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Alcoholic Hepatitis

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61. Role of CYP2E1 in mitochondrial dysfunction and hepatic tissue injury in alcoholic and non-alcoholic diseases Full Text available with Trip Pro

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

2017 Current molecular pharmacology

62. Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long-term survival. Full Text available with Trip Pro

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 (...) of predicting abstinence during long-term follow-up in patients with AH. One hundred forty-two patients with biopsy-proven AH that survived the first episode were included. Demographic, psychiatric, and biochemical variables at admission and drinking status during follow-up were obtained. Cox regression, logistic regression, and classification and regression trees (CART) analyses were used for statistical analysis. Overall mortality was 38% with a median follow-up of 55 months. During follow-up, complete

2017 Hepatology

63. Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study. Full Text available with Trip Pro

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.

2017 Hepatology

64. Alcoholic Liver Disease

. AH presents with rapid onset or worsening of jaundice, and in severe cases may transition to acute on chronic liver failure when the risk for mortality, depending on the number of extra-hepatic organ failures, may be as high as 20–50% at 1 month. Corticosteroids provide short-term survival bene? t in about half of treated patients with severe AH and long-term mortality is related to severity of underlying liver disease and is dependent on abstinence from alcohol. General measures in patients (...) be optimized to use lowest possible dose needed to prevent graft rejection. Use of sirolimus or everolimus may be con- sidered over other immunosuppression drugs Singal et al. The American Journal of GASTROENTEROLOGY VOLUME XXX | XXX 2017 www.nature.com/ajg 4 environments, especially alcohol taxes, were associated with lower alcoholic cirrhosis mortality rates ( 12 ). Alcohol abuse or alcohol dependence is not synonymous with clinically important ALD, as only about 10–20% of chronic heavy drinkers develop

2018 American College of Gastroenterology

65. CRACKCast E155 – Toxic alcohols

syndrome? “Benzyl alcohol poisoning can cause the gasping syndrome in neonates. The infants had a typical course of gradual neurologic deterioration, severe metabolic acidosis, the striking onset of gasping respirations, thrombocytopenia, hepatic and renal failure, hypotension, cardiovascular collapse and death.” [4] How does propylene glycol toxicity present? As always – coma, seizures and hypoglycemia metabolized into pyruvic acid / acetic acid / lactic acid and propionaldehyde (a potentially (...) is the difference between the measured serum osmolality and calculated serum osmolarity, with a normal range of −15 to +10 mOsm. The classic finding of an elevated osmolar and anion gap should raise suspicion of methanol or ethylene glycol toxicity but may not be present, depending on the timing of ingestion . Early ingestion has a high osmolar gap without acidosis, and late ingestion has acidosis without an osmolar gap. A normal osmolar gap does not exclude toxic alcohol ingestion. Initiate therapy based

2018 CandiEM

66. CRACKCast Episode 185 – Alcohol Related Disease

physiologic effects of different levels are UNPREDICTABLE, some people are intolerant of levels as low as 5 mmol/L; a level of 32 mmol/L is where 50% of the adult population will be obviously intoxicated. Chronic alcoholics are tolerant of much higher levels. Excretion Excreted through the lungs, urine, and sweat [2] Define substance dependence. What are the signs of dependence? This is a misleading question, because some of the current terminology has shifted based on the DSM-V. Replacing the two DSM-IV (...) Great deal of time spent obtaining, using, or recovering from alcohol Important activities given up or reduced because of drinking Continued drinking despite knowledge of physical or psychological problems caused by alcohol Alcohol craving -The above compiled from Uptodate 2018 [3] Describe the AUDIT-C screening test. Some sources confirm that 25-30% patients visiting the ER meet the criteria for at risk drinking. The CAGE questionnaire is designed to assess for LIFETIME ETOH dependence

2018 CandiEM

67. A review of behavioral alcohol interventions for transplant candidates and recipients with alcohol-related liver disease. (Abstract)

A review of behavioral alcohol interventions for transplant candidates and recipients with alcohol-related liver disease. Alcohol-related liver disease (ALD) is a common indication for liver transplantation. Reflecting growing consensus that early transplant (ie, prior to sustained abstinence) can be a viable option for acute alcoholic hepatitis, access to liver transplantation for ALD patients has increased. Prevention of alcohol relapse is critical to pretransplant stabilization (...) and posttransplant survival. Behavioral interventions are a fundamental component of alcohol use disorder treatment, but have rarely been studied in the transplant context. This scoping review summarizes published reports of behavioral and psychosocial alcohol interventions conducted with ALD patients who were liver transplant candidates and/or recipients. A structured review identified 11 eligible reports (3 original research studies, 8 descriptive papers). Intervention characteristics and clinical outcomes

2019 American Journal of Transplantation

68. The High-Risk Alcoholism Relapse Score Predicts Alcohol Relapse Among Liver Transplant Candidates with Less Than Six Months of Abstinence. (Abstract)

2016 (n=309), excluding alcoholic hepatitis. Odds ratios (OR; 95%CI) for AR were analyzed by multinomial logistic regression. Cox regression with time-dependent covariates was used to analyze patient survival and graft cirrhosis.Seventy (23%) patients presented AR (median follow-up: 68 months), most of them (n=44, 63%) presenting heavy AR. The probability of heavy AR was 2.3%, 7.5%, 12% and 29% at 1, 3, 5, and 10 years after LT, respectively. The independent risk factors for heavy AR included (...) =3.44; 95% CI (1.58-7.57); p=0.002) compared to non-relapsers with no differences in patient survival.The HRAR score is helpful to identify the risk of harmful AR after LT in candidates with less than 6 months of alcohol abstinence without alcoholic hepatitis. These patients could benefit from a long-term integrative patient-centered approach after LT until lifestyle changes are consolidated. This article is protected by copyright. All rights reserved.This article is protected by copyright. All

2019 Liver Transplantation

69. Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users. Full Text available with Trip Pro

Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users. Problem alcohol use is common among illicit drug users and is associated with adverse health outcomes. It is also an important factor in poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opiate overdose in opioid users.To assess the effects of psychosocial interventions for problem alcohol use in illicit drug users (...) (principally problem drug users of opiates and stimulants).We searched the Cochrane Drugs and Alcohol Group trials register (November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 11, November 2011), PUBMED (1966 to 2011); EMBASE (1974 to 2011); CINAHL (1982 to 2011); PsycINFO (1872 to 2011) and reference list of articles. We also searched: 1) conference proceedings (online archives only) of the Society for the Study of Addiction (SSA), International Harm

2012 Cochrane

70. Non-alcoholic fatty liver disease (NAFLD): assessment and management

the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information. 1.1 Assessment for NAFLD Identifying NAFLD in higher-risk groups Identifying NAFLD in higher-risk groups 1.1.1 Be aware that non-alcoholic fatty liver disease (NAFLD) is more common in people who have: type 2 diabetes or metabolic syndrome. 1.1.2 T ake an alcohol history to rule out alcohol-related liver disease. See also NICE's cirrhosis guideline. 1.1.3 Do not use routine liver blood tests (...) to rule out NAFLD. Diagnosing NAFLD in children and y Diagnosing NAFLD in children and young people oung people 1.1.4 Offer a liver ultrasound to test children and young people for NAFLD if they: have type 2 diabetes or metabolic syndrome and do not misuse alcohol. Non-alcoholic fatty liver disease (NAFLD): assessment and management (NG49) © NICE 2018. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and- conditions#notice-of-rights). Page 5 of 161.1.5 Refer children

2016 National Institute for Health and Clinical Excellence - Clinical Guidelines

71. Ethanol and unsaturated dietary fat induce unique patterns of hepatic ω-6 and ω-3 PUFA oxylipins in a mouse model of alcoholic liver disease. Full Text available with Trip Pro

Ethanol and unsaturated dietary fat induce unique patterns of hepatic ω-6 and ω-3 PUFA oxylipins in a mouse model of alcoholic liver disease. Alcoholic liver disease (ALD), a significant health problem, progresses through the course of several pathologies including steatosis, steatohepatitis, fibrosis, and cirrhosis. There are no effective FDA-approved medications to prevent or treat any stages of ALD, and the mechanisms involved in ALD pathogenesis are not well understood. Bioactive lipid (...) metabolites play a crucial role in numerous pathological conditions, as well as in the induction and resolution of inflammation. Herein, a hepatic lipidomic analysis was performed on a mouse model of ALD with the objective of identifying novel metabolic pathways and lipid mediators associated with alcoholic steatohepatitis, which might be potential novel biomarkers and therapeutic targets for the disease. We found that ethanol and dietary unsaturated, but not saturated, fat caused elevated plasma ALT

2018 PLoS ONE

72. Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy Full Text available with Trip Pro

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).

2017 Hepatology communications

73. Alcoholic Hepatitis: Lost in Translation Full Text available with Trip Pro

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

2017 Journal of clinical and translational hepatology

74. Survival from alcoholic hepatitis has not improved over time. Full Text available with Trip Pro

Survival from alcoholic hepatitis has not improved over time. We aimed to describe changes in survival in alcoholic hepatitis (AH) over time by examining published data.A systematic literature search of Ovid Embase and PubMed was undertaken using the MESH terms 'hepatitis, alcoholic' to identify randomised controlled trials (RCT) and observational studies (OS) in alcoholic hepatitis. Data were extracted from included studies regarding 28-day, 90-day, 180-day mortality, as well as biochemical (...) for effective treatments for this alcoholic hepatitis.

2018 PLoS ONE

75. Peripheral TNFα elevations in abstinent alcoholics are associated with hepatitis C infection. Full Text available with Trip Pro

Peripheral TNFα elevations in abstinent alcoholics are associated with hepatitis C infection. Substantial evidence supports the view that inflammatory processes contribute to brain alterations in HIV infection. Mechanisms recently proposed to underlie neuropathology in Alcohol Use Disorder (AUD) include elevations in peripheral cytokines that sensitize the brain to the damaging effects of alcohol. This study included 4 groups: healthy controls, individuals with AUD (abstinent from alcohol (...) at examination), those infected with HIV, and those comorbid for HIV and AUD. The aim was to determine whether inflammatory cytokines are elevated in AUD as they are in HIV infection. Cytokines showing group differences included interferon gamma-induced protein 10 (IP-10) and tumor necrosis factor α (TNFα). Follow-up t-tests revealed that TNFα and IP-10 were higher in AUD than controls but only in AUD patients who were seropositive for Hepatitis C virus (HCV). Specificity of TNFα and IP-10 elevations to HCV

2018 PLoS ONE

76. Correction: Survival from alcoholic hepatitis has not improved over time. Full Text available with Trip Pro

Correction: Survival from alcoholic hepatitis has not improved over time. [This corrects the article DOI: 10.1371/journal.pone.0192393.].

2018 PLoS ONE

77. Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease. Full Text available with Trip Pro

Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) is a chronic liver disease commonly associated with hepatic fibrosis. NASH patients have an increased risk for hepatocellular carcinoma (HCC). An altered retinol metabolism is one of the pathways involved in the process of hepatic fibrosis, and enzymes involved in retinol metabolism (...) have been associated with HCC. We aimed to determine the association between plasma retinol levels and hepatic expression of genes related to retinol metabolism, as well as to assess the hepatic expression of transcription factors regulated by retinoic acid in patients with NAFLD. Cross-sectional study where hepatic gene expression (Illumina microarray) and plasma retinol levels (HPLC) were measured in 17 patients with simple steatosis (SS), 15 with NASH, and 22 living liver donors (LD) as controls

2018 PLoS ONE

78. Interaction between the patatin‐like phospholipase domain‐containing protein 3 genotype and coffee drinking and the risk for acute alcoholic hepatitis Full Text available with Trip Pro

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

2017 Hepatology communications

79. Role of gp91phox in hepatic macrophage programming and alcoholic liver disease Full Text available with Trip Pro

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

2017 Hepatology communications

80. Severe Alcoholic Hepatitis: Atypical Presentation with Markedly Elevated Alkaline Phosphatase Full Text available with Trip Pro

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.

2017 Journal of clinical and translational hepatology

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