Can G-CSF Cause Elevated Liver Enzymes?
Yes, G-CSF can cause elevated liver enzymes, though this is a rare adverse effect that is not mentioned in major clinical practice guidelines.
Evidence for Hepatotoxicity
The most compelling evidence comes from a 2025 case report of drug-induced liver injury (DILI) in a healthy stem cell donor 1. This case documented:
- AST elevation to 171 U/L (6× upper limit of normal) on Day 7
- ALT elevation to 244 U/L (6× ULN) on Day 11
- ALP elevation to 371 U/L (3× ULN) on Day 5
- γ-GTP elevation to 93 U/L (1.5× ULN) on Day 9
Critically, the hepatobiliary dysfunction became evident after G-CSF administration had ended, and was confirmed by positive drug lymphocyte stimulation testing. The donor's liver function normalized within 1 month with supportive treatment alone.
A second 2025 case report documented G-CSF-induced isolated hyperbilirubinemia in a patient with acute myelogenous leukemia, where total bilirubin rose progressively while all liver enzymes (ALT, AST, γ-GTP) remained normal 2. This represents a distinct pattern of hepatic injury.
Clinical Context and Guideline Silence
Major clinical practice guidelines from ASCO 3 and AGIHO 4 do not list hepatotoxicity or elevated liver enzymes among the documented adverse effects of G-CSF. The well-established side effects include:
- Bone pain (most common)
- Thrombocytopenia
- Splenic rupture (rare)
- Fatigue
This absence from guidelines reflects the rarity of this adverse effect in clinical practice.
Monitoring Implications
Given these case reports, clinicians should:
- Monitor liver enzymes if unexplained symptoms develop during or shortly after G-CSF administration
- Be aware that hepatotoxicity may manifest days after G-CSF discontinuation (not just during active treatment)
- Consider G-CSF as a potential cause when evaluating new-onset transaminitis in patients receiving colony-stimulating factors
- Recognize that both hepatocellular (elevated transaminases) and cholestatic (isolated hyperbilirubinemia) patterns can occur
Important Caveats
The hepatoprotective studies in animal models 5, 6 showing G-CSF reducing liver enzyme elevations in toxin-induced injury are not clinically relevant to this question—they address G-CSF as a therapeutic agent for pre-existing liver damage, not as a cause of hepatotoxicity.
In healthy donors and patients without pre-existing liver disease, G-CSF-induced liver injury appears to be self-limited and reversible with supportive care alone 1.