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Three Part Question

In [patient presenting with alcoholic hepatitis] does [course of steroids] improve [short term survival]

Clinical Scenario

A 38 year old man presents with one week history of jaundice. He admits to drink alcohol excessively of about 10 units per day for the last 10 years. Clinical examination reveals jaundice, spider naevi over chest and tender, palpable hepatomegaly with no clinical signs of ascites. Hepatitis screen and septic screen are negative . A diagnosis of alcoholic hepatitis is made. You wonder whether early commencement of steroids would improve his short term survival.

Search Strategy

Medline 1966-2006 using the OVID interface.
[exp Alcohol hepatitis OR Alcohol hepatitis.mp OR Alcoholic liver disease.mp] AND [exp Steroids OR Steroids.mp] limited to humans and english language and adult.

Search Outcome

93 papers of which 4 are directly relavant to the question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Mathurin P et al 2002 France	Individual data of patients with severe Alcoholic hepatitis with discriminant function (DF)> or =32 were collected from the three principal investigators. 102 placebo and 113 corticosteroid patients (prednisolone 40mg/day) with Discrimination factor (DF) > or =32 were analyzed.	Data analysis of the three randomized placebo controlled double blind trials	Short term survival in patients with severe alcoholic hepatitis receiving corticosteroids	At 28 days, corticosteroid patients had significantly higher survival: 84.6+/-3.4% vs. 65.1+/-4.8%, P=0.001.
Cabre E et al 2000 spain	A total of 71 patients (80% cirrhotic) were randomized to receive 40 mg/d prednisolone (n = 36) or enteral tube feeding (2,000 kcal/d) for 28 days (n = 35), and were followed for 1 year or until death.	Multicenter randomized trial. Level 1 b	Short term effects of total enteral nutrition or steroids in patients with alcoholic hepatitis	enteral feeding(69%) does not seem to be worse than steroids(75%) in the short-term treatment of severe alcohol-induced hepatitis
			Mortality in patients treated by total enteral nutrition or steroidis in patients with alcoholic hepatitis	Mortality during treatment was similar in both groups (9 of 36 vs. 11 of 35, intention-to-treat) but occurred earlier with enteral feeding (median 7 vs. 23 days; P =.025). Mortality during follow-up was higher with steroids (10 of 27 vs. 2 of 24 intention-to-treat; P =. 04).
Ramond MJ et al 1992 France	Randomised, double-blind trial comparing 28 days of prednisolone treatment (40 mg per day) with placebo in 61 patients with biopsy-proved alcoholic hepatitis and either spontaneous hepatic encephalopathy (n = 19) or a discriminant-function value higher than 32. The discriminant function used was as follows: 4.6 (prothrombin time-control time [in seconds]) + serum bilirubin (in micromoles per liter)/17.	Randomised double-blind trial	Short term survival of patients with alcohol hepatitis on steroids	By the 66th day after randomization, 16 of 29 placebo recipients had died (mean [+/- SE] survival, 45 +/- 8 percent), as compared with 4 of 32 prednisolone recipients (survival, 88 +/- 5 percent) (log-rank test, 10.9; P = 0.001).
Imperiale TF et al 1990 USA	11 randomised studies (10 of which were placebo controlled) that assessed mortality in hospitalized patients diagnosed with acute alcoholic hepatitis and treated with corticosteroids	Meta-analysis of randomised trials	The protective efficacy (or percent reduction in mortality)	The protective efficacy of corticosteroids was 37% (95% CI, 20% to 50%).

Comment(s)

Corticosteroids have been the most extensively-studied form of therapy for alcoholic hepatitis, but their role remains limited.The rationale for steroid use is to decrease the immune response and proinflammatory cytokine response. Most randomised studies and meta-analysis support the use of steroids for severe acute alcoholic hepatitis to improve short term survival.

Editor Comment

Dr Paul Yap currently updating 10/03/10 KW

Clinical Bottom Line

Even though corticosteroids are efficient in severe alcoholic hepatitis to improve short-term survival, it is important to note that the pateints selected should be free from infections(spontaneous bacterial peritonitis), and gastrointestinal bleeding.

References

1. Mathurin P, Mendenhall CL, Carithers RL Jr, Ramond MJ, Maddrey WC, Garstide P, Rueff B, Naveau S, Chaput JC, Poynard T. Corticosteroids improve shortterm survival in patients with severe alcoholic hepatitis:individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids Journal of hepatology 2002 Apr;36(4):480-7.
2. Cabr E, Rodrguez-Iglesias P, Caballeria J, Quer JC, Sanchez-Lombrana JL, Pares A, Papo M, Planas R, Gassull MA. Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial. Hepatology 2000 Jul;32(1):36-42.
3. Ramond MJ, Poynard T, Rueff B, Mathurin P, Theodore C, Chaput JC, Benhamou JP A randomized trial of prednisolone in patients with severe alcoholic hepatitis New England Journal Of Medicine 1992 Feb 20;326(8):507-12.
4. Imperiale TF, McCullough AJ. Do corticosteroids reduce mortality from alcoholic hepatitis? A meta-analysis of the randomized trials. Annals of Internal Medicine 1990 Aug 15;113(4):299-307