Granulocyte Colony-Stimulating Factor Improves Survival in Severe Alcoholic Hepatitis

Summary and Comment |
September 15, 2014

Granulocyte Colony-Stimulating Factor Improves Survival in Severe Alcoholic Hepatitis

  1. Atif Zaman, MD, MPH

Impressive preliminary findings warrant further study.

  1. Atif Zaman, MD, MPH

Experimental models have suggested that granulocyte colony-stimulating factor (G-CSF) has the ability to mobilize hematopoietic stem cells, induce liver regeneration, and improve survival in patients with severe alcoholic hepatitis.

In the current prospective, open-label, pilot study, investigators randomized 46 patients with severe alcoholic hepatitis, defined as having a modified Maddrey's discriminant function of ≥32, to standard of care (400 mg of pentoxifylline 3 times daily) plus G-CSF (5 µg/kg subcutaneously every 12 hours for 5 days) or standard of care alone. The primary outcome was 90-day survival, and secondary outcomes included improvement in Model for End-stage Liver Disease (MELD) and Child-Pugh scores, safety, and mobilization of CD34+ cells in peripheral blood (a marker of stem cell mobilization).

Compared with patients receiving standard of care alone, the G-CSF group had significantly better outcomes in:

  • 90-day survival (78.3% vs. 30.4%)

  • Number of CD34+ cells in the peripheral blood at day 6 (0.47 ±0.57 vs. 0.16 ±0.2)

  • Reduction in median percent change in Child-Pugh, MELD, and Maddrey's scores at 1, 2, and 3 months

G-CSF was well tolerated; adverse effects included minor complaints of bone pain in three patients and headache in two patients.

Comment

This open-label, single-center pilot study conducted in India demonstrates that a 5-day course of G-CSF in patients with severe alcoholic hepatitis is not only safe, but improves 90-day survival. Larger, multicenter studies are warranted to validate these impressive findings. Additionally, future studies need to compare the efficacy of G-CSF with that of corticosteroids, which is the current standard, and better elucidate the mechanism by which G-CSF improves survival.

Editor Disclosures at Time of Publication

  • Disclosures for Atif Zaman, MD, MPH at time of publication Nothing to disclose

Citation(s):

Reader Comments (3)

JAYAN GOPINATH Physician, Gastroenterology

In the setting of alcoholic hepatitis how is it possible to rule out cirrhosis since use of steroids pentoxyfylline and GM CSF may be assosciated with complications

Pozzi Alessandro, MD Physician, Internal Medicine, Civil Hospital-Brescia

Is pentoxifylline the best standard of care? In other word, the impressive better outcome in G-CSF could be explained by the low efficacy of standard of care

barakat emam Physician, Gastroenterology, kasr alaini

Is liver biopsy mandatory and if so when it can be done

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