What CDK4/6 inhibitor liver injury looks like on biopsy

Design

Retrospective single-centre case series

Population

7 women with metastatic breast cancer and biopsied CDK4/6 inhibitor liver injury

Primary outcome

Histological pattern and clinical resolution

Effect

Severe acute hepatitis 5/7; zone 3 necrosis in all acute biopsies; all resolved after withdrawal (mean 63 days)

A single cancer centre identified seven women with metastatic breast cancer who had liver biopsy for enzyme rises on a CDK4/6 inhibitor (six on ribociclib, one on palbociclib), with causality supported by a RUCAM score of 6 or more.

Enzymes rose a mean 60 days after starting. Five biopsies showed severe acute hepatitis. Every acute biopsy had perivenular (zone 3) confluent necrosis, and five had lymphocytic cholangitis. Three patients were ANA positive, but none had histological autoimmune hepatitis. All normalised after the drug was stopped, and six went on to a different agent.

Seven cases describe a pattern rather than its frequency, but the pattern is distinctive and worth recognising when a breast cancer patient's liver biopsy arrives with zone 3 necrosis.

• Ask about CDK4/6 inhibitor use when a liver biopsy shows zone 3 confluent necrosis.
• Look for lymphocytic cholangitis as a supporting feature.
• Do not diagnose autoimmune hepatitis on a positive ANA alone in these patients.
• Note that injury resolved in every case after withdrawal.

Why it matters

It helps separate a reversible drug injury from autoimmune hepatitis or metastasis.

Don't overread it

Seven cases from one centre cannot give the incidence or the full range of patterns.

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