Alcoholic hepatitis: from pathogenesis to treatment

Sougioultzis, Stavros; Dalakas, Evangelos; Hayes, Peter; Plevris, John

doi:10.1185/030079905x56493

Cited by 34 publications

(13 citation statements)

References 90 publications

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“…ALD has a broad disease spectrum that encompasses simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC) [3]. Of these diseases, alcoholic hepatitis (AH) is histologically characterized by steatosis, hepatocellular inflammation, necrosis, and pericellular fibrosis [4]. Patients with severe AH have a reported 30-day mortality of up to 50% [5]–[8].…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis

et al. 2014

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The accurate prognostic stratification of alcoholic hepatitis (AH) is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort) and 106 patients with AH between 2005 and 2012 (a validation cohort). The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL) were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC). For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001). In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment.

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Section: Introductionmentioning

confidence: 99%

Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis

et al. 2014

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“…For NASH, the main use of drugs is for the correction of concurrent metabolic disorders (statins, antihypertensive agents, antidiabetic drugs, etc.). Pharmacologic treatment of alcoholic liver disease should be based on the stage of the disease and the aims of treatment [117] . As for NASH, there are no approved medications and all the drugs in use are experimental.…”

Section: Treatmentmentioning

confidence: 99%

ASH and NASH

Scaglioni

Ciccia

Marino

et al. 2011

Dig Dis

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Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) have a similar pathogenesis and histopathology but a different etiology and epidemiology. NASH and ASH are advanced stages of non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). NAFLD is characterized by excessive fat accumulation in the liver (steatosis), without any other evident causes of chronic liver diseases (viral, autoimmune, genetic, etc.), and with an alcohol consumption ≤20–30 g/day. On the contrary, AFLD is defined as the presence of steatosis and alcohol consumption >20–30 g/day. The most common phenotypic manifestations of primary NAFLD/NASH are overweight/obesity, visceral adiposity, type 2 diabetes, hypertriglyceridemia and hypertension. The prevalence of NAFLD in the general population in Western countries is estimated to be 25–30%. The prevalence and incidence of NASH and ASH are not known because of the impossibility of performing liver biopsy in the general population. Up to 90% of alcoholics have fatty liver, and 5–15% of these subjects will develop cirrhosis over 20 years. The risk of cirrhosis increases to 30–40% in those who continue to drink alcohol. About 10–35% of alcoholics exhibit changes on liver biopsy consistent with alcoholic hepatitis. Natural histories of NASH and ASH are not completely defined, even if patients with NASH have a reduced life expectancy due to liver-related death and cardiovascular diseases. The best treatment of AFLD/ASH is to stop drinking, and the most effective first-line therapeutic option for NAFLD/NASH is non-pharmacologic lifestyle interventions through a multidisciplinary approach including weight loss, dietary changes, physical exercise, and cognitive-behavior therapy.

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“…Numerous clinical and experimental studies have shown that the increased level of hepatic TNFα and monocyte TNFα production in alcoholic hepatitis are positively correlated with disease severity [2,32]. Chronic ethanol exposure enhances LPS-stimulated TNF production in RAW264.7 cells as well as Kupffer cells [21,22].…”

Section: Discussionmentioning

confidence: 99%

Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice

Lee

Eun²

2012

Korean J Physiol Pharmacol

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Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor α (TNFα) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNFα production in vitro and in vivo, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNFα mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP-activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNFα production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The in vivo effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNFα mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNFα production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNFα production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNFα production by cilostazol.

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Alcoholic hepatitis: from pathogenesis to treatment

Abstract: Medline 1966-2005, EMBASE/Excerpta Medica 1980-2005, The Cochrane Library (2005 Issue 2) and contact with authors of published reports.

Cited by 34 publications

References 90 publications

Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis

Spontaneous Evolution in Bilirubin Levels Predicts Liver-Related Mortality in Patients with Alcoholic Hepatitis

ASH and NASH

Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice

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