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Alcoholic Hepatitis

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21. Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data From Controlled Trials

Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo-a Meta-analysis of Individual Data From Controlled Trials We performed a meta-analysis of individual patient data from 11 randomized controlled trials comparing corticosteroids, pentoxifylline, or their combination in patients with severe alcoholic hepatitis. We compared the effects of the treatments on survival for 28 days or 6 months, and response (...) to treatment based on the Lille model.We searched PubMed for randomized controlled trials of pharmacologic therapy for severe alcoholic hepatitis. Our final analysis comprised 11 studies, of 2111 patients. We performed 4 meta-analyses of the effects of corticosteroids vs placebo or control, corticosteroids vs pentoxifylline, corticosteroids and pentoxifylline vs corticosteroids and placebo or control, and pentoxifylline vs placebo. In each meta-analysis, the effect of treatment on the primary outcome

2018 EvidenceUpdates

22. In vivo imaging of hepatic neutrophil migration in severe alcoholic hepatitis with 111In-radiolabelled leucocytes (PubMed)

In vivo imaging of hepatic neutrophil migration in severe alcoholic hepatitis with 111In-radiolabelled leucocytes The study's aim was to image severe alcoholic hepatitis (SAH) using 111In-labelled leucocytes with two objectives in mind: firstly for non-invasive diagnosis and secondly to provide a platform for experimental therapies aiming to inhibit intrahepatic neutrophil migration. 111In-leucocyte scintigraphy was performed 30 min and 24 h post-injection in 19 patients with SAH, 14 abstinent (...) patients with alcohol-related cirrhosis and 11 normal controls. Eleven with SAH and seven with cirrhosis also had 99mTc-nanocolloid scintigraphy. Change in hepatic 111In radioactivity was expressed as decay-corrected 24 h:30 min count ratio and, in SAH, compared with histological grading of steatohepatitis and expression of granulocyte marker, CD15. Hepatic microautoradiography on biopsy specimens obtained 24 h post-injection of 111In-leucocytes was performed in one patient. Median 24 h:30 min hepatic

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2018 Bioscience reports

23. Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis. (PubMed)

Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis. Severe alcoholic hepatitis patients have high mortality and limited response to corticosteroids. Microvesicles reflect cellular stress and disease conditions.To investigate whether microvesicles are associated with severity, response to steroid therapy and inflammation in severe alcoholic hepatitis.Microvesicles originating from different cells were studied pre-therapy (...) regeneration. Also, microvesicles of 0.2-0.4 μm size were higher in nonresponders (P < 0.03) at baseline. Microvesicles from patients trigger more (P = 0.04) ROS generation, TNF-α production (P = 0.04) and up-regulate pro-inflammatory cytokine related genes in neutrophils in vitro.Pre-therapy peripheral plasma levels of CD34+ and ASGPR+ microvesicles are reliable non-invasive markers of steroid nonresponse and mortality in patients with severe alcoholic hepatitis.© 2018 John Wiley & Sons Ltd.

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2018 Alimentary Pharmacology & Therapeutics

24. Pentoxifylline vs. Prednisolone: A Comparison of Efficacy in the Treatment of Severe Alcoholic Hepatitis in Adult Patients

Pentoxifylline vs. Prednisolone: A Comparison of Efficacy in the Treatment of Severe Alcoholic Hepatitis in Adult Patients "Pentoxifylline vs. Prednisolone: A Comparison of Efficacy in the Treat" by Ashley A. Hilliker < > > > > > Title Author Date of Graduation Summer 8-13-2016 Degree Type Capstone Project Degree Name Master of Science in Physician Assistant Studies First Advisor Professor Sommers Rights . Abstract Background: Alcoholic hepatitis is a chronic, inflammatory liver disease (...) that is on the rise in the United States. Traditionally, the progression of severe alcoholic hepatitis has been slowed with a 28-day course of prednisolone. However, since corticosteroids such as prednisolone have been associated with increased risk of infection and multiple unpleasant side effects, newer research is aimed at using pentoxifylline (PTX) as an alternative treatment. PTX has been shown to have a better safety profile than prednisolone, but its effectiveness in the treatment of severe alcoholic

2016 Pacific University EBM Capstone Project

25. Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy (PubMed)

Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy The clinical presentation of alcoholic hepatitis (AH) can be mimicked by other alcoholic liver diseases. The aim of this study was to identify clinical features that predict AH on liver biopsy. Biopsies from patients hospitalized for presumed severe AH were used to identify a derivation cohort (101 patients) and validation cohort (71 patients). Using histologic scores for hepatocyte (...) characteristic curve of 0.72. Conclusion: The combination of an elevated leukocyte count and a nodular liver surface in the absence of active infection retrospectively identified patients with a high likelihood of histologic AH for whom liver biopsy may not be necessary. For patients with suspected severe AH who do not fulfill these criteria, liver biopsy is important to exclude other variants of alcoholic liver disease. (Hepatology Communications 2017;1:1070-1084).

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2017 Hepatology communications

26. Alcoholic Hepatitis: Lost in Translation (PubMed)

Alcoholic Hepatitis: Lost in Translation Alcoholic hepatitis is the most severe and acute form of alcoholic liver disease. The mortality rate associated with alcoholic hepatitis is high, largely due to the lack of suitable pharmacological interventions. While there has been substantial research in the area, generating pharmacological interventions has been plagued by the lack of a robust mouse model both for testing and for understanding the underlying pathology. A number of major notable (...) advances have been made in this area recently, with the goal of generating a mouse model of alcoholic hepatitis. The purpose of this article is to review recent advances in modeling alcoholic liver disease both in vitro and in vivo in the mouse, and place them in the context of the greater spectrum of alcoholic liver disease, with a focus on how we can translate current advances into a high-fidelity model of alcoholic hepatitis. In addition, we will review the basic mechanisms of alcoholic hepatitis

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2017 Journal of clinical and translational hepatology

27. Role of gp91phox in hepatic macrophage programming and alcoholic liver disease (PubMed)

Role of gp91phox in hepatic macrophage programming and alcoholic liver disease Hepatic macrophages (MΦs) are important in the development and progression of alcoholic liver disease (ALD). This study investigates the role of gp91phox (nicotinamide adenine dinucleotide phosphate oxidase 2) in the severity of ALD and specifically in regulating hepatic MΦ efferocytic capability and the subsequent reprogramming associated with resolution of inflammation. After 4 weeks of ethanol feeding, more severe (...) ALD developed in gp91phox-/- mice than in wild-type (WT) C57Bl/6J mice, evidenced by increased liver injury and inflammation. This phenomenon was not sex dependent, and thus the majority of experiments were performed with female mice. While total hepatic MΦ numbers did not differ between genotypes, hepatic infiltrating MΦs (IMs) were slightly more numerous in gp91phox-/- mice, and both IMs and resident Kupffer cells displayed enhanced proinflammatory and reduced tissue-restorative programming

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2017 Hepatology communications

28. Severe Alcoholic Hepatitis: Atypical Presentation with Markedly Elevated Alkaline Phosphatase (PubMed)

Severe Alcoholic Hepatitis: Atypical Presentation with Markedly Elevated Alkaline Phosphatase Alcoholic hepatitis (AH) is an acute inflammatory liver disease with poor prognosis. Infections in AH are difficult to detect and contribute to short-term mortality. Intrahepatic cholestasis and elevated alkaline phosphatase levels are also associated with worse outcomes. This report describes an uncommon presentation of severe AH.

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2017 Journal of clinical and translational hepatology

29. Osteopontin deletion drives hematopoietic stem cell mobilization to the liver and increases hepatic iron contributing to alcoholic liver disease (PubMed)

Osteopontin deletion drives hematopoietic stem cell mobilization to the liver and increases hepatic iron contributing to alcoholic liver disease The aim of this study was to investigate the role of osteopontin (OPN) in hematopoietic stem cell (HPSC) mobilization to the liver and its contribution to alcoholic liver disease (ALD). We analyzed young (14-16 weeks) and old (>1.5 years) wild-type (WT) littermates and global Opn knockout (Opn-/- ) mice for HPSC mobilization to the liver. In addition (...) to old Opn-/- mice. Granulocyte colony-stimulating factor and macrophage colony-stimulating factor were increased in Opn-/- mice, suggesting potential migration of HPSCs from the BM to the liver. Furthermore, ethanol-fed Opn-/- mice showed significant hepatic PMN infiltration and hemosiderin compared to WT mice. As a result, ethanol feeding caused greater liver injury in Opn-/- compared to WT mice. Conclusion: Opn deletion promotes HPSC mobilization, PMN infiltration, and iron deposits in the liver

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2017 Hepatology communications

30. Interaction between the patatin‐like phospholipase domain‐containing protein 3 genotype and coffee drinking and the risk for acute alcoholic hepatitis (PubMed)

Interaction between the patatin‐like phospholipase domain‐containing protein 3 genotype and coffee drinking and the risk for acute alcoholic hepatitis Only a subset of subjects with excessive alcohol consumption develops alcoholic liver disease (ALD). One of the major risk factors for ALD is the genetic variant of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene. Coffee is one of the most commonly consumed beverages, and coffee consumption has been associated (...) with lower levels of serum alanine aminotransferase. The aim of this study was to investigate the role of coffee drinking and PNPLA3 rs738409 and their association with alcoholic hepatitis (AH) in a well-characterized cohort of subjects from the Translational Research and Evolving Alcoholic Hepatitis Treatment consortium. AH subjects and heavy drinking controls without a history of liver disease who were enrolled between May 2013 and May 2016 were included (n = 339), and the details of alcohol and coffee

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2017 Hepatology communications

31. The effect of low glycemic index and glycemic load diets on hepatic fat mass, insulin resistance, and blood lipid panels in individuals with non-alcoholic fatty liver disease: a systematic review

The effect of low glycemic index and glycemic load diets on hepatic fat mass, insulin resistance, and blood lipid panels in individuals with non-alcoholic fatty liver disease: a systematic review Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears

2019 PROSPERO

32. Dipeptidyl peptidase IV inhibitors for the treatment of non-alcoholic hepatic steatohepatitis

Dipeptidyl peptidase IV inhibitors for the treatment of non-alcoholic hepatic steatohepatitis Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content of this registration record, any associated files or external

2019 PROSPERO

33. Extra-hepatic mortality and morbidity in alcohol related liver disease

Extra-hepatic mortality and morbidity in alcohol related liver disease Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. The registrant confirms that the information supplied for this submission is accurate and complete. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation

2019 PROSPERO

34. Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia (PubMed)

Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia 26921783 2016 08 08 2019 01 18 1528-0012 150 4 2016 Apr Gastroenterology Gastroenterology Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia. 785-90 10.1053/j.gastro.2016.02.042 S0016-5085(16)00233-X Crabb David W DW (...) Medical School, Worcester, Massachusetts. NIAAA Alcoholic Hepatitis Consortia eng U01 AA021883 AA NIAAA NIH HHS United States U01 AA021893 AA NIAAA NIH HHS United States U01 AA021901 AA NIAAA NIH HHS United States U01 AA021840 AA NIAAA NIH HHS United States P20 GM113226 GM NIGMS NIH HHS United States U01 AA021886 AA NIAAA NIH HHS United States P50 AA024337 AA NIAAA NIH HHS United States U01 AA 021840 AA NIAAA NIH HHS United States U01 AA021908 AA NIAAA NIH HHS United States U01 AA021890 AA NIAAA NIH

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2016 Gastroenterology

35. Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long-term survival. (PubMed)

Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long-term survival. Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease. Most studies have focused on short-term prognosis, whereas factors associated with long-term survival are largely unknown. The aims of our study were to (1) determine the impact of complete abstinence from alcohol on long-term survival and (2) identify prognostic factors at admission capable (...) abstinence was reported in 39% and was associated with better long-term survival (hazard ratio, 0.53; P = 0.03). After adjustment for baseline prognostic scoring systems (Model for End-Stage Liver Disease and age, bilirubin, international normalized ratio, creatinine scores), complete abstinence was independently associated with survival (P < 0.05). Age and lack of past alcoholism treatments were independently associated with complete abstinence (P < 0.001 and P = 0.02, respectively) during follow-up

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2017 Hepatology

36. Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study. (PubMed)

Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study. Alcoholic hepatitis (AH) develops in only a small proportion of heavy drinkers. To better understand the mechanisms underlying this disparity, we conducted a study to define the relationship between AH development and dysregulated immune responses that might be ameliorated by alcohol abstinence. Sixty-eight AH patients, 65 heavy drinking controls without liver (...) alpha, IL-8, IL-10, fibroblast growth factor 2, and IL-7 remained higher.AH patients were in a highly immune-dysregulated state, whereas HDC showed little evidence of immune activation; alcohol abstinence reversed most, but not all, of the immunological abnormalities. (Hepatology 2017;66:575-590).© 2017 by the American Association for the Study of Liver Diseases.

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2017 Hepatology

37. Role of CYP2E1 in mitochondrial dysfunction and hepatic tissue injury in alcoholic and non-alcoholic diseases (PubMed)

Role of CYP2E1 in mitochondrial dysfunction and hepatic tissue injury in alcoholic and non-alcoholic diseases Alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) are two pathological conditions that are spreading worldwide. Both conditions are remarkably similar with regard to the pathophysiological mechanism and progression despite different causes. Oxidative stressinduced mitochondrial dysfunction through post-translational protein modifications (...) and/or mitochondrial DNA damage has been a major risk factor in both AFLD and NAFLD development and progression. Cytochrome P450-2E1 (CYP2E1), a known important inducer of oxidative radicals in the cells, has been reported to remarkably increase in both AFLD and NAFLD. Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity

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2017 Current molecular pharmacology

38. Changes in the Prevalence of Hepatitis C Virus Infection, Non-alcoholic Steatohepatitis, and Alcoholic Liver Disease Among Patients with Cirrhosis or Liver Failure on the Waitlist for Liver Transplantation (PubMed)

Changes in the Prevalence of Hepatitis C Virus Infection, Non-alcoholic Steatohepatitis, and Alcoholic Liver Disease Among Patients with Cirrhosis or Liver Failure on the Waitlist for Liver Transplantation Concurrent to development of more effective drugs for treatment of hepatitis C virus (HCV) infection, there has been an increase in the incidence of nonalcoholic fatty liver disease. Data indicate that liver transplantation prolongs survival times of patient with acute hepatitis associated (...) with alcoholic liver disease (ALD). We compared data on disease prevalence in the population with data from liver transplantation waitlists to evaluate changes in the burden of liver disease in the United States.We collected data on the prevalence of HCV from the 2010 and 2013-2014 cycles of the National Health and Nutrition Examination Survey. We also collected data from the HealthCore Integrated Research Database on patients with cirrhosis and chronic liver failure (CLF) from 2006 through 2014, and data

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2017 Gastroenterology

39. Inhibition of Caspase-8 does not protect from alcohol-induced liver apoptosis but alleviates alcoholic hepatic steatosis in mice (PubMed)

Inhibition of Caspase-8 does not protect from alcohol-induced liver apoptosis but alleviates alcoholic hepatic steatosis in mice Hepatic apoptosis is involved in the progression of alcoholic liver disease (ALD). Caspase-8, the apical initiator in death receptor-mediated apoptosis, has been implicated in acute liver injury and in non-alcoholic steatohepatitis. However, the relevance of Caspase-8 in the pathogenesis of ALD remains unclear. In the present study, we investigated the impact (...) -independent manner. Surprisingly, EtOH-fed Casp8Δhepa mice displayed significantly attenuated steatosis and reduced hepatic triglyceride and free fatty acids content. Caspase-8 is dispensable for alcohol-induced apoptosis, but plays an unexpected role for alcohol-dependent fat metabolism. We provide evidence that simultaneous inhibition of extrinsic and intrinsic apoptosis signaling using pan-caspase inhibitors in vivo might be an optimal approach to treat alcohol-induced liver injury.

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2017 Cell death & disease

40. Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis. (PubMed)

Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis. Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether (...) M30, M65, and SHH were measured by ELISA.Notably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p < 0.0001), steatosis grade (rho = 0.554, P < 0.001), Mallory-Denk bodies (rho = 0.54, P < 0.001), pericellular fibrosis (rho = 0.527, P < 0.001), and lymphocytic infiltration (rho = 0.435, P < 0.0002). Additionally, hepatic SHH expression correlated with circulating M65 (rho = 0.588, p < 0.0001), and circulating M30 (rho = 0.375, p = 0.001), as well as AST

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2019 BMC Gastroenterology

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