Incidence and mortality of alcoholic hepatitis in Denmark 1999–2008: A nationwide population based cohort study

Sandahl, Thomas Damgaard; Jepsen, Peter; Thomsen, Karen Louise; Vilstrup, Hendrik

doi:10.1016/j.jhep.2010.07.016

Cited by 133 publications

(97 citation statements)

References 9 publications

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“…However, a recent animal study indicates immune dysfunction even in dietary fatty livers (48). Also, with the progression from alcoholic steatosis to AH both the overall mortality (5-yr mortality; 17 vs. 56%) and the fraction of deaths attributed to infections increase (0.4 vs. 15%), which seems to point mostly at the former possibility (8,16,37,44).…”

Section: Discussionmentioning

confidence: 98%

Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced activation in patients with alcoholic hepatitis

Støy

Dige

Sandahl

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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The dynamics and role of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and NKT cells in the life-threatening inflammatory disease alcoholic hepatitis is largely unknown. These cells directly kill infected and damaged cells through, e.g., degranulation and interferon-γ (IFNγ) production, but cause tissue damage if overactivated. They also assist tissue repair via IL-22 production. We, therefore, aimed to investigate the frequency, functionality, and activation state of such cells in alcoholic hepatitis. We analyzed blood samples from 24 severe alcoholic hepatitis patients followed for 30 days after diagnosis. Ten healthy abstinent volunteers and 10 stable abstinent alcoholic cirrhosis patients were controls. Using flow cytometry we assessed cell frequencies, NK cell degranulation capacity following K562 cell stimulation, activation by natural killer group 2 D (NKG2D) expression, and IL-22 and IFNγ production. In alcoholic hepatitis we found a decreased frequency of CTLs compared with healthy controls (P < 0.001) and a similar trend for NK cells (P = 0.089). The NK cell degranulation capacity was reduced by 25% compared with healthy controls (P = 0.02) and by 50% compared with cirrhosis patients (P = 0.04). Accordingly, the NKG2D receptor expression was markedly decreased on NK cells, CTLs, and NKT cells (P < 0.05, all). The frequencies of IL-22-producing CTLs and NK cells were doubled compared with healthy controls (P < 0.05, all) but not different from cirrhosis patients. This exploratory study for the first time showed impaired cellular cytotoxicity and activation in alcoholic hepatitis. This is unlikely to cause hepatocyte death but may contribute toward the severe immune incompetence. The results warrant detailed and mechanistic studies.

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Section: Discussionmentioning

confidence: 98%

Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced activation in patients with alcoholic hepatitis

Støy

Dige

Sandahl

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Use of diagnostic coding is an accepted method of identifying patients with AH, based on previously published literature. 5, 13, 14 We stratified these patients into those with and without CDI, based on the presence of an additional diagnosis code for CDI (ICD-9-CM code 008.45).…”

Section: Methodsmentioning

confidence: 99%

“…One-month mortality rates for this disease range from less than 10% in non-severe AH, to as high as 30–50% in severe AH. 1–5 Infection is a major cause of mortality in this population, and a prior study from Louvet et al demonstrated that severe AH patients are at particularly high risk of developing infection, with bacteremia, urinary tract infection (UTI), and spontaneous bacterial peritonitis (SBP) among the most prevalent. 6 Based on these findings, guidelines from the European Association for the Study of the Liver have recommended routine screening with blood, urine and ascites fluid cultures prior to corticosteroid administration.…”

Section: Introductionmentioning

confidence: 97%

Effects of Clostridium difficile Infection in Patients With Alcoholic Hepatitis

Sundaram

May

Manne

et al. 2014

Clinical Gastroenterology and Hepatology

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Background & Aims Infection increases mortality in patients with alcoholic hepatitis (AH). Little is known about the association between Clostridium difficile infection (CDI) and AH. We examined the prevalence and effects of CDI in patients with AH, compared with those of other infections. Methods We performed a cross-sectional analysis using data collected from the Nationwide Inpatient Sample, from 2008 through 2011. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with AH. We used multivariable logistic regression to determine risk factors that affect mortality, negative binomial regression to evaluate the effects of CDI on predicted length of stay (LOS), and poisson regression to determine the effects of CDI on predicted hospital charges. χ2 and Wilcoxon rank-sum analyses were used to compare mortality, LOS, and hospital charges associated with CDI to those associated with urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP). Results Of 10,939 patients with AH, 177 had CDI (1.62%). Patients with AH and CDI had increased odds of inpatient mortality (adjusted odds ratio, 1.75; P=.04), longer predicted LOS (10.63 days vs 5.75 days, P<.001) and greater predicted hospital charges ($36,924.30 vs $29,136.58, P<.001), compared to those without CDI. Compared to UTI, CDI was associated with similar mortality but greater LOS (9 vs 6 days, P<.001) and hospital charges ($45,607 vs $32,087, P<.001). SBP was associated with higher mortality than CDI (17.3% vs 10.1%, P=0.045), but similar LOS and hospital charges. Conclusions In patients with AH, CDI is associated with greater mortality and healthcare utilization. These effects appear similar to those for UTI and SBP. We propose further studies to determine the cost-effectiveness of screening for CDI among patients with AH.

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“…Population based studies estimate approximately 4.5 hospitalizations for AH per 100,000 persons each year, with a slight male predominance (Sandahl et al, 2011). Patients typically present with rapidly progressive jaundice, which can be accompanied by fever, abdominal pain, anorexia, and weight loss.…”

Section: Alcoholic Hepatitismentioning

confidence: 99%

Alcoholic and non-alcoholic steatohepatitis

Neuman

French

et al. 2014

Experimental and Molecular Pathology

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This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.

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Incidence and mortality of alcoholic hepatitis in Denmark 1999–2008: A nationwide population based cohort study

Cited by 133 publications

References 9 publications

Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced activation in patients with alcoholic hepatitis

Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced activation in patients with alcoholic hepatitis

Effects of Clostridium difficile Infection in Patients With Alcoholic Hepatitis

Alcoholic and non-alcoholic steatohepatitis

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