Efficacy of Granulocyte Colony-stimulating Factor in the Management of Steroid-Nonresponsive Severe Alcoholic Hepatitis: A Double-Blind Randomized Controlled Trial.

Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 8302946 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-3350 (Electronic) Linking ISSN: 02709139 NLM ISO Abbreviation: Hepatology Subsets: MEDLINE

Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc.
Original Publication: Baltimore, MD : Williams & Wilkins, [c1981]-

Disease Progression* ; Drug Resistance*; Granulocyte Colony-Stimulating Factor/*administration & dosage ; Hepatitis, Alcoholic/*drug therapy ; Prednisolone/*administration & dosage; Adult ; Analysis of Variance ; Biopsy, Needle ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Administration Schedule ; Female ; Hepatitis, Alcoholic/diagnosis ; Hepatitis, Alcoholic/mortality ; Humans ; Immunohistochemistry ; India ; Injections, Subcutaneous ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Proportional Hazards Models ; Reference Values ; Retreatment ; Risk Assessment ; Severity of Illness Index ; Survival Rate ; Treatment Outcome ; Young Adult

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 nonresponders. A randomized, double-blind, single-center trial (NCT01820208) was conducted between March 2013 and June 2016 in patients with histologically proven SAH, nonresponsive to 40 mg/day of prednisolone were randomized to G-CSF (12 doses, 300 μg each in 28 days) or placebo. Responders were continued with prednisolone. Of the 430 patients with SAH, 132 received steroid therapy. Of these, 33 (25%) were nonresponders 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 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% versus 71%; P < 0.001) with lower 90-day mortality (35.7% versus 71.4%; P = 0.04) in the G-CSF than in the placebo group. On Cox regression analysis, receiving G-CSF (hazard ratio, 0.37; SD, 0.14-0.98; P = 0.04), and high baseline serum creatinine (hazard ratio, 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. Conclusion: 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.
(© 2019 by the American Association for the Study of Liver Diseases.)

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ClinicalTrials.gov NCT01820208

143011-72-7 (Granulocyte Colony-Stimulating Factor)
9PHQ9Y1OLM (Prednisolone)

Date Created: 20190122 Date Completed: 20200703 Latest Revision: 20200703

20250114

10.1002/hep.30516

30664267