Granulocyte Colony–Stimulating Factor Mobilizes CD34+ Cells and Improves Survival of Patients With Acute-on-Chronic Liver Failure

Abstract

Background & aims Acute-on-chronic liver failure (ACLF) develops in patients with chronic liver disease and has high mortality. Mobilization of bone marrow-derived stem cells with granulocyte colony-stimulating factor (G-CSF) could promote hepatic regeneration. Methods Consecutive patients with ACLF were randomly assigned to groups given 5 μg/kg G-CSF subcutaneously (12 doses; group A, n = 23) or placebo (group B, n = 24) plus standard medical therapy. We assessed survival until day 60; Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), and Sequential Organ Failure Assessment (SOFA) scores; and the development of other related complications. Results After 1 week of treatment, group A had higher median leukocyte and neutrophil counts than group B (P < .001). Sixteen patients in group A (69.6%) and 7 in group B (29%) survived; the actuarial probability of survival at day 60 was 66% versus 26%, respectively (P = .001). Treatment with G-CSF also reduced CTP scores in group A by a median of 33.3% compared with an increase of 7.1% in group B (P = .001), along with MELD (median reduction of 15.3% compared with an increase of 11.7% in group B; P = .008) and SOFA scores (median reduction of 50% compared with an increase of 50% in group B; P = .001). The percentages of patients who developed hepatorenal syndrome, hepatic encephalopathy, or sepsis were lower in group A than in group B (19% vs 71% [P = .0002], 19% vs 66% [P = .001], and 14% vs 41% [P = .04], respectively). After 1 month of treatment, G-CSF increased the number of CD34(+) cells in the liver (by 45% compared with 27.5% in group B; P = .01). Conclusions G-CSF therapy more than doubles the percentage of patients with ACLF who survive for 2 months; it also significantly reduces CTP, MELD, and SOFA scores and prevents the development of sepsis, hepatorenal syndrome, and hepatic encephalopathy.