Hepatitis – Grade 2

Management escalation pathway

  • Withhold ICPI treatment until normalisation of ALT/AST to grade I
  • If rising ALT/AST when re-checked wait until normalisation unless grade III or bilirubin increases: start methylprednisolone 1mg/kg (https://www.ncbi.nlm.nih.gov/pubmed/29427729)

Assessment and Investigations

  • 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 – Anti-ANA/SMA/LKM/SLA/LP/LCI – Iron studie
  • Consider imaging for metastases/portal trombosis
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 steroids:

– 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



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