Chemotherapy Does Not Improve Liver Function—It Causes Liver Damage
Chemotherapy does not increase or improve liver function; rather, it causes hepatotoxicity and worsens liver function tests, with the severity depending on the specific agent used and number of treatment cycles. 1
Mechanisms of Chemotherapy-Induced Liver Damage
Chemotherapy causes predictable, dose-dependent hepatotoxicity through multiple mechanisms:
Oxaliplatin-based regimens (such as FOLFOX) cause vascular lesions including sinusoidal obstruction syndrome, hemorrhagic centrilobular necrosis, and regenerative nodular hyperplasia, which increase operative bleeding risk and transfusion requirements if liver resection is needed 1
Irinotecan-based regimens induce steatohepatitis, which may be associated with increased 90-day mortality from liver failure after hepatic surgery 1
General steatosis from chemotherapy impairs hepatic microcirculation, decreases resistance to ischemia-reperfusion injury, and increases post-hepatic liver failure (PHLF) risk to 14% compared to 4% in patients without steatosis 1
Clinical Evidence of Worsening Liver Function
The evidence consistently demonstrates deterioration of liver function with chemotherapy:
Liver function tests worsen progressively with chemotherapy cycles, showing significantly elevated ALT, AST, ALP, and total bilirubin levels after treatment compared to pre-treatment values 2
Positive correlation exists between the number of chemotherapy cycles and worsening liver function test abnormalities 2
Morbidity rates directly correlate with the number of chemotherapy cycles administered, with postoperative complications more frequent in patients receiving neoadjuvant chemotherapy 1
Reversibility and Clinical Management
The hepatotoxicity is often reversible but requires careful monitoring:
Chemotherapy-related hepatotoxicity is reversible with cessation of therapy in most cases 1
Duration of treatment matters more than the regimen itself for determining severity of liver damage 1
In the EORTC 40983/EPOC study, 3 months of preoperative FOLFOX-4 caused postoperative complications that mainly prolonged hospital stay but were reversible, with only 1 out of 180 patients refused surgery due to liver damage 1
Critical Clinical Pitfalls
Common mistake: Assuming abnormal liver function tests in cancer patients on chemotherapy represent disease progression rather than drug toxicity 3, 4
Key distinction: Most chemotherapeutic hepatotoxicity is idiosyncratic and unpredictable, but certain agents have predictable, dose-dependent direct hepatotoxicity 5, 3
Agents requiring greatest caution in hepatic dysfunction include taxanes, vinca alkaloids, irinotecan, and anthracyclines, which may cause unacceptable toxicity 6
Relatively better-tolerated agents in liver dysfunction include continuous-infusion fluorouracil, capecitabine, mechlorethamine, cyclophosphamide, topotecan, and oxaliplatin 6
Practical Implications
Pre-treatment liver function assessment is mandatory before chemotherapy initiation to determine appropriate drug selection and dose modifications 3, 6
Avoid overtreatment: The benefits of neoadjuvant therapy in decreasing tumor burden may counterbalance hepatotoxic effects, but excessive cycles increase liver damage without additional benefit 1
Consider alternative diagnoses: Not all liver function abnormalities during chemotherapy are drug-related—hepatitis and other processes must be excluded 3, 4