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[Acute alcoholic hepatitis: treatments]
1Service d'Hépato-Gastroentérologie, Hôpital Antoine Béclère, 157, rue de la Porte de Trivaux, F 92141 Clamart. sylvie.naveau@abc.ap-hop-paris.fr
Insights
Acute alcoholic hepatitis (AAH) is a severe liver disease with high mortality. Corticosteroids are the gold standard treatment for severe AAH, improving short-term survival, but new therapies are needed.
Area of Science:
- Hepatology and Gastroenterology
- Alcohol-Related Liver Disease Research
- Clinical Trial Analysis
Context:
- Acute alcoholic hepatitis (AAH) presents a significant short-term mortality risk, potentially reaching 50%.
- Long-term prognosis is contingent upon sustained alcohol abstinence and the progression to cirrhosis.
- Effective management strategies for AAH are critical due to its severity.
Purpose:
- To review and evaluate various therapeutic strategies for acute alcoholic hepatitis (AAH).
- To identify the most effective treatments based on existing clinical trial data.
- To establish the current gold standard of care and explore future therapeutic directions.
Summary:
- Abstinence from alcohol is the primary and essential therapeutic measure for AAH.
- Numerous drug treatments and nutritional support strategies have been investigated, including anti-inflammatory agents, hepatoprotective compounds, and nutritional interventions.
- Corticosteroid therapy is the only strategy with proven efficacy, particularly for severe AAH (Maddrey index ≥ 32), with oral prednisolone as the gold standard.
Impact:
- Corticosteroid therapy improves short-term survival in severe AAH, though mortality remains substantial (around 30% at 2 months).
- The findings underscore the need for continued research into novel treatments, with anti-TNF alpha antibodies showing promise.
- This evidence base guides clinical practice and highlights areas for future therapeutic development in AAH.
Prognosis:
Acute alcoholic hepatitis (AAH) is a severe form of alcohol-related liver disease with a high short-term mortality that can reach 50%. Long-term outcome depends on definitive weaning from alcohol and the development of cirrhosis.
Essential Therapeutic Step:
Abstention from alcohol is the number one therapeutic measure required for treating AAH. Abstention must be total and definitive.
Therapeutic Strategies:
The pathogenic mechanisms involved in AAH have led to close assessment of numerous treatment protocols. Thirty-three randomized trials have evaluated drug treatments based on various strategies: antiinflammatory action using corticosteroids or colchicine; reduction of the hypermetabolism using propylthiouracil; hepatoprotective effect against oxidative stress using cyanidalol, alpha lipoid acid, silymarine, amlopidine, malotilate; vasodilatation to improve oxygenation of the centrolublular region using a calcium channel inhibitor, amlopidine; increased liver regeneration using anabolism steroids, intravenous perfusion combining insulin and glucagon; antifibrosis action using colchicine, D penicillamine; improved microcirculation due to increased deformability of the red cells and inhibition of TNF-alpha using pentoxifyllin. Eleven therapeutic trials have investigated the effect of parenteral or enteral artificial nutrition.
Gold Standard Treatment:
Among all these strategies, the only one with a proven efficacy is corticosteroid therapy. Four trials have demonstrated the effect of corticosteroid therapy on short-term survival and 3 of the 4 meta-analyses devoted to the topic have demonstrated the usefulness of corticosteroid therapy in severe forms defined by a Maddrey index > or = 32: bilirubin in mumol per liter/17 + 4.6 (patient's PT in seconds--control PT in seconds) and the presence or not of encephalopathy. The gold standard treatment for severe AAH is oral prednisolone 40 mg/d for 1 month (excluding contraindications).
Perspectives:
Despite the effect of corticosteroid therapy, mortality at 2 months in severe AAH is still about 30%. Recent experimental data suggest that monoclonal anti-TNF alpha antibodies could be useful.