Symptom Grade

Grade 1

ALT or AST > ULN – 3x ULN

Grade 2

ALT or AST 3 – 5x ULN

Grade 3

ALT or AST 5 – 20x ULN

Grade 4

ALT or AST > 20x ULN

Management escalation pathway

Continue treatment
If both ALT & AST are Grade 1: postpone 1 week
Withhold ICPI treatment If rising ALT/AST when re-checked start oral prednisolone 1 mg/kg Cease treatment ALT/AST < 10 x ULN and normal bilirubin/INR/albumin: oral prednisolone 1 mg/kg ALT/AST > 10 x ULN or raised bilirubin/INR/low albumin: i.v. (methyl)prednisolone 2 mg/kg i.v. (methyl)prednisolone 2 mg/kg Permanently discontinue treatment

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 at consultant discretion

Worsening despite

  • If on oral change to i.v. (methyl)prednisolone
  • If on i.v. add MMF 500-1000 mg b.d.
  • If worse on MMF, consider addition of tacrolimus
  • A case report has described the use of anti-thymocyte globulin in steroid + MMF-refractory fulminant hepatitis

Assessment and Investigations

If > ULN – 3x ULN repeat in 1 week

Control until normalisation

Re-check LFTs/INR/albumin every 3 days

Review medications, e.g. statins, antibiotics and alcohol history

Perform liver screen:
– Hepatitis A/B/C serology
– Hepatitis E PCR
– Iron studie

Consider imaging for metastases/portal trombosis

As above; daily LFTs/INR/albumin

Perform US with Doppler

Low threshold to admit if clinical concern

If refractory aer 3 days consult hepatologist

As above; hepatology consult

Consider liver biopsy



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
LCA: Liver Cytosolic Antigen
US: Ultra Sound