Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis
Status:
Completed
Trial end date:
2021-02-28
Target enrollment:
Participant gender:
Summary
Alcoholic hepatitis is related to very high mortality rate. About 40% of the patients 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 conditions. The studies have 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 these 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 acute 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 4 weeks of NAC plus G-CSF
in patient with severe alcoholic hepatitis.
Therefore the investigators plan to study the safety and efficacy of combination therapy of
G-CSF and 4 weeks of NAC in the patients with alcoholic hepatitis.
Phase:
Phase 4
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research