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Alcoholic Hepatitis

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41. Current trials and novel therapeutic targets for alcoholic hepatitis. (PubMed)

Current trials and novel therapeutic targets for alcoholic hepatitis. Alcoholic hepatitis is a clinical syndrome in which patients present with acute-on-chronic liver failure and a high risk of short-term mortality. The current treatment of alcoholic hepatitis is suboptimal. Results recently published from the STOPAH study have improved our understanding of how best to design clinical trials for this condition. Although emerging data on liver transplantation for patients with alcoholic (...) hepatitis are encouraging, less than 2% of these patients qualify. Clearly, there is an unmet need for novel treatments to improve the survival of these patients. Changes in the gut microbiota, inflammatory and cytokine signalling, oxidative stress and mitochondrial dysfunction, and abnormalities in the hepatic regenerative capacity alone or in combination contribute to the pathology of alcoholic hepatitis. In this chapter, we will describe the novel therapeutic agents targeting various pathways

2019 Journal of Hepatology

42. Liver transplantation for alcoholic hepatitis. (PubMed)

Liver transplantation for alcoholic hepatitis. While liver transplantation (LT) has become a standard therapy for life-threatening alcohol related cirrhosis, LT as a treatment for severe alcoholic hepatitis (AH) has remained a taboo owing to concerns about the limited organ supply and the risk that the AH liver recipient will return to harmful drinking. The adoption of a 6-month abstinence requirement (the so-called '6-month rule') by many centres made AH a contraindication to LT. Given (...) studies are urgently needed to resolve the controversies that still surround the criteria for selection of patients with AH for LT and the long-term outcomes of the associated alcohol use disorder.Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

2019 Journal of Hepatology

43. Endpoints and patient stratification in clinical trials for alcoholic hepatitis. (PubMed)

Endpoints and patient stratification in clinical trials for alcoholic hepatitis. In some areas of medicine the clinical development pathway through phase II and III clinical trials has been well mapped out and refined through extensive experience. In contrast, a number of key questions remain unanswered in the development of novel therapeutics for alcoholic hepatitis. The use of mortality as an endpoint in phase II clinical trials will potentially restrict the appeal of this therapeutic area

2019 Journal of Hepatology

44. Liver transplantation for alcoholic hepatitis: A systematic review with meta-analysis. (PubMed)

Liver transplantation for alcoholic hepatitis: A systematic review with meta-analysis. The rate of alcohol relapse among patients who underwent liver transplantation for alcoholic hepatitis (AH) is not precisely known.Synthesize the available evidence on liver transplantation for AH to assess alcohol relapse and 6-month survival.Meta-analysis of trials evaluating liver transplantation for AH, either clinically severe or diagnosed on the explant.Eleven studies were included. The pooled estimate (...) rate for alcohol relapse was 0.22 (95% CI = 0.12-0.36) in overall analysis with high heterogeneity between studies (I2 = 76%), 0.20 (95% CI = 0.07-0.43) in the subgroup analysis including patients with clinically severe AH (I2 = 84%), 0.14 (95% CI = 0.08-0.23) among patients with clinically severe AH in sensitivity analysis excluding the discrepant studies that did not use stringent selection criteria for liver transplantation (I2 = 0%), and 0.15 (95% CI = 0.07-0.27) for recurrent harmful alcohol

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2018 PLoS ONE

45. Survival from alcoholic hepatitis has not improved over time. (PubMed)

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.

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2018 PLoS ONE

46. Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK. (PubMed)

Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK. This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage (...) to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot

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2017 Lancet

47. A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Non-Alcoholic Fatty Liver Disease. (PubMed)

A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Non-Alcoholic Fatty Liver Disease. Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes. We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based (...) cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at over 400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding p=6.9×10-6) with replication at Bonferroni corrected p<8.6×10-4 Mendelian randomization analyses supported the association of hypomethylation

2019 Diabetes

48. Evaluating the association of serum ferritin and hepatic iron with disease severity in non-alcoholic fatty liver disease. (PubMed)

Evaluating the association of serum ferritin and hepatic iron with disease severity in non-alcoholic fatty liver disease. Hyperferritinemia, with or without increased hepatic iron, represents a common finding in non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether it reflects hepatic inflammation or true iron-overload and, in case the latter is confirmed, whether this influences disease progression. We therefore explored the association between serum ferritin, degree (...) and pattern of hepatic iron deposition and liver disease severity in patients with NAFLD.We selected 468 patients with biopsy-proven NAFLD from two European centres. Iron, hepatic and metabolic parameters were collected at the time of liver biopsy. Iron deposits in hepatocytes and reticuloendothelial cells were assessed and graded. Diagnosis of non-alcoholic steatohepatitis (NASH) and fibrosis staging were performed.122 (26%) patients had hyperferritinemia, whereas stainable hepatic iron was found in 116

2019 Liver International

49. Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis. (PubMed)

Intestinal fungal dysbiosis and systemic immune response to fungi in patients with alcoholic hepatitis. Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder (...) or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to non-alcoholic controls. Within the alcoholic hepatitis patient cohort, patients with levels of ≥34 IU/ml, had a significantly lower 90-day survival (60%) compared to those with ASCA levels <34 IU/ml (80%) with an adjusted hazard ratio of 3.13 (95% CI 1.11-8.82, p=0.031). In conclusion, patients with alcohol-associated

2019 Hepatology

50. Systematic review with meta-analysis: high mortality in patients with nonsevere alcoholic hepatitis. (PubMed)

Systematic review with meta-analysis: high mortality in patients with nonsevere alcoholic hepatitis. Alcoholic hepatitis is a serious complication of alcohol misuse. Severe alcoholic hepatitis with its high mortality, has been investigated in detail but 'nonsevere alcoholic hepatitis' is poorly characterised. Survival of this group of patients is unknown.To conduct a systematic review and meta-analysis to determine 28-day, 90-day and 1-year mortality of patients with nonsevere alcoholic (...) hepatitis.The protocol was registered on the PROSPERO database (CRD42018107451). Embase, Medline and Cochrane Central databases were searched until July 2018. All study designs reporting mortality rates in patients with nonsevere alcoholic hepatitis were eligible. Mortality data were extracted and meta-analysis performed using a random effects model. Risk of bias was assessed by Cochrane risk of bias or National Institutes of Health quality assessment tool for case series studies.Twenty-five studies (n

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2019 Alimentary Pharmacology & Therapeutics

51. Antisteatotic and antioxidant activities of Thymbra spicata L. extracts in hepatic and endothelial cells as in vitro models of non-alcoholic fatty liver disease. (PubMed)

Antisteatotic and antioxidant activities of Thymbra spicata L. extracts in hepatic and endothelial cells as in vitro models of non-alcoholic fatty liver disease. Thymbra spicata, a member of the Lamiaceae family, is native to eastern Mediterranean area. Leaves of this plant are rich in phenolic compounds and are a popular remedy of traditional medicine in Lebanon to prevent and/or counteract hyperlipidemia and hyperglycemia.To evaluate the antisteatotic and antioxidant activities of extracts (...) from leaves of Thymbra spicata L. using in vitro models of non-alcoholic fatty liver disease (NAFLD), a leading cause of liver-related morbidity and mortality worldwide, for whom no effective treatments are still available.Two different extracts from Thymbra spicata L. aerial parts were prepared using water (TW) or ethanol (TE) as solvent. Their chemical composition was characterized by gas and liquid chromatography coupled with mass spectrometry. Both extracts were tested on cultured hepatic

2019 Journal of Ethnopharmacology

52. Heparin-like Effect Associated With Risk of Bleeding, Sepsis, and Death in Patients With Severe Alcohol-Associated Hepatitis. (PubMed)

Heparin-like Effect Associated With Risk of Bleeding, Sepsis, and Death in Patients With Severe Alcohol-Associated Hepatitis. Endogenous heparinoids or heparin-like effects (HLEs) can cause coagulation failure in patients with cirrhosis and sepsis. We performed a prospective study of the association between HLE and bleeding events, sepsis, and outcomes of patients with severe alcohol-associated hepatitis.Our final analysis comprised 78 patients with severe alcohol-associated hepatitis (44.3 (...) of sepsis (HR, 2.5; 95% CI, 2.2-4.3; P = .002), bleeding (HR, 1.4; 95% CI, 1.2-5.3; P = .004) and death (HR, 1.2; 95% CI, 1.4-1.7; P = .044).In a prospective study of patients with severe alcohol-associated hepatitis, we associated HLE with coagulation abnormalities, risk of sepsis, and mortality. Clinicaltrials.govNCT02307409.Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.

2019 Clinical Gastroenterology and Hepatology

53. Letter to the Editor: Impact of non-alcoholic steatohepatitis on liver-related outcomes in chronic hepatitis B. (PubMed)

Letter to the Editor: Impact of non-alcoholic steatohepatitis on liver-related outcomes in chronic hepatitis B. We read with great interest the article by Choi et al.(1) reporting the impacts of concomitant non-alcoholic steatohepatitis (NASH) on the clinical outcomes and all-cause mortality in chronic hepatitis B (CHB) patients. Although the number of patients and follow-up duration are quite impressive, several points require further clarification.© 2019 by the American Association

2019 Hepatology

54. Non-Alcoholic steatohepatitis is associated with liver-related outcomes and all-cause mortality in chronic hepatitis B. (PubMed)

Non-Alcoholic steatohepatitis is associated with liver-related outcomes and all-cause mortality in chronic hepatitis B. Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease are increasingly observed together in clinical practice, and development of non-alcoholic steatohepatitis (NASH) represents another leading cause of liver-related morbidity and mortality. Our aims were to determine whether biopsy-proven NASH impacts clinical outcomes in CHB patients and assess prognostic risk

2019 Hepatology

55. Patterns of drug, alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment during and following hepatitis C virus treatment with direct-acting antiviral therapies: An international study (PubMed)

Patterns of drug, alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment during and following hepatitis C virus treatment with direct-acting antiviral therapies: An international study In many settings, recent or prior injection drug use remain barriers to accessing direct-acting antiviral treatment (DAA) for hepatitis C virus (HCV) infection. We examined longitudinal patterns of drug and alcohol use and injection equipment (...) , they completed a behavioural questionnaire before, during and after treatment, up to two years following treatment initiation. The impact of time in HCV treatment and follow-up on longitudinally measured behavioural outcomes was estimated using generalized estimating equations analyses.At screening, of 190 participants (mean age: 47; 74% male), 62% reported any past-month injecting (47% opioids, 39% stimulants), 16% past-month injection equipment sharing and 61% current OAT. Median alcohol use was 2 (AUDIT-C

2019 Clinical Infectious Diseases

56. Baseline neutrophil-to-lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis. (PubMed)

Baseline neutrophil-to-lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis. Treating severe alcoholic hepatitis involves the exposure of patients to corticosteroids for 7 days to assess "response".To assess the prognostic and therapeutic implications of baseline neutrophil-to-lymphocyte ratio (NLR) in patients with severe alcoholic hepatitis.Patients recruited to the STOPAH trial and an independent validation group (...) were analysed retrospectively. Area under the receiver operating curve (AUC) analysis was performed. Kaplan-Meier analysis was used to assess survival. Log-rank test and odds ratio (OR) were used for comparative analysis.Baseline NLR was available for 789 STOPAH patients. The AUC for NLR was modest for 90-day outcome (0.660), but was associated with infection, acute kidney injury (AKI) and severity of alcoholic hepatitis. Ninety-day survival was not affected by prednisolone treatment if NLR < 5

2019 Alimentary Pharmacology & Therapeutics

57. Assessment and Management of Infection in Alcoholic Hepatitis. (PubMed)

Assessment and Management of Infection in Alcoholic Hepatitis. Severe alcoholic hepatitis (SAH) is a condition characterized by jaundice and liver failure that develops after heavy and prolonged alcohol consumption. Infection frequently complicates the natural history of the disease and is independently associated with mortality. Objective recognition and recording of infection are therefore essential in the evaluation of therapeutic interventions and for antibiotic stewardship. This review

2019 Seminars in Liver Disease

58. Efficacy of g-csf in the management of steroid-nonresponsive severe alcoholic hepatitis: a double-blind randomized controlled trial. (PubMed)

Efficacy of g-csf in the management of steroid-nonresponsive severe alcoholic hepatitis: a double-blind randomized controlled trial. Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille-score>0.45) are limited. We assessed the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in steroid non-responders.Randomized, double-blind, single-center trial

2019 Hepatology (Baltimore, Md.) Controlled trial quality: predicted high

59. The effects of curcumin supplementation on liver enzymes, lipid profile, glucose homeostasis, and hepatic steatosis and fibrosis in patients with non-alcoholic fatty liver disease. (PubMed)

The effects of curcumin supplementation on liver enzymes, lipid profile, glucose homeostasis, and hepatic steatosis and fibrosis in patients with non-alcoholic fatty liver disease. Nonalcoholic fatty liver disease (NAFLD) is a major global health problem. The most common cause of death in these patients is due to cardiovascular disorders. The aim of this study was to examine the effects of curcumin supplementation on cardiovascular risk factors in patients with NAFLD.In this randomized, placebo (...) -controlled, clinical trial, fifty two patients with NAFLD were randomly assigned to receive life style recommendations plus either 1500 mg curcumin or placebo for 12 weeks. Anthropometric indices, blood lipid profile, insulin resistance, as well as hepatic steatosis and fibrosis scores were measured at the beginning and the end of the study, and compared between and within groups.Hepatic fibrosis, serum cholesterol, glucose and alanin aminotransferase (ALT) reduced significantly only in curcumin group (p

2019 European journal of clinical nutrition Controlled trial quality: uncertain

60. Standardized Nigella sativa seed oil ameliorates hepatic steatosis, aminotransferase and lipid levels in non-alcoholic fatty liver disease: a randomized, double-blind and placebo-controlled clinical trial. (PubMed)

Standardized Nigella sativa seed oil ameliorates hepatic steatosis, aminotransferase and lipid levels in non-alcoholic fatty liver disease: a randomized, double-blind and placebo-controlled clinical trial. Nigella sativa (N. sativa) seeds are used in the Iranian traditional medicine for the treatment of liver diseases.To study the efficacy and safety of N. sativa seed oil in the treatment of patients with non-alcoholic fatty liver disease (NAFLD).Sixty patients received 2.5 mL fully (...) standardized N. sativa seed oil every 12 h and 60 other patients received placebo for 3 months. At the baseline and endpoint, hepatic steatosis ultrasound grade and blood levels of triglycerides, LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), ALT (alanine aminotransferase), AST (aspartate aminotransferase), blood urea nitrogen, creatinine and complete blood cell count as well as body mass index were determined in the oil and placebo groups and compared.Grade

2019 Journal of Ethnopharmacology Controlled trial quality: uncertain

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