Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma

Ryan A. Hlady, Aishwarya Sathyanarayan, Joyce J. Thompson, Dan Zhou, Qunfeng Wu, Kien Pham, Jeong‐Heon Lee, Chen Liu, Keith D. Robertson – 22 August 2018 – Disruption of epigenetic mechanisms has been intimately linked to the etiology of human cancer. Understanding how these epigenetic mechanisms (including DNA methylation [5mC], hydroxymethylation [5hmC], and histone post‐translational modifications) work in concert to drive cancer initiation and progression remains unknown. Hepatocellular carcinoma (HCC) is increasing in frequency in Western countries but lacks efficacious treatments.

Discovery of the Novel Entecavir‐Resistant Hepatitis B Virus Reverse Transcriptase A181C Substitution From an Integrated Genotypic Analysis

Ronald E. Rose, Dennis Hernandez, Paul J. Falk, Karen Ericson, Nannan Zhou, Alexandra Thiry, Fiona McPhee – 21 August 2018 – Entecavir (ETV) is a first‐line therapy for chronic hepatitis B virus (HBV), demonstrating potent suppression of HBV DNA and a high barrier to viral resistance. Previous studies revealed that ETV‐resistant (ETVr) HBV DNA resulted from substitutions in the HBV reverse transcriptase (RT) at positions rtT184, rtS202, or rtM250 in combination with lamivudine resistance (LVDr) substitutions rtM204I/V±rtL180M.

Hyponatremia in Cirrhosis: Implications for Liver Transplantation

Michael Leise, Andrés Cárdenas – 21 August 2018 – Hyponatremia in cirrhosis is defined as a serum sodium level ≤130 mEq/L and occurs in approximately 22% of patients with cirrhosis. The appearance of hyponatremia in patients with cirrhosis portends a poor prognosis before liver transplantation (LT), independent of the Model for End‐Stage Liver Disease (MELD) score. With the development of the MELD‐sodium score, the management of hyponatremia has become more relevant than ever before.

Longterm Survival and Cost‐Effectiveness of Immunosuppression Withdrawal After Liver Transplantation

Tommaso Maria Manzia, Roberta Angelico, Luca Toti, Cristina Angelico, Claudia Quaranta, Alessandro Parente, Francesca Blasi, Samuele Iesari, Daniele Sforza, Leonardo Baiocchi, Jan Lerut, Giuseppe Tisone – 20 August 2018 – Lifelong immunosuppression (IS) after liver transplantation is associated with severe adverse effects and increased recipients’ morbidity and mortality. Clinical operational tolerance has been reported in up to 40% in very well‐selected recipients. Longterm survival and cost savings within the Italian national health system in operational tolerant recipients is reported.

The NACSTOP Trial: A Multicenter, Cluster‐Controlled Trial of Early Cessation of Acetylcysteine in Acetaminophen Overdose

Anselm Wong, Richard McNulty, David Taylor, Marco Sivilotti, Shaun Greene, Naren Gunja, Zeff Koutsogiannis, Andis Graudins – 19 August 2018 – Historically, intravenous acetylcysteine has been delivered at a fixed dose and duration of 300 mg/kg over 20 to 21 hours to nearly every patient deemed to be at any risk for hepatotoxicity following acetaminophen overdose. We investigated a 12‐hour treatment regimen for selected low‐risk patients. This was a multicenter, open‐label, cluster‐controlled trial at six metropolitan emergency departments.

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