Alcoholic hepatitis is related to very high mortality rate. About 40% of the patients are
died within first 6 months after the detection of the clinical syndrome. Therefore, it is
very essential for proper diagnosis and early treatment. In response to acute or chronic
liver damage, bone marrow derived stem cells can spontaneously populate liver and
differentiate into hepatic cells. Animal and human studies suggested that injured hepatocyte
may be replaced by pluripotent bone marrow cells. However, this hepatocyte repopulation is
highly dependent on varieties of liver injury and therapeutic conditions6. The studies has
suggested Granulocyte-colony stimulating factors (G-CSF) can regenerate hepatocyte by fusing
with hematopoietic cells, thereby enhancing the liver histology and survival rate.
G-CSF is a cytokine capable to regulate a number of functions in neutrophils. In three recent
studies mobilization of bone marrow stem cells induced by G-CSF was observed in patients with
alcoholic hepatitis. In two of this studies there was a survival benefit with the use of
G-CSF.
Alcoholism leads to decrease in endogenous antioxidant potential. Alcoholic liver disease
(ALD) patients show low endogenous antioxidants. Chronic ethanol consumption cause selective
deficiency in the availability of reduced glutathione (GSH) in mitochondria has been
reported. This is due to impaired functioning of GSH transporter from cytosol to
mitochondrial matrix. The effect on glutathione replenishing potential by N-acetyl cysteine
(NAC) can be used to reduce oxidative stress, which also has excellent safety profile.
Therefore, NAC can be used for severe alcoholic hepatitis treatment due to its therapeutic
potential factor. NAC also inhibit apoptosis and pro-inflammatory cytokine production. In a
study high doses of intravenous N-acetyl cysteine therapy for 14 days conferred neither
survival benefits nor early biological improvement in severe alcoholic hepatitis patients
with adequate nutritional support.However, these results must be viewed with caution, since
the study suffered from a lack of power. In a recent study, NAC and corticosteroids
combination therapy benefits among patients with severe acute alcoholic hepatitis in 1 month
survival, although the final outcome at 6 month survival was not improved. There are no
studies on the use of combination therapy of NAC plus G-CSF in patient with severe alcoholic
hepatitis.
Therefore we plan to study the safety and efficacy of combination therapy of G-CSF and NAC in
the patients with alcoholic hepatitis.
Phase:
Phase 4
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research