Granulocyte Colony Stimulating Factor And Growth Hormone In Cirrhosis Of Liver: An Open Label Study
Condition: Cirrhosis
MeSH terms: Liver Cirrhosis; Fibrosis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Cirrhosis of liver is a leading cause of morbidity and mortality worldwide . Complications
      including ascites, spontaneous bacterial peritonitis (SBP), variceal bleed, hepatic
      encephalopathy, hepatorenal syndrome (HRS) and development of hepatocellular carcinoma (HCC)
      have poor prognosis and further decreases the survival in these patients. It has been
      believed that cirrhosis is irreversible and that treatment should focus on preventing the
      progression of liver fibrosis/dysfunction and its complications.

      Currently the only effective treatment is liver transplantation, an increasingly limited and
      expensive resource especially in developing countries. Furthermore, transplantation comes
      with a requirement for lifelong immunosuppression, and considerable long-term side effects
      that include chronic renal failure, post-transplant lymphoproliferative disease, and
      cardiovascular complications.

      Short of liver transplant, recently, reports of unexpected plasticity in adult bone marrow
      have raised hopes that stem cell therapy may offer exciting therapeutic possibilities for
      patients with end stage liver diseases. It has been shown that in response to acute or
      chronic liver damage, bone marrow derived stem cells can spontaneously populate the liver and
      differentiate into hepatic cells. Animal and human studies suggested that such cells might
      contribute to the regeneration after different kinds of liver injuries . In animal models,
      after liver injury, bone marrow-derived circulating pluripotent cells have been reported to
      participate in liver repopulation with both non-parenchymal cells and hepatocytes. This
      repopulation process, however, seems to be highly dependent on the type of liver injury and
      experimental conditions. Fusion with hematopoietic cells has been substantiated as a
      mechanism by which hepatocytes can regenerate, and studies have demonstrated improved liver
      histology and survival in patients with cirrhosis following mobilization of bone marrow stem
      cells by granulocyte-colony stimulating factor (G-CSF) . Three recent studies have
      demonstrated G-CSF induced mobilization of bone marrow stem cells (CD34 cells) in peripheral
      blood and their subsequent increase in liver tissue and improved survival in patients with
      alcoholic hepatitis and acute on chronic liver failure (ACLF) . However there is insufficient
      data on whether G-CSF improves survival and prognosis in patients with cirrhosis.

      Also, Malnutrition is commonly seen (60-70%) in cirrhotics and have adverse prognosis on its
      outcome . The protein catabolic state of cirrhosis is associated with severe growth hormone
      (GH) resistance, with low levels of insulin-like growth factor (IGF)-I and its major binding
      protein (IGFBP)-3 . GH therapy in cirrhosis have been shown to improve nitrogen economy and
      to improve the GH resistance in a small pilot study. Also, GH therapy of short duration has
      shown to increase IGF1 levels, IGFBP-3 levels in patients of cirrhosis . GH therapy has also
      shown to improve liver regeneration and protein synthesis after hepatectomy in patients of
      HCC with cirrhosis . However there is scarcity of data on clinical impact of long term
      administration of GH therapy in patients of cirrhosis.
    


Intervention name(s): standard medical therapy; G-CSF; Growth Hormone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): diuretics, albumin infusion, antibiotics, nutrition, and variceal banding wherever needed; G-CSF at the dosage of 5 µg/Kg subcutaneously every 12 hr for five consecutive days then every 3 monthly for 3 days till 1 year; Growth Hormone in low dose of 1unit sc daily for 1 year
Intervention MeSH terms: Hormones
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Regenerative medicine