PNPLA3, CGI‐58, and Inhibition of Hepatic Triglyceride Hydrolysis in Mice

Yang Wang, Nora Kory, Soumik BasuRay, Jonathan C. Cohen, Helen H. Hobbs – 25 February 2019 – A variant (148M) in patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) is a major risk factor for fatty liver disease. Despite its clinical importance, the pathogenic mechanism linking the variant to liver disease remains poorly defined. Previously, we showed that PNPLA3(148M) accumulates to high levels on hepatic lipid droplets (LDs). Here we examined the effect of that accumulation on triglyceride (TG) hydrolysis by adipose triglyceride lipase (ATGL), the major lipase in the liver.

Emergence of the Dedifferentiated Phenotype in Hepatocyte‐Derived Tumors in Mice: Roles of Oncogene‐Induced Epigenetic Alterations

Kenji Watanabe, Masahiro Yamamoto, Bing Xin, Takako Ooshio, Masanori Goto, Kiyonaga Fujii, Yang Liu, Yoko Okada, Hiroyuki Furukawa, Yuji Nishikawa – 25 February 2019 – Hepatocellular carcinoma often reactivates the genes that are transiently expressed in fetal or neonatal livers. However, the mechanism of their activation has not been elucidated.

A Call to Standardize Definitions, Data Collection, and Outcome Assessment to Improve Care in Alcohol‐Related Liver Disease

Nicole T. Shen, Annaheta Salajegheh, Robert S. Brown – 25 February 2019 – Alcohol‐related liver disease (ALD) is highly prevalent and appears to be increasingly reported with worsening mortality; thus, optimizing care in this patient population is imperative. This will require a multidisciplinary, multifaceted approach that includes recognizing alcohol use disorder (AUD) and existing treatments for AUD. We must also acknowledge the full spectrum of ALD clinically and histologically.

NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis

Stephen A. Harrison, Stephen J. Rossi, Angelo H. Paredes, James F. Trotter, Mustafa R. Bashir, Cynthia D. Guy, Rajarshi Banerjee, Mark J. Jaros, Sandra Owers, Bryan A. Baxter, Lei Ling, Alex M. DePaoli – 25 February 2019 – NGM282, an engineered fibroblast growth factor 19 analogue, rapidly and significantly reduced liver fat content in a multicenter, randomized, double‐blind, placebo‐controlled study in patients with biopsy‐confirmed nonalcoholic steatohepatitis (NASH). However, it is unclear whether these changes would be accompanied by histological improvement.

Interleukin‐33/ST2‐Mediated Inflammation Plays a Critical Role in the Pathogenesis and Severity of Type I Autoimmune Hepatitis

Kazumichi Abe, Atsushi Takahashi, Masashi Fujita, Manabu Hayashi, Ken Okai, Yoshihiro Nozawa, Hiromasa Ohira – 25 February 2019 – Interleukin (IL)‐33 was recently described as a new member of the IL‐1 family; members of this family have proinflammatory activity. IL‐33 and its soluble receptor ST2 (sST2) have been implicated in the pathogenesis of autoimmune diseases. This study investigated serum IL‐33 and sST2 in type I autoimmune hepatitis (AIH) and the relationship of these molecules with clinical and pathologic parameters.

Expression of Metastatic Tumor Antigen 1 Splice Variant Correlates With Early Recurrence and Aggressive Features of Hepatitis B Virus–Associated Hepatocellular Carcinoma

Yung‐Tsung Li, Hui‐Lin Wu, Jia‐Horng Kao, Huei‐Ru Cheng, Ming‐Chih Ho, Chih‐Chiang Wang, Pei‐Jer Chen, Ding‐Shinn Chen, Chun‐Jen Liu – 25 February 2019 – Overexpression of metastatic tumor antigen 1 (MTA1) was correlated with poor prognosis of hepatitis B virus (HBV)‐associated hepatocellular carcinoma (HBV‐HCC). The aim of this study was to examine the clinical significance of the expression of MTA1 and its exon 4‐excluded form (MTA1dE4), the most abundant spliced variant of MTA1, in patients receiving curative resection for HBV‐HCC.

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