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Hepatology Communications

Jesus M Banales, Ariel E Feldstein, Hanna Sänger, Veronika Lukacs-Kornek, Gyongyi Szabo, Miroslaw Kornek
Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by cells and found in all biological fluids. They are effective intercellular communicators, acting on a number of close and/or distant target cells. EV cargo may reflect the cell of origin as well as the specific stress that induces their formation and release. They transport a variety of bioactive molecules, including messenger RNA, noncoding RNAs, proteins, lipids, and metabolites, that can be transferred among cells, regulating various cell responses...
February 2019: Hepatology Communications
Yun Zhou, Vatsalya Vatsalya, Leila Gobejishvili, Richard J Lamont, Craig J McClain, Wenke Feng
Bacterial infection is frequently observed in patients with alcoholic liver disease (ALD). We examined a possible role of Porphyromonas gingivalis in the development/progression and severity of disease in patients with acute alcoholic hepatitis (AAH). Plasma specimens from 47 patients with AAH (16 moderate, Model for End-Stage Liver Disease [MELD] score <20]; 31 severe, MELD score >20) and 22 healthy controls (HCs) were collected. Clinical, drinking history (lifetime drinking history [LTDH]), and demographic data were collected...
February 2019: Hepatology communications
Nataliya Razumilava, Junya Shiota, Nureen H Mohamad Zaki, Ramon Ocadiz-Ruiz, Christine M Cieslak, Kais Zakharia, Benjamin L Allen, Gregory J Gores, Linda C Samuelson, Juanita L Merchant
Hedgehog (HH) signaling participates in hepatobiliary repair after injury and is activated in patients with cholangiopathies. Cholangiopathies are associated with bile duct (BD) hyperplasia, including expansion of peribiliary glands, the niche for biliary progenitor cells. The inflammation-associated cytokine interleukin (IL)-33 is also up-regulated in cholangiopathies, including cholangiocarcinoma. We hypothesized that HH signaling synergizes with IL-33 in acute inflammation-induced BD hyperplasia. We measured extrahepatic BD (EHBD) thickness and cell proliferation with and without an IL-33 challenge in wild-type mice, mice overexpressing Sonic HH ( pCMV-Shh ), and mice with loss of the HH pathway effector glioma-associated oncogene 1 ( Gli1lacZ/lacZ )...
February 2019: Hepatology Communications
Sereana Wan, Folkert Kuipers, Rick Havinga, Hiromi Ando, Dennis E Vance, René L Jacobs, Jelske N van der Veen
Phosphatidylethanolamine N -methyltransferase (PEMT) is a hepatic integral membrane protein localized to the endoplasmic reticulum (ER). PEMT catalyzes approximately 30% of hepatic phosphatidylcholine (PC) biosynthesis. Pemt-/- mice fed a high-fat diet (HFD) develop steatohepatitis. Interestingly, portions of the ER located close to the canaliculus are enriched in PEMT. Phospholipid balance and asymmetrical distribution by adenosine triphosphatase phospholipid transporting 8B1 (ATP8B1) on the canalicular membrane is required for membrane integrity and biliary processes...
February 2019: Hepatology Communications
Barbara Ulmasov, Hidenao Noritake, Peter Carmichael, Kiyoko Oshima, David W Griggs, Brent A Neuschwander-Tetri
The presence and stage of liver fibrosis in patients with nonalcoholic steatohepatitis (NASH) is strongly associated with mortality. Thus, both preventing and reversing fibrosis are critically important approaches to prevent death or the need for liver transplantation from NASH. Recently, fibrosis in several mouse models of organ injury was shown to be prevented and reversed with the potent small molecule, arginine-glycine-aspartic acid tripeptide (RGD)-binding, integrin antagonist (3S)-3-(3-bromo-5-(tert-butyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid (Center for World Health and Medicine [CWHM]-12)...
February 2019: Hepatology Communications
Lisa Katharina Maresch, Pia Benedikt, Ursula Feiler, Sandra Eder, Kathrin A Zierler, Ulrike Taschler, Stephanie Kolleritsch, Thomas O Eichmann, Gabriele Schoiswohl, Christina Leopold, Beatrix I Wieser, Caroline Lackner, Thomas Rülicke, Jan van Klinken, Dagmar Kratky, Tarek Moustafa, Gerald Hoefler, Guenter Haemmerle
Murine hepatic carboxylesterase 2c ( Ces2c ) and the presumed human ortholog carboxylesterase 2 ( CES2 ) have been implicated in the development of nonalcoholic fatty liver disease (NAFLD) in mice and obese humans. These studies demonstrated that Ces2c hydrolyzes triglycerides (TGs) in hepatocytes. Interestingly, Ces2c / CES2 is most abundantly expressed in the intestine, indicating a role of Ces2c / CES2 in intestinal TG metabolism. Here we show that Ces2c is an important enzyme in intestinal lipid metabolism in mice...
February 2019: Hepatology Communications
Gil Ben-Yakov, Hawwa Alao, John P Haydek, Nancy Fryzek, Min Ho Cho, Mehdi Hemmati, Vikram Samala, Margaret Shovlin, Kieron Dunleavy, Wyndham Wilson, Elizabeth C Jones, Yaron Rotman
Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non-Hodgkin lymphoma (NHL). In this retrospective case-control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R-CHOP) or R-CHOP + etoposide (EPOCH-R). Patients with liver disease or steatosis were excluded...
February 2019: Hepatology Communications
Julie Di Martino, Patrice Mascalchi, Philippe Legros, Sabrina Lacomme, Etienne Gontier, Paulette Bioulac-Sage, Charles Balabaud, Violaine Moreau, Frédéric Saltel
Liver sinusoidal endothelial cells (LSECs) possess fenestrae, which are key for the exchange between blood and hepatocytes. Alterations in their number or diameter have important implications for hepatic function in liver diseases. They are lost early in the development of hepatic fibrosis through a process called capillarization. In this study, we aimed to demonstrate whether in vitro dedifferentiated LSECs that have lost fenestrae are able to re-form these structures. Using stimulated emission depletion super-resolution microscopy in combination with transmission electron microscopy, we analyzed fenestrae formation in a model mimicking the capillarization process in vitro ...
February 2019: Hepatology Communications
Tawfik Khoury, Muhammad Massarwa, Saleh Daher, Ariel A Benson, Wadi Hazou, Eran Israeli, Harold Jacob, Julia Epstein, Rifaat Safadi
There are limited efficacious therapeutic options for management of gastric variceal bleeding. Treatment modalities include transjugular intrahepatic portosystemic shunt, surgical shunts, and endoscopic interventions, including the recent advancement of endoscopic ultrasound (EUS)-guided coiling. We present a case series of 10 patients with portal hypertension (7 with liver cirrhosis and 3 without cirrhosis), complicated by gastric varices (GV) with bleeding. All cases were treated successfully with EUS-guided coiling leading to variceal eradication...
February 2019: Hepatology Communications
Bruce Wang, Sean Rudnick, Brent Cengia, Herbert L Bonkovsky
The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Their diagnoses are often missed or delayed because the clinical symptoms mimic other more common disorders. Recent results indicate that acute intermittent porphyria, the most severe of the more common types of AHP, is more prevalent than previously thought, occurring in about 1 in 1600 Caucasians, but with low clinical penetrance (approximately 2%-3%)...
February 2019: Hepatology Communications
Li Chen, David A Brenner, Tatiana Kisseleva
Hepatic fibrosis results from chronic injury and inflammation in the liver and leads to cirrhosis, liver failure, and portal hypertension. Understanding the molecular mechanisms underlying hepatic fibrosis has advanced the prospect of developing therapies for regression of the disease. Resolution of fibrosis requires a reduction of proinflammatory and fibrogenic cytokines, a decrease in extracellular matrix (ECM) protein production, an increase in collagenase activity, and finally, a disappearance of activated myofibroblasts...
February 2019: Hepatology Communications
Michael Pimienta, Alexander Beletsky, Ekihiro Seki
The most important argument of this study is that modulation of intestinal lipid metabolism by enhancing intestinal Ces2c expression has the potential to affect hepatic and systemic lipid metabolism, regulating the development of NAFLD and systemic insulin resistance.
February 2019: Hepatology Communications
Tian-Cheng Li, Huimin Bai, Sayaka Yoshizaki, Yasushi Ami, Yuriko Suzaki, Yen Hai Doan, Kazuaki Takahashi, Shunji Mishiro, Naokazu Takeda, Takaji Wakita
Neither an animal model nor a cell culture system has been established for the genotype 5 hepatitis E virus (G5 HEV), and the pathogenicity, epidemiology, and replication mechanism of the virus remain unclear. In this study, we used a reverse genetics system to generate G5 HEV and examined the possibility of zoonotic infection. Capped and uncapped genomic G5 HEV RNAs generated by in vitro transcription were transfected into PLC/PRF/5 cells. Infectious G5 HEV was recovered from the capped G5 HEV RNA-transfected PLC/PRF/5 cells and the subsequently passaged cells...
January 2019: Hepatology Communications
Kang Ho Kim, Jong Min Choi, Feng Li, Bingning Dong, Clavia Ruth Wooton-Kee, Armando Arizpe, Sayeepriyadarshini Anakk, Sung Yun Jung, Sean M Hartig, David D Moore
Bile acid (BA) homeostasis is tightly regulated by multiple transcription factors, including farnesoid X receptor (FXR) and small heterodimer partner (SHP). We previously reported that loss of the FXR/SHP axis causes severe intrahepatic cholestasis, similar to human progressive familial intrahepatic cholestasis type 5 (PFIC5). In this study, we found that constitutive androstane receptor (CAR) is endogenously activated in Fxr:Shp double knockout (DKO) mice. To test the hypothesis that CAR activation protects DKO mice from further liver damage, we generated Fxr ; Shp ; Car triple knockout (TKO) mice...
January 2019: Hepatology Communications
Esther A Peterson, Zsuzsanna Polgar, Gnanapackiam S Devakanmalai, Yanfeng Li, Fadi L Jaber, Wei Zhang, Xia Wang, Niloy J Iqbal, John W Murray, Namita Roy-Chowdhury, Wilber Quispe-Tintaya, Alexander Y Maslov, Tatyana L Tchaikovskaya, Yogeshwar Sharma, Leslie E Rogler, Sanjeev Gupta, Liang Zhu, Jayanta Roy-Chowdhury, David A Shafritz
Hepatocyte transplantation is an attractive alternative to liver transplantation. Thus far, however, extensive liver repopulation by adult hepatocytes has required ongoing genetic, physical, or chemical injury to host liver. We hypothesized that providing a regulated proliferative and/or survival advantage to transplanted hepatocytes should enable repopulation in a normal liver microenvironment. Here, we repopulated livers of DPPIV- (dipeptidyl peptidase-4) rats and Ugt1a1 (uridinediphosphoglucuronate glucuronosyltransferase 1a1)-deficient Gunn rats (model of Crigler-Najjar syndrome type 1), both models without underlying liver injury, for up to 1 year by transplanting lenti-hYAP-ERT2 (mutated estrogen receptor ligand-binding domain 2)-transduced hepatocytes (YAP-Hc)...
January 2019: Hepatology Communications
Débora Raquel Benedita Terrabuio, Marcio Augusto Diniz, Lydia Teofilo de Moraes Falcão, Ana Luiza Vilar Guedes, Larissa Akeme Nakano, Andréia Silva Evangelista, Fabiana Roberto Lima, Clarice Pires Abrantes-Lemos, Flair José Carrilho, Eduardo Luiz Rachid Cancado
Between 50% and 86% of patients with autoimmune hepatitis (AIH) relapse after immunosuppression withdrawal; long-term immunosuppression is associated with increased risk of neoplasias and infections. Chloroquine diphosphate (CQ) is an immunomodulatory drug that reduces the risk of flares in rheumatologic diseases. Our aims were to investigate the efficacy and safety of CQ for maintenance of biochemical remission of AIH in a double-blind randomized trial and to define a subgroup that obtained a greater benefit from its use...
January 2019: Hepatology Communications
David Tornai, Istvan Furi, Zu T Shen, Alexander B Sigalov, Sahin Coban, Gyongyi Szabo
Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD...
January 2019: Hepatology communications
Kim Loh, Shanna Tam, Lisa Murray-Segal, Kevin Huynh, Peter J Meikle, John W Scott, Bryce van Denderen, Zhiping Chen, Rohan Steel, Nicholas D LeBlond, Leah A Burkovsky, Conor O'Dwyer, Julia R C Nunes, Gregory R Steinberg, Morgan D Fullerton, Sandra Galic, Bruce E Kemp
Adenosine monophosphate-activated protein kinase (AMPK) regulates multiple signaling pathways involved in glucose and lipid metabolism in response to changes in hormonal and nutrient status. Cell culture studies have shown that AMPK phosphorylation and inhibition of the rate-limiting enzyme in the mevalonate pathway 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase (HMGCR) at serine-871 (Ser871; human HMGCR Ser872) suppresses cholesterol synthesis. In order to evaluate the role of AMPK-HMGCR signaling in vivo, we generated mice with a Ser871-alanine (Ala) knock-in mutation (HMGCR KI)...
January 2019: Hepatology Communications
Tamoore Arshad, Pegah Golabi, James Paik, Alita Mishra, Zobair M Younossi
There is a paucity of recent data about the epidemiology and long-term outcomes of nonalcoholic fatty liver disease (NAFLD) in the female population. Our aim was to assess the prevalence, risk factors, and mortality of NAFLD in female adults of the United States. Data from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014 were used. NAFLD status was determined by the U.S. Fatty Liver Index (US-FLI) in the absence of other liver diseases and excessive alcohol consumption...
January 2019: Hepatology Communications
Runping Liu, Vishwadeep Ahluwalia, Jason D Kang, Siddhartha S Ghosh, Huiping Zhou, Yunzhou Li, Derrick Zhao, Emily Gurley, Xiaojiaoyang Li, Melanie B White, Andrew Fagan, H Robert Lippman, James B Wade, Phillip B Hylemon, Jasmohan S Bajaj
Patients with cirrhosis are growing older, which could have an impact on brain dysfunction beyond hepatic encephalopathy. Our aim was to study the effect of concomitant aging and cirrhosis on brain inflammation and degeneration using human and animal experiments. For the human study, age-matched patients with cirrhosis and controls between 65 and 85 years underwent cognitive testing, quality of life (QOL) assessment, and brain magnetic resonance (MR) spectroscopy and resting state functional MR imaging (rs-fMRI) analysis...
January 2019: Hepatology communications
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