Granulocyte Colony Stimulating Factor And Growth Hormone In Cirrhosis Of Liver: An Open Label Study
Status:
Completed
Trial end date:
2016-06-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research