Decompensated Cirrhosis
Conditions
Keywords
GCSF, Decompensated cirrhosis, Darbepoetin
Brief summary
Chronic liver disease is a growing health concern, with limited access to liver transplants. This study addresses the urgent need for alternatives by exploring regenerative therapies, like G-CSF, to boost the liver's natural repair. The goal is to develop safe, effective, and accessible treatments for patients who cannot undergo transplant.
Detailed description
The incidence of deaths from chronic liver diseases (CLD) and cirrhosis are rapidly increasing globally, including India. Liver transplant is the only curative option. Unfortunately, transplant is often not feasible. There is a need for nearly 100,000 liver transplants every year in India, though, only about 2,500 transplants are being done at present across the country. There is therefore, a huge unmet need of developing non-transplant options for chronic liver disease patients. In this regard emerging science of regenerative therapy holds great promises but therapeutic benefit of these therapies is limited due to lack of clinical validation. Novelty: Cirrhosis as a result of hepatitis B and C can regress with effective antiviral therapy. Therapeutic options for patients with cryptogenic or alcoholic cirrhosis are, however, limited. With limited options for transplant. Liver failure is failure of regeneration hence, potentiating native liver repair and regeneration can serve as potential non-transplant approaches. Growth factors {like GCSF, darbepoetin (EPO) have shown survival benefits with improve liver repair and regeneration in clinical trials by us (Gastroenterology 2012, 2015, Liver Int. 2019; Hepatology 2021) and others, however the effect is transient. In the proposed National Collaborative Centre for Hepatic Regenerative Medicine (NC-CHRM) we will use this novel regenerative medicine approaches GCSF therapy (for management of chronic liver failure) to develop safe and effective regenerative therapy clinical protocol for transplant free management of liver failure in cirrhosis. Using integrated cellular, molecular and functional analysis we will also establish their mechanism of action and identify biomarker to access therapeutic response.
Interventions
DRUGGcsf
G-CSF will be given at a dose of 5 μg/kg s/c at days 1, 2, 3, 4, 5 and then every third and 7th day till day 30
DRUGDarbepoetin
Darbepoetin will be given s/c at dose of 40mcg once a week for 1 month
OTHERStandard Medical Treatment
Standard Medical Treatment
Sponsors
Indian Council of Medical Research
Institute of Liver and Biliary Sciences, India
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Early decompensated cirrhosis patients with MELD \<16
Exclusion criteria
* Patients with age less than 18 years or more than 65 years * Patients with Grade III ascites * CHILD C cirrhosis * Patients with a known focus of sepsis; spontaneous Bacterial Peritonitis (SBP) * variceal bleeding in past 3months * Hepatocellular Carcinoma (HCC) or other malignancy * Acute Kidney Injury (AKI) with serum Creatinine \>1.5 mg/ dl, multi-organ failure, grade 3 or 4 Hepatic Encephalopathy (HE), * HIV seropositivity * Medically uncontrolled essential hypertension * Pregnancy * Viral etiology of liver disease * Co-existent Hepatitis B, Hepatitis C, HIV * Chronic kidney disease * Lack of informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Transplant-free survival of GCSF + darbepoetin in patients with early decompensated cirrhosis in both groups. | 3 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patient developed new-onset of Liver Related Event (such as ascites, hepatic encephalopathy , acute kidney injury, bleed and sepsis) or show mortality in both the groups | 6-month, one year, 2 year and 3 year | — |
| Cumulative incidence of sepsis, acute kidney injury or secondary organ dysfunction in both groups | 6-month, one year, 2 year and 3 year | — |
| Cumulative incidence of second decompensation | 6-month, one year, 2 year and 3 year | — |
| Improvement in liver disease severity indices, including the Child-Turcotte-Pugh (CTP) score (ΔCTP). | 6-month, one year, 2 year and 3 year | — |
| Improvement in liver disease severity indice like Model for End-Stage Liver Disease (MELD) score (ΔMELD). | 6-month, one year, 2 year and 3 year | — |
| Transplant-free survival | 6-month, one year, 2 year and 3 year | — |
| Impact on liver injury (assessed by AST and ALT levels in blood). | 6-month, one year, 2 year and 3 year | — |
| Impact on fibrosis (evaluated using Masson's Trichome stain and the Enhanced Liver Fibrosis [ELF] score). | 6-month, one year, 2 year and 3 year | — |
| Impact on regeneration (measured by plasma Alpha-Fetoprotein levels). | 6-month, one year, 2 year and 3 year | — |
| Impact on bone marrow stem cell reserve (CD34⁺ cell count in peripheral blood) | One year, 2 year and 3 year | — |
| Proportion of patients completing treatment without major adverse effects | 6-month, one year, 2 year and 3 year | Adverse effects will be graded in accordance to CTCAE |
Countries
India
Contacts
Primary ContactDr. Anupam Kumar, PhD
Backup ContactFagun Sharma, M.Sc.
Outcome results
None listed