Table 1.
Characteristics of the 7 included studies.
| Authors | Location of the study | Aetiology | Group of patients/study design | No. of patients | G-CSF doses | Age (years, range) | Sex ratio (No. of males, %) | MELD score at baseline∗ | Maddrey's discriminant function at baseline∗ |
|---|---|---|---|---|---|---|---|---|---|
| Spahr et al. (2008)13 | Geneva, Switzerland, Europe | AH (alcoholic steatohepatitis) | Patients randomly assigned to receive standard care + G-CSFc (5 patients received steroids) | 13 | 10 μg/kg/day (5 days) | 53 (34–69)∗ | 11 (85%) | 15 (13–22) | 34 (25–60) |
| Patients randomly assigned to receive standard care + placeboc (7 patients received steroids) | 11 | 54 (42–61)∗ | 6 (54%) | 16 (11–20) | 38.7 (21–59) | ||||
| Garg et al. (2012)17 | New Delhi, India, Asia | ACLFad | Patients randomly assigned to receive G-CSF (no patient received steroids)c | 23 | 5 μg/kg/day (5 days) and every 3 days (1 month) | 40 (30–65)∗ | 20 (87%) | 29 (21–40) | NA |
| Patients randomly assigned to receive placebo or pentoxifylline (no patient received steroids)c | 24 | 40 (19–55)∗ | 21 (87%) | 31.5 (20–40) | NA | ||||
| Singh et al. (2014)36 | Chandigarh, India, Asia | Severe AH | Patients randomly assigned to receive G-CSF + pentoxifylline (no patient received steroids) | 23 | 10 μg/kg/day (5 days) | 41.7 ± 7.5∗∗ | 23 (100%) | 27 | 85.5 |
| Patients randomly assigned to receive pentoxifylline (no patient received steroids) | 23 | 44.3 ± 13∗∗ | 23 (100%) | 30 | 79.2 | ||||
| Sharma et al. (2017)26 | Jaipur, India, Asia | Severe AH | Patients randomly assigned to receive G-CSF (no patient received steroids) | 25 | 5 μg/kg/day (5 days) | 49.4 ± 11.5∗∗ | 25 (100%) | 25.40 ± 9.07∗∗ | 84.54 ± 59.2∗∗ |
| Patients randomly assigned to receive placebo (no patient received steroids) | 25 | 48.6 ± 14.4∗∗ | 25 (100%) | 30.25 ± 10.42∗∗ | 124.78 ± 90.7∗∗ | ||||
| Singh et al. (2018)12 | Chandigarh, India, Asia | Severe AH | Patients randomly assigned to receive G-CSF + pentoxifylline (no patient received steroids) | 18 | 10 μg/kg/day (5 days) | 41.6 ± 8.1∗∗ | 18 (100%) | 26 (19–37) | 84 (56–185) |
| Patients randomly assigned to receive pentoxifylline (no patient received steroids) | 20 | 44.7 ± 9.4∗∗ | 20 (100%) | 27.5 (19–41) | 77.4 (37–235) | ||||
| Shasthry et al. (2019)25 | New Delhi, India, Asia | Severe AH with no responsiveness to steroids | Patients randomly assigned to receive G-CSF (all patients were non-responders to steroids) | 14 | 5 μg/kg/day (5 days) and every 3 days (1 month) | 39.6 ± 9.0∗∗ | 27 (96%) | 24.6 ± 3.9∗∗ | 74.8 ± 22.8∗∗ |
| Patients randomly assigned to receive placebo (all patients were non-responders to steroids) | 14 | 40.7 ± 11.7∗∗ | 27.6 ± 4.4∗∗ | 87.5 ± 28.7∗∗ | |||||
| Engelmann et al. (2019)28 | Multicentric, Europe | ACLFbd | Patients randomly assigned to receive G-CSF | 81e | 5 μg/kg/day (5 days) and every 3 days (1 month) | 54.2 ± 10.1∗∗ | 46 (57%) | 24.5 ± 6∗∗ | NA |
| Patients randomly assigned to receive placebo | 82e | 56.9 ± 9.6∗∗ | 56 (68%) | 23.9 ± 5.6∗∗ | NA |
ACLF, acute-on-chronic liver failure; AH, alcoholic hepatitis; EASL-CLIF, European Association for the Study of the Liver-chronic liver failure; G-CSF, granulocyte colony-stimulating factor; NA, not available; RCT, randomised controlled trial.
Expressed as median.
Expressed as mean ± SD.
ACLF was defined according to the Asian Pacific Association for the Study of the Liver criteria, as an acute hepatic insult manifesting as jaundice (serum bilirubin level ≥5 mg/dl) and coagulopathy (international normalised ratio ≥1.5), complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease.
ACLF according to the EASL-CLIF criteria.
65% of the patients had ACLF caused by AH in the G-CSF group and 50% of the patients had ACLF caused by AH in the control group. Patients with reactivation of hepatitis B and AH were treated with tenofovir and pentoxifylline, respectively.
69.2% of the patients had ACLF caused by AH in the G-CSF group and 69.4% of the patients had ACLF caused by AH in the control group.
Eighty-one patients were randomised in the G-CSF group, but 60 patients ended the study, and 82 patients were randomised in the control group, but 52 patients ended the study (interim analysis).