Liver Biopsy Reveals Distinct Patterns of Checkpoint Inhibitor–Related Liver Injury: Hepatology Communications | August 2026

Introduction:

Immune checkpoint inhibitors (ICIs) can cause immune-mediated liver injury, ranging from hepatocellular hepatitis to cholestatic or mixed patterns. Although liver biopsy may clarify the diagnosis and severity, its optimal timing and clinical value remain uncertain. This study evaluated standardized histological findings in 67 patients with ICI-related liver injury and correlated them with clinical presentation, treatment, and ICI regimen.

Why was this study needed?

ICI-related liver injury is increasingly encountered in oncology practice.

Histological patterns vary considerably and may depend on the type of ICI.

The clinical value and timing of liver biopsy remain uncertain.

Corticosteroid treatment before biopsy may alter histological interpretation.

Results:

Hepatocellular injury showed greater inflammation, granulomas, and necrosis, whereas cholestatic/mixed injury demonstrated more ductular reaction and cholangitis.

Patients biopsied after starting corticosteroids had substantially less inflammation, fewer granulomas, and less cholestasis, suggesting steroids can modify biopsy findings.

Pembrolizumab-associated injury occurred later and more often showed a cholestatic biochemical pattern with ductular injury compared with ipilimumab–nivolumab.

Mild steatosis was common but correlated with BMI and diabetes rather than ICI treatment or corticosteroid exposure.

Clinical Impact:

Liver biopsy can help characterize the phenotype of ICI-related hepatotoxicity, particularly when the diagnosis is uncertain or cholestatic injury is suspected. Importantly, clinicians should recognize that corticosteroids given before biopsy can substantially suppress histological inflammation, potentially affecting interpretation and subsequent management decisions.

Bottom Line:

ICI-related liver injury has distinct histological patterns that correlate with biochemical presentation and treatment type. Because corticosteroids can markedly alter biopsy findings, the timing of liver biopsy relative to steroid initiation is crucial when histology is needed to guide management.