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.

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.

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