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Alcoholic Hepatitis

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121. 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

122. 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

123. 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

124. 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

125. 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

126. 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

127. Corrigendum to "A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study". Full Text available with Trip Pro

Corrigendum to "A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study". [This corrects the article DOI: 10.1155/2018/9159281.].

2019 BioMed research international Controlled trial quality: predicted high

128. Liver Transplantation for Alcoholic Hepatitis is Likely Underestimated in the National Transplant Database. Full Text available with Trip Pro

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

129. Evaluating the association of serum ferritin and hepatic iron with disease severity in non-alcoholic fatty liver disease. Full Text available with Trip Pro

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

130. Baseline neutrophil-to-lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis. Full Text available with Trip Pro

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

131. 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

132. 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

133. 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

134. 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

135. 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

136. 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

137. 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

138. 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

139. Diagnosis and treatment of alcohol use disorder in patients with end-stage alcoholic liver disease. (Abstract)

Diagnosis and treatment of alcohol use disorder in patients with end-stage alcoholic liver disease. Between 14%-30% of the world's population is affected by alcohol use disorder (AUD), and excessive alcohol consumption represents the most common cause of liver disease in the western world. The clinical picture of alcoholic end-stage liver disease is rendered extremely complex, as manifestations such as alcohol withdrawal syndrome, craving and physical dependence, as well as extrahepatic alcohol (...) -related diseases merge with the complications of advanced cirrhosis. This makes AUD recognition and assessment difficult and its management arduous as many drugs commonly used to treat complications such as alcohol withdrawal syndrome are often contraindicated by the presence of hepatic encephalopathy or hepatorenal syndrome. Reaching and maintaining abstinence represents the mainstay of managing patients with AUD and end-stage liver disease. Psychosocial interventions are an essential component

2018 Hepatology

140. Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: An observational study. Full Text available with Trip Pro

and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78).At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died (...) Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: An observational study. Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear.To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death.Data related to the occurrence of HCC

2017 PLoS ONE

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