26
Treatment
Table 2. Gastrointestinal (GI) Toxicities
G3: AST or ALT 5–20×
ULN and/or total
bilirubin 3–10× ULN,
OR symptomatic liver
dysfunction; fibrosis by
biopsy; compensated
cirrhosis; 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 1–2 mg/kg
methylprednisolone or equivalents.
• 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 mycophenolate
**
if infectious cause is ruled out.
• Labs daily or every other day; consider inpatient
monitoring for patients with AST/ALT >8× ULN
and/or elevated total bilirubin 3× >ULN.
• If no improvement is achieved with steroid or for
patients on ICPi therapy combined with a novel agent,
with standard chemotherapy, or with targeted therapy
refer to hepatologist for further pathologic evaluation
of hepatitis.
• Steroid taper can be attempted around 4–6 weeks
when ≤G1, re-escalate if needed, optimal duration
unclear.
• Consider transfer to tertiary care facility if necessary.
G4: AST or ALT >20×
ULN and/or total
bilirubin >10× ULN
OR decompensated
liver function (e.g.,
ascites, coagulopathy,
encephalopathy, coma)
Follow G3 recommendations as listed, with the
following additions for G4:
• Administer 2 mg/kg/day methylprednisolone
equivalents.
Additional considerations:
• Infliximab is contraindicated for immune-related hepatitis.
Footnotes:
*
Anecdotal experience suggests azathioprine may be beneficial in steroid-refractory immune-related
hepatitis. If using azathioprine, should test for thiopurine methyltransferase (TPMT) deficiency.
**
A case study reports use of mycophenolate mofetil in steroid-refractory immune-related hepatitis
with some success.
(cont'd)
