The University of Southampton
University of Southampton Institutional Repository

Prednisolone or pentoxifylline for alcoholic hepatitis

Prednisolone or pentoxifylline for alcoholic hepatitis
Prednisolone or pentoxifylline for alcoholic hepatitis

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 ).

1619-1628
Thursz, Mark R.
efe8e73d-555b-4b44-a8be-e77a8809208d
Richardson, Paul
8b08e854-841d-419d-86fa-c371b0a9b1a9
Allison, Michael
d4822379-801a-44ff-bcb2-53c53bed362e
Austin, Andrew
f6fbddd9-28fa-446a-85db-ea11ee6bd322
Bowers, Megan
e76368dc-819f-4069-93f2-e1eee7bc691e
Day, Christopher P.
4f414f3d-0f22-4384-974b-9368fb93dc0a
Downs, Nichola
f22ed202-1f46-4554-90b4-f40d3bf23393
Cert, P.G.
1ae4c977-9571-400a-a514-c0eb6886b9ea
Gleeson, Dermot
7d0d89ab-920f-44fb-9b34-dd201b0eafad
MacGilchrist, Alastair
5216f9e4-4c68-41ce-a1e7-03e49a47015a
Grant, Allister
1d4c4dd3-c4cb-42d9-a1cc-48af190c087d
Hood, Steven
414488b9-ac07-44f7-a04a-8b1c652c3d3d
Masson, Steven
9b1cc3af-4236-473a-9830-b38e60dccbef
McCune, Anne
2798f414-04f4-46db-8f12-205084f83318
Mellor, Jane
748aff30-b9fb-420a-8c4b-8b95beb6ecd0
O’Grady, John
e356767b-6977-457a-aa6e-aa58a7035e77
Patch, David
2fb3e4a8-6eef-484f-bae7-8cfaf7ec9b88
Ratcliffe, Ian
0688ee1f-37ac-42ee-8238-fc3e9ea5bb68
Roderick, Paul
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Stanton, Louise
8b827763-d839-4b4b-bbf2-358a84110294
Vergis, Nikhil
1386b79c-a077-4e71-b38f-0adee912baea
Wright, Mark
43325ef9-3459-4c75-b3bf-cf8d8dac2a21
Ryder, Stephen
7d252d42-2744-466d-83e5-91a6ea0bb0c8
Forrest, Ewan H.
975d6bd8-6db9-4bb8-b62a-1e32bc7a2887
Thursz, Mark R.
efe8e73d-555b-4b44-a8be-e77a8809208d
Richardson, Paul
8b08e854-841d-419d-86fa-c371b0a9b1a9
Allison, Michael
d4822379-801a-44ff-bcb2-53c53bed362e
Austin, Andrew
f6fbddd9-28fa-446a-85db-ea11ee6bd322
Bowers, Megan
e76368dc-819f-4069-93f2-e1eee7bc691e
Day, Christopher P.
4f414f3d-0f22-4384-974b-9368fb93dc0a
Downs, Nichola
f22ed202-1f46-4554-90b4-f40d3bf23393
Cert, P.G.
1ae4c977-9571-400a-a514-c0eb6886b9ea
Gleeson, Dermot
7d0d89ab-920f-44fb-9b34-dd201b0eafad
MacGilchrist, Alastair
5216f9e4-4c68-41ce-a1e7-03e49a47015a
Grant, Allister
1d4c4dd3-c4cb-42d9-a1cc-48af190c087d
Hood, Steven
414488b9-ac07-44f7-a04a-8b1c652c3d3d
Masson, Steven
9b1cc3af-4236-473a-9830-b38e60dccbef
McCune, Anne
2798f414-04f4-46db-8f12-205084f83318
Mellor, Jane
748aff30-b9fb-420a-8c4b-8b95beb6ecd0
O’Grady, John
e356767b-6977-457a-aa6e-aa58a7035e77
Patch, David
2fb3e4a8-6eef-484f-bae7-8cfaf7ec9b88
Ratcliffe, Ian
0688ee1f-37ac-42ee-8238-fc3e9ea5bb68
Roderick, Paul
dbb3cd11-4c51-4844-982b-0eb30ad5085a
Stanton, Louise
8b827763-d839-4b4b-bbf2-358a84110294
Vergis, Nikhil
1386b79c-a077-4e71-b38f-0adee912baea
Wright, Mark
43325ef9-3459-4c75-b3bf-cf8d8dac2a21
Ryder, Stephen
7d252d42-2744-466d-83e5-91a6ea0bb0c8
Forrest, Ewan H.
975d6bd8-6db9-4bb8-b62a-1e32bc7a2887

Thursz, Mark R., Richardson, Paul, Allison, Michael, Austin, Andrew, Bowers, Megan, Day, Christopher P., Downs, Nichola, Cert, P.G., Gleeson, Dermot, MacGilchrist, Alastair, Grant, Allister, Hood, Steven, Masson, Steven, McCune, Anne, Mellor, Jane, O’Grady, John, Patch, David, Ratcliffe, Ian, Roderick, Paul, Stanton, Louise, Vergis, Nikhil, Wright, Mark, Ryder, Stephen and Forrest, Ewan H. (2015) Prednisolone or pentoxifylline for alcoholic hepatitis. New England Journal of Medicine, 372 (17), 1619-1628. (doi:10.1056/NEJMoa1412278).

Record type: Article

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 ).

Full text not available from this repository.

More information

Published date: 23 April 2015
Organisations: Primary Care & Population Sciences, Clinical Trials Unit

Identifiers

Local EPrints ID: 395992
URI: https://eprints.soton.ac.uk/id/eprint/395992
PURE UUID: 4f307b8e-1390-4cf6-ad2f-ff54d02cebe8
ORCID for Paul Roderick: ORCID iD orcid.org/0000-0001-9475-6850

Catalogue record

Date deposited: 27 May 2016 15:53
Last modified: 06 Jun 2018 13:05

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×