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Alcoholic Steatohepatitis

Shinji Furuya, Joseph A Cichocki, Kranti Konganti, Kostiantyn Dreval, Takeki Uehara, Yuuki Katou, Hisataka Fukushima, Hiroshi Kono, Igor P Pogribny, Josepmaria Argemi, Ramon Bataller, Ivan Rusyn
Human alcoholic hepatitis (AH) carries a high mortality rate. AH is an acute-on-chronic form of liver injury characterized by hepatic steatosis, ballooned hepatocytes, neutrophil infiltration, and pericellular fibrosis. We aimed to study the pathogenesis of AH in an animal model which combines chronic hepatic fibrosis with intragastric alcohol administration. Adult male C57BL6/J mice were treated with CCl4 (0.2 ml/kg, 2×weekly by intraperitoneal injections for 6 weeks) to induce chronic liver fibrosis. Then, ethyl alcohol (up to 25 g/kg/day for 3 weeks) was administered continuously to mice via a gastric feeding tube, with or without one-half dose of CCl4...
December 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Brett McGettigan, Rachel McMahan, David Orlicky, Matthew Burchill, Thomas Danhorn, Prashanth Francis, Lin Ling Cheng, Lucy Golden-Mason, Claudia Jakubzick, Hugo Rosen
A crucial component of non-alcoholic fatty liver disease (NAFLD) pathogenesis is lipid stress, which may contribute to hepatic inflammation and activation of innate immunity in the liver. However, little is known regarding how dietary lipids, including fat and cholesterol, may facilitate innate immune activation in vivo. We hypothesized that dietary fat and cholesterol drive NAFLD progression to steatohepatitis and hepatic fibrosis by altering the transcription and phenotype of hepatic macrophages METHODS: This hypothesis was tested by using RNA-seq methods to characterize and analyze sort-purified hepatic macrophage populations that were isolated from mice fed diets with varying amounts of fat and cholesterol RESULTS: The addition of cholesterol to a high fat diet triggered hepatic pathology reminiscent of advanced non-alcoholic steatohepatitis (NASH) in humans characterized by signs of cholesterol dysregulation, generation of oxidized LDL, increased recruitment of hepatic macrophages, and significant fibrosis...
December 5, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
O Khukhlina, A Antoniv, L Kanovska, O Mandryk, V Smandych
The article presents a theoretical generalization of the research results the effectiveness of heparisin on the state of the carbohydrate-protein components of the extracellular matrix of connective tissue in liver in patients with non-alcoholic steatohepatitis with obesity I-II degree and chronic kidney disease І-ІІ stage. The purpose of the study is to find out the effectiveness of heparisin (glycyrizine 40 mg, glycine 400 mg, L-cysteine hydrochloride 20 mg) on the state of the carbohydrate-protein components of the extracellular matrix in connective tissue of the liver in patients with non-alcoholic steatohepatitis (NASH) with obesity I-II degree and chronic kidney disease (CKD) І-ІІ stage...
October 2018: Georgian Medical News
Hussam Alamri, Nathan Heath Patterson, Ethan Yang, Pablo Zoroquiain, Anthoula Lazaris, Pierre Chaurand, Peter Metrakos
Hepatic lipid accumulation, mainly in the form of triglycerides (TGs), is the hallmark of non-alcoholic fatty liver disease (NAFLD). To date, the spatial distribution of individual lipids in NAFLD-affected livers is not well characterized. This study aims to map the triglyceride distribution in normal human liver samples and livers with NAFLD and cirrhosis with imaging mass spectrometry (MALDI IMS). Specifically, whether individual triglyceride species differing by fatty acid chain length and degree of saturation correlate with the histopathological features of NAFLD as identified with classical H&E...
December 5, 2018: Analytical and Bioanalytical Chemistry
Yasir Al-Azzawi, Lidia Spaho, Mohammed Mahmoud, Joan Kheder, Anne Foley, David Cave
Background: The features of the portal hypertension enteropathy (PHE) vary from mild mucosal changes to varices with or without bleeding. The prevalence and the development are not fully understood. Aim: Our aim is to examine the prevalence and the different manifestations of PHE using video capsule endoscopy (VCE). Methods: It is a single center retrospective study of patients with cirrhosis, who had VCE. Based on the published literature, we divided the PHE lesions into vascular lesions and mucosal lesions...
2018: International Journal of Hepatology
Marica Meroni, Miriam Longo, Raffaela Rametta, Paola Dongiovanni
Alcoholic liver disease (ALD), a disorder caused by excessive alcohol consumption is a global health issue. More than two billion people consume alcohol in the world and about 75 million are classified as having alcohol disorders. ALD embraces a wide spectrum of hepatic lesions including steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). ALD is a complex disease where environmental, genetic, and epigenetic factors contribute to its pathogenesis and progression...
December 3, 2018: International Journal of Molecular Sciences
Da Zhou, Yuan-Wen Chen, Ze-Hua Zhao, Rui-Xu Yang, Feng-Zhi Xin, Xiao-Lin Liu, Qin Pan, Huiping Zhou, Jian-Gao Fan
Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients...
December 3, 2018: Experimental & Molecular Medicine
Saleh Daher, Namma Lev Cohen, Muhammad Massarwa, Mahmud Mahamid, Mira Nasser, Wadi Hazou, Rani Oren, Rifaat Safadi, Tawfik Khoury
BACKGROUND AND AIM: The progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is believed to be the driver for future development of fibrosis and cirrhosis. Nevertheless, there remains a clear deficit in non-invasive methods for the diagnosis of NASH. The aim of the present study was to evaluate the prevalence of portal lymphadenopathy (PL) in biopsy- proven NAFLD patients and to determine whether PL correlates with NAFLD stage and severity. METHODS: A retrospective study included biopsy-proven NAFLD patients with up to date (within one year) abdominal imaging by computed tomography (CT) and/or magnetic resonance imaging (MRI)...
2018: PloS One
Maria Isabel Alcoriza-Balaguer, Juan Carlos García-Cañaveras, Adrian Lopez, Isabel Conde, Oscar Juan, Julian Carretero, Agustín Lahoz
High resolution LC-MS-untargeted lipidomics using data-independent acquisition (DIA) has the potential to increase lipidome coverage as it enables the continuous and unbiased acquisition of all eluting ions. However, the loss of the link between the precursor and the product ions combined with the high dimensionality of DIA data sets hinder accurate feature annotation. Here, we present LipidMS, an R-package aimed to confidently identify lipid species in untargeted LC-DIA-MS. To this end, LipidMS combines a coelution score, which links precursor and fragment ions, with fragmentation and intensity rules...
November 30, 2018: Analytical Chemistry
Anne-Catherine Schwarz, Adrian T Billeter, Katharina M Scheurlen, Matthias Blüher, Beat P Müller-Stich
Metabolic diseases, comprising type 2 diabetes mellitus (T2DM), dyslipidemia, and non-alcoholic steatohepatitis (NASH), are rapidly increasing worldwide. Conservative medical therapy, including the newly available drugs, has only limited effects and does neither influence survival or the development of micro- or macrovascular complications, nor the progression of NASH to liver cirrhosis, nor the development of hepatocellular carcinomas in the NASH liver. In contrast, metabolic surgery is very effective independent of the preoperative body mass index (BMI) in reducing overall and cardiovascular mortality in patients with T2DM...
October 2018: Visceral Medicine
Xia Li, Quan Jin, Yu Zhang, Yan-Ling Wu, Cheng-Min Jin, Ben-Wen Cui, Ying Li, Ming-Ji Jin, Yue Shang, Min Jiang, Hong-Xu Yang, Mei Wu, Jian Liu, Li-Hua Lian, Ji-Xing Nan
Pleurotus citrinopileatus (golden oyster mushroom) is a widely used edible mushroom. We investigated the inhibitory effect of P. citrinopileatus aqueous extract against alcoholic steatohepatitis and its underlying mechanism. Acute and chronic ethanol feeding murine models were established by intragastrically administering ethanol or feeding ethanol-containing Lieber-DeCarli liquid diet to male C57BL/6 mice. In both models, P. citrinopileatus decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), triglyceride (TG) and hepatic TG levels...
November 29, 2018: Journal of Agricultural and Food Chemistry
Bruno Ramos-Molina, Daniel Castellano-Castillo, Oscar Pastor, Luis Ocaña-Wilhelmi, Diego Fernández-García, Manuel Romero-Gómez, Fernando Cardona, Francisco J Tinahones
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is present in a high percentage of obese patients undergoing bariatric surgery. A significant proportion of patients still present NASH even after considerable weight loss and metabolic improvements after surgery. OBJECTIVE: To determine whether the changes in the serum lipidome after sleeve gastrectomy could be used to discriminate obese patients with NASH patients to those with non-alcoholic fatty liver (NAFL). METHODS: This study involved 24 patients with grade 3 obesity diagnosed with either NAFL (n = 8) or NASH (n = 16) using the non-invasive OWLiver assay...
November 28, 2018: Obesity Surgery
Umberto Vespasiani-Gentilucci, Paolo Gallo, Chiara Dell'Unto, Mara Volpentesta, Raffaele Antonelli-Incalzi, Antonio Picardi
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma (HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis...
November 21, 2018: World Journal of Gastroenterology: WJG
Susumu Shiomi
Because of improved treatment of cirrhosis, patients are living longer and bone disesae such as osteoporosis is found in an increasing proportion of patients with cirrhosis. As the causes for bone diseases in cirrhosis, inhibition of vitamin D hydration and inhibition of vitamin D absorption due to decreased secretion of cholic acid have been reported, and various other causes are concerned. These bone diseases have been treated with bisphosphonates, but no definite opinion has been obtained in relation to therapeutic effects...
2018: Clinical Calcium
Abdul Malik Thalha, Sanjiv Mahadeva, Alexander Tong Boon Tan, Kein Seong Mun
A 33-year-old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non-compliant, complaining of "heaviness of head" after consuming oral diabetic agents, without symptoms of hypoglycemia...
October 2018: JGH open: an open access journal of gastroenterology and hepatology
Sui-Weng Wong, Yi-Wen Ting, Wah-Kheong Chan
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver pathology that is characterized by the excessive accumulation of fat in the liver attributable to overnutrition and is strongly associated with the metabolic syndrome. Non-alcoholic steatohepatitis is the more severe form of NAFLD that is defined histologically by the presence of lobular inflammation and hepatocyte ballooning...
October 2018: JGH open: an open access journal of gastroenterology and hepatology
Cheng Guo, Yinhu Li, Peipei Wang, Yingchao Li, Chuangzhao Qiu, Muxia Li, Daxi Wang, Ruiqin Zhao, Dongfang Li, Ye Wang, Shuaicheng Li, Wenkui Dai, Lin Zhang
Cholestasis is a major hepatic disease in infants, with increasing morbidity in recent years. Accumulating evidence has revealed that the gut microbiota (GM) is associated with liver diseases, such as non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, GM alterations in cholestatic infants and the correlation between the GM and hepatic functions remain uninvestigated. In this study, 43 cholestatic infants (IC group) and 37 healthy infants (H group) were enrolled to detect GM discrepancies using 16S rDNA analysis...
2018: Frontiers in Microbiology
Ya-Jie Pan, Xing Ren, Ying-Ying Zhang, Jun Lv, Qing-Lei Zeng, Hong-Yu Zhang, Zu-Jiang Yu
Interleukin (IL)-17A is pro-inflammatory cytokine which has been identified as a noninvasive marker of the pathogenesis of non-alcoholic steatohepatitis (NASH). However, the underlying role of IL-17A in NASH progression remains unclear. This study was designed to investigate the biological function and molecular mechanism of IL-17A in the induction of NASH. The results showed that IL-17A was highly expressed in high-fat diet (HFD)-induced NASH mouse model. Intravenous injection of IL-17A exacerbated steatohepatitis process via promoting hepatocyte apoptosis...
November 27, 2018: IUBMB Life
Zhibin Yan, Xiaokang Miao, Bangzhi Zhang, Junqiu Xie
Non-alcoholic fatty liver disease (NAFLD) derives from the accumulation of hepatic lipids, which leads to liver steatosis and then triggers non-alcoholic steatohepatitis, sometimes worsening to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Although the molecular mechanisms of NAFLD have been intensively investigated, its pathogenesis remains poorly understood and needs to be clarified. Tumor-suppressor factor p53 has a crucial role in many signaling pathways that induce apoptosis and has become an emerging focus for liver disease research...
December 15, 2018: Life Sciences
Ranjeet Prasad Dash, R Jayachandra Babu, Nuggehally R Srinivas
Number of drugs with different mechanisms of actions is undergoing clinical trials for non-alcoholic steatohepatitis (NASH). Given the complexity of the disease with respect to pathophysiology in the liver and associated changes in the renal function, it becomes apparent that a clear ADME (absorption, distribution, metabolism and excretion) strategy needs to be put in place for a successful nomination of a drug candidate for NASH. This review discusses using in vitro and in vivo ADME screens to understand the properties of drugs and to establish whether or not the chosen drug(s) can overcome the challenges related hepatic and renal transporters covering both uptake and efflux mechanisms imposed by NASH...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
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