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Alcoholic Hepatitis

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1. Baclofen Abuse due to Its Hypomanic Effect in Patients with Alcohol Dependence and Comorbid Major Depressive Disorder Full Text available with Trip Pro

Baclofen Abuse due to Its Hypomanic Effect in Patients with Alcohol Dependence and Comorbid Major Depressive Disorder Baclofen is a gamma-aminobutyric acid type B receptor agonist used as an anti-craving agent for treatment of alcohol dependence. It has gained popularity in the recent times because it is well tolerated even in patients with hepatic impairments. Herein we are summarizing the latest literature about baclofen induced hypomania and are reporting a case of baclofen abuse because (...) of its mood elevating property in a patient of alcohol dependence with comorbid major depressive disorder. Literature review and case study of a 36-year-old male with alcohol dependence with comorbid major depressive disorder was prescribed with tablet baclofen as an anti-craving agent along with antidepressant medicines. The patients who did not improve with conventional antidepressant therapy started feeling better in terms of his mood symptoms on taking tablet baclofen. Owing to the mood elevating

2017 Clinical Psychopharmacology and Neuroscience

2. Hepatic NK cells attenuate fibrosis progression of non-alcoholic steatohepatitis in dependent of CXCL10-mediated recruitment. (Abstract)

Hepatic NK cells attenuate fibrosis progression of non-alcoholic steatohepatitis in dependent of CXCL10-mediated recruitment. Non-alcoholic steatohepatitis (NASH) is a major cause of chronic liver disease. The precise role of NK cells in the progression of NASH has yet to be elucidated.Using methionine- and choline-deficient diets (MCD)-induced NASH model, the role of NK cells was identified in WT mice compared with conventional NK cell-deficient Nfil3-/- mice.After 8 weeks of MCD treatment

2020 Liver International

3. Direct-acting antiviral interactions with opioids, alcohol or illicit drugs of abuse in HCV-infected patients. Full Text available with Trip Pro

Direct-acting antiviral interactions with opioids, alcohol or illicit drugs of abuse in HCV-infected patients. The hepatitis C virus (HCV) prevalence is extremely high in patients who consume and inject illicit drugs. Concerns about poor adherence and fear of interaction with drugs of abuse could constitute further disincentive for treatment initiation in these patients. We discussed the pharmacokinetics (PKs) and pharmacodynamics (PD) of currently prescribed direct antiviral agents (NSA5 (...) inhibitors: daclatasvir, elbasvir, ledipasvir, pibrentasvir, velpatasvir; NS5B inhibitor: sofosbuvir; NS3/4A protease inhibitors: glecaprevir, grazoprevir, voxilaprevir) and most common substances of abuse (opioids: buprenorphine, fentanyl, heroin, methadone, morphine, oxycodone; stimulants: amphetamines, cathinones, cocaine; cannabinoids; ethanol). Overall, most direct-acting antivirals (DAAs) are substrates and inhibitors of the transmembrane transporter P-glycoprotein (P-gp), and several of them

2020 Liver International

4. Apical sodium-dependent bile acid transporter inhibition with volixibat improves metabolic aspects and components of non-alcoholic steatohepatitis in Ldlr-/-.Leiden mice. Full Text available with Trip Pro

Apical sodium-dependent bile acid transporter inhibition with volixibat improves metabolic aspects and components of non-alcoholic steatohepatitis in Ldlr-/-.Leiden mice. Interruption of bile acid recirculation through inhibition of the apical sodium-dependent bile acid transporter (ASBT) is a promising strategy to alleviate hepatic cholesterol accumulation in non-alcoholic steatohepatitis (NASH), and improve the metabolic aspects of the disease. Potential disease-attenuating effects (...) significantly attenuated the HFD-induced increase in hepatocyte hypertrophy, hepatic triglyceride and cholesteryl ester levels, and mesenteric white adipose tissue deposition. Non-alcoholic fatty liver disease activity score (NAS) was significantly lower in volixibat-treated mice than in the HFD controls. Gene profiling showed that volixibat reversed the inhibitory effect of the HFD on metabolic master regulators, including peroxisome proliferator-activated receptor-γ coactivator-1β, insulin receptor

2019 PLoS ONE

5. Does Treatment With GLP-1 Reduce Alcohol Intake in Patients With Alcohol Dependence?

/l Former medullary thyroid carcinoma (MTC) and/or family history with MTC and/or Multiple Endo-crine Neoplasia syndrome type 2 (MEN 2) Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >110 mmHg) Concomitant pharmacotherapy against alcohol dependence including disulfiram, naltrexone, acamprosate (...) and written consent Diagnosed with alcohol dependence according to the criteria of International Classification of Diseases (ICD) 10, World Health Organization and DSM-5 Alcohol use disorder identification test (AUDIT) score >15 Age 18 - 70 years Heavy alcohol drinking defined as having alcohol consumption over 60 g of alcohol per day (men) or 48 g of alcohol per day (women) for at least 5 days in the past 30 days prior to inclusion measured by the TLFB method. Exclusion Criteria: Severe psychiatric

2017 Clinical Trials

6. Hepatitis C infection substantially reduces survival of alcohol-dependent patients Full Text available with Trip Pro

Hepatitis C infection substantially reduces survival of alcohol-dependent patients Heavy alcohol use is associated with life-threatening complications including progressive liver disease. We aimed to analyze the impact of hepatitis C virus (HCV) infection on survival and liver-related death in alcohol-dependent patients.This is a longitudinal study in patients seeking treatment of alcohol abuse between 2000 and 2010. Information on alcohol use characteristics, alcoholic liver disease, and HCV (...) , 0.86). The main causes of death in the HCV-positive and -negative patients were liver-related mortality (48.4%) and neoplasia (22.4%), respectively. The liver-related mortality was significantly higher among the HCV-positive patients (adjusted sub-distribution hazard ratio [asHR] 3.65; 95% CI: 1.72, 7.78; P=0.001).HCV infection compromises the survival of patients with alcohol abuse/dependence. The new direct antiviral agents for the treatment of HCV infection may result in better clinical outcomes.

2018 Clinical epidemiology

7. The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise. Full Text available with Trip Pro

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.)

8. Efficacy and Safety Evaluating Study of Odelepran for the Use in Patient With Alcohol Dependence

) according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria. Patients diagnosed with alcohol dependence according to the International Classification of Diseases (ICD)-10, assessed with the Mini-International Neuropsychiatric Interview (MINI). Abstaining from alcohol during 3 days prior to screening and 3 days before randomization confirmed by the test for alcohol in exhaled air (less than 0,02 %). For women retaining childbearing potential - negative pregnancy test and consent (...) or other psychoneurological functioning (verified for head injury with the loss of consciousness that lasted more than 1 hour, or resulted in cognitive or behavioral impairment, stroke, encephalopathy, dementia, neurodegenerative disorder, etc). Except for mild cognitive impairment. Mental retardation of syndromes of severe organic brain injury. Use of drugs of abuse (opioids, cannabinoids, amphetamines, etc.) or diagnoses of substance addiction/dependence at the moment of screening or positive urine

2018 Clinical Trials

9. B-hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. Full Text available with Trip Pro

B-hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. Sterile inflammation resulting in alcoholic hepatitis (AH) occurs unpredictably after many years of excess alcohol intake. The factors responsible for the development of AH are not known but mitochondrial damage with loss of mitochondrial function are common features. Hcar2 is a G-protein coupled receptor which is activated by β-hydroxybutyrate (BHB). We aimed to determine the relevance of the BHB (...) ) induced by BHB.Collectively, our data shows that BHB production during excess alcohol consumption has an anti-inflammatory and hepatoprotective role through an Hcar2 dependent pathway. This introduces the concept of metabolite-based therapy for AH.Alcoholic hepatitis is a life-threatening condition with no approved therapy that occurs unexpectedly in people who consume excess alcohol. The liver makes many metabolites, and we demonstrate that loss of one such metabolite β-hydroxybutyrate occurs

2018 Journal of Hepatology

10. FOXO3-dependent apoptosis limits alcohol-induced liver inflammation by promoting infiltrating macrophage differentiation Full Text available with Trip Pro

that in response to alcohol, approximately 10% of mouse hepatic macrophages undergo FOXO3-dependent apoptosis. By 3 days of alcohol exposure total hepatic macrophage numbers declined by 30% but these were restored to normal after 10 days of continued exposure. Whole body or myeloid specific Foxo3-/- mice failed to show this apoptotic response. After 10 days of alcohol exposure, Foxo3-/- mice had an increased basal inflammatory phenotype and an increase in the proportion of pro-inflammatory CD11b+, Ly6C (...) FOXO3-dependent apoptosis limits alcohol-induced liver inflammation by promoting infiltrating macrophage differentiation Alcohol consumption is generally well tolerated by the liver but in some individuals it results in persistent inflammation and liver disease. The mechanisms that regulate alcohol-induced liver inflammation are poorly understood. The transcription factor FOXO3 has previously been shown to be involved in suppressing alcohol-induced liver injury. In this study we demonstrate

2018 Cell Death Discovery

11. Alcohol Abuse

, alcohol abuse - persistent , alcohol abuse - persistent (diagnosis) , Alcohol dependency , Alcohol dependence , Alcohol dependence syndrome , Dipsomania , Chronic alcoholism , Chronic alcohol abuse , Persistent alcohol abuse , Alcohol problem drinking , Alcohol dependence (disorder) , Alcoholism (disorder) , Persistent alcohol abuse (disorder) , dipsomania , chronic; drunkenness , dependence; alcohol , drunkenness; chronic , addiction; alcohol , alcohol; addiction , alcohol; dependence , Alcoholism (...) (& [dipsomania]) , Chronic alcoholism NOS (disorder) , [X]Alcohol addiction , [X]Dipsomania , (Alcohol dependence syndrome [including alcoholism]) or (alcohol problem drinking) (disorder) , Alcohol dependence syndrome NOS (disorder) , Chronic alcoholism (& [dipsomania]) (disorder) , (Alcohol dependence syndrome [including alcoholism]) or (alcohol problem drinking) , Dipsomania (finding) , [X]Mental and behavioral disorders due to use of alcohol: dependence syndrome (disorder) , [X]Chronic alcoholism

2018 FP Notebook

12. Alcohol - problem drinking

disorders: diagnosis and management of physical complications [ ]. This CKS topic covers the screening, identification, and management of people who misuse alcohol including harmful drinkers and people who are dependent on alcohol. This CKS topic does not specifically cover problem drinking in pregnancy, the management of acute alcohol intoxication, the management of problem drinking in younger people and children (younger than 18 years of age), or the management of alcohol-related disabilities (...) further help. Signs of severe alcohol-related impairment, or has a related comorbidity (e.g. liver disease or alcohol-related mental health problems). Have I got the right topic? Have I got the right topic? From age 18 years onwards. This CKS topic is largely based on the National Institute of Health and Care Excellence (NICE) guidelines Alcohol-use disorders: prevention [ ], Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence [ ], and Alcohol-use

2018 NICE Clinical Knowledge Summaries

13. Inhibition of MD2‐dependent inflammation attenuates the progression of non‐alcoholic fatty liver disease Full Text available with Trip Pro

Inhibition of MD2‐dependent inflammation attenuates the progression of non‐alcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD) can progress to the more serious non-alcoholic steatohepatitis (NASH), characterized by inflammatory injury and fibrosis. The pathogenic basis of NAFLD progressing to NASH is currently unknown, but growing evidence suggests MD2 (myeloid differentiation factor 2), an accessory protein of TLR4, is an important signalling component contributing (...) knockout in preventing the HFD-induced hepatic lipid accumulation, pro-fibrotic changes and expression of pro-inflammatory molecules. Direct challenge of HepG2 with PA (200 μM) increased MD2-TLR4 complex formation and expression of pro-inflammatory and pro-fibrotic genes and L6H21 pre-treatment prevented these PA-induced responses. Interestingly, MD2 knockout or L6H21 increased expression of the anti-inflammatory molecule, PPARγ, in liver tissue and the liver cell line. Our results provide further

2017 Journal of cellular and molecular medicine

14. Age-dependent Protein Abundance of Cytosolic Alcohol and Aldehyde Dehydrogenases in Human Liver Full Text available with Trip Pro

Age-dependent Protein Abundance of Cytosolic Alcohol and Aldehyde Dehydrogenases in Human Liver Hepatic cytosolic alcohol and aldehyde dehydrogenases (ADHs and ALDHs) catalyze the biotransformation of xenobiotics (e.g., cyclophosphamide and ethanol) and vitamin A. Because age-dependent hepatic abundance of these proteins is unknown, we quantified protein expression of ADHs and ALDH1A1 in a large cohort of pediatric and adult human livers by liquid chromatography coupled with tandem mass

2017 Drug Metabolism and Disposition

15. Gene signature-MELD score and alcohol relapse determine long-term prognosis of patients with severe alcoholic hepatitis. Full Text available with Trip Pro

Gene signature-MELD score and alcohol relapse determine long-term prognosis of patients with severe alcoholic hepatitis. The gene-signature-model for end stage liver disease (gs-MELD) score has been shown to be a strong predictor of 6-month survival in severe alcoholic hepatitis (AH). Currently, only a few studies have evaluated the long-term prognosis of patients with severe AH.To assess the prognostic value of the gs-MELD score at 5 years in patients with severe AH.Forty-eight consecutive (...) % (95% CI: 10-47) in abstainers and in consumers (P < .001) respectively. In multivariable competing risk regression modelling, gs-MELD score (subdistribution hazard ratio: 5.78, 95% CI: 2.17-15.38, P < .001) and recurrent alcohol consumption (subdistribution hazard ratio: 12.18, 95% CI: 3.16-46.95, P < .001) were independently associated with 5-year mortality.Both gs-MELD score and alcohol consumption drive AH long-term prognosis. The gs-MELD score may guide the development of molecularly targeted

2020 Liver International

16. Fecal microbiome distinguishes alcohol consumption from alcoholic hepatitis but does not discriminate disease severity. (Abstract)

alcoholic hepatitis (MAH and SAH) was compared to healthy (HC) and heavy drinking controls (HDC). Microbial taxa were identified by 16S pyrosequencing. Functional metagenomics was performed using PICRUSt. Fecal short chain fatty acids (SCFA) were measured using an LC/MS platform.78 participants (HC, n=24; HDC, n=20; MAH, n=10; SAH, n=24) were studied. Heavy drinking had a distinct signature compared to healthy controls with depletion of Bacteroidetes (46% vs 26%; p=0.01). Alcoholic hepatitis (...) was associated with a distinct microbiome signature compared to heavy drinking controls (AUC=0.826); differential abundance of Ruminococcaceae, Veillonellaceae, Lachnospiraceae, Porphyromonadaceae, and Rikenellaceae families were the key contributors to these differences. The beta diversity was significantly different amongst the groups (PERMANOVA p < 0.001). Severe alcoholic hepatitis was associated with increased Proteobacteria (SAH 14% vs. HDC 7% and SAH vs. HC 2%, p=0.20 and 0.01 respectively

2020 Hepatology

17. Nalmefene in Patients With Alcoholic Compensated Cirrhosis for the Treatment of Alcohol Dependence.

national health insurance. Exclusion Criteria: cirrhosis Child Pugh C (decompensated cirrhosis) cirrhosis complicated by hepatocellular carcinoma or type I or II hepatorenal syndrome or poorly controlled portal hypertension, severe acute alcoholic hepatitis, not responding to corticosteroids by the 7th day defined by a Lille model > 0.56 (www.lillemodel.com/score.asp) hepatic encephalopathy during the 6 months preceding the screening visit, patient with fewer than 6 heavy drinking days during the 4 (...) Comparator: placebo The placebo will have the same composition as the active treatment (without the drug substance) and an identical appearance. White, oval, biconvex, 6.0 x 8.75 mm film-coated tablet engraved with "S" on one side. Drug: placebo Evaluate the efficacy, tolerability and safety of nalmefene for reduction of alcohol consumption (reduction of the number of monthly heavy drinking days, and daily total alcohol consumption) in alcohol-dependent patients with alcoholic compensated cirrhosis

2016 Clinical Trials

18. Characterization of intestinal microbiota in alcoholic patients with and without alcoholic hepatitis or chronic alcoholic pancreatitis Full Text available with Trip Pro

Characterization of intestinal microbiota in alcoholic patients with and without alcoholic hepatitis or chronic alcoholic pancreatitis Excessive alcohol consumption leads to severe alcoholic hepatitis (sAH) or chronic alcoholic pancreatitis (CAP) only in a subset of patients. We aimed to characterize the intestinal microbiota profiles of alcoholic patients according to the presence and nature of the complications observed: sAH or CAP. Eighty two alcoholic patients were included according (...) to their complications: CAP (N = 24), sAH (N = 13) or no complications (alcoholic controls, AC, N = 45). We analyzed the intestinal microbiota by high-throughput sequencing. Bacterial diversity was lower in patients with CAP, who had a global intestinal microbiota composition different from that of AC. The intestinal microbiota composition of these two groups differed for 17 genera, eight of which were more frequent in patients with CAP (e.g. Klebsiella, Enterococcus and Sphingomonas). There was no significant

2018 Scientific reports

19. Alcohol Rehabilitation Within 30 Days of Hospital Discharge is Associated With Reduced Readmission, Relapse, and Death in Patients with Alcoholic Hepatitis. Full Text available with Trip Pro

Alcohol Rehabilitation Within 30 Days of Hospital Discharge is Associated With Reduced Readmission, Relapse, and Death in Patients with Alcoholic Hepatitis. Patients admitted to the hospital for alcoholic hepatitis (AH) are at increased risk of readmission and death. We aimed to identify factors associated with readmission, alcohol relapse, and mortality.We performed a retrospective analysis of consecutive patients admitted with AH to a tertiary care hospital from 1999 through 2016 (test cohort (...) , n=135). We validated our findings in a prospective analysis of patients in a multi-center AH research consortium from 2013 through 2017 (validation cohort, n=159). Alcohol relapse was defined as any amount of alcohol consumption within 30 days after hospital discharge. Early alcohol rehabilitation was defined as residential or outpatient addiction treatment or mutual support group participation within 30 days after hospital discharge.Thirty-day readmission rates were 30% in both cohorts. Alcohol

2019 Clinical Gastroenterology and Hepatology

20. Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease. Full Text available with Trip Pro

alcoholic liver diseases, including fatty liver, steatohepatitis, fibrosis, alcoholic cirrhosis, and hepatocellular carcinoma, with presence or absence of hepatitis B or C virus infection. There are three scarring types (fibrosis) that are most commonly found in alcoholic liver disease: centrilobular scarring, pericellular fibrosis, and periportal fibrosis. When liver fibrosis progresses, alcoholic cirrhosis occurs. Hepatocellular carcinoma occurs in 5% to 15% of people with alcoholic cirrhosis (...) , but people in whom hepatocellular carcinoma has developed are often co-infected with hepatitis B or C virus.Abstinence from alcohol may help people with alcoholic disease in improving their prognosis of survival at any stage of their disease; however, the more advanced the stage, the higher the risk of complications, co-morbidities, and mortality, and lesser the effect of abstinence. Being abstinent one month after diagnosis of early cirrhosis will improve the chance of a seven-year life expectancy

2016 Cochrane

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