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Alcoholic Hepatitis

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161. Proteomics and metabolomics analysis of hepatic mitochondrial metabolism in alcohol-preferring and non-preferring rats (Full text)

Proteomics and metabolomics analysis of hepatic mitochondrial metabolism in alcohol-preferring and non-preferring rats Alcohol preference induced tolerance in humans and animals when their bodily functions adapt to compensate for the disruption caused by alcohol consumption. This was thought to be an important component of the genetic predisposition to alcoholism. To investigate the underlying mechanisms of hepatic metabolic tolerance during alcohol preference, the alcohol preferring (...) and alcohol non-preferring rats were used in this study. The liver mitochondria were purified for comparative quantitative proteomics analysis, and the liver metabolite extracts were collected for metabolomics analysis. Our study identified 96 differentially expressed hepatic mitochondrial proteins that associated with alcohol preference, the further gene ontology and protein interaction network analysis suggest a down-regulation of amino acid metabolism and up-regulation of lipid metabolism. We found

2017 Oncotarget PubMed abstract

162. Clinical features of alcoholic hepatitis in latinos and caucasians: A single center experience (Full text)

Clinical features of alcoholic hepatitis in latinos and caucasians: A single center experience To study differences of presentation, management, and prognosis of alcoholic hepatitis in Latinos compared to Caucasians.We retrospectively screened 876 charts of Caucasian and Latino patients who were evaluated at University of California Davis Medical Center between 1/1/2002-12/31/2014 with the diagnosis of alcoholic liver disease. We identified and collected data on 137 Caucasians and 64 Latinos (...) who met criteria for alcoholic hepatitis, including chronic history of heavy alcohol use, at least one episode of jaundice with bilirubin ≥ 3.0 or coagulopathy, new onset of liver decompensation or acute liver decompensation in known cirrhosis within 12 wk of last drink.The mean age at presentation of alcoholic hepatitis was not significantly different between Latinos and Caucasians. There was significant lower rate of overall substance abuse in Caucasians compared to Latinos and Latinos had

2017 World Journal of Gastroenterology PubMed abstract

163. RNA-sequencing-based comparative analysis of human hepatic progenitor cells and their niche from alcoholic steatohepatitis livers (Full text)

RNA-sequencing-based comparative analysis of human hepatic progenitor cells and their niche from alcoholic steatohepatitis livers Hepatic progenitor cells (HPCs) are small cells with a relative large oval nucleus and a scanty cytoplasm situated in the canals of Hering that express markers of (immature) hepatocytes and cholangiocytes. HPCs are present in large numbers in alcoholic steatohepatitis (ASH), one of the leading causes of chronic liver disease. To date, the mechanisms responsible

2017 Cell death & disease PubMed abstract

164. Serum ferritin as a non‐invasive marker in the prediction of hepatic fibrosis among Egyptian patients with non‐alcoholic fatty liver disease (Full text)

Serum ferritin as a non‐invasive marker in the prediction of hepatic fibrosis among Egyptian patients with non‐alcoholic fatty liver disease Many studies have found a relationship between hepatic iron, serum ferritin, and non-alcoholic fatty liver disease (NAFLD) or its progress. The aim of this study is to assess the value of serum ferritin as a non-invasive marker in the prediction of hepatic fibrosis in NAFLD.This study included 113 subjects who were classified into three groups. Group I (...) included 30 healthy subjects as control with no clinical, radiological, and histological features of NAFLD. Group II included 31 NAFLD patients without hepatic fibrosis. Group III included 52 patients with hepatic fibrosis on top of NAFLD.Serum ferritin was determined using ferritin ELISA kit. Fibrosis 4 score was calculated. Liver biopsy was conducted for included patients. Significantly higher levels of serum ferritin were found in patients with hepatic fibrosis on top of NAFLD than controls

2017 JGH Open: An Open Access Journal of Gastroenterology and Hepatology PubMed abstract

165. Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease (Full text)

Hepatic regulation of VLDL receptor by PPARβ/δ and FGF21 modulates non-alcoholic fatty liver disease The very low-density lipoprotein receptor (VLDLR) plays an important role in the development of hepatic steatosis. In this study, we investigated the role of Peroxisome Proliferator-Activated Receptor (PPAR)β/δ and fibroblast growth factor 21 (FGF21) in hepatic VLDLR regulation.Studies were conducted in wild-type and Pparβ/δ-null mice, primary mouse hepatocytes, human Huh-7 hepatocytes (...) , and liver biopsies from control subjects and patients with moderate and severe hepatic steatosis.Increased VLDLR levels were observed in liver of Pparβ/δ-null mice and in Pparβ/δ-knocked down mouse primary hepatocytes through mechanisms involving the heme-regulated eukaryotic translation initiation factor 2α (eIF2α) kinase (HRI), activating transcription factor (ATF) 4 and the oxidative stress-induced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways. Moreover, by using a neutralizing antibody

2017 Molecular metabolism PubMed abstract

166. A Prospective study of the utility of plasma biomarkers to diagnose alcoholic hepatitis. (Full text)

A Prospective study of the utility of plasma biomarkers to diagnose alcoholic hepatitis. The diagnosis of alcoholic hepatitis (AH) often requires a transjugular liver biopsy (TJLB), a procedure that is not always readily accessible. We analyzed plasma biomarkers to estimate the presence of histological features of AH among patients with clinical suspicion of AH. Using enzyme-linked immunosorbent assay, we tested M65 and M30 (circulating fragments of cytokeratin-18) and their respective fraction

2017 Hepatology PubMed abstract

167. Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis. (Full text)

Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis. Carriage of rs738409:G in PNPLA3 is associated with an increased risk of developing alcohol-related cirrhosis and has a significant negative effect on survival. Short-term mortality in patients with severe alcoholic hepatitis is high; drinking behaviour is a major determinant of outcome in survivors. The aim of this study was to determine whether carriage of rs738409 (...) :G has an additional detrimental effect on survival in this patient group.Genotyping was undertaken in 898 cases with severe alcoholic hepatitis, recruited through the UK Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial, and 1188 White British/Irish alcohol dependent controls with no liver injury, recruited via University College London. Subsequent drinking behaviour was classified, in cases surviving ≥90days, as abstinent or drinking. The relationship between rs738409 genotype

2017 Journal of Hepatology PubMed abstract

168. Betaine attenuates chronic alcohol-induced fatty liver by broadly regulating hepatic lipid metabolism (Full text)

Betaine attenuates chronic alcohol-induced fatty liver by broadly regulating hepatic lipid metabolism Betaine has previously been demonstrated to protect the liver against alcohol‑induced fat accumulation. However, the mechanism through which betaine affects alcohol‑induced hepatic lipid metabolic disorders has not been extensively studied. The present study aimed to investigate the effect of betaine on alcoholic simple fatty liver and hepatic lipid metabolism disorders. A total of 36 rats were (...) and AdipoR2 were quantified. Serum and adipose tissue adiponectin levels were assessed using an enzyme‑linked immunoassay. The results demonstrated that alcohol‑induced ultramicrostructural alterations in hepatocytes, including the presence of lipid droplets and swollen mitochondria, were attenuated by betaine. Hepatic triglyceride, free fatty acid, total cholesterol and cholesterol ester contents and the expression of DGAT1, DGAT2, SREBP‑1c, SREBP‑2, FAS and HMG‑CoA reductase were increased following

2017 Molecular medicine reports PubMed abstract

169. An Exploratory Genome-Wide Analysis of Genetic Risk for Alcoholic Hepatitis (Full text)

An Exploratory Genome-Wide Analysis of Genetic Risk for Alcoholic Hepatitis To elucidate the genetic variability between heavy drinkers with and without alcoholic hepatitis (AH).An exploratory genome-wide association study (GWAS; NCT02172898) was conducted comparing 90 AH cases with 93 heavy drinking matched controls without liver disease in order to identify variants or genes associated with risk for AH. Individuals were genotyped using the multi-ethnic genotyping array, after which the data (...) underwent conventional quality control. Using bioinformatics tools, pathways associated with AH were explored on the basis of individual variants, and based on genes with a higher 'burden' of functional variation.Although no single variant reached genome-wide significance, an association signal was observed for PNPLA3 rs738409 (p = .01, OR 1.9, 95% CI 1.1-3.1), a common single nucleotide polymorphism that has been associated with a variety of liver-related pathologies including alcoholic cirrhosis

2017 Scandinavian journal of gastroenterology PubMed abstract

170. The Efficacy of Corticosteroid Therapy in a Patient with Non-alcoholic Steatohepatitis Overlapping Autoimmune Hepatitis (Full text)

The Efficacy of Corticosteroid Therapy in a Patient with Non-alcoholic Steatohepatitis Overlapping Autoimmune Hepatitis The overlap of multiple liver diseases can cause the disease activity and severity to worsen rapidly in some cases. We rarely see patients with non-alcoholic steatohepatitis (NASH) with overlapping autoimmune hepatitis (AIH). A 64-year-old woman who had been prescribed oral drugs to treat diabetes and hypertension (metformin 500 mg/day and voglibose 0.9 mg/day, and termisartan (...) 40 mg/day and amlodipine 5 mg/day, respectively) was diagnosed with NASH with histological confirmation. At 68 years of age, her liver injury worsened with an IgG of 2,871 mg/dL and a high serum anti-nuclear antibody (ANA) level of 2,560. We repeated the liver biopsy, which revealed NASH and mild interface hepatitis with some lobular focal necrosis consisting of overlapping AIH. Therefore, she was treated with 30 mg of prednisolone daily. The treatment led to an improvement in her IgG levels

2017 Internal Medicine PubMed abstract

171. Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice (Full text)

Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice The utilisation of nanoparticles as the means of targeted delivery of therapeutics and/or imaging agents could greatly enhance the specific transport of biologically active payloads to target tissues while avoiding or reducing undesired side-effects. To allow for this to become a reality, the question of potential toxicological effects needs to be addressed. In the present investigation, a cationic (...) liposome with prospective for medical applications was constructed and thoroughly assessed for any material-induced hepatic adverse effects in vivo - in healthy and alcoholic hepatic disease models and in vitro - (HepG2 cells). The data demonstrated that intravenous injection of liposomes did not cause any significant in vivo hepatic toxicity (inflammation, alterations in blood parameters, anti-oxidant depletion, acute phase response and histopathology) at doses of 200 μg per mouse in either healthy

2017 Heliyon PubMed abstract

172. Ginsenoside Rg1 inhibits inflammatory responses via modulation of the nuclear factor-κB pathway and inhibition of inflammasome activation in alcoholic hepatitis (Full text)

Ginsenoside Rg1 inhibits inflammatory responses via modulation of the nuclear factor-κB pathway and inhibition of inflammasome activation in alcoholic hepatitis Ginsenoside Rg1 (G‑Rg1) is an active ingredient of Panax ginseng, which has previously been reported to attenuate alcohol‑induced hepatic damage; however, the underlying mechanisms remain largely unknown. The present study aimed to investigate the protective effects of G‑Rg1 on alcohol‑induced cell injury in vitro and on a rat model (...) of alcoholic hepatitis in vivo. For the in vitro model, L‑O2 cells were incubated with ethanol in the presence or absence of G‑Rg1. For the in vivo model, rats were administered ethanol by intragastric injection and were treated with G‑Rg1, or dexamethasone as a control. The results indicated that serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase and total bilirubin, as well as the expression of nuclear factor (NF)‑κB pathway‑associated inflammatory cytokines

2017 International journal of molecular medicine PubMed abstract

173. Alcohol and hepatitis virus-dysregulated lncRNAs as potential biomarkers for hepatocellular carcinoma (Full text)

Alcohol and hepatitis virus-dysregulated lncRNAs as potential biomarkers for hepatocellular carcinoma Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths because of frequent late detection and poor therapeutic outcomes, necessitating the need to identify effective biomarkers for early diagnosis and new therapeutic targets for effective treatment. Long noncoding RNAs (lncRNAs) have emerged as promising molecular markers for diagnosis and treatment. Through (...) analysis of patient samples from The Cancer Genome Atlas database, we identified putative lncRNAs dysregulated in HCC and by its risk factors, hepatitis infection and alcohol consumption. We identified 184 lncRNAs dysregulated in HCC tumors versus paired normal samples, 53 lncRNAs dysregulated in alcohol-drinking patients with hepatitis B, and 5, 456 lncRNAs dysregulated in patients with hepatitis infection. A panel of these candidate lncRNAs' expressions correlated significantly with patient survival

2017 Oncotarget PubMed abstract

174. [18F]-BMS-747158-02PET imaging for evaluating hepatic mitochondrial complex 1dysfunction in a mouse model of non-alcoholic fatty liver disease (Full text)

[18F]-BMS-747158-02PET imaging for evaluating hepatic mitochondrial complex 1dysfunction in a mouse model of non-alcoholic fatty liver disease Mitochondrial dysfunction is one of the main causes of non-alcohol fatty liver disease (NAFLD). [18F]-BMS-747158-02 (18F-BMS) which was originally developed as a myocardial perfusion imaging agent was reported to bind mitochondrial complex-1 (MC-1). The aim of this study was to investigate the potential use of 18F-BMS for evaluating hepatic MC-1 activity (...) in mice fed a methionine- and choline-deficient (MCD) diet. Male C57BL/6J mice were fed a MCD diet for up to 2 weeks. PET scans with 18F-BMS were performed after 1 and 2 weeks of the MCD diet. 18F-BMS was intravenously injected into mice, and the uptake (standardized uptake value (SUV)) in the liver was determined. The binding specificity for MC-1 was assessed by pre-administration of rotenone, a specific MC-1 inhibitor. Hepatic MC-1 activity was measured using liver homogenates generated after each

2017 EJNMMI research PubMed abstract

175. Human hepatic gene expression signature of non-alcoholic fatty liver disease progression, a meta-analysis. (Full text)

Human hepatic gene expression signature of non-alcoholic fatty liver disease progression, a meta-analysis. Non-alcoholic fatty liver disease (NAFLD) is a wide-spread chronic liver condition that places patients at risk of developing cardiovascular diseases and may progress to cirrhosis or hepatocellular carcinoma if untreated. Challenges in clinical and basic research are caused by poor understanding of NAFLD mechanisms. The purpose of current study is to describe molecular changes occurring

2017 Scientific reports PubMed abstract

176. Liver transplantation for severe alcoholic hepatitis-The CON view. (Abstract)

Liver transplantation for severe alcoholic hepatitis-The CON view. In patients with severe alcoholic hepatitis (AH) who have failed medical therapy, liver transplantation (LT) remains a controversial therapeutic option. This is exemplified by the fact that most of these patients will not have had a period of abstinence prior to consideration for transplantation. Both abstinence before transplantation and the duration of abstinence are important predictors of post-transplant relapse. Furthermore

2017 Liver International

177. Liver transplantation for severe alcoholic hepatitis- The PRO view. (Abstract)

Liver transplantation for severe alcoholic hepatitis- The PRO view. Although liver transplantation has become accepted as a life-saving treatment of last resort for most life-threatening liver disorders, the use of liver transplantation to rescue patients with severe alcoholic hepatitis unresponsive to medical therapy remains controversial. I propose the concepts that alcohol use disorder is an illness, that on occasion results in alcoholic liver disease and that treatment of alcoholic liver (...) disease, including treatment of patients with severe alcoholic hepatitis, combines treatment of the alcohol use disorder and of alcoholic liver disease. From this I derive the following principal to govern selection of patients for liver transplantation of patients with alcohol use disorder: that alcohol use disorder should impact suitability for liver transplantation as a co-morbid disorder, in the same way as other common co-morbid disorders such as diabetes mellitus or systemic hypertension

2017 Liver International

178. Liver transplantation for patients with alcoholic hepatitis. (Abstract)

Liver transplantation for patients with alcoholic hepatitis. Alcoholic liver disease, considered as a self-inflected disease, is an example of how moral judgment may affect ethical exercise of medicine which requires equity and fair utilization of a scarce resource in a context of organ shortage. Some consider that selection process should prioritize access to liver transplantation (LT) for patients who develop liver failure "through no fault of their own" even if limiting care because (...) of a patient's perceived responsibility has been considered unethical. The absence of improvement after alcohol withdrawal, the high short-term mortality risk and the poor predictability of the 6-month rule in post-LT relapse in alcohol consumption in AH patients not responding to medical therapy led to recommend an evaluation of LT. In the French-Belgian pilot study, 26 patients with severe AH not responding to medical therapy underwent early LT (eLT). Stringent selection criteria were applied. Six-month

2017 Liver International

179. Corticosteroids Versus Pentoxifylline for Severe Alcoholic Hepatitis: A Sequential Analysis of Randomized Controlled Trials. (Full text)

Corticosteroids Versus Pentoxifylline for Severe Alcoholic Hepatitis: A Sequential Analysis of Randomized Controlled Trials. Despite the significant morbidity and mortality associated with alcoholic hepatitis, a consensus or generally accepted therapeutic strategy has not yet been reached. The purpose of this analysis was to evaluate the effects of corticosteroids and pentoxifylline on short-term mortality, incidence of hepatorenal syndrome, and sepsis in patients with severe alcoholic (...) ). There was no statistically significant difference in short-term mortality between pentoxifylline and placebo (RR=0.74; 95% CI, 0.46-1.18; P=0.21). Neither corticosteroids nor pentoxifylline impacted the incidence of hepatorenal syndrome or sepsis. Trial sequential analysis confirmed the results of our conventional meta-analysis.Corticosteroids demonstrated a decrease in 28-day mortality in patients with severe alcoholic hepatitis. The evidence from this study is insufficient to support any recommendations regarding

2017 Journal of clinical gastroenterology PubMed abstract

180. The Safety and Efficacy of Baclofen to Reduce Alcohol Use in Veterans with Chronic Hepatitis C: A Randomized Clinical Trial. (Abstract)

The Safety and Efficacy of Baclofen to Reduce Alcohol Use in Veterans with Chronic Hepatitis C: A Randomized Clinical Trial. Alcohol use disorders (AUDs) are common among people with chronic hepatitis C (HCV) and accelerate the development of fibrosis and cirrhosis caused by HCV. Baclofen, a gamma-aminobutyric acid (GABA) beta-receptor agonist, differs from medications for AUDs currently approved by the United States Food and Drug Administration (FDA), as it is metabolized primarily through (...) the kidneys. The primary outcome of this study was to compare baclofen with a placebo in the percentage of days abstinent from alcohol.A double-blind, placebo-controlled randomized trial.Hepatology clinics in four separate US Veteran Affairs Medical Centers in the United States.One hundred and eighty Veteran men and women older than 18 years with chronic HCV, a comorbid AUD and current alcohol use.Oral baclofen was given at dosages of 0 (placebo) or 30 mg/day over 12 weeks with concomitant manual-guided

2017 Addiction (Abingdon, England) Controlled trial quality: predicted high

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