Multiple cycles of granulocyte colony-stimulating factor in decompensated cirrhosis: a double-blind RCT

Aswath Venkitaraman, Arka De, Nipun Verma, Sunita Kumari, Bidyalaxmi Leishangthem, Ratti Ram Sharma, Naveen Kalra, Sandeep Grover, Virendra Singh, Aswath Venkitaraman, Arka De, Nipun Verma, Sunita Kumari, Bidyalaxmi Leishangthem, Ratti Ram Sharma, Naveen Kalra, Sandeep Grover, Virendra Singh

Abstract

Background: Liver transplant, the definitive treatment of decompensated cirrhosis (DC), is constrained by donor shortage and long-term complications. Granulocyte colony-stimulating factor (G-CSF) has been explored as an alternative option in open-label studies. This double-blind, randomized, placebo-controlled trial was designed to elucidate the efficacy of G-CSF in DC.

Methods: Seventy patients were randomized to either G-CSF plus standard medical therapy (group A, n = 35) or placebo plus standard medical therapy (group B, n = 35). Primary outcome was 12-month overall survival in patients who received at least one cycle of intervention. Secondary outcomes were mobilization of CD34+ cells at day 6, improvement in Child-Turcotte-Pugh (CTP), and model for end-stage liver disease (MELD), liver stiffness measurement, quality of life, nutrition, hepatic decompensation, infection, hospitalization, and acute kidney injury.

Results: Survival in group A was higher than that in Group B although the difference was not statistically significant (87.9% vs 66.7%; p = 0.053). CD34+ cells at day 6 were significantly higher in group A as compared to baseline (p < 0.001). Ascites control (p = 0.03) and CTP score improvement (p = 0.02) were better in group A at 12-months. Encephalopathy episodes (p = 0.005), infections (p = 0.005) were fewer in group A than group B at 12 months. Other secondary outcomes did not improve post-therapy. There were no treatment-related discontinuations or severe adverse events.

Conclusions: G-CSF therapy is safe. The improvement in survival at 12 months is not statistically significant. Better control of ascites, improvement of CTP score, fewer encephalopathy episodes and decreased rate of infections were observed with G-CSF therapy (NCT03911037). Trials Registration NCT03911037.

Keywords: Ascites; Chronic liver disease; Cirrhosis; End-stage liver disease; G-CSF; Growth factors; Hematopoietic stem cells; Hepatic encephalopathy; Liver regeneration; Portal hypertension; Variceal bleed.

Conflict of interest statement

Aswath Venkitaraman, Arka De, Nipun Verma, Sunita Kumari, Bidyalaxmi Leishangthem, Ratti Ram Sharma, Naveen Kalra, Sandeep Grover, Virendra Singh declare no conflicting interests and have no financial disclosures.

© 2022. Asian Pacific Association for the Study of the Liver.

Figures

Fig. 1
Fig. 1
Consort diagram of the study
Fig. 2
Fig. 2
Kaplan–Meier curve showing overall survival at 12 months in groups A and B

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