G-CSF in Decompensated Cirrhosis: an Open Label Trial
Status:
Unknown status
Trial end date:
2018-12-01
Target enrollment:
Participant gender:
Summary
Globally, cirrhosis is the fifth commonest cause of mortality. Its natural history is
typified by an initial, largely asymptomatic, "compensated" phase followed by
"decompensation" due to complications of raised portal pressures and hepatocellular
dysfunction.
Currently the only definitive treatment option for cirrhosis is liver transplantation which
is limited in its applicability due to donor shortage, exorbitant costs and lack of
widespread availability. The need for long term immunosuppression and its attendant
complications are a further drawback. The ability of stem cells to differentiate into
multiple cellular lineages makes one speculate that they can be used for tissue repair and
regeneration when tissue-resident stem cells become overwhelmed. Bone marrow derived stem
cells have amazing plasticity. They can "home" to the liver in response to injury and help in
liver regeneration by trans-differentiation, cell fusion and augmentation of tissue- resident
stem cell mediated repair. Two methods are available for the mobilisation of stem cells from
the bone marrow to the liver. One involves the administration of cytokines like
granulocyte-colony stimulating factor (G-CSF) and the other is the isolation of stem cells
from the marrow followed by their injection into the hepatic artery or portal vein after
purification. The latter is probably more cumbersome and may be potentially risky due to the
underlying coagulation abnormalities in cirrhotic patients .
G-CSF has been shown to mobilise bone marrow stem cells and even increase survival in
patients of severe alcoholic steatohepatitis and ACLF. There is conflicting evidence on the
role of G-CSF in decompensated cirrhosis with some studies showing improved survival while
others have shown a lack of clinical or biochemical benefit. Many of these studies have used
a single course of G-CSF. Verma et al, in a recent study published in 2018, elegantly
demonstrated the beneficial effect of multiple courses of G-CSF in improving mortality and
transplant free survival in decompensated cirrhotics.
The investigators too speculate that multiple cycles of G-CSF could result in better outcomes
in decompensated cirrhosis by causing more prolonged and sustained stem cell homing to the
liver. Thus, this study is being undertaken to further evaluate the safety and efficacy of
multiple cycles of G-CSF in decompensated cirrhotics.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Postgraduate Institute of Medical Education and Research