Granulocyte Colony Stimulating Factor Four Week Plus N-Acetyl Cysteine in Severe Alcoholic Hepatitis
Condition: Alcoholic Hepatitis
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Alcoholic
Study type: Interventional
Phase: Phase 4

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.
    


Intervention name(s): Standard Medical Therapy; G-CSF; G-CSF and NAC
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Standard medical therapy involves primary treatment with normal hospital nutrition (1800 to 2000 kcal per day). Diuretics, sodium restriction and albumin for treatment of ascites or fresh frozen plasma for coagulopathy or antibiotics for any focus of infection as spontaneous bacterial peritonitis (SBP), pneumonia, cellulitis, and urinary tract infection as indicated.; standard medical therapy plus G-CSF- 5μg/Kg s.c every 12 hours for 5 consecutive days; Standard Medical Therapy plus G-CSF with intravenous NAC (day 1: NAC at 150, 50, and 100 mg/kg in 250, 500, and 1000 ml of 5% glucose solution over 30 minutes, 4 hours, and 16 hours, respectively; days 2 through 5: 100 mg/kg/day in 1000 ml of 5% glucose solution followed by oral NAC from days 6 to 28)
Intervention MeSH terms: Lenograstim
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Open label randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: alcoholic hepatitis; alcoholic liver disease; regeneration