Liver regeneration as treatment target for severe alcoholic hepatitis

Table 1 Summary of human studies with granulocyte colony-stimulating factor treatment in patients with alcohol-related liver disease

Study population	Methods	Outcomes	Ref.
RCT included 24 pts with ALC and biopsy proven ASH1	Group A (13 pts) received SMT + G-CSF and group B (11 pts) received SMT only	Higher increase in CD34+ cell count, HGF, proliferating HPCs and Ki67+/cytokeratin 7+ staining in group A	Spahr et al[27], 2008
RCT included 27 pts with ALC presenting with ACLF1	Group A (15 pts) received G-CSF + SMT, and group B (12 pts) received placebo + SMT	Group A had higher median leukocyte and neutrophil counts after 1 w and higher CD34+ cell count after 1 mo, together with improvement in 60-day survival, reduced CTP, MELD and SOFA scores	Garg et al[28], 2012
RCT included 46 pts with severe AH1	Group A (23 pts) received G-CSF, while group B (23 pts) received SMT	In group A, higher CD34+ count was observed together with marked CTP, MELD and mDF score improvements after 1, 2 and 3 mo and higher survival rate at 90 d	Singh et al[29], 2014
RCT included 38 pts with ALC1	Group A (14 pts) received SMT + GH qd for 12 mo + initial G-CSF 5-d treatment and then 4 G-CSF cycles every 3 mo; group B (15 pts) received initial G-CSF 5-d treatment and then 4 G-CSF cycles every 3 mo, and group C received SMT only	Groups A and B had better TFS after 12 mo and higher QOL scores, as well as higher CD34+ mobilization rate at day 6, with lower incidence of sepsis and SBP	Verma et al[36], 2018
RCT included 35 pts with ALC1	Group A (19 pts) received G-CSF + EPO and group B (16 pts) received G-CSF only	Group A had higher improvement of CTP and MELD score, together with lower incidence of AKI, HE and ascites; histologically number of CD163+ macrophages and KI67+ index were increased	Anand et al[33], 2019
RCT included 57 pts with severe AH1	Group A (18 pts) received SMT + G-CSF, group B (19 pts) received SMT + G-CSF + NAC, and group C (20 pts) received SMT alone	Pts in group A and B had higher 90-d survival rate; in group A, improvement in mDF was observed at mo 1, 2 and 3, together with reduction in MELD score after 3 mo	Singh et al[37], 2018
RCT included 28 pts with severe AH1	Group A (14 pts) received G-CSF and group B (14 pts) received placebo	Group A had better MELD score, lower incidence of infections as well as lower 90-d mortality	Shasthry et al[38], 2019
RCT included 48 pts with ALC1	Group A (25 pts) was treated with 4 cycles of 5-d G-CSF therapy and group B (23 pts) was treated with SMT only	Group A had higher CD34+ and neutrophil count at day 6; higher 1-year survival, amelioration in CTP and MELD scores together with better ascites control and lower infection risk were observed after 12 mo	De et al[30], 2021
RCT included 176 pts with ACLF precipitated by alcohol consumption1	Group A (88 pts) was treated with G-CSF + SMT, and group B (88 pts) was treated with SMT	There were no statistically significant differences in respect of TFS, 90-d and 360-d survival rates and infection incidence	Engelmann et al[39], 2021

¹Patient(s) has/have dropped-out, underwent deceased donor liver transplant, or death outcome occurred.

ACLF: Acute-on-chronic liver failure; AKI: Acute kidney injury; ALC: Alcoholic liver cirrhosis; ASH: Alcoholic steatohepatitis; GH: Growth hormone; HE: Hepatic encephalopathy; HPC: Hepatocyte progenitor cell; mDF: Maddrey’s Discriminant Function for alcoholic hepatitis; NAC: N-acetyl-cysteine; pt(s): Patient(s); qd: Quaque die; QOL: Quality of life; SBP: Spontaneous bacterial peritonitis; SMT: Standard medical treatment; SOFA score: Sequential Organ Failure Assessment score; TFS: Transplant-free survival.