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Alcoholic Hepatitis

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141. Arid1a loss drives non-alcoholic steatohepatitis in mice via epigenetic dysregulation of hepatic lipogenesis and fatty acid oxidation. (Abstract)

Arid1a loss drives non-alcoholic steatohepatitis in mice via epigenetic dysregulation of hepatic lipogenesis and fatty acid oxidation. Nonalcoholic steatohepatitis (NASH) is a rapidly growing cause of chronic liver damage, cirrhosis, and hepatocellular carcinoma (HCC). How fatty liver pathogenesis is subject to epigenetic regulation is unknown. We hypothesized that chromatin remodeling is important for the pathogenesis of fatty liver disease. ARID1A, a DNA-binding component of the SWI/SNF ATP (...) -dependent chromatin-remodeling complex, contributes to nucleosome repositioning and access by transcriptional regulators. Liver-specific deletion of Arid1a (Arid1a LKO) caused the development of age-dependent fatty liver disease in mice. Transcriptome analysis revealed upregulation of lipogenesis and down-regulation of fatty acid oxidation genes. As evidence of direct regulation, ARID1A demonstrated direct binding to the promoters of many of these differentially regulated genes. Additionally, Arid1a LKO

2018 Hepatology

142. IL-1 Signal Inhibition in Alcoholic Hepatitis (ISAIAH)

mDF* ≥ 32 and MELD ≤ 25 at baseline visit Informed consent Women of child-bearing potential have to use an effective contraception method (as specified in section 9.6). Exclusion Criteria: Alcohol abstinence of >6 weeks prior to randomization/baseline visit Duration of clinically apparent jaundice > 3 months before baseline visit Other causes of liver disease including: Evidence of chronic viral hepatitis (Hepatitis B or C) Biliary obstruction Hepatocellular carcinoma Evidence of current (...) malignancy (except non-melanotic skin cancer) Previous entry into the study, or use of either prednisolone or PTX within 6 weeks of hospital admission AST >500 U/L or ALT >300 U/L (not compatible with alcoholic hepatitis) Patients with a serum creatinine >220 μmol/L (2.5 mg / dL) or requiring renal support (see below) Patients dependent upon inotropic support (adrenaline or noradrenaline). Terlipressin is allowed Variceal haemorrhage on this admission Untreated sepsis (see below) Patients with known

2018 Clinical Trials

143. Evaluation of the effects of dapagliflozin, an SGLT2 inhibitor, on hepatic steatosis and fibrosis by transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. (Abstract)

Evaluation of the effects of dapagliflozin, an SGLT2 inhibitor, on hepatic steatosis and fibrosis by transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. To investigate the effects of dapagliflozin on liver steatosis and fibrosis evaluated in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).In a randomized, active-controlled, open-label trial, 57 patients with type 2 diabetes and NAFLD were randomized to a dapagliflozin group (...) (5 mg/d; n = 33) or a control group (n = 24) and were treated for 24 weeks. Hepatic steatosis and fibrosis were assessed using transient elastography to measure controlled attenuation parameter (CAP) and liver stiffness, respectively.Baseline liver stiffness measurement (LSM) was positively correlated with several markers and scoring systems for liver fibrosis. In week 24, there was a significant decrease in CAP from 314 ± 61 to 290 ± 73 dB/m (P = 0.0424) in the dapagliflozin group, while

2018 obesity & metabolism Controlled trial quality: uncertain

144. A Validated Score Predicts Acute Kidney Injury and Survival in Patients with Alcoholic Hepatitis: A Multicentric International Prospective Cohort Study. Full Text available with Trip Pro

A Validated Score Predicts Acute Kidney Injury and Survival in Patients with Alcoholic Hepatitis: A Multicentric International Prospective Cohort Study. Identifying patients at high risk for acute kidney injury (AKI) during hospitalization among patients admitted with severe alcoholic hepatitis (AH) is an unmet clinical need. We performed a multicentric prospective cohort study using data from 4 different cohorts on well-characterized patients hospitalized with severe AH. Data collected on 773 (...) AH patients from 4 cohorts across the globe were randomly split into test (n = 390) and validation (n = 383) cohorts. We found that 32% of the patients developed inpatient AKI in the test cohort. Approximately 60% of patients met criteria for systemic inflammatory response syndrome (SIRS) at admission. Hepatic encephalopathy, SIRS, and Model for End-Stage Liver Disease score at admission predicted inpatient AKI with odds ratios of 3.86, 2.24, and 1.14, respectively. The AKI risk score developed

2018 Liver Transplantation

145. Efficacy and Safety of Orally Administered DS102 in Patients With Acute Alcoholic Hepatitis

in DS102 capsules or placebo capsules. Duration of clinically apparent jaundice >3 months prior to baseline Other causes of liver disease including: Evidence of chronic viral hepatitis (Hepatitis B DNA positive or Hepatitis C (HCV) RNA positive) Biliary obstruction Hepatocellular carcinoma Wilsons disease Budd Chiari Syndrome Non-alcoholic fatty liver disease History of or active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas). Treatment (...) Efficacy and Safety of Orally Administered DS102 in Patients With Acute Alcoholic Hepatitis Efficacy and Safety of Orally Administered DS102 in Patients With Acute Alcoholic Hepatitis - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more

2018 Clinical Trials

146. Effect of Omega 5 Fatty Acid as an Adyuvant Treatment to Prednisone in Patients With Severe Alcoholic Hepatitis

(Total bilirubin greater than 5 mg/dl in absence of biliary tract obstruction evidenced by ultrasound, history of chronic alcohol intake (greater than 50 g / day for at least 3 months), leukocytosis, neutrophilia, elevation of transaminases with an aspartate aminotransferase / alanine aminotransferase ratio equal or greater than 2), discriminant function greater than 32. Exclusion Criteria: Hepatorenal syndrome, Hepatocellular carcinoma. Hepatitis C virus, hepatitis B virus or human immunodeficiency (...) of 3 blood tubes (2 purple and 1 yellow) for the measurement of cytokines, markers of oxidative stress, lipid peroxidation and protein carbonyls. The initial evaluation will include liver ultrasound, heart rate, blood pressure, temperature, anthropometric evaluation (weight, height, BMI), evaluation of ascites (abdominal circumference), hepatic encephalopathy (West Haven Scale). Alcohol abuse will be assessed using the AUDIT and CAGE score. Start-up laboratories will be carried out: TP, INR

2018 Clinical Trials

147. Hepatic expression of Yin Yang 1 (YY1) is associated with the non-alcoholic fatty liver disease (NAFLD) progression in patients undergoing bariatric surgery. Full Text available with Trip Pro

Hepatic expression of Yin Yang 1 (YY1) is associated with the non-alcoholic fatty liver disease (NAFLD) progression in patients undergoing bariatric surgery. This study is to investigate the association between the hepatic expression of Yin Yang 1 (YY1) and the progression of non-alcoholic fatty liver disease (NAFLD) in patients undergoing bariatric surgery.Obese patients undergoing bariatric surgery were included. Liver tissues were subjected to the quantitative real-time PCR, Western blot (...) analysis, and immunohistochemical assay, to determine the expression levels of YY1.Totally 88 patients were included. According to the NAFLD activity score (NAS), these patients were divided into the control (n = 12), steatosis (n = 20), non-defining NASH (n = 38), and NASH (n = 18) groups. Significant differences in the serum glucose, insulin, ALT, AST, and HOMA-IR levels were observed among these different NAFLD groups. Hepatic YY1 expression had correlation with serum glucose, insulin, HOMA-IR, ALT

2018 BMC Gastroenterology

148. Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis. Full Text available with Trip Pro

Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis. Liver transplantation (LT) has a demonstrated survival benefit in select patients with severe acute alcoholic hepatitis (SAH) who do not respond to steroids, but prior studies suggest low adoption among US LT centers. Our study explored current perceptions and practice patterns of LT for SAH in the United States. We administered a Web-based survey to medical directors of US LT centers between May and October of 2017 (...) psychiatric disorder (91.3%), and official psychosocial evaluation (87.0%). Reported posttransplant survival of SAH patients was excellent, with 17 (73.9%) centers reporting 1-year posttransplant survival exceeding 90%. Among centers that had not performed LT for SAH, the most commonly cited reason was perceived high risk of alcohol relapse. In conclusion, our data demonstrate that LT is increasingly adopted as a therapeutic intervention for patients with SAH and that careful selection allows

2018 Liver Transplantation

149. Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2-deficient mice and humans: roles of acetaldehyde and glucocorticoids. Full Text available with Trip Pro

Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2-deficient mice and humans: roles of acetaldehyde and glucocorticoids. Aldehyde dehydrogenase 2 (ALDH2), a key enzyme to detoxify acetaldehyde in the liver, exists in both active and inactive forms in humans. Individuals with inactive ALDH2 accumulate acetaldehyde after alcohol consumption. However, how acetaldehyde affects T-cell hepatitis remains unknown.Wild-type (WT) and Aldh2 knockout (Aldh2-/-) mice were subjected to chronic (...) had higher levels of serum corticosterone, a well-known factor that inhibits aerobic glycolysis. Blockade of corticosterone partially restored ConA-mediated hepatitis in ethanol-fed Aldh2-/- mice. Acute alcohol drinking elevated plasma cortisol and corticosterone levels in human subjects with higher levels in those with inactive ALDH2 than those with active ALDH2.ALDH2 deficiency is associated with elevated acetaldehyde and glucocorticoids post-alcohol consumption, thereby inhibiting T-cell

2018 Gut

150. Liver transplantation for severe alcoholic hepatitis: where are we now? Full Text available with Trip Pro

Liver transplantation for severe alcoholic hepatitis: where are we now? 30218596 2019 03 12 2019 03 12 1527-6473 24 10 2018 10 Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Liver Transpl. Liver Transplantation for Severe Alcoholic Hepatitis: Where Are We Now? 1327-1328 10.1002/lt.25337 Gelu-Simeon Moana M Centre Hospitalier Universitaire Guadeloupe, Université des Antilles, Service (...) d'Hépato-Gastroentérologie, Pointe-à-Pitre, Guadeloupe. INSERM, Unités Mixtes de Recherche en Santé1085/IRSET, Rennes, France. Mathurin Philippe P Service des Maladies de l'Appareil Digestif, Hôpital Huriez, CHRU Lille, Université Lille 2, INSERM U795, Lille, France. eng Editorial Comment United States Liver Transpl 100909185 1527-6465 IM Liver Transpl. 2018 Oct;24(10):1357-1362 30141270 Hepatitis, Alcoholic Humans Liver Transplantation Patient Selection Recurrence Surveys and Questionnaires 2018 09 10

2018 Liver Transplantation

151. Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis. Full Text available with Trip Pro

Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis. Intestinal microbiota plays an important role in bile acid homeostasis.To study the structure of the intestinal microbiota and its function in bile acid homeostasis in alcoholic patients based on the severity of alcoholic liver disease.In this prospective study, we included four groups of active alcoholic patients (N = 108): two noncirrhotic, with (noCir_AH, n = 13) or without alcoholic hepatitis (noCir_noAH, n = 61 (...) ), and two cirrhotic, with (Cir_sAH, n = 17) or without severe alcoholic hepatitis (Cir_noAH, n = 17). Plasma and faecal bile acid profiles and intestinal microbiota composition were assessed.Plasma levels of total bile acids (84.6 vs 6.8 μmol/L, P < 0.001) and total ursodeoxycholic acid (1.3 vs 0.3 μmol/L, P = 0.03) were higher in cirrhosis with severe alcoholic hepatitis (Cir_sAH) than Cir_noAH, whereas total faecal (2.4 vs 11.3, P = 0.01) and secondary bile acids (0.7 vs 10.7, P < 0.01) levels were

2018 Alimentary Pharmacology & Therapeutics

152. Influence of Chronic Alcohol Use on Osteoblastic Differentiation of Bone Marrow Cells, Bone Properties, and Hepatic and Renal Morphology of Rats Full Text available with Trip Pro

Influence of Chronic Alcohol Use on Osteoblastic Differentiation of Bone Marrow Cells, Bone Properties, and Hepatic and Renal Morphology of Rats Chronic alcohol exposure can affect the osteoblastic activity and the proliferation and differentiation of cells due to its toxic effect, which can affect negatively bone repair and bone microarchitecture. The aim of this study was to evaluate the effects of chronic use of 20% alcohol on rats regarding osteoblastic differentiation, extrinsic (...) and intrinsic properties of the tibia, and hepatic and renal morphology. Wistar rats were divided into three groups (n = 9) in accordance with a 24-week diet. After euthanasia, kidneys, liver, and tibias were removed for analysis and femurs mesenchymal cells were collected. The results showed that chronic use of 20% alcohol influenced neither the alkaline phosphatase production nor total protein (p > 0.05) in rats, with similar formation of nodules in all groups (p > 0.05). However, significant changes

2018 The Scientific World Journal

153. Iron-Overload triggers ADAM-17 mediated inflammation in Severe Alcoholic Hepatitis Full Text available with Trip Pro

Iron-Overload triggers ADAM-17 mediated inflammation in Severe Alcoholic Hepatitis Severe alcoholic hepatitis (SAH) is associated with iron accumulation in hepatocytes/macrophages. This possibly correlates with inflammation and stress but the exact mechanism still remains obscure. To understand the role of iron and the mechanisms of systemic iron-overload, a transcriptomic study of liver and Peripheral Blood -Mononuclear-Cells (PBMCs) was undertaken in SAH patients, with and without hepatic

2018 Scientific reports

154. CCL20 is up-regulated in non-alcoholic fatty liver disease fibrosis and is produced by hepatic stellate cells in response to fatty acid loading Full Text available with Trip Pro

CCL20 is up-regulated in non-alcoholic fatty liver disease fibrosis and is produced by hepatic stellate cells in response to fatty acid loading Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood.Gene expression profiling using microarray, PCR array, and RNA (...) sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity. Patients were grouped based on histological findings including normal liver histology with no steatosis, lobular inflammation, or fibrosis, and grades 1, 2, 3, and 4 fibrosis with coexistent steatosis and lobular inflammation. Validation of expression was conducted using quantitative PCR. Serum analysis was performed using ELISA. Expression analysis of hepatocytes and hepatic stellate cells in response to lipid

2018 Journal of translational medicine

155. A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study Full Text available with Trip Pro

A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade free-curcuminoids delivery system (curcumin-galactomannoside complex; CGM) in improving the hepatic function markers (inflammation and oxidative stress) in chronic alcoholics (...) from the significant increase (p <0.001) in endogenous antioxidants (GSH, SOD, and GPx) and decrease in inflammatory markers (IL-6 and CRP) levels (p <0.001) as compared to both the baseline and placebo group. To summarize, the nutritional intervention of CGM-curcumin was found to offer a significant hepatoprotective effect to attenuate the alcohol induced alterations to hepatic function markers. The Indian Medical Council and Drug Controller General of India approved Clinical Trial Registry

2018 BioMed research international Controlled trial quality: uncertain

156. A case of non‐alcoholic steatohepatitis complicated with severe acute pancreatitis induced by decreased lipoprotein lipase and hepatic triglyceride lipase activity levels in a young Japanese woman Full Text available with Trip Pro

A case of non‐alcoholic steatohepatitis complicated with severe acute pancreatitis induced by decreased lipoprotein lipase and hepatic triglyceride lipase activity levels in a young Japanese woman We report a case of non-alcoholic steatohepatitis complicated with acute pancreatitis induced by hypertriglyceridemia in a young Japanese woman. A precise examination of the lipid profile showed decreased lipoprotein lipase (LPL) and hepatic triglyceride lipase activity levels, while the LPL mass

2018 Clinical Case Reports

157. Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress Full Text available with Trip Pro

Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress Alcoholic liver disease (ALD) is a major chronic liver disease worldwide and can range from simple steatosis, inflammation to fibrosis/cirrhosis possibly through leaky gut and systemic endotoxemia. We investigated whether pomegranate (POM) protects against binge alcohol-induced gut leakiness, endotoxemia, and inflammatory liver damage. After POM pretreatment for 10 (...) days, rats were exposed to 3 oral doses of binge alcohol (5 g/kg/dose) or dextrose (as control) at 12-h intervals. Binge alcohol exposure induced leaky gut with significantly elevated plasma endotoxin and inflammatory fatty liver by increasing the levels of oxidative and nitrative stress marker proteins such as ethanol-inducible CYP2E1, inducible nitric oxide synthase, and nitrated proteins in the small intestine and liver. POM pretreatment significantly reduced the alcohol-induced gut barrier

2018 Redox biology

158. Male-specific association between subclinical hypothyroidism and the risk of non-alcoholic fatty liver disease estimated by hepatic steatosis index: Korea National Health and Nutrition Examination Survey 2013 to 2015 Full Text available with Trip Pro

Male-specific association between subclinical hypothyroidism and the risk of non-alcoholic fatty liver disease estimated by hepatic steatosis index: Korea National Health and Nutrition Examination Survey 2013 to 2015 Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease encompassing a broad spectrum of pathologic changes in the liver. Metabolic derangements are suggested to be main causes of NAFLD. As thyroid hormone is a main regulator of energy metabolism, there may be a link (...) between NAFLD and thyroid function. In previous studies, the association between NAFLD and thyroid function was not conclusive. The aim of this study was to clarify the relationship between NAFLD and thyroid function, focusing on subclinical hypothyroidism, using nationwide survey data representing the Korean population. NAFLD was defined as a hepatic steatosis index of 36 or higher. Based on the analysis of nationwide representative data, subclinical hypothyroidism was related to a high risk of NAFLD

2018 Scientific reports

159. Decreased monocyte shedding of the migration inhibitor soluble CD18 in alcoholic hepatitis Full Text available with Trip Pro

Decreased monocyte shedding of the migration inhibitor soluble CD18 in alcoholic hepatitis During alcoholic hepatitis (AH) monocytes traverse the vascular boundaries and massively invade the liver. In principle, tissue extravasation can be limited through shedding of CD18 integrins from leukocytes, including monocytes. The soluble (s) product sCD18 conceals adhesion receptors on the endothelium, which reduces monocyte extravasation. In AH, monocytes are dysfunctional, but whether this involves (...) their self-generated anti-migration is unknown. Our aim was, therefore, to investigate monocyte CD18 dynamics in AH.We studied 50 AH patients and 20 healthy controls. We measured monocyte expression and conformational activation of CD18, plasma (P)-sCD18, stimulated in vitro CD18 shedding and P-sCD18 in a short-term chronic-binge mouse model.AH-derived monocytes had a 30-60% higher expression of active CD18 receptors (p < 0.01), but the sCD18 concentration per monocyte was reduced in vivo by 30

2018 Clinical and translational gastroenterology

160. Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation Full Text available with Trip Pro

Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model.C57BL/6 mice were fed with a high fat

2018 International journal of molecular sciences

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