# Immune-mediated hepatitis from checkpoint inhibitors, by grade

Source: https://onco.cc/protocols/irae-hepatitis/  
OnCo record `irae-hepatitis` (Protocol). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Immunotherapy can inflame the liver, usually without symptoms, so liver blood tests are checked before every dose. If the tests rise, immunotherapy is paused and steroids are given; severe cases mean stopping immunotherapy. Yellow skin or eyes, dark urine or pale stools need a call to your cancer team the same day.

## Summary

Hepatitis (raised ALT or AST) occurs in about 5% on PD-(L)1 or CTLA-4 inhibitors alone and 19% on combinations (9% grade 3 or more), typically 1 to 15 weeks after starting (SITC 2021); AASLD 2023 gives 1 to 15% across trials and observational studies, mostly asymptomatic in the first 6 to 12 weeks. Only about 30% of demonstrable liver injury in advanced cancer is drug-induced, so metastases, sepsis and other causes are excluded with imaging (AASLD).

SITC 2021: liver tests before every infusion. From grade 2, a workup including clotting, bilirubin, iron studies, an autoimmune hepatitis panel and viral hepatitis serology; imaging for grade 3 or more if there is liver disease or suspected metastases. Recheck weekly for grades 1 to 2, every 1 to 2 days for grade 3 or more. Grade 2: prednisone 0.5 to 1 mg/kg/day; grades 3 to 4: methylprednisolone 1 to 2 mg/kg/day; taper over 4 to 6 weeks once tests are grade 1 or less (LE: 1). No improvement in 10 to 14 days, or relapse on taper: mycophenolate mofetil (LE: 4). Never infliximab (LE: 1).

AASLD 2023 agrees on grade 2 (withhold and consider prednisone 0.5 to 1.0 mg/kg/day), and for grade 3 or more permanently discontinues the checkpoint inhibitor, with intravenous steroids at 1 to 1.5 mg/kg/day and admission for jaundice, keeping liver biopsy for persistent grade 3 injury or jaundice despite steroids. ESMO 2022 could not be read.

## Fields

- Kind: Protocol
- Last checked: 2026-11-11
- Also known as: checkpoint inhibitor hepatitis; ICI hepatotoxicity; immune-related hepatitis; IMH; immunotherapy liver inflammation
- Tags: protocol; irae; acute-oncology

## Connected records

- protocols: [Baseline tests and monitoring before and during checkpoint inhibitor treatment](https://onco.cc/protocols/checkpoint-inhibitor-baseline-and-monitoring/), [Immune-related diarrhoea and colitis from checkpoint inhibitors, by grade](https://onco.cc/protocols/irae-colitis/), [Immune-related pneumonitis from checkpoint inhibitors, by grade](https://onco.cc/protocols/irae-pneumonitis/), [Restarting a checkpoint inhibitor after an immune-related side effect](https://onco.cc/protocols/irae-rechallenge/), [Steroid taper after immunotherapy side effects, with Pneumocystis prophylaxis and adrenal checks](https://onco.cc/protocols/irae-steroid-taper-and-pjp/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Avelumab](https://onco.cc/drugs/avelumab/), [Cemiplimab](https://onco.cc/drugs/cemiplimab/), [Dostarlimab](https://onco.cc/drugs/dostarlimab/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Methylprednisolone](https://onco.cc/drugs/methylprednisolone/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Prednisone](https://onco.cc/drugs/prednisone/), [Tremelimumab](https://onco.cc/drugs/tremelimumab/)
- institutions: [American Society of Clinical Oncology (ASCO)](https://onco.cc/institutions/asco/), [European Society for Medical Oncology (ESMO)](https://onco.cc/institutions/esmo/), [Society for Immunotherapy of Cancer](https://onco.cc/institutions/sitc/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/)
- key papers: [ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors](https://onco.cc/key-papers/paper-asco-irae-guideline-jco-2021/)

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