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Alcoholic Hepatitis

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181. Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease. Full Text available with Trip Pro

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease. This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD).In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle (...) arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion

2017 PLoS ONE

182. Dysregulation of serum bile acids and FGF19 in alcoholic hepatitis. Full Text available with Trip Pro

Dysregulation of serum bile acids and FGF19 in alcoholic hepatitis. The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis.Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum (...) bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis.We found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased

2018 Journal of Hepatology

183. Non‐alcoholic fatty liver disease in patients with autoimmune hepatitis Full Text available with Trip Pro

Non‐alcoholic fatty liver disease in patients with autoimmune hepatitis The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing all over the world. NAFLD develops in patients with liver disease, including patients with autoimmune hepatitis (AIH). NAFLD and AIH have some similar laboratory and histological findings. The aim of this study was to elucidate the characteristics of AIH patients with NAFLD.We re-evaluated the nationwide survey performed in Japan in 2015 of AIH (...) patients diagnosed between 2009 and 2013.A total of 1151 subjects (144 men and 1007 women) were enrolled in the present study. The overall prevalence of NAFLD was 17.0%. Compared to AIH without NAFLD, AIH patients with NAFLD had the following characteristics: (i) low female-to-male ratio, (ii) older age, (iii) mild elevation in hepatobiliary enzymes, (iv) histologically progressive fibrosis and mild plasma cell infiltration or mild lobular hepatitis, (v) lower prevalence of prednisolone administration

2018 JGH Open: An Open Access Journal of Gastroenterology and Hepatology

184. Early liver transplant for severe alcoholic hepatitis: establishing a new frontier by ignoring the rule? Full Text available with Trip Pro

Early liver transplant for severe alcoholic hepatitis: establishing a new frontier by ignoring the rule? 30498738 2018 12 07 2305-5839 6 20 2018 Oct Annals of translational medicine Ann Transl Med Early liver transplant for severe alcoholic hepatitis: establishing a new frontier by ignoring the rule? 411 10.21037/atm.2018.09.57 Zhu Julie J Division of Gastroenterology, University of British Columbia, Vancouver General Hospital, Vancouver, BC, Canada. Hussaini Trana T The Faculty

2018 Annals of Translational Medicine

185. Role of liver transplantation in severe alcoholic hepatitis Full Text available with Trip Pro

Role of liver transplantation in severe alcoholic hepatitis Severe alcoholic hepatitis has very high short term mortality and corticosteroids have been the mainstay of treatment for decades. Patients with Lille score >0.45 are considered non-responders to steroids and have poor outcome. Recently Orthotopic Liver Transplantation (OLT) is being increasingly used as rescue treatment for these patients, without waiting for 6 months of abstinence. Liver transplant is the only rescue treatment which (...) can potentially provide long term benefit for patients who are steroid non-responders. However, with scarcity of organs being a concern, all patients of severe alcoholic hepatitis cannot be chosen for transplantation in an arbitrary way. There is a need for development of predictive tools and objective protocols to select patients who can justify the use of precious liver grafts. With a stringent criteria for selection of patients receiving the graft, liver transplantation in severe alcoholic

2018 Clinical and molecular hepatology

186. SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease Full Text available with Trip Pro

SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severity is largely unknown in NAFLD. We assessed the hypothesis that SPARC (...) expression. High expression of SPARC paralleled hepatocellular damage and increased mRNA expression of pro-fibrogenic factors in the liver. In line with these findings, in the NASH animal model SPARC knockout mice were protected from inflammatory injury, and showed less inflammation and fibrosis. Hepatic SPARC expression is associated with liver injury and fibrogenic processes in NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.

2018 Scientific reports

187. Collagen proportionate area correlates to hepatic venous pressure gradient in non-abstinent cirrhotic patients with alcoholic liver disease Full Text available with Trip Pro

Collagen proportionate area correlates to hepatic venous pressure gradient in non-abstinent cirrhotic patients with alcoholic liver disease To explore the relationship between collagen proportionate area (CPA) and portal hypertension-related clinical manifestations in alcoholic liver disease (ALD).Retrospective study with chart review of patients with ALD adressed to our center between January 2012 and December 2013 for a transjugular liver biopsy (TJLB) and hepatic hemodynamic study. Patients (...) , subdivided in 41 active alcohol drinkers and 20 durably abstinent patients. Nine healthy liver donors served as controls. Mean CPA in patients with ALD was 7.1%, with no difference between active drinkers and abstinent patients (P = 0.17). Using a fibrosis density cutoff of 5%, we observed a positive correlation between high fibrosis density and the hepatic venous pressure gradient (HVPG) only in active drinkers (P = 0.02). At 12-mo of follow-up, in the group of active alcohol drinkers, patients reaching

2018 World journal of hepatology

188. Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease Full Text available with Trip Pro

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls.We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal (...) with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

2018 World journal of hepatology

189. Arid1a loss drives non-alcoholic steatohepatitis in mice via epigenetic dysregulation of hepatic lipogenesis and fatty acid oxidation. Full Text available with Trip Pro

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

190. Transplantation for Alcoholic Hepatitis: Are We Achieving Justice and Utility? (Abstract)

Transplantation for Alcoholic Hepatitis: Are We Achieving Justice and Utility? Early liver transplantation for alcoholic hepatitis is a potentially life-saving treatment. As this practice becomes increasingly common, however, the liver transplant community is taking a fresh look at a familiar challenge: best stewardship of donor organs. Herein, we examine a few basic, necessary ethical and practical concerns relevant to this indication.© 2018 by the American Association for the Study of Liver

2018 Hepatology

191. 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

192. 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

193. 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

194. Complements are involved in alcoholic fatty liver disease, hepatitis and fibrosis Full Text available with Trip Pro

Complements are involved in alcoholic fatty liver disease, hepatitis and fibrosis The complement system is a key component of the body's immune system. When abnormally activated, this system can induce inflammation and damage to normal tissues and participate in the development and progression of a variety of diseases. In the past, many scholars believed that alcoholic liver disease (ALD) is induced by the stress of ethanol on liver cells, including oxidative stress and dysfunction

2018 World journal of hepatology

195. Comprehensive Laboratory Analysis of Korean Acute Alcoholic Intoxication Patients Reveals the Need for a National Hepatitis B Virus Vaccination Program in Korea Full Text available with Trip Pro

Comprehensive Laboratory Analysis of Korean Acute Alcoholic Intoxication Patients Reveals the Need for a National Hepatitis B Virus Vaccination Program in Korea Acute alcoholic intoxication patients (AAIP) are a common public health problem. The aim of this study was to perform a comprehensive laboratory analysis for these patients to investigate the co-morbid medical problem.We retrospectively reviewed laboratory findings of AAIP who were transferred to the emergency department (ED) from (...) hemoglobin A1c (HbA1c) level (>7.0%). Positive rates of hepatitis B surface antigen and antiHBs antibody (anti-HBs Ab) were 3.5% (5/141) and 49.0% (68/141), respectively.Patients with AAIP who were transferred to ED had various laboratory abnormalities (anemia, thrombocytopenia, high HbA1c). They had low positive rate of anti-HBs Ab. This might be a public health problem, suggesting the need of hepatitis B virus vaccination program for AAIP. Our data suggest the need of further nationwide studies.

2018 Korean journal of family medicine

196. The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. Full Text available with Trip Pro

The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non-alcoholic fatty liver disease (NAFLD (...) % ± 6.8%; P = 0.635; n = 9). The predominant SCFA from colonic fermentation of inulin is acetate, which, in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate-mediated increase in IHCL.© 2018 John Wiley & Sons Ltd.

2018 obesity & metabolism Controlled trial quality: uncertain

197. Grand Rounds: Alcoholic Hepatitis. Full Text available with Trip Pro

Grand Rounds: Alcoholic Hepatitis. A 33-year-old Caucasian male was admitted to hospital with recent onset of jaundice of 2-3 weeks duration. He reported heavy use of alcohol for the last 10 years with the last drink a day prior to the onset of symptoms. At admission, he was alert and oriented to time, place, and person, and was deeply jaundiced. His laboratory profile can be summarised as follows: haemoglobin 12.1 g/dl, white blood cell count 18,700 with 81% neutrophils, serum bilirubin 33 (...) (direct 22) mg/dl, aspartate aminotransferase 147 IU/L, alanine aminotransferase 62 IU/L, alkaline phosphatase 117 IU/L, serum albumin 2.8 gm/dl, serum creatinine 0.6 mg/dl, prothrombin time 18.3 (control 14.5) seconds, and international normalized ratio 1.48. He was diagnosed with severe alcoholic hepatitis (Maddrey discriminant function score of 50) and treated with prednisolone for 28 days with symptomatic and biochemical improvement. His Lille score at seven days was 0.4, and his serum bilirubin

2018 Journal of Hepatology

198. Evaluation of hepatic integrin αvβ3 expression in non-alcoholic steatohepatitis (NASH) model mouse by 18F-FPP-RGD2 PET Full Text available with Trip Pro

Evaluation of hepatic integrin αvβ3 expression in non-alcoholic steatohepatitis (NASH) model mouse by 18F-FPP-RGD2 PET Activated hepatic stellate cells (HSCs), which express integrin αvβ3, are a major fibrogenic factor in NASH pathophysiology. 18F-labeled cyclic arginine-glycine-aspartic acid penta-peptide (18F-FPP-RGD2) has been used as a PET probe for tumors expressing integrin αvβ3. The aim of this study was to assess the potential of PET with 18F-FPP-RGD2 to detect hepatic integrin αvβ3 (...) expression in non-alcoholic steatohepatitis (NASH) model mice.Thirty-two male C57BL/6 mice aged 6 weeks were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 3 and 8 weeks. 18F-FPP-RGD2 PET imaging of the liver was performed at 3 and 8 weeks after CDAHFD feeding. After PET scanning, levels of hepatic integrin αvβ, 3α-smooth muscle actin (α-SMA), and collagen type 1 alpha 1(col1a1) were measured. Histopathological analysis of hepatic steatosis, inflammation, and fibrosis, as well

2018 EJNMMI research

199. 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

200. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease Full Text available with Trip Pro

Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD) is currently the world's most common liver disease, estimated to affect up to one-fourth of the population. Hallmarked by hepatic steatosis, NAFLD is associated with a multitude of detrimental effects and increased mortality. This narrative review investigates the molecular mechanisms of hepatic steatosis in NAFLD, focusing on the four major pathways contributing (...) to lipid homeostasis in the liver. Hepatic steatosis is a consequence of lipid acquisition exceeding lipid disposal, i.e., the uptake of fatty acids and de novo lipogenesis surpassing fatty acid oxidation and export. In NAFLD, hepatic uptake and de novo lipogenesis are increased, while a compensatory enhancement of fatty acid oxidation is insufficient in normalizing lipid levels and may even promote cellular damage and disease progression by inducing oxidative stress, especially with compromised

2018 Cellular and Molecular Life Sciences

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