| In vitro steroid resistance correlates with outcome in severe alcoholic hepatitis. | |
| | |
MedLine Citation:
|
PMID: 21400552 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Steroids improve the outcome in alcoholic hepatitis (AH), but up to 40% of patients fail to respond adequately. Interleukin-2 (IL-2) exacerbates steroid resistance in vitro. We performed a prospective study to determine if intrinsic steroid sensitivity correlates with response to steroids in individuals with severe AH and if IL-2 receptor blockade can reverse this. Peripheral blood mononuclear cells (PBMCs) were isolated from 20 patients with AH and a Maddrey's score >32. Patients were treated with oral prednisolone plus full supportive measures. Clinical resistance to oral steroid treatment was defined as a drop in serum bilirubin of <25% within 7 days or death within 6 months. In vitro steroid resistance was measured in PBMC using the dexamethasone suppression of lymphocyte proliferation assay and repeated after the addition of the anti-IL-2 receptor (anti-CD25) monoclonal antibody, basiliximab. Suppression of lymphocyte proliferation <60% was considered to indicate steroid resistance. In all, 82% (9/11) of in vitro steroid-resistant patients were dead at 6 months as compared to 21% (2/9) of steroid-sensitive patients (P = 0.03). Similarly, 91% (10/11) of in vitro steroid-resistant patients failed to show a significant fall in bilirubin at day 7 as compared to 44% (4/9) of steroid-sensitive patients (P < 0.05). Basiliximab improved the maximal proliferation count in 91% (10/11) of in vitro steroid-resistant patients (P = 0.003). Conclusion: Clinical outcome of steroid therapy in this patient cohort correlated with in vitro steroid resistance. IL-2 blockade improved in vitro steroid sensitivity. This suggests that intrinsic lack of steroid sensitivity may contribute to poor clinical response to steroids in severe AH. IL-2 receptor blockade represents a possible mechanism to overcome this. (HEPATOLOGY 2011;). |
| | |
Authors:
|
A J di Mambro; R Parker; A McCune; F Gordon; C M Dayan; P Collins |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-1-10 |
Journal Detail:
|
Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2011-3-14 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 American Association for the Study of Liver Diseases. |
Affiliation:
|
Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK; Department of Liver Medicine, Bristol Royal Infirmary, Bristol, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Analyses of benzodiazepines and their metabolites in various biological matrices by LC-MS(/MS).
Next Document: Regulation of hepatic fat and glucose oxidation in rats with lipid-induced hepatic insulin resistanc...