Advances in Hepatology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury Wed, 25 Jun 2014 07:08:40 +0000 http://www.hindawi.com/journals/ahe/2014/621380/ Total parenteral nutrition (TPN), a lifesaving therapy, involves providing nutrition by bypassing the gut. Unfortunately it is associated with significant complications including gut atrophy and parenteral nutrition associated liver disease (PNALD). PNALD includes steatosis, cholestasis, disrupted glucose metabolism, disrupted lipid metabolism, cirrhosis, and liver failure. The etiopathogenesis remains poorly defined; however, an altered enterohepatic circulation, disrupting nuclear receptor signaling, is emerging as a promising mechanism. Rodent models and our piglet TPN model have shown that, during regular feeding, bile acids activate farnesoid X receptor (FXR) in the gut and enhance fibroblast growth factor 19 (FGF19) level. FGF19 regulates bile acid, lipid, and glucose metabolism. We noted reduced FGF19 with TPN use and substantial improvement in FGF19, bilirubin, and metabolic profiles with the FXR agonist chenodeoxycholic acid (CDCA). Additionally, CDCA caused gut growth and enhanced expression of glucagon like peptides (GLPs). GLPs regulate gut trophic effects, insulin, glucose homeostasis, and hepatic steatosis. GLP secretion is regulated by the CDCA activated receptor TGR5. This leads to an important conclusion that, in addition to a disrupted FXR-FGF19 axis, a disrupted TGR5-GLP axis may contribute to TPN related pathologies. Thus modulators of FXR-FGF19 and the TGR5-GLP axis could help bring forward novel treatment strategies. Ajay Kumar Jain and Jeffrey H. Teckman Copyright © 2014 Ajay Kumar Jain and Jeffrey H. Teckman. All rights reserved. Cholangiocarcinomas: New Insights from the Discovery of Stem Cell Niches in Peribiliary Glands of the Biliary Tree Thu, 24 Apr 2014 06:12:38 +0000 http://www.hindawi.com/journals/ahe/2014/794953/ Peribiliary glands (PBGs) are located in the large intrahepatic and extrahepatic bile ducts. Although they were described many years ago, their functions have been elucidated only in the last couple of years when our group demonstrated that PBGs are niches of multipotent stem/progenitor cells of endodermal origin. These cells express genes of multipotency and can be rapidly differentiated in vitro into hepatocytes, cholangiocytes, and endocrine pancreatic cells. PBGs share common features, in terms of stem/progenitor cell niches, with pancreatic duct glands and colon crypts, glandular structures representing in the adult life the endodermal remnants of fetal life. PBG stem/progenitor cells participate in the renewal of surface biliary epithelium and are active players in chronic pathologies of the biliary tree as well as in cholangiocarcinomas (CCA). Specifically, a large amount of recent evidence indicates that the pure mucin-CCA originates from PBGs; this could explain the similarities with pancreatic ductal adenocarcinoma and colorectal cancer, which also originate from transformed gland cells. In this paper, we summarized our recent findings concerning structure and functions of PBGs with the implications for liver pathophysiology and, specifically, for cancers of the biliary tree. Vincenzo Cardinale, Maria Consiglia Bragazzi, Guido Carpino, Alessia Torrice, Yunfang Wang, Lola McAdams Reid, Eugenio Gaudio, and Domenico Alvaro Copyright © 2014 Vincenzo Cardinale et al. All rights reserved. Noninvasive Biomarkers of Liver Fibrosis: An Overview Tue, 15 Apr 2014 09:03:10 +0000 http://www.hindawi.com/journals/ahe/2014/357287/ Chronic liver diseases of differing etiologies are among the leading causes of mortality and morbidity worldwide. Establishing accurate staging of liver disease is very important for enabling both therapeutic decisions and prognostic evaluations. A liver biopsy is considered the gold standard for assessing the stage of hepatic fibrosis, but it has many limitations. During the last decade, several noninvasive markers for assessing the stage of hepatic fibrosis have been developed. Some have been well validated and are comparable to liver biopsy. This paper will focus on the various noninvasive biochemical markers used to stage liver fibrosis. Hind I. Fallatah Copyright © 2014 Hind I. Fallatah. All rights reserved. Targeting Hepatic Glycerolipid Synthesis and Turnover to Treat Fatty Liver Disease Thu, 10 Apr 2014 11:07:01 +0000 http://www.hindawi.com/journals/ahe/2014/498369/ Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of metabolic abnormalities ranging from simple hepatic steatosis (accumulation of neutral lipid) to development of steatotic lesions, steatohepatitis, and cirrhosis. NAFLD is extremely prevalent in obese individuals and with the epidemic of obesity; nonalcoholic steatohepatitis (NASH) has become the most common cause of liver disease in the developed world. NASH is rapidly emerging as a prominent cause of liver failure and transplantation. Moreover, hepatic steatosis is tightly linked to risk of developing insulin resistance, diabetes, and cardiovascular disease. Abnormalities in hepatic lipid metabolism are part and parcel of the development of NAFLD and human genetic studies and work conducted in experimentally tractable systems have identified a number of enzymes involved in fat synthesis and degradation that are linked to NAFLD susceptibility as well as progression to NASH. The goal of this review is to summarize the current state of our knowledge on these pathways and focus on how they contribute to etiology of NAFLD and related metabolic diseases. George G. Schweitzer and Brian N. Finck Copyright © 2014 George G. Schweitzer and Brian N. Finck. All rights reserved.