Journal of Hepatology
Volume 50, Issue 3 , Pages 584-591 , March 2009

Infliximab monotherapy for severe alcoholic hepatitis and predictors of survival: An open label trial

  • Praveen Sharma

      Affiliations

    • Department of Gastroenterology, G B Pant Hospital, Affiliated to University of Delhi, 201, Academic Block, Jawahar Lal Nehru Road, New Delhi 110 002, India
    • Department of Hepatology, Institute of Liver & Biliary Sciences (ILBS), New Delhi, India
  • ,
  • Ashish Kumar

      Affiliations

    • Department of Gastroenterology, G B Pant Hospital, Affiliated to University of Delhi, 201, Academic Block, Jawahar Lal Nehru Road, New Delhi 110 002, India
    • Department of Hepatology, Institute of Liver & Biliary Sciences (ILBS), New Delhi, India
  • ,
  • Barjesh Chander Sharma

      Affiliations

    • Department of Gastroenterology, G B Pant Hospital, Affiliated to University of Delhi, 201, Academic Block, Jawahar Lal Nehru Road, New Delhi 110 002, India
  • ,
  • Shiv Kumar Sarin

      Affiliations

    • Department of Gastroenterology, G B Pant Hospital, Affiliated to University of Delhi, 201, Academic Block, Jawahar Lal Nehru Road, New Delhi 110 002, India
    • Department of Hepatology, Institute of Liver & Biliary Sciences (ILBS), New Delhi, India
    • Corresponding Author InformationCorresponding author. Tel.: +91 11 23232013; fax: +91 11 23219710.

Received 7 February 2008 ,Revised 14 October 2008 ,Accepted 23 October 2008.

References 

  1. Ramond MJ, Poynard T, Rueff B, Mathurin P, Théodore C, Chaput JC, et al. A randomized trial of prednisolone in patients with severe alcoholic hepatitis. N Engl J Med. 1992;326:507–512
  2. Hardison WG, Lee FI. Prognosis in acute liver disease of the alcoholic patient. N Engl J Med. 1966;275:61–66
  3. Lopez-Talavera JC, Merrill WW, Groszmann RJ. Tumor necrosis factor alpha: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats. Gastroenterology. 1995;108:761–767
  4. Lopez-Talavera JC, Cadelina G, Olchowski J, Merrill W, Groszmann RJ. Thalidomide inhibits tumor necrosis factor alpha, decreases nitric oxide synthesis, and ameliorates the hyperdynamic circulatory syndrome in portal-hypertensive rats. Hepatology. 1996;23:1616–1621
  5. McClain CJ, Barve S, Deaciuc I, Kugelmas M, Hill D. Cytokines in alcoholic liver disease. Semin Liver Dis. 1999;19:205–219
  6. Bird GL, Sheron N, Goka AK, Alexander GJ, Williams RS. Increased plasma tumor necrosis factor in severe alcoholic hepatitis. Ann Intern Med. 1990;112:917–920
  7. Alvarez MA, Cabré E, Lorenzo-Zúñiga V, Montoliu S, Planas R, Gassull MA. Combining steroids with enteral nutrition: a better therapeutic strategy for severe alcoholic hepatitis? Results of a pilot study. Eur J Gastroenterol Hepatol. 2004;16:1375–1380
  8. Reynolds TB. Corticosteroid therapy of alcoholic hepatitis: how many studies will it take?. Hepatology. 1990;12:619–621
  9. Imperiale TF, McCullough AJ. Do corticosteroids reduce mortality from alcoholic hepatitis? A meta-analysis of the randomized trials. Ann Intern Med. 1990;113:299–307
  10. Mathurin P, Mendenhall CL, Carithers RL, Ramond MJ, Maddrey WC, Garstide P, 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
  11. Taïeb J, Mathurin P, Elbim C, Cluzel P, Arce-Vicioso M, Bernard B, et al. Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids. J Hepatol. 2000;32:579–586
  12. Tilg H, Jalan R, Kaser A, Davies NA, Offner FA, Hodges SJ, et al. Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis. J Hepatol. 2003;38:419–425
  13. Mookerjee RP, Sen S, Davies NA, Hodges SJ, Williams R, Jalan R. Tumour necrosis factor alpha is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis. Gut. 2003;52:1182–1187
  14. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999;354:1932–1939
  15. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340:1398–1405
  16. Naveau S, Chollet-Martin S, Dharancy S, Mathurin P, Jouet P, Piquet MA, et al. Foie-Alcool group of the Association Française pour l’Etude du Foie. A double-blind randomized controlled trial of infliximab associated with prednisolone in acute alcoholic hepatitis. Hepatology. 2004;39:1390–1397
  17. Louvet A, Naveau S, Abdelnour M, Ramond MJ, Diaz E, Fartoux L, 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
  18. Spahr L, Rubbia-Brandt L, Pugin J, Giostra E, Frossard JL, Borisch B, et al. Rapid changes in alcoholic hepatitis histology under steroids: correlation with soluble intercellular adhesion molecule-1 in hepatic venous blood. J Hepatol. 2001;35:582–589
  19. Spahr L, Rubbia-Brandt L, Frossard JL, Giostra E, Rougemont AL, Pugin J, et al. Combination of steroids with infliximab or placebo in severe alcoholic hepatitis: a randomized controlled pilot study. J Hepatol. 2002;37:448–455
  20. Rongey C, Kaplowitz N. Current concepts and controversies in the treatment of alcoholic hepatitis. World J Gastroenterol. 2006;12:6909–6921
  21. Mookerjee RP, Tilg H, Williams R, Jalan R. Infliximab and alcoholic hepatitis. Hepatology. 2004;40:499–500
  22. Boetticher NC, Peine CJ, Kwo P, Abrams GA, Patel T, Aqel B, et al. A randomized, double-blinded, placebo-controlled multi-center trial of etanercept in the treatment of alcoholic hepatitis. Gastroenterology. 2008;135:1953–1960
  23. Hanck C, Rossol S, Böcker U, Tokus M, Singer MV. Presence of plasma endotoxin is correlated with tumour necrosis factor receptor levels and disease activity in alcoholic cirrhosis. Alcohol Alcohol. 1998;33:606–608
  24. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275–2285
  25. Theis VS, Rhodes JM. Review article: minimizing tuberculosis during anti-tumour necrosis factor-alpha treatment of inflammatory bowel disease. Aliment Pharmacol Ther. 2008;27:19–30
  26. Mathurin P, Abdelnour M, Ramond MJ, Carbonell N, Fartoux L, Serfaty L, et al. Early change in bilirubin levels is an important prognostic factor in severe alcoholic hepatitis treated with prednisolone. Hepatology. 2003;38:1363–1369

 The abstract of this work was presented at the Annual Conference of the American College of Gastroenterology (ACG), November, 2007. The authors who have taken part in the research of this paper declared that they do not have a relationship with the manufacturers of the drug involved either in the past or present and they did not receive funding from the manufacturers to carry out their research.

PII: S0168-8278(08)00792-7

doi: 10.1016/j.jhep.2008.10.024

Journal of Hepatology
Volume 50, Issue 3 , Pages 584-591 , March 2009