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Alcoholic Hepatitis

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101. Assessment and Management of Infection in Alcoholic Hepatitis. Full Text available with Trip Pro

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

102. 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 (Abstract)

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

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

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

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

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

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

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

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

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

107. 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. Full Text available with Trip Pro

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

108. Biomarkers of macrophage activation and immune danger signals predict clinical outcomes in alcoholic hepatitis. (Abstract)

Biomarkers of macrophage activation and immune danger signals predict clinical outcomes in alcoholic hepatitis. Although mortality due to acute alcoholic hepatitis (AH) correlates with Model for End-Stage Liver Disease (MELD) scores, biomarkers are critically needed to manage this disease. Increases in inflammatory markers and macrophage activation are associated with acute AH and could be potential biomarkers of clinical events and/or mortality. We enrolled 89 clinically diagnosed AH patients (...) in four US academic medical centers. Plasma from AH patients had a significant increase in gut microbial translocation indicators (endotoxin, bacterial 16S ribosomal DNA) and host response indicators (soluble cluster of differentiation 14 [sCD14] and lipopolysaccharide binding protein [LBP]) compared to controls. Patient MELD score and Glasgow Alcoholic Hepatitis score (GAHS) correlated with endotoxin levels. AH patients also had a significant increase in high mobility group protein 1 (HMGB1

2019 Hepatology

109. Liver Transplantation for Alcoholic Hepatitis is Likely Underestimated in the National Transplant Database. (Abstract)

Liver Transplantation for Alcoholic Hepatitis is Likely Underestimated in the National Transplant Database. Alcohol-associated liver disease (ALD) can be coded in United Network for Organ Sharing (UNOS) as either alcoholic cirrhosis or alcoholic hepatitis (AH), without having specific criteria to assign either diagnosis. In this multicenter American Consortium of Early Liver Transplantation for Alcoholic Hepatitis (ACCELERATE-AH) study, we sought to assess the concordance of the clinician (...) , we determined the reason for alternate classification. Among 124 ACCELERATE-AH LT recipients with a chart-review diagnosis of AH, only 43/124 (35%) had AH as listing diagnosis in UNOS; 80 (64%) were listed as alcoholic cirrhosis, and 1 (1%) as fulminant hepatic necrosis. Of the 81 patients missing AH as a UNOS listing diagnosis code, the reasons for alternate classification were 44 (54%) due to a lack of awareness of a separate diagnosis code for AH; 13 (16%) due to concomitant clinical diagnosis

2019 Liver Transplantation

110. 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. (Abstract)

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

111. 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. Full Text available with Trip Pro

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

2017 Lancet

112. In Patients With Severe Alcoholic Hepatitis, Prednisolone Increases Susceptibility to Infection and Infection-Related Mortality, and Is Associated With High Circulating Levels of Bacterial DNA Full Text available with Trip Pro

In Patients With Severe Alcoholic Hepatitis, Prednisolone Increases Susceptibility to Infection and Infection-Related Mortality, and Is Associated With High Circulating Levels of Bacterial DNA Infections are common in patients with severe alcoholic hepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but can increase susceptibility to infection. We compared the effects of infection

2017 EvidenceUpdates

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

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

114. Current trials and novel therapeutic targets for alcoholic hepatitis. Full Text available with Trip Pro

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

115. Endpoints and patient stratification in clinical trials for alcoholic hepatitis. Full Text available with Trip Pro

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

116. Liver transplantation for alcoholic hepatitis. Full Text available with Trip Pro

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

117. Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis. Full Text available with Trip Pro

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

2019 BMC Gastroenterology

118. Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis. (Abstract)

Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis. Acute alcoholic hepatitis (AAH) is a major cause of liver-related morbidity and mortality; there are no good blood biomarkers for diagnosis or determining magnitude of cell death. Keratin 18 (KRT18, also called K18), found in epithelial cells, is released from hepatocytes upon death. We investigated whether level of K18 is a better marker of hepatocyte death than standard biomarkers and might be used to identify (...) patients with AAH at risk for death within 90 days.We analyzed data from 173 participants in a large trial performed at 4 medical centers. Participants with AAH were classified as severe (n = 57, model for end-stage liver disease [MELD] scores above 20) or moderate (n = 27, MELD scores from 12 to 19); 38 participants had alcohol use disorder with mild (n = 28) or no liver injury (n = 10); 34 participants had non-alcoholic steatohepatitis; and 17 participants were healthy (controls). We quantified serum

2019 Clinical Gastroenterology and Hepatology

119. Non-alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion. (Abstract)

Non-alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion. We recently showed that the functional capacity for ureagenesis is deficient in non-alcoholic fatty liver disease (NAFLD) patients. The aim of this study was to assess expression of urea cycle-related genes to elucidate a possible gene regulatory basis to the functional problem.Liver mRNA expression analyses within the gene pathway governing hepatic nitrogen conversion were performed in 20 non (...) -diabetic, biopsy-proven NAFLD patients (8 simple steatosis; 12 non-alcoholic steatohepatitis [NASH]) and 12 obese and 14 lean healthy individuals. Sixteen NAFLD patients were included for gene expression validation. Relationship between gene expressions and functional capacity for ureagenesis was described.Gene expression of most urea cycle-related enzymes were downregulated in NAFLD vs both control groups; markedly so for the urea cycle flux-generating carbamoyl phosphate synthetase (CPS1) (~3.5-fold

2019 Liver International

120. An Open-Label, Dose-Escalation Study to Assess the Safety and Efficacy of IL-22 Agonist F-652 in Patients With Alcohol-associated Hepatitis. (Abstract)

An Open-Label, Dose-Escalation Study to Assess the Safety and Efficacy of IL-22 Agonist F-652 in Patients With Alcohol-associated Hepatitis. Interleukin-22 has beneficial effects on inflammation and impaired hepatic regeneration that characterize alcohol-associated hepatitis (AH). F-652 is a recombinant fusion protein of human interleukin-22 and immunoglobulin G2 fragment crystallizable. This study aims to assess the safety and efficacy signals of F-652 in patients with moderate and severe AH.A (...) used. Plasma extracellular vesicles and multiplex serum cytokines were measured to assess inflammation and hepatic regeneration. Eighteen patients (9 moderate and 9 severe AH) were enrolled, 66% were male, and the mean age was 48 years. The half-life of F-652 following the first dose was 61-85 hours. There were no serious adverse events leading to discontinuation. The MELD score and serum aminotransferases decreased significantly at days 28 and 42 from baseline (P < 0.05). Day-7 Lille score

2019 Hepatology

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