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.

Gadoxetic acid disodium–enhanced magnetic resonance imaging outperformed multidetector computed tomography in diagnosing small hepatocellular carcinoma: A meta‐analysis

Xijiao Liu, Hanyu Jiang, Jie Chen, You Zhou, Zixing Huang, Bin Song – 8 September 2017 – Early detection of small hepatocellular carcinoma (HCC) lesions can improve longterm patient survival. A systematic review and meta‐analysis of the diagnostic performance of gadoxetic acid disodium (Gd‐EOB‐DTPA)–enhanced magnetic resonance imaging (MRI) and multidetector computed tomography (MDCT) was performed in diagnosing small HCCs measuring up to 2 cm (≤2 cm).

Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

Eung Chang Lee, Seong Hoon Kim, Jae Ryong Shim, Sang‐Jae Park – 8 September 2017 – Living donor liver transplantation (LDLT) has been reported to have high rates of hepatocellular carcinoma (HCC) recurrence compared with deceased donor liver transplantation (DDLT). This has been assumed to be due to the frequent use of small‐for‐size grafts (SFSGs) in LDLT rather than DDLT, but the relationship between graft size and prognosis remains controversial. This study aimed to clarify the effect of SFSGs on the oncologic outcomes of patients with HCC who underwent LDLT.

Impact of donor age in donation after circulatory death liver transplantation: Is the cutoff “60” still of relevance?

Andrea Schlegel, Irene Scalera, M. Thamara P. R. Perera, Marit Kalisvaart, Hynek Mergental, Darius F. Mirza, John Isaac, Paolo Muiesan – 8 September 2017 – Advanced donor age has been identified as a risk factor when combined with donor warm ischemia time (WIT), eg, in donation after circulatory death (DCD). In several countries, DCD livers older than 60 years are not considered suitable due to concerns related to poor graft function and development of ischemic cholangiopathy. In this study, we evaluate outcomes after DCD liver transplantation using grafts from donors older than 60 years.

Overt hepatic encephalopathy impairs learning on the EncephalApp stroop which is reversible after liver transplantation

Chathur Acharya, James B. Wade, Andrew Fagan, Melanie White, Edith Gavis, Dinesh Ganapathy, HoChong Gilles, Douglas M. Heuman, Jasmohan S. Bajaj – 8 September 2017 – After an initial exposure, patients can develop test‐taking/learning strategies called the “test sophistication effect.” Patients with cirrhosis with prior overt hepatic encephalopathy (OHE) could have persistent learning impairments.

A multifunctional nanocarrier for efficient TRAIL‐based gene therapy against hepatocellular carcinoma with desmoplasia in mice

Chun‐Hung Liu, Guann‐Jen Chern, Fu‐Fei Hsu, Kuan‐Wei Huang, Yun‐Chieh Sung, Hsi‐Chien Huang, Jiantai Timothy Qiu, Sheng‐Kai Wang, Chu‐Chi Lin, Chien‐Hsun Wu, Han‐Chung Wu, Jia‐Yu Liu, Yunching Chen – 8 September 2017 – The anticancer efficacy of TNF‐related apoptosis‐inducing ligand (TRAIL)‐based therapy is limited because of systemic toxicity, poor bioavailability, and development of TRAIL resistance.

LiverLearning®: 2017 Webinar: New DAA's and Controversies in HCV: What Clinicians Need to Know

Two new HCV meds have been approved over the summer. This webinar is meant to provide an update on how these fit into current practice. We will also cover the ongoing controversy on the risk of HCC with DAA's and the recent Cochrane report on the benefits of HCV therapy.Insook Kim (Moderator) Insook Kim, PhD is a clinical pharmacology team leader for gastroenterology and hepatology products in the Office of Clinical Pharmacology at FDA.

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