LiverLearning®: Hyman J. Zimmerman Hepatotoxicity SOA: Assessing DILI Risk in the Life Cycle of Drugs and Biologics: A Challenge for Regulatory Science

Drug-induced liver injury (DILI) remains the leading cause of acute liver failure in the U.S. This session will review methods that are used by clinical and regulatory scientists to gather information about the hepatotoxicity of a drug or biological agent, during each phase of its life cycle.  The session will highlight the diverse clinical signatures and mechanisms that underlie DILI and discuss critical challenges when analyzing drug-related risk for serious liver toxicity.James L. Boyer James L.

LiverLearning®: Advances for Practitioners: Cholestatic and Autoimmune Liver Disease

This session will highlight recent key studies in the field of cholestatic and autoimmune liver diseases. Speakers will review data on new therapies for the treatment of PBC and discuss the role of risk stratification in the management of this disease. Additionally, recent studies evaluating new biomarkers and surveillance strategies in PSC will be reviewed to determine their usefulness and applicability. Finally, the session will evaluate the evidence underlying the use of specific second line therapies in autoimmune hepatitis and a treatment algorithm will be proposed.Christopher L.

Barrier to autointegration factor 1, procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase 3, and splicing factor 3b subunit 4 as early‐stage cancer decision markers and drivers of hepatocellular carcinoma

Qingyu Shen, Jung Woo Eun, Kyungbun Lee, Hyung Seok Kim, Hee Doo Yang, Sang Yean Kim, Eun Kyung Lee, Taemook Kim, Keunsoo Kang, Seongchan Kim, Dal‐Hee Min, Soon‐Nam Oh, Young‐Joon Lee, Hyuk Moon, Simon Weonsang Ro, Won Sang Park, Jung Young Lee, Suk Woo Nam – 23 October 2017 – An accurate tool enabling early diagnosis of hepatocellular carcinoma (HCC) is clinically important, given that early detection of HCC markedly improves survival. We aimed to investigate the molecular markers underlying early progression of HCC that can be detected in precancerous lesions.

Telomere length and reactive oxygen species levels are positively associated with a high risk of mortality and recurrence in hepatocellular carcinoma

Eunkyong Ko, Hyun‐Wook Seo, Guhung Jung – 23 October 2017 – Telomeres protect chromosomal ends from deterioration and have been shown to be susceptible to shortening by reactive oxygen species (ROS)‐induced damage. ROS levels increase during the progression from early to advanced hepatocellular carcinoma (HCC). An independent study found that the telomeres in most HCC tissues lengthened during carcinogenic advancement.

Benefit‐risk assessment for sofosbuvir/velpatasvir/voxilaprevir based on patient population and hepatitis C virus genotype: U. S. Food and Drug Administration's evaluation

Kimberly Struble, Kirk Chan‐Tack, Karen Qi, Lisa K. Naeger, Debra Birnkrant – 23 October 2017 – On July 18, 2017, the U.S. Food and Drug Administration (FDA) approved sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) fixed‐dose combination (FDC), an interferon‐free, complete regimen for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child‐Pugh A) who have:

Partial splenic artery embolization for severe hepatic myelopathy in cirrhosis

Cyriac Abby Philips, Lijesh Kumar, Philip Augustine – 23 October 2017 – Hepatic myelopathy (HM) is a devastating but rare complication of cirrhosis and portal hypertension that profoundly affects quality of life and improves only with liver transplantation. We present a case where progressive severe spastic paraparesis due to HM was substantially reversed with partial splenic artery emobilization (PSAE). (Hepatology 2018;67:1169–1171)

Interferon regulatory factor 1–Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury

Mu‐qing Yang, Qiang Du, Julie Goswami, Patrick R. Varley, Bin Chen, Rong‐hua Wang, Adrian E. Morelli, Donna B. Stolz, Timothy R. Billiar, Jiyu Li, David A. Geller – 23 October 2017 – The role and regulators of extracellular vesicle (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a guanosine triphosphatase known to control EV release. Interferon regulatory factor 1 (IRF‐1) is a transcription factor that plays an important role in liver IR and regulates certain guanosine triphosphatases.

Increase in liver stiffness after transjugular intrahepatic portosystemic shunt is associated with inflammation and predicts mortality

Christian Jansen, Philipp Möller, Carsten Meyer, Carl Christian Kolbe, Christopher Bogs, Alessandra Pohlmann, Robert Schierwagen, Michael Praktiknjo, Zeinab Abdullah, Jennifer Lehmann, Daniel Thomas, Christian P. Strassburg, Eicke Latz, Sebastian Mueller, Martin Rössle, Jonel Trebicka – 23 October 2017 – Transjugular intrahepatic portosystemic shunt (TIPS) efficiently treats complications of portal hypertension. Liver and spleen stiffness might predict clinically significant portal hypertension.

Fat‐free muscle mass in magnetic resonance imaging predicts acute‐on‐chronic liver failure and survival in decompensated cirrhosis

Michael Praktiknjo, Marius Book, Julian Luetkens, Alessandra Pohlmann, Carsten Meyer, Daniel Thomas, Christian Jansen, Andreas Feist, Johannes Chang, Jochen Grimm, Jennifer Lehmann, Christian P. Strassburg, Juan Gonzalez Abraldes, Guido Kukuk, Jonel Trebicka – 23 October 2017 – Muscle mass seems to be a prognostic marker in patients with liver cirrhosis. However, reported methods to quantify muscle mass are heterogeneous, consented cutoff values are missing, and most studies have used computed tomography.

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