g-csf in alcoholic hepatitis

8/10/2019 G-CSF in alcoholic hepatitis

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Granulocyte Colony-StimulatingFactor in Severe Alcoholic Hepatitis:

A Randomized Pilot Study

Virendra Singh, MD, DM, FASGE1, Arun K. Sharma,MD, DM1, R. Lakshmi Narasimhan, MD2, AshishBhalla, MD2, Navneet Sharma, MD2 and Ratiram

Sharma, MD3


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INTRODUCTION

Severe alcoholic hepatitis has very high short-

term mortality

In response to acute or chronic liver injury,

bone marrowderived stem cells can

spontaneously populate the liver anddifferentiate into hepatic cells


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INTRODUCTION

CD34 + cells might contribute to hepaticregeneration and repair of acute liver injury

Several studies have demonstrated the safetyand efficacy of G-CSF in promoting themobilization of bone marrow stem cells toimproved histology and survival after liverinjury


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INTRODUCTION

This trial is designed to evaluate the safety

and efficacy of G-CSF in the treatment of

patients with severe alcoholic hepatitis


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METHODS


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Patients

Between July 2010 and June 2012

Patients with alcoholic hepatitis with amodified 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


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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)


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Patients

Inclusion criteria

age 1875 years

average alcohol intake of more than 100 g/day during the 3 months beforeenrollment

Exclusion criteria

HCC or portal vein thrombosis, refusal to participate in the study, priortreatment with steroids, any significant comorbidities including hepatorenal

syndrome, grade 3 or 4 hepatic encephalopathy, UGIB within the pre- ceding10 days, uncontrolled bacterial infection, HIV infection, HBV infection, HBCvirus seropositivity, autoimmune hepatitis, hemochromatosis, Wilsonsdisease, alpha-1-antitrypsin deficiency, pregnancy, or any previous knownhypersensitivity to G-CSF


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Patients


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Patients


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Study outcomes

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

The secondary end points

mobilization of CD34 + cells in peripheral blood

improvement in clinical scores (MELD, mDF, andCTP)

safety of G-CSF in alcoholic hepatitis patients


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Estimation of hemopoietic stem cells in

peripheral blood

Venous blood-->automated-->centrifuged formononuclear cell

Two flow tubes(test/negative control)-->coatedwith anti-CD34 antibody and mixed-->centrifuged-->flow cytometry analysis

Data were captured and analyzed according tothe International Society of Hematotherapy andGraft Engineering guidelines


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Ethics approval

The study protocol was approved by theinstitutional ethics com- mittee and the study

conformed to the Helsinki Declaration of 1977

All patients gave informed written consent


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Statistical analysis

The statistical analysis was carried out using StatisticalPackage for Social Sciences (SPSS Inc.)

For normally distributed data, means were compared usingStudents t-test for two groups

For nonparametric data the MannWhit- ney test was applied

Proportions were compared using the 2 or Fishers exact

test

All statistical tests were two-sided and were performed at asignificance level of = 0.05


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RESULTS


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RESULTS


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g-csf in alcoholic hepatitis

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