Hepatitis – Grade 3

Management escalation pathway

  • Suspend ICPI
  • If ALT/AST < 10 x ULN and normal bilirubin/INR/albumin: wait and see (https://www.ncbi.nlm.nih.gov/pubmed/29427729)
  • If bilirubin > 3ULN or if patient was treated with anti-CTLA4/anti-PD(L)1 treatment: oral prednisolone 1 mg/kg
  • Low threshold to admit if clinical concern (hypoglycaemia, increasing bilirubin, lowering INR or albumin) treat intravenously: i.v. (methyl)prednisolone 2 mg/kg

Assessment and Investigations

  • Daily LFTs/INR/albumin
  • Perform US with Doppler with liver biopsy if no bleeding diathesis (should be discussed with specialised anatomopathologist)
  • If refractory after 3 days to corticoids or bleeding diathesis: consult hepatologist


More information

Steroid wean:

-G2: once G1, wean over 2 weeks; re-escalate if worsening; treatment may be resumed once prednisolone < 10 mg

-G3/4: once improved to G2, can change to oral prednisolone and wean over 4 weeks; for G3, rechallenge only after multidisciplinary discussion

Worsening despite steroids:

– If on oral change to i.v. (methyl)prednisolone or higher dose of i.v. (methyl)prednisolone

– If on i.v. add MMF 500-1000 mg b.d. (after discussion with hepatologist)

– If worse on MMF, consider addition of tacrolimus



ICPi: Immune Checkpoint Blockade Inhibition
ALT: Alanine Transaminase
AST: Aspartate Transaminase
ANA: Anti Nuclear Antibodies
ULN: Upper Limit of Normal
LFT: Liver Function Test
SMA: Smooth Muscle Antibody
LKM: Liver/Kidney Microsome type 1
SLA: Soluble Liver Antigen
LP: Liver/Pancreas
US: Ultra Sound