From the Guidelines
Management of drug-induced liver injury (DILI) in chemotherapy patients requires prompt recognition and intervention, with the primary recommendation being to immediately discontinue the offending chemotherapy agent upon suspicion of DILI. This approach is crucial to prevent further liver damage and support liver recovery, as highlighted in recent reviews 1.
Key steps in management include:
- Discontinue the suspected chemotherapy drug
- Monitor liver function tests (LFTs) closely, typically every 2-3 days initially
- Provide supportive care, including IV fluids and nutritional support
- Consider N-acetylcysteine (NAC) administration, especially in cases of acetaminophen toxicity or severe DILI
- IV NAC: 150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, followed by 100 mg/kg over 16 hours
- Avoid hepatotoxic medications, including acetaminophen and alcohol
- In severe cases, consult hepatology for potential use of corticosteroids or other immunosuppressants
For mild DILI (ALT/AST < 5x upper limit of normal), close monitoring may suffice, whereas for moderate to severe DILI, more aggressive intervention is necessary 1. If chemotherapy must be continued, consider dose reduction or alternative agents with lower hepatotoxicity profiles. Rechallenge with the offending agent should only be attempted with caution and close monitoring, taking into account the patient's underlying liver disease and the potential risks and benefits of rechallenge 1.
The rationale for this approach is to prevent further liver damage while supporting liver recovery, with NAC acting as an antioxidant and potentially mitigating liver injury, and corticosteroids being beneficial in cases of immune-mediated DILI 1. Early recognition and management of DILI in chemotherapy patients is crucial to prevent progression to liver failure and allow for continuation of necessary cancer treatment.
From the Research
Management of Drug-Induced Liver Injury (DILI) in Patients Undergoing Chemotherapy
- The management of DILI in patients undergoing chemotherapy involves several key steps, including the immediate discontinuation of the offending drug 2, 3, 4, 5.
- Patients with suspected DILI should undergo comprehensive medical history collection, liver biochemical tests, and abdominal imaging to aid in diagnosis and differential diagnosis 2, 4.
- The RUCAM scale is recommended as the primary method for assessing causality in DILI cases, and expert opinions should be combined for reliable assessment in complex cases 2, 3.
- Treatment options for DILI include hepatoprotective drugs, anticholestatic drugs, immunosuppressants, and specific treatment agents, although the evidence for these treatments is largely based on anecdotal reports and case series 3, 4, 5.
- N-acetylcysteine (NAC) is the only specific antidote for acute DILI, and is primarily used for acetaminophen poisoning, although it may also be beneficial in some cases of non-acetaminophen DILI in adults 3, 5.
- Corticosteroids may be effective for DILI associated with autoimmune or systemic hypersensitivity features, and ursodeoxycholic acid, silymarin, and glycyrrhizin have been used to treat DILI, although success remains anecdotal 3, 4, 5.
- Primary prevention appears to be the key to avoiding DILI, and pharmacogenomics, including human leukocyte antigen genotyping and the discovery of specific DILI biomarkers, offers significant promise for the future 5.
Specific Treatment Options for DILI
- Hepatoprotective drugs: N-acetylcysteine, glutathione, glycyrrhizin acid preparation, polyene phosphatidylcholine, bicyclol, silymarin 4.
- Anticholestatic drugs: ursodeoxycholic acid, S-adenosylmethionine, cholestyramine 4.
- Immunosuppressants: glucocorticoids 4.
- Specific treatment agents: L-carnitine, anticoagulants 4.
Monitoring and Prevention of DILI
- Patients without high-risk factors should have monthly liver biochemical monitoring, while high-risk patients or those using hepatotoxic drugs should be monitored every 2 weeks during the first 2 months of treatment, then monthly 2.
- Baseline testing, including liver biochemistry, HBsAg, anti-HCV testing, and abdominal imaging, is recommended before starting treatment 2.
- The use of preventive hepatoprotective drugs may be considered in people with high risk factors for liver damage, although routine use in the general population is not recommended 2.