| 1 | Therapy for alcoholic liver disease显示文摘Alcoholism results in about 2.5 million deaths annually worldwide,representing 4%of all mortality.Although alcoholism is associated with more than 60 diseases,most mortality from alcoholism results from alcoholic liver disease(ALD).ALD includes alcoholic steatosis,alcoholic hepatitis,and alcoholic cirrhosis,in order of increasing severity.Important scoring systems of ALD severity include:Child-Pugh,a semi-quantitative scoring system useful to roughly characterize clinical severity;model for end-stage liver disease,a quantitative,objective scoring system used for prognostication and prioritization for liver transplantation;and discriminant function,used to determine whether to administer corticosteroids for alcoholic hepatitis.Abstinence is the cornerstone of ALD therapy.Psychotherapies,including twelve-step facilitation therapy,cognitive-behavioral therapy,and motivational enhancement therapy,help support abstinence.Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum,but disulfiram can be hepatotoxic.Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone,acamprosate,and baclofen.Nutritional therapy helps reverse muscle wasting,weight loss,vitamin deficiencies,and trace element deficiencies associated with ALD.Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy,a diet containing1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting.Corticosteroids are firstline therapy for severe alcoholic hepatitis(discriminant function≥32),but proof of their efficacy in decreasing mortality remains elusive.Pentoxifylline is an alternative therapy.Complications of advanced ALD include ascites,spontaneous bacterial peritonitis,esophageal variceal bleeding,hepatic encephalopathy,hepatorenal syndrome,hepatopulmonary syndrome,and portopulmonary hypertension.Alcoholic cirrhotics have increased risk of developing hepatomas.Liver transplantation is the ultimate therapy for severe ALD,but generally requires 6mo of proven abstinence for eligibility.Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation. | Maryconi M Jaurigue Mitchell S Cappell | 2014 | World Journal of Gastroenterology2014，20，9： | 13 |
| 2 | Molecular targets in the treatment of alcoholic hepatitis显示文摘Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease. | Ashwin D Dhanda Richard WL Lee Peter L Collins C Anne McCune | 2012 | World Journal of Gastroenterology2012，18，39： | 9 |
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