Granulocyte Colony-Stimulating

Factor in Severe Alcoholic Hepatitis:

A Randomized Pilot Study
Virendra Singh, MD, DM, FASGE1, Arun K. Sharma,
MD, DM1, R. Lakshmi Narasimhan, MD2, Ashish
Bhalla, MD2, Navneet Sharma, MD2 and Ratiram
Sharma, MD3

INTRODUCTION
Severe alcoholic hepatitis has very high shortterm mortality
In response to acute or chronic liver injury,
bone marrowderived stem cells can
spontaneously populate the liver and
differentiate into hepatic cells

INTRODUCTION
CD34 + cells might contribute to hepatic
regeneration and repair of acute liver injury

Several studies have demonstrated the safety

and efficacy of G-CSF in promoting the
mobilization of bone marrow stem cells to
improved histology and survival after liver
injury

INTRODUCTION

This trial is designed to evaluate the safety

and efficacy of G-CSF in the treatment of
patients with severe alcoholic hepatitis

METHODS

Patients
Between July 2010 and June 2012
Patients with alcoholic hepatitis with a
modified Maddreys discriminant function
(mDF) of 32 or more admitted to our Liver
Intensive Care Unit (Depart- ment of
Hepatology) within a tertiary care center were
evaluated for eligibility

Patients
Diagnosis of alcoholic hepatitis
total serum bilirubin level > 5 mg/100 ml
AST/ALT> 2
AST < 300 U/l
All patients had
elevated INR
leukocytosis
ascites
history of heavy alcohol use (mean intake, ~100 g/day)

Patients
Inclusion criteria
age 1875 years
average alcohol intake of more than 100 g/day during the 3 months before
enrollment
Exclusion criteria
HCC or portal vein thrombosis, refusal to participate in the study, prior
treatment with steroids, any significant comorbidities including hepatorenal
syndrome, grade 3 or 4 hepatic encephalopathy, UGIB within the pre- ceding
10 days, uncontrolled bacterial infection, HIV infection, HBV infection, HBC
virus seropositivity, autoimmune hepatitis, hemochromatosis, Wilsons
disease, alpha-1-antitrypsin deficiency, pregnancy, or any previous known
hypersensitivity to G-CSF

Patients

Patients

Study outcomes
The primary end point of the study was survival at 90
days

The secondary end points

mobilization of CD34 + cells in peripheral blood
improvement in clinical scores (MELD, mDF, and
CTP)
safety of G-CSF in alcoholic hepatitis patients

Estimation of hemopoietic stem cells in

peripheral blood
Venous blood-->automated-->centrifuged for
mononuclear cell
Two flow tubes(test/negative control)-->coated
with anti-CD34 antibody and mixed->centrifuged-->flow cytometry analysis
Data were captured and analyzed according to
the International Society of Hematotherapy and
Graft Engineering guidelines

Ethics approval

The study protocol was approved by the

institutional ethics com- mittee and the study
conformed to the Helsinki Declaration of 1977
All patients gave informed written consent

Statistical analysis
The statistical analysis was carried out using Statistical
Package for Social Sciences (SPSS Inc.)
For normally distributed data, means were compared using
Students t-test for two groups
For nonparametric data the MannWhit- ney test was applied
Proportions were com- pared using the 2 or Fishers exact
test
All statistical tests were two-sided and were performed at a
significance level of = 0.05

RESULTS

RESULTS