How Should Acute Alcoholic Hepatitis be Treated?

One small, randomized trial comparing pentoxifylline with prednisolone demonstrated that pentoxifylline was superior.¹³ Pentoxifylline can be prescribed to patients who have contraindications to corticosteroid use (infection or gastrointestinal bleeding). The recommended dose is 400 mg orally three times daily (TID) for four weeks. Common side effects are nausea and vomiting. Pentoxifylline cannot be administered by nasogastric tubes and should not be used in patients with recent cerebral or retinal hemorrhage.

Other therapies. Several studies have examined vitamin E, N-acetylcystine, and other antioxidants as treatment for alcoholic hepatitis. No clear benefit has been demonstrated for any of these drugs. Tumor necrosis factor (TNF)-alpha inhibitors (e.g. infliximab) have been studied, but increased mortality was demonstrated and these studies were discontinued. Patients are not usually considered for liver transplantation until they have at least six months of abstinence from alcohol as recommended by the American Society of Transplantation.¹⁴

Discharge considerations. No clinical trials have studied optimal timing of discharge. Expert opinion based on clinical experience recommends that patients be kept in the hospital until they are eating, signs of alcohol withdrawal and encephalopathy are absent, and bilirubin is less than 10 mg/dL.¹⁴ These patients often are quite sick and hospitalization frequently exceeds 10 days. Careful outpatient follow-up and assistance with continued abstinence is very important.

Back to the Case

The patient fits the typical clinical picture of alcoholic hepatitis. Cessation of alcohol consumption is the most important treatment and is accomplished by admission to the hospital. Because of his daily alcohol consumption, folate, thiamine, multivitamins, and oral vitamin K are ordered. Though he has no symptoms of alcohol withdrawal, a note is added about potential withdrawal to the handoff report.

An infectious workup is completed by ordering blood and urine cultures, a chest X-ray, and performing paracentesis to exclude spontaneous bacterial peritonitis. A dietary consult with calorie count is given, along with a plan to discuss with the patient the importance of consuming at least 2,500 calories a day is made. Tube feedings will be considered if the patient does not meet this goal in 48 hours. Clinical calculators determine his Maddrey’s and MELD scores (50 and 25, respectively). If he is actively bleeding or infected, pentoxifylline (400 mg TID for 28 days) is favored due to its lower-side-effect profile.

His MELD score predicts a 90-day mortality of 43%; a meeting is planned to discuss code status and end-of-life issues with the patient and his family. Due to the severity of his illness, a gastroenterology consultation is recommended.

Bottom Line

Alcoholic hepatitis is a serious disease with significant short-term mortality. Treatment options are limited but include abstinence from alcohol, supplemental nutrition, and, for select patients, pentoxifylline or corticosteroids. Because most transplant centers require six months of abstinence, these patients usually are not eligible for urgent liver transplantation.

Dr. Parada is a clinical instructor and chief medical resident in the Department of Internal Medicine at the University of New Mexico School of Medicine and the University of New Mexico Hospital, Albuquerque. Dr. Pierce is associate professor in the Division of Hospital Medicine at the University of New Mexico School of Medicine and the University of New Mexico Hospital.

References

1. Naveau S, Giraud V, Borotto E, Aubert A, Capron F, Chaput JC. Excess weight risk factor for alcoholic liver disease. Hepatology. 1997;25:108-111.
2. Pessione F, Ramond MJ, Peters L, et al. Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence. Liver Int. 2003;23:45-53.
3. Mendenhall CL, Anderson S, Weesner RE, Goldberg SJ, Crolic KA. Protein-calorie malnutrition associated with alcoholic hepatitis. Veterans Administration Cooperative Study Group on alcoholic hepatitis. Am J Med. 1984;76:211-222.
4. Cabre E, Rodriguez-Iglesias P, Caballeria J, et al. Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: a multicenter randomized trial. Hepatology. 2000;32:36-42.
5. O’Shea RS, Dasarathy S, McCullough AJ, Practice Guideline Committee of the American Association for the Study of Liver Diseases, Practice Parameters Committee of the American College of Gastroenterology. Alcoholic liver disease. Hepatology. 2010;51:307-328.
6. Rambaldi A, Saconato HH, Christensen E, Thorlund K, Wetterslev J, Gluud C. Systematic review: Glucocorticosteroids for alcoholic hepatitis—a Cochrane hepato-biliary group systematic review with meta-analyses and trial sequential analyses of randomized clinical trials. Aliment Pharmacol Ther. 2008;27:1167-1178.
7. Mathurin P, Mendenhall CL, Carithers RL Jr., et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH. J Hepatol. 2002;36:480-487.
8. Louvet A, Naveau S, Abdelnour M, et al. The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids. Hepatology. 2007;45:1348-1354.
9. Louvet A, Diaz E, Dharancy S, et al. Early switch topentoxifylline in patients with severe alcoholic hepatitis is inefficient in non-responders to corticosteroids. J Hepatol. 2008;48:465-470.
10. Amini M, Runyon BA. Alcoholic hepatitis 2010: A clinician’s guide to diagnosis and therapy. World J Gastroenterol. 2010;16:4905-4912.
11. Akriviadis E, Botla R, Briggs W, Han S, Reynolds T, Shakil O. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial. Gastroenterology. 2000;119:1637-1648.
12. Whitfield K, Rambaldi A, Wetterslev J, Gluud C. Pentoxifylline for alcoholic hepatitis. Cochrane Database Syst Rev. 2009;(4):CD007339.
13. De BK, Gangopadhyay S, Dutta D, Baksi SD, Pani A, Ghosh P. Pentoxifylline versus prednisolone for severe alcoholic hepatitis: A randomized controlled trial. World J Gastroenterol. 2009;15:1613-1619.
14. Lucey MR, Brown KA, Everson GT, et al. Minimal criteria for placement of adults on the liver transplant waiting list: a report of a national conference organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases. Liver Transpl Surg. 1997;3:628-637.