Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy

Aliment Pharmacol Ther. 2019 Oct;50(7):800-808. doi: 10.1111/apt.15413. Epub 2019 Jul 15.


Background: Pembrolizumab immunotherapy has been associated with hepatotoxicity in 1%-10% of oncology patients treated in clinical trials.

Aim: To describe the incidence, phenotypes and outcomes of liver injury in a large cohort of solid organ tumour patients receiving pembrolizumab METHODS: Liver injury was defined by serum alanine aminotransferase, alkaline phosphatase, and/or total bilirubin levels exceeding threshold values. The likelihood of drug-induced liver injury was adjudicated by expert opinion.

Results: Seventy (14.3%) of the 491 pembrolizumab-treated patients developed liver injury at a median of 62 days (6-478) and 71.4% had a cholestatic injury profile at onset. The median age, gender and tumour types of liver injury patients were similar to those without, but hepatic metastases (53% vs 21%, P < 0.01) and prior systemic and liver-directed therapy (71% vs 53%, P < 0.01) were more commonly observed in liver injury patients. During follow-up, liver injury patients were less likely to experience tumour remission (10% vs 40.4%) and had higher mortality (67.1% vs 33.7%). Only 20 (28.6%) liver injury cases were adjudicated as probable drug-induced hepatotoxicity; these patients were significantly more likely to present with an hepatocellular/mixed injury pattern (65% vs 12%), to receive corticosteroids (55% vs 12%) and had lower mortality (45% vs 76%) during follow-up.

Conclusions: Oncology patients treated with pembrolizumab who develop liver injury experience poorer outcomes during follow-up. The low incidence of confirmed drug hepatotoxicity highlights the need for thorough medical evaluation before initiating corticosteroids to optimise patient care.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Chemical and Drug Induced Liver Injury / epidemiology*
  • Cholestasis / epidemiology
  • Cohort Studies
  • Female
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Immunotherapy
  • Incidence
  • Liver Function Tests
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • pembrolizumab
  • Alanine Transaminase
  • Alkaline Phosphatase