Human serum leads to differentiation of human hepatoma cells, restoration of very‐low‐density lipoprotein secretion, and a 1000‐fold increase in HCV Japanese fulminant hepatitis type 1 titers

Rineke H.G. Steenbergen, Michael A. Joyce, Bradley S. Thomas, Daniel Jones, John Law, Rodney Russell, Michael Houghton, D. Lorne Tyrrell – 14 June 2013 – In this study, we differentiated the human hepatoma cell line Huh7.5 by supplementing tissue culture media with human serum (HS) and examined the production of hepatitis C virus (HCV) by these cells. We compared the standard tissue culture protocol, using media supplemented with 10% fetal bovine serum (FBS), to media supplemented with 2% HS.

Paracrine signals from liver sinusoidal endothelium regulate hepatitis C virus replication

Ian A. Rowe, Sukhdeep K. Galsinh, Garrick K. Wilson, Richard Parker, Sarah Durant, Catalin Lazar, Norica Branza‐Nichita, Roy Bicknell, David H. Adams, Peter Balfe, Jane A. McKeating – 14 June 2013 – Hepatitis C virus (HCV) is a major cause of global morbidity, causing chronic liver injury that can progress to cirrhosis and hepatocellular carcinoma. The liver is a large and complex organ containing multiple cell types, including hepatocytes, sinusoidal endothelial cells (LSEC), Kupffer cells, and biliary epithelial cells.

Elevated body mass index as a causal risk factor for symptomatic gallstone disease: A Mendelian randomization study

Stefan Stender, Børge G. Nordestgaard, Anne Tybjærg‐Hansen – 14 June 2013 – Elevated body mass index (BMI) is associated with an increased risk of gallstone disease. Whether this reflects a causal association is unknown. Using a Mendelian randomization approach, we studied 77,679 individuals from the general population. Of these, 4,106 developed symptomatic gallstone disease during up to 34 years of follow‐up. Subjects were genotyped for three common variants known to associate with BMI: FTO(rs9939609); MC4R(rs17782313); and TMEM18(rs6548238).

AASLD clinical practice guidelines: A critical review of scientific evidence and evolving recommendations

Christopher Koh, Xiongce Zhao, Niharika Samala, Sasan Sakiani, T. Jake Liang, Jayant A. Talwalkar – 14 June 2013 – The American Association for the Study of Liver Diseases (AASLD) practice guidelines provide recommendations in diagnosing and managing patients with liver disease from available scientific evidence in combination with expert consensus opinions. The aim was to systematically review the evolution of recommendations from AASLD guidelines and identify gaps limiting the evidence‐based foundations of these guidelines.

Liver transplantation normalizes serum hepcidin level and cures iron metabolism alterations in HFE hemochromatosis

Edouard Bardou‐Jacquet, Julie Philip, Richard Lorho, Martine Ropert, Marianne Latournerie, Pauline Houssel‐Debry, Dominique Guyader, Olivier Loréal, Karim Boudjema, Pierre Brissot – 14 June 2013 – Defects in human hemochromatosis protein (HFE) cause iron overload due to reduced hepatic hepcidin secretion. Liver transplantation (LT) is a key treatment for potential complications from HFE‐related hereditary hemochromatosis (HH). This study evaluated hepcidin secretion and iron burden after LT to elucidate HH pathophysiology.

Isolate‐dependent use of claudins for cell entry by hepatitis C virus

Sibylle Haid, Christina Grethe, Michael T. Dill, Markus Heim, Lars Kaderali, Thomas Pietschmann – 14 June 2013 – Hepatitis C Virus (HCV) entry involves at least four cellular factors, including CD81, the scavenger receptor class B type I (SCARB‐1), occludin (OCLN), and claudin‐1 (CLDN1). In addition, CLDN6 and CLDN9 have been shown to substitute for CLDN1 as HCV entry factors in human nonliver cells. We examined the role of different CLDN proteins during HCV entry by using cell lines expressing either predominantly CLDN1 (Huh‐7.5) or CLDN6 (HuH6).

Hepatocyte nuclear factor‐4α reverses malignancy of hepatocellular carcinoma through regulating miR‐134 in the DLK1‐DIO3 region

Chuan Yin, Pei‐Qin Wang, Wen‐Ping Xu, Yuan Yang, Qing Zhang, Bei‐Fang Ning, Ping‐Ping Zhang, Wei‐Ping Zhou, Wei‐Fen Xie, Wan‐Sheng Chen, Xin Zhang – 14 June 2013 – Hepatocyte nuclear factor‐4α (HNF4α) is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis. There is striking suppression of hepatocellular carcinoma (HCC) by HNF4α, although the mechanisms by which HNF4α reverses HCC malignancy are largely unknown.

Population‐based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis

Kirsten Boonstra, Rinse K. Weersma, Karel J. Erpecum, Erik A. Rauws, B.W. Marcel Spanier, Alexander C. Poen, Karin M. Nieuwkerk, Joost P. Drenth, Ben J. Witteman, Hans A. Tuynman, Anton H. Naber, Paul J. Kingma, Henk R. Buuren, Bart Hoek, Frank P. Vleggaar, Nan Geloven, Ulrich Beuers, Cyriel Y. Ponsioen, on behalf of the EpiPSCPBC Study Group – 14 June 2013 – Extensive population‐based studies are much needed to accurately establish epidemiology and disease course in patients with primary sclerosing cholangitis (PSC).

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