Correspondence

Alcoholic Hepatitis

N Engl J Med 2009; 361:1512-1513October 8, 2009

Article

To the Editor:

Lucey et al. (June 25 issue)1 provide an excellent review of alcoholic hepatitis, but their recommendation of using gut-cleansing antibiotics for the treatment of hepatic encephalopathy is outdated and not evidence-based. Although neomycin has been used to treat hepatic encephalopathy for many years, no controlled studies have found it to be effective, as compared with standard treatment alone. A randomized trial2 comparing neomycin at a dose of 6 g per day with placebo showed no difference in outcomes between the two study groups. A downside to using neomycin is its association with ototoxicity and nephrotoxicity.

Metronidazole, vancomycin,3 and rifaximin4 have shown some effectiveness in small clinical trials, but convincing evidence of effectiveness is lacking, and these antibiotics may cause alterations in gut flora that may lead to the development of bacterial overgrowth syndromes.

Faiyaz Mohammed, M.B., B.S.
Chorley and South Ribble Hospital, Chorley, United Kingdom
faiyaz@doctors.org.uk

4 References

1. 1

   Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med 2009;360:2758-2769
   Full Text | Web of Science | Medline

2. 2

   Strauss E, Tramote R, Silva EP, et al. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology 1992;39:542-545
   Web of Science | Medline

3. 3

   Tarao K, Ikeda T, Hayashi K, et al. Successful use of vancomycin hydrochloride in the treatment of lactulose resistant chronic hepatic encephalopathy. Gut 1990;31:702-706
   CrossRef | Web of Science | Medline

4. 4

   Williams R, James OF, Warnes TW, Morgan MY. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol 2000;12:203-208
   CrossRef | Web of Science | Medline

Author/Editor Response

We agree with Mohammed that clinical studies have reached differing conclusions regarding the effectiveness of antibiotics in treating hepatic encephalopathy and that the use of oral antibiotics carries certain risks. However, a Cochrane review found that antibiotics were superior to nonabsorbable disaccharides in improving hepatic encephalopathy.1 Furthermore, in a recent multicenter, randomized, placebo-controlled trial (whose findings are currently available only in abstract form),2 among patients who had cirrhosis and hepatic encephalopathy that was not controlled with lactulose alone, the oral administration of rifaximin at a dose of 550 mg twice a day was more effective than placebo during a 6-month period. Thus, there is some evidence that antibiotics are beneficial in the treatment of hepatic encephalopathy.

Michael R. Lucey, M.D.
University of Wisconsin School of Medicine and Public Health, Madison, WI
mrl@medicine.wisc.edu

Philippe Mathurin, M.D., Ph.D.
Hôpital Claude Huriez, Lille, France

Timothy R. Morgan, M.D.
VA Long Beach Healthcare System, Long Beach, CA

2 References

1. 1

   Als-Nielsen B, Gluud LL, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev 2004;2:CD003044-CD003044
   Medline

2. 2

   Bass N, Mullen K, Sigal S, et al. Rifaximin is effective in maintaining remission in hepatic encephalopathy: results of a large, randomized, placebo-controlled study. J Hepatol 2009;50:Suppl 1:S39-S39
   CrossRef | Web of Science