Systems biology for hepatologists

José M. Mato, M. Luz Martínez‐Chantar, Shelly C. Lu – 21 January 2014 – Medicine is expected to benefit from combining usual cellular and molecular studies with high‐throughput methods (genomics, transcriptomics, proteomics, and metabolomics). These methods, collectively known as omics, permit the determination of thousands of molecules (variations within genes, RNAs, proteins, metabolites) within a tissue, cell, or biological fluid. The use of these methods is very demanding in terms of the design of the study, acquisition, storage, analysis, and interpretation of the data.

ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response

Jacinta A. Holmes, Stuart K. Roberts, Rachel J. Ali, Gregory J. Dore, William Sievert, Geoffrey W. McCaughan, Darrell H. Crawford, Wendy S. Cheng, Martin D. Weltman, Sara Bonanzinga, Kumar Visvanathan, Vijaya Sundararajan, Paul V. Desmond, D. Scott Bowden, Gail V. Matthews, Alexander J. Thompson, on behalf of the CHARIOT Study Group – 21 January 2014 – On‐treatment anemia is associated with higher sustained virological response (SVR) rates during peginterferon plus ribavirin (RBV) therapy.

Systems biology for hepatologists

José M. Mato, M. Luz Martínez‐Chantar, Shelly C. Lu – 21 January 2014 – Medicine is expected to benefit from combining usual cellular and molecular studies with high‐throughput methods (genomics, transcriptomics, proteomics, and metabolomics). These methods, collectively known as omics, permit the determination of thousands of molecules (variations within genes, RNAs, proteins, metabolites) within a tissue, cell, or biological fluid. The use of these methods is very demanding in terms of the design of the study, acquisition, storage, analysis, and interpretation of the data.

Intestinal lymphangiectasia and reversible high liver stiffness

Laura Milazzo, Anna Maria Peri, Lucia Lodi, Guido Gubertini, Anna Lisa Ridolfo, Spinello Antinori – 21 January 2014 – Primary intestinal lymphangiectasia (PIL) is a protein‐losing enteropathy characterized by tortuous and dilated lymph channels of the small bowel. The main symptoms are bilateral lower limb edema, serosal effusions, and vitamin D malabsorption resulting in osteoporosis. We report here a case of long‐lasting misdiagnosed PIL with a peculiar liver picture, characterized by a very high stiffness value at transient elastography, which decreased with clinical improvement.

Epigenetic reprogramming modulates malignant properties of human liver cancer

Chiara Raggi, Valentina M. Factor, Daekwan Seo, Agnes Holczbauer, Matthew C. Gillen, Jens U. Marquardt, Jesper B. Andersen, Marian Durkin, Snorri S. Thorgeirsson – 21 January 2014 – Reversal of DNA hypermethylation and associated gene silencing is an emerging cancer therapy approach. Here we addressed the impact of epigenetic alterations and cellular context on functional and transcriptional reprogramming of hepatocellular carcinoma (HCC) cells.

Intestinal lymphangiectasia and reversible high liver stiffness

Laura Milazzo, Anna Maria Peri, Lucia Lodi, Guido Gubertini, Anna Lisa Ridolfo, Spinello Antinori – 21 January 2014 – Primary intestinal lymphangiectasia (PIL) is a protein‐losing enteropathy characterized by tortuous and dilated lymph channels of the small bowel. The main symptoms are bilateral lower limb edema, serosal effusions, and vitamin D malabsorption resulting in osteoporosis. We report here a case of long‐lasting misdiagnosed PIL with a peculiar liver picture, characterized by a very high stiffness value at transient elastography, which decreased with clinical improvement.

Alpha‐1‐antitrypsin inhibits acute liver failure in mice

Nils Jedicke, Nina Struever, Nupur Aggrawal, Tobias Welte, Michael P. Manns, Nisar P. Malek, Lars Zender, Sabina Janciauskiene, Torsten Wuestefeld – 21 January 2014 – Acute liver failure remains a critical clinical condition, with high mortality rates, and increased apoptosis of hepatocytes represents a key event in the cause of liver failure. Alpha‐1‐antitrypsin (AAT) is synthesized and secreted mainly by hepatocytes, and plasma purified AAT is used for augmentation therapy in patients with AAT deficiency.

CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by SIRT1

Ben Zhou, Yi Zhang, Fang Zhang, Yulei Xia, Jun Liu, Rui Huang, Yuangao Wang, Yanan Hu, Jingxia Wu, Changgui Dai, Hui Wang, Yanyang Tu, Xiaozhong Peng, Yiqian Wang, Qiwei Zhai – 18 January 2014 – The protein deacetylase, sirtuin 1 (SIRT1), involved in regulating hepatic insulin sensitivity, shows circadian oscillation and regulates the circadian clock. Recent studies show that circadian misalignment leads to insulin resistance (IR); however, the underlying mechanisms are largely unknown.

Acute hepatitis C: A 24‐week course of pegylated interferon alpha‐2b versus a 12‐week course of pegylated interferon alpha‐2b alone or with ribavirin

Teresa Santantonio, Massimo Fasano, Evangelista Sagnelli, Paolo Tundo, Sergio Babudieri, Paolo Fabris, Mario Toti, Giovanni Perri, Nicoletta Marino, Eligio Pizzigallo, Gioacchino Angarano, the Acute Hepatitis C Study Group – 18 January 2014 – Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24‐week course of pegylated IFN (Peg‐IFN) alpha‐2b versus a 12‐week course of Peg‐IFN alpha‐2b alone or with ribavirin (RBV) in AHC patients.

NF‐E2‐related factor 2 promotes compensatory liver hypertrophy after portal vein branch ligation in mice

Keiichi Shirasaki, Keiko Taguchi, Michiaki Unno, Hozumi Motohashi, Masayuki Yamamoto – 17 January 2014 – Hepatectomy is a standard therapy that allows liver cancer patients to achieve long‐term survival. Preceding hepatectomy, portal vein embolization (PVE) is frequently performed to increase the remnant liver size and reduce complications. Although the clinical importance of PVE is widely accepted, molecular mechanisms by which PVE leads to compensatory hypertrophy of nonembolized lobes remain elusive.

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