In vitro steroid resistance correlates with outcome in severe alcoholic hepatitis.
Hepatology
; 53(4): 1316-22, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21400552
ABSTRACT
UNLABELLED 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Prednisolona
/
Hepatitis Alcohólica
Tipo de estudio:
Observational_studies
Límite:
Humans
Idioma:
En
Revista:
Hepatology
Año:
2011
Tipo del documento:
Article
País de afiliación:
Reino Unido