, researchers from India reported.
Among patients with SAH, the combination of G-CSF and prednisolone was associated with a 90-day survival rate of 88.1%, compared with 78.6% for patients assigned to G-CSF alone, and 64.3% for patients assigned to prednisolone alone (P = .03).
The G-CSF/prednisolone combination was also associated with significantly better steroid responsiveness, as determined by the Lille Model for Alcoholic Hepatitis, reported Shiv K. Sarin, MD, from the Institute of Liver and Biliary Sciences, New Delhi.
The drug combo in steroid-eligible patients also “reduces morbidity related to infections, rehospitalizations, and hepatic encephalopathy [and] reduces infection rates,” Dr. Sarin said at the annual meeting of the American Association for the Study of Liver Diseases. He did caution that the treatment requires close monitoring.
Prednisolone-only drawbacks
For patients with SAH, 30-day mortality ranges from 20%-50%. While some patients respond to treatment with corticosteroids, the response is often modest and limited in duration, Dr. Sarin said.
The STOPAH trial found that 15% of patients with SAH treated with prednisolone developed serious infections, compared with 8% of patients on placebo (P = .002), he noted.
Dr. Sarin also pointed to a recent worldwide study attempting to identify the optimal therapeutic window for steroid use in patients with alcoholic hepatitis. The investigators found that corticosteroids reduced 30-day mortality by 41% but only among patients with SAH, especially those with Model for End-Stage Liver Disease (MELD) scores between 25 and 39.
In previous studies, G-CSF has been shown to improve survival in patients with acute-on-chronic liver failure, including patients with SAH; in patients with SAH alone; and in steroid nonresponders, Dr. Sarin said.
Regenerative properties
In an interview with this news organization, Dr. Sarin said that although the use of G-CSF for patients with severe SAH is still under investigation at his center, “we are using G-CSF routinely for decompensated cirrhosis, where it is like an in vivo extension of regenerative stem cells. G-CSF recruits from bone marrow a lot of hematopoietic stem cells and mesenchymal stem cells.”
Dr. Sarin and colleagues hypothesized that G-CSF, with its immunomodulatory and regenerative properties, would be effective either alone or in combination with steroids in steroid-eligible patients with SAH.
To test this idea, they enrolled 126 patients ages 18-65 with SAH, defined as a Maddrey’s Discriminant Function (mDF) score greater than 32. They excluded patients with active infections, acute gastrointestinal bleeding, hepatorenal syndrome, an mDF score greater than 90, autoimmune hepatitis, hepatitis B or C, HIV, pregnancy, hemophagocytic lymphohistiocytosis, and those with hemoglobin below 8 and baseline white blood cell count over 25,000.
The patients were randomly assigned, 42 in each group, to receive one of the following:
- Prednisolone monotherapy 40 mg/day for 7 days, with the drug stopped at 7 days for patients with Lille scores above 0.45 or continued for up to 21 days for those with Lille scores below 0.45;
- Prednisolone plus G-CSF 300 mcg/day for 7 days, with those who achieve a Lille score above 0.45 stopping the steroid but continuing G-CSF, while those with Lille scores below 0.45 continuing on prednisolone for 21 days, plus G-CSF once every 3 days for 5 additional doses; or
- G-CSF monotherapy at a dose of 150-300 mcg/day for 7 days, then every 3 days for 28 days up to a total of 12 doses.
