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Alcoholic Hepatitis

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41. Management of Alcohol-Related Liver Disease

proven to have good sensitivity and speci?city in clinical settings across different countries. 34 TheAUDIThas10questionsthatexploreconsumption(1–3), dependence (4–6), and alcohol-related problems (7–10) (Table 3). There are two cut-off points, one for dependence and one for risky drinking. Shorter versions have been devel- oped. The AUDIT-C includes just the ?rst three questions of the AUDIT and is reliable for the screening of ‘risky drink- ing’. 35,36 Infact,itisastandardisedwaytoquicklyapplyaquan (...) should include determi- nationofLFTsandameasureofliver?brosis.(GradeA1) Abstinence can be accurately monitored by measure- ment of EtG in urine or hair (Grade A2) Management of alcoholic hepatitis De?nition and diagnosis Alcoholic hepatitis is a distinct clinical syndrome characterised by the recent onset of jaundice with or without other signs of liver decompensation (i.e. ascites and/or encephalopathy) in patients with ongoing alcohol abuse. 176 It is not uncommon for patients to have ceased

2018 European Association for the Study of the Liver

42. What is the excess cost/use of health and social resources related to alcohol?

and indirect, health, and societal. • Service utilisation – treatment, hospitalisation, accident and emergency attendance, ambulance call outs, outpatient visits, social services. • Injury - road accidents, assault, falls. • Fetal Alcohol Spectrum Disorders (FASD). • Health and wellbeing – illness, child welfare, carers, dependents. • Impact of problem drinking on family and the community. • Productivity losses – absence, unemployment. Costs Only 15 papers (1, 2, 7, 10-21) gave actual costs, some (...) ? KLS Evidence Briefing 19/07/18 https://masshealthpolicyforum.brandeis.edu/forums/Documents/FINAL-SEN- IssueBrief_For-Print.pdf 35. Mortimer D, Segal L 2006. Economic evaluation of interventions for problem drinking and alcohol dependence: Do within-family external effects make a difference? Alcohol and Alcoholism 41(1) 92-8. Available: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=psy c5&AN=2006-00560-014 36. Balsa AI, French MT 2012. The impact of parental drinking

2018 Public Health England - Evidence Briefings

43. Effects of Alcohol Consumption and Metabolic Syndrome on Mortality in Patients with Non-alcoholic and Alcohol-Related Fatty Liver Disease. (Abstract)

Survey III for adults (20-74 years old) with hepatic steatosis, detected by ultrasound, for whom mortality and follow-up data were available. We collected data from the alcohol use questionnaire (self-reported number of days a participant drank alcohol; the number of drinks [10 g alcohol] per day on a drinking day; the number of days the participant had 5 or more drinks) and calculated the average amount of alcohol consumption in drinks/day for each participant during the year preceding enrollment (...) . Excessive alcohol consumption for men was >3 drinks/day and for women was >1.5 drinks/day. We also collected clinical data, and mortality data were obtained from the National Death Index. Demographic and clinical parameters were compared among consumption groups using the χ2 test for independence or survey regression models. We used Cox proportional hazard models to identify independent predictors of all-cause and cause-specific mortality.The study cohort included 4264 individuals with hepatic steatosis

2018 Clinical Gastroenterology and Hepatology

44. Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users. Full Text available with Trip Pro

Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users. Problem alcohol use is common among illicit drug users and is associated with adverse health outcomes. It is also an important factor contributing to a poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opiate overdose in opioid users.To assess the effects of psychosocial interventions for problem alcohol use in illicit (...) drug users (principally problem drug users of opiates and stimulants).We searched the Cochrane Drugs and Alcohol Group trials register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 11, June 2014), MEDLINE (1966 to June 2014); EMBASE (1974 to June 2014); CINAHL (1982 to June 2014); PsycINFO (1872 to June 2014) and the reference lists of eligible articles. We also searched: 1) conference proceedings (online archives only) of the Society

2014 Cochrane

45. Zinc deficiency and advanced liver fibrosis among HIV and hepatitis C co-infected anti-retroviral naïve persons with alcohol use in Russia. Full Text available with Trip Pro

Zinc deficiency and advanced liver fibrosis among HIV and hepatitis C co-infected anti-retroviral naïve persons with alcohol use in Russia. Liver disease in people living with HIV co-infected with hepatitis C virus is a source of morbidity and mortality in Russia. HIV accelerates liver fibrosis in the setting of HCV co-infection and alcohol use. Zinc deficiency is common among people living with HIV and may be a factor that facilitates the underlying mechanisms of liver fibrosis. We (...) investigated the association between zinc deficiency and advanced liver fibrosis in a cohort of HIV/HCV co-infected persons reporting heavy drinking in Russia.This is a secondary data analysis of baseline data from 204 anti-retroviral treatment naïve HIV/HCV co-infected Russians with heavy drinking that were recruited into a clinical trial of zinc supplementation. The primary outcome of interest in this cross-sectional study was advanced liver fibrosis. Zinc deficiency, the main independent variable

2019 PLoS ONE

46. NAMPT overexpression alleviates alcohol-induced hepatic steatosis in mice. Full Text available with Trip Pro

NAMPT overexpression alleviates alcohol-induced hepatic steatosis in mice. Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD)+ biosynthesis. Through its NAD+-biosynthetic activity, NAMPT influences the activity of NAD+-dependent enzymes, such as sirtuins. NAMPT is able to modulate processes involved in the pathogenesis of non-alcohol induced fatty liver disease (NAFLD), but the roles NAMPT plays in development (...) of alcoholic liver disease (ALD) still remain unknown. Here, we show that ethanol treatment suppresses the expression of Nampt in hepatocytes. Consistently, chronic ethanol administration also reduces Nampt expression in the mouse liver. We next demonstrate that hepatocytes infected with Ad-NAMPT adenovirus exhibit significantly elevated intracellular NAD+ levels and decreased ethanol-induced triglyceride (TG) accumulation. Similarly, adenovirus-mediated overexpression of NAMPT in mice ameliorates ethanol

2019 PLoS ONE

47. In Severe Alcoholic Hepatitis, Serum Keratin-18 Fragments Are Diagnostic, Prognostic, and Theragnostic Biomarkers. (Abstract)

In Severe Alcoholic Hepatitis, Serum Keratin-18 Fragments Are Diagnostic, Prognostic, and Theragnostic Biomarkers. Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH.Total (K18-M65) and caspase-cleaved K18 (K18-M30) were (...) quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls.K18 fragments were markedly elevated in severe AH and strongly predicted steatohepatitis (alcoholic steatohepatitis) on biopsy (area under receiver operating characteristics: 0.787 and 0.807). Application of published thresholds to predict alcoholic steatohepatitis would have rendered biopsy unnecessary in 84% of all AH

2020 American Journal of Gastroenterology

48. Intestinal virome in patients with alcoholic hepatitis. (Abstract)

Intestinal virome in patients with alcoholic hepatitis. Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.We extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD

2020 Hepatology

49. Reply: Relevance of Circulating Extracellular Vesicles Carrying Sphingolipid Cargo in Alcoholic Hepatitis: Need for more validation! (Abstract)

Reply: Relevance of Circulating Extracellular Vesicles Carrying Sphingolipid Cargo in Alcoholic Hepatitis: Need for more validation! We thank Arora et al. for their interest in our study. They comment on the limitations of our study which proposes the use of extracellular vesicles (EVs) and associated sphingolipid cargo as a novel biomarker for alcoholic hepatitis (AH) and reiterate our own conclusion for the need of validation of our findings in a larger cohort.This article is protected

2020 Hepatology

50. Serum Transferrin Is an Independent Predictor of Mortality in Severe Alcoholic Hepatitis. (Abstract)

Serum Transferrin Is an Independent Predictor of Mortality in Severe Alcoholic Hepatitis. Severe alcoholic hepatitis (sAH) confers substantial mortality, but the disease course is difficult to predict. As iron parameters are attractive outcome predictors in other liver diseases, we tested their prognostic ability in sAH.Serum ferritin, transferrin, iron, transferrin saturation, nontransferrin-bound iron, soluble transferrin receptor, and hepcidin were measured in 828 patients with sAH recruited (...) was comparable with the composite scores, namely model of end-stage liver disease, Glasgow alcoholic hepatitis score, and discriminant function, and was independently associated with survival in multivariable analysis. These results were confirmed in a validation cohort. Transferrin did not correlate with markers of liver synthesis nor with non-transferrin-bound iron or soluble transferrin receptor (as markers of excess unbound iron and functional iron deficiency, respectively).In patients with sAH, serum

2020 American Journal of Gastroenterology

51. Trace element deficiency is highly prevalent and associated with infection and mortality in patients with alcoholic hepatitis. (Abstract)

Trace element deficiency is highly prevalent and associated with infection and mortality in patients with alcoholic hepatitis. Malnutrition is common in patients with alcohol-related liver disease and is associated with outcome in patients with alcoholic hepatitis. Trace elements (cobalt, copper, iron, selenium and zinc) are micronutrients essential for many cellular processes including antioxidant pathways. The prevalence and relevance of trace element deficiency is unknown in alcoholic (...) hepatitis.To determine the prevalence of trace element deficiency and its association with clinical outcomes in patients with alcoholic hepatitis.Serum was obtained from patients with alcoholic hepatitis, alcohol-related cirrhosis and healthy volunteers as part of clinical trials, cohort studies and a biobank. Trace element concentration was measured by inductively coupled plasma mass spectrometry. Association of trace element levels with development of infection within 90 days and mortality within 28

2020 Alimentary Pharmacology & Therapeutics

52. Meeting Report: The Dallas Consensus Conference on Liver Transplantation for Alcohol Associated Hepatitis. Full Text available with Trip Pro

Meeting Report: The Dallas Consensus Conference on Liver Transplantation for Alcohol Associated Hepatitis. Liver transplantation (LT) for alcohol associated hepatitis (AH) remains controversial. We convened a consensus conference to examine various aspects of LT for AH. The goal was not to unequivocally endorse LT for AH; instead, it was to propose recommendations for programs that perform or plan to perform LT for AH. Criteria were established to determine candidacy for LT in the setting of AH (...) unsuccessful attempts at addiction rehabilitation, lack of other substance use/dependency, acceptance of diagnosis/insight with a commitment of the patient/family to sobriety, and formalized agreement to adhere to total alcohol abstinence and counseling. LT should be avoided in AH patients who are likely to spontaneously recover. Short-term and longterm survival comparable to other indications for LT must be achieved. There should not be further disparity in LT either by indication, geography, or other

2020 Liver Transplantation

53. Debate on Selection Criteria for Liver Transplantation for Alcoholic Hepatitis: Tighten or Loosen? (Abstract)

Debate on Selection Criteria for Liver Transplantation for Alcoholic Hepatitis: Tighten or Loosen? Although liver transplantation (LT) for alcohol-associated liver disease (ALD) is a well-accepted practice, LT for severe alcoholic hepatitis (AH) remains controversial due to concerns about the limited organ supply and the risk of return to harmful drinking. Recognizing an increasing body of favorable evidence, a convergence of practice guideline recommendations from leading hepatology

2020 Liver Transplantation

54. Early Liver Transplantation in Acute Alcoholic Hepatitis. (Abstract)

Early Liver Transplantation in Acute Alcoholic Hepatitis. Alcohol-related liver disease (ALD) is currently the leading indication for liver transplantation in the United States. Among patients with ALD, those with acute alcoholic hepatitis who do not respond to medical treatment have a 6-month mortality of 70% without transplantation. Despite the high mortality, the majority of patients will not be eligible for transplant, given that most centers follow the 6-month abstinence rule. A handful (...) of centers in Europe and the United States perform early liver transplantation (< 6 months abstinence) in these patients, as it provides a substantial survival benefit. Short-term outcomes for these recipients are favorable, and relapse rates parallel those seen in alcoholic cirrhosis transplant recipients who have completed the 6-month wait period. Moving forward, studies examining long-term outcomes and candidate selection are necessary for this growing subset of liver transplant candidates.Thieme

2020 Seminars in Liver Disease

55. Chronic hepatitis B and non-alcoholic fatty liver disease: Conspirators or competitors? Full Text available with Trip Pro

Chronic hepatitis B and non-alcoholic fatty liver disease: Conspirators or competitors? Despite the widespread use of vaccines and antiviral drugs, approximately 350-400 million patients with chronic hepatitis B (CHB) remain worldwide, who carry high risk of cirrhosis and liver carcinoma. Moreover, owing to improvements in global living standards and lifestyle changes, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. Coexistence of NAFLD and CHB

2020 Liver International

56. Dimethyl fumarate ameliorates hepatic inflammation in alcohol related liver disease. Full Text available with Trip Pro

Dimethyl fumarate ameliorates hepatic inflammation in alcohol related liver disease. Alcohol-related liver disease (ALD) comprises different liver disorders which impose a health care issue. ALD and particularly alcoholic steatohepatitis, an acute inflammatory condition, cause a substantial morbidity and mortality as effective treatment options remain elusive. Inflammation in ALD is fuelled by macrophages (Kupffer cells [KCs]) which are activated by intestinal pathogen associated molecular (...) by histology, biochemical- and immunoassays. Moreover, we investigated a direct immunosuppressive effect of DMF on KCs and explored a potential impact on ethanol-induced intestinal barrier disruption.Dimethyl-fumarate protected against ethanol-induced hepatic injury, steatosis and inflammation in mice. Specifically, we observed reduced hepatic triglyceride and ALT accumulation, reduced hepatic expression of inflammatory cytokines (Tnf-α, Il-1β, Cxcl1) and reduced abundance of neutrophils and macrophages

2020 Liver International

57. Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy. (Abstract)

Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy. Obesity is associated with non-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients with chronic liver disease of different aetiologies (eg HCV, alcohol). However, information on the prevalence and clinical

2020 Liver International

58. Attenuated effect of PNPLA3 on hepatic fibrosis by HSD17B13 in Japanese patients with non-alcoholic fatty liver disease. (Abstract)

Attenuated effect of PNPLA3 on hepatic fibrosis by HSD17B13 in Japanese patients with non-alcoholic fatty liver disease. PNPLA3 rs738409 has been associated with increased risks of fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Recently, carriage of the rs6834314 G allele, which is in high linkage with rs72613567 of 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13), was reported to be associated with a reduced risk of liver injury in NAFLD patients. We estimated (...) the impact of these genetic variants on hepatic fibrosis in Japanese patients with NAFLD.We analysed the associations of these genetic variants with liver histology in 290 Japanese patients with biopsy-proven NAFLD diagnosed during 2002-2019. During follow-up, 14 patients (4.8%) developed hepatocellular carcinoma.Prevalences of the PNPLA3 rs738409 genotypes were 0.17 for CC, 0.41 for CG, 0.42 for GG, and those for HSD17B13 rs6834314 were 0.54 for AA, 0.39 for AG and 0.07 for GG. There was no significant

2020 Liver International

59. Alcohol Use Is Associated With Hepatic Steatosis Among Persons With Presumed Nonalcoholic Fatty Liver Disease. Full Text available with Trip Pro

multivariable-adjusted logistic regression models to evaluate the association between alcohol drinking patterns and hepatic steatosis. Models were adjusted for sociodemographic factors, diet, and the components of the metabolic syndrome. We excluded heavy alcohol users, defined as women who consume more than 14 alcohol drinks per week and men who consume more than 21 alcohol drinks per week.In our sample (mean age, 49.8 ± 10.2 y; 50.3% women), the prevalence of hepatic steatosis was 17.5%. The total number (...) Alcohol Use Is Associated With Hepatic Steatosis Among Persons With Presumed Nonalcoholic Fatty Liver Disease. Many individuals presumed to have nonalcoholic fatty liver disease (NAFLD) consume moderate amounts of alcohol. Little is known about patterns of alcohol use in patients with NAFLD or how drinking behaviors affect liver fat.We conducted a cross-sectional study of 2475 participants of the Framingham Heart Study with hepatic steatosis, as determined by computed tomography. We performed

2020 Clinical Gastroenterology and Hepatology

60. Protocol for a phase IV, open-label feasibility study investigating non-invasive markers of hepatic fibrosis in people living with HIV-1 and non-alcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT Full Text available with Trip Pro

Protocol for a phase IV, open-label feasibility study investigating non-invasive markers of hepatic fibrosis in people living with HIV-1 and non-alcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT At least 30% of people living with HIV (PLWH) infection have non-alcoholic fatty liver disease (NAFLD), which has now become a leading cause of hepatic fibrosis and cirrhosis. Management is based largely on lifestyle modifications, which (...) are difficult to achieve, and therapeutic options are urgently needed. Maraviroc (MVC), through antagonism of CCR5 receptors, may reduce hepatic fibrosis progression and could be an effective treatment for NAFLD. However, dosing is usually two times per day, unlike most currently recommended antiretroviral therapies. This study will investigate the feasibility and acceptability of addition of MVC to combination antiretroviral therapy in PLWH and NAFLD as a treatment for NAFLD.This is a phase IV, randomised

2020 BMJ open

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