Prednisolone or pentoxifylline for alcoholic hepatitis
Mark R Thursz, Paul Richardson, Michael Allison, Andrew Austin, Megan Bowers, Christopher P Day, Nichola Downs, Dermot Gleeson, Alastair MacGilchrist, Allister Grant, Steven Hood, Steven Masson, Anne McCune, Jane Mellor, John O'Grady, David Patch, Ian Ratcliffe, Paul Roderick, Louise Stanton, Nikhil Vergis, Mark Wright, Stephen Ryder, Ewan H Forrest, STOPAH Trial, Mark R Thursz, Paul Richardson, Michael Allison, Andrew Austin, Christopher P Day, Dermot Gleeson, Steven Masson, Anne McCune, Jane Mellor, John O'Grady, David Patch, Paul Roderick, Louise Stanton, Mark Wright, Stephen Ryder, Ewan H Forrest, Megan Bowers, Jessica Comper Nichola Downs, Ian Ratcliffe, Jennifer Silk, Christopher Hawkey, Philip Newsome, Debbie Hepworth, Stephen Falk, Andrew Protheroe, Sally Stenning, Colin Standfield, George Abouda, Anurag Agrawal, Aftab Ala, Mark Aldersley, Richard Aspinall, Sundaramoorthy Bharathi, Peter Bramley, Alison Brind, John Christie, Chin Lye Ch'ng, Matthew Cramp, Carole Collins, Andrew Davis, Hugh Dalziel, Keith Dear, John Dillon, Andrew Fraser, Daniel Forton, Graham Foster, Matthew Foxton, Keith George, John Greenaway, Dara De Las Heras, Mathis Heydtmann, Andrew Holt, Stephen Hood, Hyder Hussaini, Gary James, Anthoor Jayaprakash, Mazn Karmo, Julia Maltby, Rudi Matull, Peter Mills, Sharat Misra, Harriet Mitchison, Jonathan Mitchell, Sulleman Moreea, Judith Morris, David Parker, Michael Perry, Martin Phillips, Matthew Priest, Subrata Saha, Sambit Sen, Nicholas Sharer, Saket Singhal, Aravamuthan Sreedharan, Sushma Saksena, Ian Shaw, Gurjit Singh, Stephen Stewart, Christopher Shorrock, Aileen Smith, Sam Thompson, Joanne Topping, Nikhil Vergis, Balasubramaniam Vijayan, Mark Welfare, Earl Williams, Gavin Wright, Andrew Yeoman, Mark R Thursz, Paul Richardson, Michael Allison, Andrew Austin, Megan Bowers, Christopher P Day, Nichola Downs, Dermot Gleeson, Alastair MacGilchrist, Allister Grant, Steven Hood, Steven Masson, Anne McCune, Jane Mellor, John O'Grady, David Patch, Ian Ratcliffe, Paul Roderick, Louise Stanton, Nikhil Vergis, Mark Wright, Stephen Ryder, Ewan H Forrest, STOPAH Trial, Mark R Thursz, Paul Richardson, Michael Allison, Andrew Austin, Christopher P Day, Dermot Gleeson, Steven Masson, Anne McCune, Jane Mellor, John O'Grady, David Patch, Paul Roderick, Louise Stanton, Mark Wright, Stephen Ryder, Ewan H Forrest, Megan Bowers, Jessica Comper Nichola Downs, Ian Ratcliffe, Jennifer Silk, Christopher Hawkey, Philip Newsome, Debbie Hepworth, Stephen Falk, Andrew Protheroe, Sally Stenning, Colin Standfield, George Abouda, Anurag Agrawal, Aftab Ala, Mark Aldersley, Richard Aspinall, Sundaramoorthy Bharathi, Peter Bramley, Alison Brind, John Christie, Chin Lye Ch'ng, Matthew Cramp, Carole Collins, Andrew Davis, Hugh Dalziel, Keith Dear, John Dillon, Andrew Fraser, Daniel Forton, Graham Foster, Matthew Foxton, Keith George, John Greenaway, Dara De Las Heras, Mathis Heydtmann, Andrew Holt, Stephen Hood, Hyder Hussaini, Gary James, Anthoor Jayaprakash, Mazn Karmo, Julia Maltby, Rudi Matull, Peter Mills, Sharat Misra, Harriet Mitchison, Jonathan Mitchell, Sulleman Moreea, Judith Morris, David Parker, Michael Perry, Martin Phillips, Matthew Priest, Subrata Saha, Sambit Sen, Nicholas Sharer, Saket Singhal, Aravamuthan Sreedharan, Sushma Saksena, Ian Shaw, Gurjit Singh, Stephen Stewart, Christopher Shorrock, Aileen Smith, Sam Thompson, Joanne Topping, Nikhil Vergis, Balasubramaniam Vijayan, Mark Welfare, Earl Williams, Gavin Wright, Andrew Yeoman
Abstract
Background: Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists.
Methods: We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline.
Results: A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002).
Conclusions: Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).
Source: PubMed