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Alcoholic Hepatitis

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121. Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis. (Full text)

Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis. Liver transplantation (LT) has a demonstrated survival benefit in select patients with severe acute alcoholic hepatitis (SAH) who do not respond to steroids, but prior studies suggest low adoption among US LT centers. Our study explored current perceptions and practice patterns of LT for SAH in the United States. We administered a Web-based survey to medical directors of US LT centers between May and October of 2017 (...) psychiatric disorder (91.3%), and official psychosocial evaluation (87.0%). Reported posttransplant survival of SAH patients was excellent, with 17 (73.9%) centers reporting 1-year posttransplant survival exceeding 90%. Among centers that had not performed LT for SAH, the most commonly cited reason was perceived high risk of alcohol relapse. In conclusion, our data demonstrate that LT is increasingly adopted as a therapeutic intervention for patients with SAH and that careful selection allows

2018 Liver Transplantation

122. A Validated Score Predicts Acute Kidney Injury and Survival in Patients with Alcoholic Hepatitis: A Multicentric International Prospective Cohort Study. (PubMed)

A Validated Score Predicts Acute Kidney Injury and Survival in Patients with Alcoholic Hepatitis: A Multicentric International Prospective Cohort Study. Identifying patients at high risk for acute kidney injury (AKI) during hospitalization among patients admitted with severe alcoholic hepatitis (AH) is an unmet clinical need. We performed a multicentric prospective cohort study using data from 4 different cohorts on well-characterized patients hospitalized with severe AH. Data collected on 773 (...) AH patients from 4 cohorts across the globe were randomly split into test (n = 390) and validation (n = 383) cohorts. We found that 32% of the patients developed inpatient AKI in the test cohort. Approximately 60% of patients met criteria for systemic inflammatory response syndrome (SIRS) at admission. Hepatic encephalopathy, SIRS, and Model for End-Stage Liver Disease score at admission predicted inpatient AKI with odds ratios of 3.86, 2.24, and 1.14, respectively. The AKI risk score developed

2018 Liver Transplantation

123. Diagnostic accuracy of point shear wave elastography and transient elastography for staging hepatic fibrosis in patients with non-alcoholic fatty liver disease: a meta-analysis. (Full text)

Diagnostic accuracy of point shear wave elastography and transient elastography for staging hepatic fibrosis in patients with non-alcoholic fatty liver disease: a meta-analysis. This study aimed to assess the accuracy of staging liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) usingpoint shear wave elastography (pSWE) and transient elastography (TE).Relevant records on NAFLD were retrieved from PubMed, Embase, Web of Science and the China National Knowledge (...)  contingency tables can be calculated via the reported number of cases; sensitivity and specificity were excluded according to the following criteria: history of other hepatic damage, such as chronic hepatitis C, concurrent active hepatitis B infection, autoimmune hepatitis, suspicious drug usage and alcohol abuse.Nine pSWE studies comprising a total of 982 patients and 11 TE studies comprising a total of 1753 patients were included. For detection of significant fibrosis, advanced fibrosis and cirrhosis

2018 BMJ open

124. Liver transplantation for severe alcoholic hepatitis: where are we now? (PubMed)

Liver transplantation for severe alcoholic hepatitis: where are we now? 30218596 2019 03 12 2019 03 12 1527-6473 24 10 2018 10 Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society Liver Transpl. Liver Transplantation for Severe Alcoholic Hepatitis: Where Are We Now? 1327-1328 10.1002/lt.25337 Gelu-Simeon Moana M Centre Hospitalier Universitaire Guadeloupe, Université des Antilles, Service (...) d'Hépato-Gastroentérologie, Pointe-à-Pitre, Guadeloupe. INSERM, Unités Mixtes de Recherche en Santé1085/IRSET, Rennes, France. Mathurin Philippe P Service des Maladies de l'Appareil Digestif, Hôpital Huriez, CHRU Lille, Université Lille 2, INSERM U795, Lille, France. eng Editorial Comment United States Liver Transpl 100909185 1527-6465 IM Liver Transpl. 2018 Oct;24(10):1357-1362 30141270 Hepatitis, Alcoholic Humans Liver Transplantation Patient Selection Recurrence Surveys and Questionnaires 2018 09 10

2018 Liver Transplantation

125. Evaluation of the effects of dapagliflozin, an SGLT2 inhibitor, on hepatic steatosis and fibrosis by transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. (PubMed)

Evaluation of the effects of dapagliflozin, an SGLT2 inhibitor, on hepatic steatosis and fibrosis by transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. To investigate the effects of dapagliflozin on liver steatosis and fibrosis evaluated in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).In a randomized, active-controlled, open-label trial, 57 patients with type 2 diabetes and NAFLD were randomized to a dapagliflozin group (...) (5 mg/d; n = 33) or a control group (n = 24) and were treated for 24 weeks. Hepatic steatosis and fibrosis were assessed using transient elastography to measure controlled attenuation parameter (CAP) and liver stiffness, respectively.Baseline liver stiffness measurement (LSM) was positively correlated with several markers and scoring systems for liver fibrosis. In week 24, there was a significant decrease in CAP from 314 ± 61 to 290 ± 73 dB/m (P = 0.0424) in the dapagliflozin group, while

2018 obesity & metabolism Controlled trial quality: uncertain

126. Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis. (Full text)

Bile acid homeostasis and intestinal dysbiosis in alcoholic hepatitis. Intestinal microbiota plays an important role in bile acid homeostasis.To study the structure of the intestinal microbiota and its function in bile acid homeostasis in alcoholic patients based on the severity of alcoholic liver disease.In this prospective study, we included four groups of active alcoholic patients (N = 108): two noncirrhotic, with (noCir_AH, n = 13) or without alcoholic hepatitis (noCir_noAH, n = 61 (...) ), and two cirrhotic, with (Cir_sAH, n = 17) or without severe alcoholic hepatitis (Cir_noAH, n = 17). Plasma and faecal bile acid profiles and intestinal microbiota composition were assessed.Plasma levels of total bile acids (84.6 vs 6.8 μmol/L, P < 0.001) and total ursodeoxycholic acid (1.3 vs 0.3 μmol/L, P = 0.03) were higher in cirrhosis with severe alcoholic hepatitis (Cir_sAH) than Cir_noAH, whereas total faecal (2.4 vs 11.3, P = 0.01) and secondary bile acids (0.7 vs 10.7, P < 0.01) levels were

2018 Alimentary Pharmacology & Therapeutics

127. Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2-deficient mice and humans: roles of acetaldehyde and glucocorticoids. (Full text)

Alcohol inhibits T-cell glucose metabolism and hepatitis in ALDH2-deficient mice and humans: roles of acetaldehyde and glucocorticoids. Aldehyde dehydrogenase 2 (ALDH2), a key enzyme to detoxify acetaldehyde in the liver, exists in both active and inactive forms in humans. Individuals with inactive ALDH2 accumulate acetaldehyde after alcohol consumption. However, how acetaldehyde affects T-cell hepatitis remains unknown.Wild-type (WT) and Aldh2 knockout (Aldh2-/-) mice were subjected to chronic (...) had higher levels of serum corticosterone, a well-known factor that inhibits aerobic glycolysis. Blockade of corticosterone partially restored ConA-mediated hepatitis in ethanol-fed Aldh2-/- mice. Acute alcohol drinking elevated plasma cortisol and corticosterone levels in human subjects with higher levels in those with inactive ALDH2 than those with active ALDH2.ALDH2 deficiency is associated with elevated acetaldehyde and glucocorticoids post-alcohol consumption, thereby inhibiting T-cell

2018 Gut

128. The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. (Full text)

The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non-alcoholic fatty liver disease (NAFLD (...) % ± 6.8%; P = 0.635; n = 9). The predominant SCFA from colonic fermentation of inulin is acetate, which, in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate-mediated increase in IHCL.© 2018 John Wiley & Sons Ltd.

2018 obesity & metabolism Controlled trial quality: uncertain

129. Non-parenchymal hepatic cell lipotoxicity and the coordinated progression of non-alcoholic fatty liver disease and atherosclerosis. (Full text)

Non-parenchymal hepatic cell lipotoxicity and the coordinated progression of non-alcoholic fatty liver disease and atherosclerosis. Non-alcoholic fatty liver disease (NAFLD) appears to be independently associated with the development of atherosclerosis. The biological mechanisms underlying this association are complex, and likely involve liver-resident cell types other than hepatocytes. Thus, we review recent evidence that non-parenchymal hepatic cell responses to lipid excess contribute (...) to the pathogenesis of both NAFLD and atherosclerosis.Significant independent associations between NAFLD and atherosclerosis have been identified through cross-sectional studies and meta-analyses. Mechanistic studies in cell cultures and in rodent models suggest that liver-resident macrophages, activated hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) mount lipotoxic responses under NAFLD conditions which can contribute to the progression of both NAFLD and atherosclerosis.Non

2018 Current Opinion in Lipidology

130. Hepatitis B virus infection and risk of non-alcoholic fatty liver disease (NAFLD): a population-based cohort study. (Full text)

Hepatitis B virus infection and risk of non-alcoholic fatty liver disease (NAFLD): a population-based cohort study. Although non-alcoholic fatty liver disease (NAFLD) has been studied extensively, the potential risk factors for NAFLD among chronic hepatitis B (CHB) patients have not been fully known.A population-based cohort of adult CHB patients without a history of alcohol drinking or NAFLD were recruited and followed up from October 2012 to January 2015 in Jiangsu province, China. Using Cox

2018 Liver International

131. Ductular reaction cells display an inflammatory profile and recruit neutrophils in alcoholic hepatitis. (PubMed)

Ductular reaction cells display an inflammatory profile and recruit neutrophils in alcoholic hepatitis. Chronic liver diseases are characterized by the expansion of ductular reaction (DR) cells and the expression of liver progenitor cell (LPC) markers. In alcoholic hepatitis (AH), the degree of DR expansion correlates with disease progression and short-term survival. However, little is known about the biological properties of DR cells, their impact on the pathogenesis of human liver disease (...) , and their contribution to tissue repair. In this study, we have evaluated the transcriptomic profile of DR cells by laser capture microdissection in patients with AH and assessed its association with disease progression. The transcriptome analysis of cytokeratin 7-positive (KRT7+ ) DR cells uncovered intrinsic gene pathways expressed in DR and genes associated with alcoholic liver disease progression. Importantly, DR presented a proinflammatory profile with expression of neutrophil recruiting C-X-C motif chemokine

2018 Hepatology

132. DEPTOR Suppresses Lipogenesis and Ameliorates Hepatic Steatosis and Acute-on-Chronic Liver Injury in Alcoholic Liver Disease. (Full text)

DEPTOR Suppresses Lipogenesis and Ameliorates Hepatic Steatosis and Acute-on-Chronic Liver Injury in Alcoholic Liver Disease. Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver injury. However, how chronic alcohol consumption causes hepatic lipid accumulation remains elusive. The present study demonstrates that activation of the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in alcoholic steatosis, inflammation, and liver injury. Chronic-plus (...) overexpression of hepatic DEPTOR suppressed mTORC1 signaling and ameliorated alcoholic hepatosteatosis, inflammation, and acute-on-chronic liver injury. Mechanistically, the lipid-lowering effect of hepatic DEPTOR was attributable to decreased proteolytic processing, nuclear translocation, and transcriptional activity of the lipogenic transcription factor sterol regulatory element-binding protein-1 (SREBP-1). DEPTOR-dependent inhibition of mTORC1 also attenuated alcohol-induced cytoplasmic accumulation

2018 Hepatology

133. Arid1a loss drives non-alcoholic steatohepatitis in mice via epigenetic dysregulation of hepatic lipogenesis and fatty acid oxidation. (PubMed)

Arid1a loss drives non-alcoholic steatohepatitis in mice via epigenetic dysregulation of hepatic lipogenesis and fatty acid oxidation. Nonalcoholic steatohepatitis (NASH) is a rapidly growing cause of chronic liver damage, cirrhosis, and hepatocellular carcinoma (HCC). How fatty liver pathogenesis is subject to epigenetic regulation is unknown. We hypothesized that chromatin remodeling is important for the pathogenesis of fatty liver disease. ARID1A, a DNA-binding component of the SWI/SNF ATP (...) mice were more susceptible to high-fat diet-induced liver steatosis and fibrosis. We deleted Pten in combination with Arid1a to synergistically drive fatty liver progression. Inhibition of lipogenesis using CAT-2003, a potent SREBP inhibitor, mediated improvements in markers of fatty liver disease progression in this Arid1a/Pten double knockout model. CONCLUSION: ARID1A plays a role in the epigenetic regulation of hepatic lipid homeostasis, and its suppression contributes to fatty liver

2018 Hepatology

134. Health-related Quality of Life in Non-alcoholic Fatty Liver Disease Associates With Hepatic Inflammation. (PubMed)

Health-related Quality of Life in Non-alcoholic Fatty Liver Disease Associates With Hepatic Inflammation. Chronic liver disease has negative effects on health-related quality of life (HRQL). We analyzed data from the European non-alcoholic fatty liver disease (NAFLD) registry to assess the effects of NAFLD on HRQL.We collected data from 304 patients (mean age, 52.3±12.9 years) with histologically defined NAFLD enrolled prospectively into the European NAFLD Registry in Germany, the United

2018 Clinical Gastroenterology and Hepatology

135. Transplantation for Alcoholic Hepatitis: Are We Achieving Justice and Utility? (PubMed)

Transplantation for Alcoholic Hepatitis: Are We Achieving Justice and Utility? Early liver transplantation for alcoholic hepatitis is a potentially life-saving treatment. As this practice becomes increasingly common, however, the liver transplant community is taking a fresh look at a familiar challenge: best stewardship of donor organs. Herein, we examine a few basic, necessary ethical and practical concerns relevant to this indication.© 2018 by the American Association for the Study of Liver

2018 Hepatology

136. The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise. (Full text)

The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise. The prevalence of alcohol misuse increased substantially over a decade in adults, particularly in those aged 65 years or older. Ramifications for brain structural integrity are significant, especially in older adults.To combine cross-sectional, longitudinal data to test age-alcoholism interactions and examine the association between prevalent comorbidities (drug dependence and hepatitis C virus (...) [HCV] infection) and cortical volume deficits in alcohol dependence.During 14 years, 826 structural magnetic resonance images were acquired in 222 individuals with alcohol dependence and 199 age-matched control participants (aged 25-75 years at initial study), parcellated with a common atlas, and adjusted for brain volume. Longitudinal data were available on 116 participants with alcoholism and 96 control participants. DSM-IV criteria determined alcohol and drug diagnoses; serology testing

2018 JAMA psychiatry (Chicago, Ill.)

137. The hepatic BMAL1/AKT/Lipogenesis axis protects against alcoholic liver disease via promoting PPARα pathway. (Full text)

The hepatic BMAL1/AKT/Lipogenesis axis protects against alcoholic liver disease via promoting PPARα pathway. Alcohol liver disease (ALD) is one of the major chronic liver diseases worldwide, ranging from fatty liver, alcoholic hepatitis, cirrhosis, and potentially, hepatocellular carcinoma. Epidemiological studies suggest a potential link between ALD and impaired circadian rhythms, but the role of hepatic circadian proteins in the pathogenesis of ALD remains unknown. Here we show (...) hepatic fatty acid oxidation but also alleviates ethanol-induced fatty liver and liver injury. Furthermore, hepatic over-expression of lipogenic transcription factor ChREBP, but not SREBP-1c, in the liver of Bmal1-LKO mice also increases fatty acid oxidation and partially reduces ethanol-induced fatty liver and liver injury.we identified a novel protective role of BMAL1 in hepatocytes against ALD. The protective action of BMAL1 during alcohol consumption depends on its ability to couple ChREBP-induced

2018 Hepatology

138. The prognostic value of Acute-on-Chronic Liver Failure during the course of severe alcoholic hepatitis. (PubMed)

The prognostic value of Acute-on-Chronic Liver Failure during the course of severe alcoholic hepatitis. A better identification of factors predicting death is needed in alcoholic hepatitis (AH). Acute-on-chronic liver failure (ACLF) occurs during the course of liver disease and can be identified when AH is diagnosed (prevalent ACLF [pACLF]) or during follow-up (incidental ACLF [iACLF]). This study analyzed the impact of ACLF on outcomes in AH and the role of infection on the onset of ACLF (...) the course of severe alcoholic hepatitis. In severe alcoholic hepatitis, acute-on-chronic liver failure is associated with high mortality and frequently occurs after an infection.Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

2018 Journal of Hepatology

139. Comprehensive Laboratory Analysis of Korean Acute Alcoholic Intoxication Patients Reveals the Need for a National Hepatitis B Virus Vaccination Program in Korea (Full text)

Comprehensive Laboratory Analysis of Korean Acute Alcoholic Intoxication Patients Reveals the Need for a National Hepatitis B Virus Vaccination Program in Korea Acute alcoholic intoxication patients (AAIP) are a common public health problem. The aim of this study was to perform a comprehensive laboratory analysis for these patients to investigate the co-morbid medical problem.We retrospectively reviewed laboratory findings of AAIP who were transferred to the emergency department (ED) from (...) hemoglobin A1c (HbA1c) level (>7.0%). Positive rates of hepatitis B surface antigen and antiHBs antibody (anti-HBs Ab) were 3.5% (5/141) and 49.0% (68/141), respectively.Patients with AAIP who were transferred to ED had various laboratory abnormalities (anemia, thrombocytopenia, high HbA1c). They had low positive rate of anti-HBs Ab. This might be a public health problem, suggesting the need of hepatitis B virus vaccination program for AAIP. Our data suggest the need of further nationwide studies.

2018 Korean journal of family medicine

140. Acute alcoholic hepatitis and cellular Th1 immune responses to alcohol dehydrogenase. (PubMed)

Acute alcoholic hepatitis and cellular Th1 immune responses to alcohol dehydrogenase. Alcoholic hepatitis is characterised by florid hepatic inflammation, liver failure, and death within 28 days in 35% of patients. We recently showed proliferative peripheral blood mononuclear cell (PBMC) responses to alcohol dehydrogenase (ADH) in patients with alcohol-related cirrhosis, associated with T-helper-type 1 (Th1) immunity and disease severity. We aimed to define whether ADH-specific cellular (...) immunity is present in alcoholic hepatitis.PBMCs were collected from 15 patients with alcoholic hepatitis (modified Maddrey's discriminant function >32), nine with alcohol-related cirrhosis (long-term alcohol abstinence), and three healthy controls. 25 overlapping peptides, spanning the human ADH β1 subunit, were constructed. Proliferation to ADH peptides (1 × 10(5) cells per well, cultured with 10 mM peptides for 7 days) was assessed by (3)H-thymidine incorporation. A stimulation index (SI) of 2·5

2015 Lancet

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