To Study the Influence of GCSF on Natural History of Acute On Chronic Liver Failure After the Acute Phase

Study Overview
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Brief Summary
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All consecutive ACLF (Acute on Chronic Liver failure) patients presenting to the institute of liver and biliary sciences, irrespective of the etiology , who have survived the acute phase (i.e. 90 days of onset of the acute on chronic liver failure) and who are willing to participate in the study would be enrolled. After performing baseline biochemical tests, patients will undergo transjugular liver biopsy (TJLB), HVPG (Hepatic Venous Pressure Gradient), Circulating CD34 cells, Bone marrow aspiration and biopsy (Histopathological and immunohistochemical examination will be done).

Official Title
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To Study the Influence of GCSF on Natural History of Acute On Chronic Liver Failure After the Acute Phase - A Randomized Controlled Study

Conditions
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Acute on Chronic Liver Failure

Intervention / Treatment
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* Drug: Peg GCSF
* Biological: 20% Albumin
* Dietary Supplement: Nutrition
* Other: Bowel wash
* Drug: Terlipressin 1- 4mg,if indicated
* Drug: Meropenem or Imepenem, if indicated
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 18-65 years All patients who were known to have ACLF and have survived 3 months of the onset of acute event Patients willing to participate in the study Exclusion Criteria: Presence of AKI (Acute Kidney Injury) Active sepsis (Blood/ urine culture positive, SBP (Spontaneous bacterial Peritonitis, LRTI (lower Respiratory Tract infection) Sickle cell anemia HepatoCellular Carcinoma Hematological malignancies Multi organ failure Grade 3/ 4 HE (Hepatic Encephalopathy) HIV seropositivity Pregnancy Patients being taken up for transplant Refusal to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peg GCSF with standard medical therapy<br> | Drug: Peg GCSF<br> <br> Biological: 20% Albumin<br> <br> Dietary Supplement: Nutrition<br> <br> Other: Bowel wash<br> <br> Drug: Terlipressin 1- 4mg,if indicated<br> <br> Drug: Meropenem or Imepenem, if indicated<br> <br> |
| Active Comparator: Placebo with standard medical therapy<br> | Biological: 20% Albumin<br> <br> Dietary Supplement: Nutrition<br> <br> Other: Bowel wash<br> <br> Drug: Terlipressin 1- 4mg,if indicated<br> <br> Drug: Meropenem or Imepenem, if indicated<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant free survival in both groups |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative assessment of CD34 positive cells in serum in both groups. | On Immunohistochemistry of liver biopsy tissue,quantification of + ve CD34 cells will be done | 1 year | 
| Quantitative assessment of CD34 positive cells in liver biopsy samples in both groups. | On Immunohistochemistry of liver biopsy tissue,quantification of + ve CD34 cells will be done | 1 year | 
| Reduction in liver disease severity indices like CTP (Child-Turcotte-Pugh) by more than one point in both groups. |  | 1 year | 
| Reduction in liver disease severity indices like MELD Na ((Model for End Stage liver disease) by more than 2 points in both groups. |  | 1 year | 
| Development of new onset complications such as hepatic encephalopathy in both groups. |  | 1 year | 
| Development of new onset complications such as hepatorenal syndrome in both groups. |  | 1 year | 
| Development of new onset complications such as sepsis in both groups. |  | 1 year | 
| Development of new onset complications such as Hepatocellular carcinoma (HCC). |  | 1 year | 
| Total number of CD34 positive cells in histopathological examination of bone marrow in both groups |  | 1 year | 
| No of adverse events in both groups |  | 1 year | 
| Reduction in HVPG (Hepatic Venous Pressure Gradient) in both groups |  | 1 year | 
| Reduction in HBV DNA level in both groups. |  | 1 year | 
| Number of patients who will restart alcohol abuse during the follow up period in both groups. |  | 1 year |