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Advances in alcoholic liver disease

https://doi.org/10.1016/S1521-6918(03)00053-2Get rights and content

Abstract

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. Interactions between acetaldehyde, reactive oxygen and nitrogen species, inflammatory mediators and genetic factors appear to play prominent roles in the development of ALD. The cornerstone of therapy for ALD is lifestyle modification, including drinking and smoking cessation and losing weight, if appropriate. Nutrition intervention has been shown to play a positive role on both an inpatient and outpatient basis. Corticosteroids are effective in selected patients with alcoholic hepatitis and pentoxifylline appears to be a promising anti-inflammatory therapy. Some complementary and alternative medicine agents, such as milk thistle and S-adenosylmethionine, may be effective in alcoholic cirrhosis. Treatment of the complications of ALD can improve quality of life and, in some cases, decrease short-term mortality.

Section snippets

Risk factors

In order to develop liver disease, a ‘threshold’ regarding daily amount and length of time of alcohol intake has to be exceeded. Daily intake of alcohol for 10–12 years with doses in excess of 40–80 g/day for males and of 20–40 g/day for females are generally needed to cause ALD.5., 6., 7., 8. Because alcoholic beverages have different alcohol content, it is important to convert ‘usual serving’ sizes to g of alcohol. Thus, 12 oz of beer (5% v/v alcohol) provides 13.85 g of alcohol versus 4 oz of

Mechanisms of liver injury

The following will be reviewed: (i) alcohol metabolism, (ii) oxidative stress, (iii) cytokines/inflammatory mediators, (iv) genetic factors and the interactions of these factors. There are multiple potential overlapping mechanisms for liver injury in ALD (Figure 1).

Therapy for alcoholic liver disease

We have reviewed the major advances that have been made in our understanding of mechanisms of alcohol-induced liver injury, and these concepts are being translated into clinical trials. Moreover, we are now in a position to better understand some of the mechanisms of actions of some traditionally-used therapies for ALD, ranging from steroids to antioxidant therapy. This section on therapy will touch on the importance of: (i) life-style change, including abstinence; (ii) nutrition; (iii) drug

Conclusions

In summary, all patients should stop or markedly decrease alcohol intake and employ other lifestyle modifications where appropriate (Table 1). Proper nutrition and nutritional support have consistently been shown to be important. Certain drugs (e.g. corticosteroids or pentoxifylline) may be effective in selected patients. While no FDA-approved therapies are available, many new agents, such as anti-TNF antibody, are under investigation. Transplantation is life-saving in certain abstinent

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