Efficacy of g-csf in the management of steroid-nonresponsive severe alcoholic hepatitis: a double-blind randomized controlled trial.
Hepatology. 2019 Jan 21;:
Authors: Saggere Muralikrishna S, Kumar Sharma M, Shasthry V, Pande A, Sarin SK
Abstract
BACKGROUND AND AIMS: Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille-score>0.45) are limited. We assessed the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in steroid non-responders.
PATIENTS AND METHODS: Randomized, double-blind, single-center trial (NCT01820208) was conducted between March 2013-June 2016 in patients with histologically proven SAH, non-responsive to 40 mg/day of prednisolone were randomized to G-CSF (12 doses, 300μg each in 28 days) or placebo. Responders were continued with prednisolone.
RESULTS: Of the 430 patients with SAH, 132 received steroid therapy. Of these, 33(25%) were non-responders and were randomized to G-CSF or placebo (14 in each group after exclusions). The baseline characteristics of both groups were comparable. The 28-day mortality was comparable between the groups (21.4%, G-CSF; 28.6%, placebo; P=0.69). At 90 days, in the G-CSF but not in the placebo group, the Model for End-Stage Liver Disease (MELD) reduced from 24.6 ± 3.9 to 19.4 ± 3.7 (P=0.002) and Maddrey's Discriminant Function from 74.8 ± 22.8 to 57. 4±31 (P=0.26). Infections were less common (28% vs. 71%; P < 0.001) with lower 90-day mortality (35.7% vs.71.4%; P=0.04) in the G-CSF than in the placebo group. On Cox regression analysis, receiving G-CSF (hazard ratio [HR], 0.37; SD, 0.14-0.98; P=0.04), and high baseline serum creatinine (HR, 4.12; SD, 1.7-10.3; P=0.002) predicted day-90 outcomes in steroid nonresponsive SAH. Patients tolerated G-CSF without any major adverse events.
CONCLUSIONS: Approximately one quarter of patients with SAH do not respond to corticosteroid therapy. Administration of G-CSF is safe and helps to reduce the disease severity and 90-day mortality in these patients. This article is protected by copyright. All rights reserved.
PMID: 30664267 [PubMed - as supplied by publisher]