioxidants on hepatocarcinogenesis by altering DNA repair in mice

Bibo Wang, Jing Fu, Ting Yu, An Xu, Wenhao Qin, Zhishi Yang, Yao Chen, Hongyang Wang – 12 September 2017 – Conflicting effects of antioxidant supplementation on cancer prevention or promotion is of great concern to healthy people and cancer patients. Despite recent studies about antioxidants accelerating the progression of lung cancer and melanoma, antioxidants may still play a role in cancer prevention. Both tumor and antioxidants types influence the actual efficacy.

Organic solute transporter‐β (SLC51B) deficiency in two brothers with congenital diarrhea and features of cholestasis

Mutaz Sultan, Anuradha Rao, Orly Elpeleg, Frédéric M. Vaz, Bassam Abu‐Libdeh, Saul J. Karpen, Paul A. Dawson – 12 September 2017 – Primary bile acid malabsorption is associated with congenital diarrhea, steatorrhea, and a block in the intestinal return of bile acids in the enterohepatic circulation. Mutations in the ileal apical sodium‐dependent bile acid transporter (ASBT; SLC10A2) can cause primary bile acid malabsorption but do not appear to account for most familial cases.

Complete response under sorafenib in patients with hepatocellular carcinoma: Relationship with dermatologic adverse events

Jordi Rimola, Álvaro Díaz‐González, Anna Darnell, María Varela, Fernando Pons, Manuel Hernandez‐Guerra, Manuel Delgado, Javier Castroagudin, Ana Matilla, Bruno Sangro, Carlos Rodriguez de Lope, Margarita Sala, Carmen Gonzalez, Carlos Huertas, Beatriz Minguez, Carmen Ayuso, Jordi Bruix, María Reig – 12 September 2017 – The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic reactions have shown to have a positive outcome.

LiverLearning®: 2017 Webinar: Fibrosis Regression: Mechanisms and Clinical Consequences

For most of the modern era in medicine, cirrhosis has been regarded as an irreversible condition. For most of the modern era in medicine, cirrhosis has been regarded as an irreversible condition.  Contrary to this perception, cirrhosis in animal models of liver injury has long been known to be reversible and case reports from decades ago documenting “reversal” of cirrhosis indicated that fibrosis regression was also possible in human liver disease.

Drug‐induced cholestasis

Vinay Sundaram, Einar S. Björnsson – 11 September 2017 – Cholestatic drug‐induced liver injury (DILI) can be a diagnostic challenge due to a large differential diagnosis, variability in clinical presentation, and lack of serologic biomarkers associated with this condition. The clinical presentation of drug‐induced cholestasis includes bland cholestasis, cholestatic hepatitis, secondary sclerosing cholangitis, and vanishing bile duct syndrome.

Nicotinamide N‐methyltransferase expression decreases in iron overload, exacerbating toxicity in mouse hepatocytes

Tiago Koppe, Bonnie Patchen, Aaron Cheng, Manoj Bhasin, Chris Vulpe, Robert E. Schwartz, Jose Maria Moreno‐Navarrete, Jose Manuel Fernandez‐Real, Pavlos Pissios, Paula G. Fraenkel – 11 September 2017 – Iron overload causes the generation of reactive oxygen species that can lead to lasting damage to the liver and other organs. The goal of this study was to identify genes that modify the toxicity of iron overload.

The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial

Rohit Loomba, Eric Lawitz, Parvez S. Mantry, Saumya Jayakumar, Stephen H. Caldwell, Hays Arnold, Anna Mae Diehl, C. Stephen Djedjos, Ling Han, Robert P. Myers, G. Mani Subramanian, John G. McHutchison, Zachary D. Goodman, Nezam H. Afdhal, Michael R. Charlton, for the GS‐US‐384‐1497 Investigators – 11 September 2017 – Inhibition of apoptosis signal–regulating kinase 1, a serine/threonine kinase, leads to improvement in inflammation and fibrosis in animal models of nonalcoholic steatohepatitis.

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