| 2.2. Hepatitis |
Work-up and evaluation: - Monitor patient for abnormal liver blood tests: AST, ALT, and bilirubin before each infusion and/or consider weekly if grade 1 LFT elevations. No treatment is recommended for grade 1 LFT abnormality.
- Review medications and supplements that may cause hepatotoxicity and rule out abnormal liver enzymes from development or progression of liver metastases.
- Liver biopsy should be considered if the patient is steroid-refractory or if concern for other differential diagnoses that would alter medical management.
- For grade ≥2:
- Work-up for other causes of elevated liver enzymes (eg, viral hepatitis, alcohol history, iron studies, thromboembolic event, or potential liver metastasis from primary malignancy) by doing blood work and imaging (ultrasound and cross-sectional imaging). If suspicion for primary autoimmune hepatitis is high, can consider ANA/ASMA/ANCA. If patients with elevated ALKP alone, GGT should be tested. For isolated elevation of transaminases, consider checking CK for other etiologies.
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| Grading | Management |
| G1: Asymptomatic (AST or ALT >ULN to 3.0 times ULN and/or total bilirubin >ULN to 1.5 times ULN). | - Continue ICPi with close monitoring; consider alternate etiologies.
- Consider monitoring labs 1 to 2 times weekly.
- Manage with supportive care for symptom control.
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| G2: Asymptomatic (AST or ALT >3.0 to ≤5 times ULN and/or total bilirubin >1.5 to ≤3 times ULN). | - Hold ICPi temporarily.
- Patients should be advised to stop unnecessary medications and any known hepatotoxic drugs. Temporarily hold other potentially hepatotoxic oncologic agents.
- For grade 2 hepatic toxicity, may administer steroid (prednisone 0.5 to 1 mg/kg/day) or equivalent if no improvement is seen after 3 to 5 days.
- Increase frequency of monitoring to every 3 days.
- If inadequate improvement after 3 days, consider adding mycophenolate mofetil.
- May initiate steroid taper when symptoms improve to ≤G1 and may resume ICPi treatment when steroid ≤10 mg/d. Taper over at least 1 month.
- Consider hepatology consult for G2 and above.
- May resume if recover to ≤G1 on prednisone ≤10 mg/day.
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| G3: AST or ALT 5 to 20 times ULN and/or total bilirubin 3 to 10 times ULN, or symptomatic liver dysfunction; fibrosis by biopsy; compensated cirrhosis; and reactivation of chronic hepatitis. | - Follow G2 recommendations as listed, with the following additions for G3:
- Consider permanently discontinuing ICPi if asymptomatic; permanently discontinue if symptomatic.
- Immediately start steroid (methylprednisolone 1 to 2 mg/kg/day or equivalent).
- If steroid refractory, consider liver biopsy to rule out NASH, tumor, cholestatic variants, other drug-related hepatic inflammation, infection, or other autoimmune entity and consider adding azathioprine¶ or mycophenolateΔ if infectious cause is ruled out.
- Labs daily or every other day; consider inpatient monitoring for patients with AST/ALT >8 times ULN and/or elevated total bilirubin 3 times >ULN.
- If no improvement is achieved with steroid or for patients on ICPi therapy combined with a novel agent, with standard CTX, or with targeted therapy, refer to hepatologist for further pathologic evaluation of hepatitis.
- Steroid taper can be attempted around 4 to 6 weeks when ≤G1, re-escalate if needed, optimal duration unclear.
- Consider transfer to tertiary care facility if necessary.
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| G4: AST or ALT >20 times ULN and/or total bilirubin >10 times ULN or decompensated liver function (eg, ascites, coagulopathy, encephalopathy, and coma). | - Follow G3 recommendations as listed, with the following additions for G4:
- Administer methylprednisolone 2 mg/kg/day or equivalent.
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Additional considerations: - Infliximab is contraindicated for immune-related hepatitis.
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