The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy
Abstract
Summary: 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.
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“A diagnosis of ILICI requires exclusion of alternative etiologies via serological testing along with contrast-enhanced cross-sectional imaging of the liver to exclude hepatic metastases and biliary obstruction.42,43”
From The contemporary epidemiology, causes, and management of drug-induced liver injury (2026) · cites this paper as [42]
In the citing paper
“The pattern of liver injury with ILICI is hepatocellular in 40%–50% of patients, with older individuals more likely to present with a mixed or cholestatic profile, and typically occurs in the first 6 months of therapy.42,43,46”
From The contemporary epidemiology, causes, and management of drug-induced liver injury (2026) · cites this paper as [42]
In the citing paper
“Immune-mediated liver injury from checkpoint inhibitors (ILICIs) is an increasingly recognized cause of liver injury with an incidence of 5%–10%.41–43”
From The contemporary epidemiology, causes, and management of drug-induced liver injury (2026) · cites this paper as [42]
In the citing paper
“Recent studies suggest that bona fide DILI is only responsible for 30% of cases of demonstrable liver injury in patients with advanced cancer, whereas hepatic metastases, sepsis, and other causes of liver disease account for the remainder, emphasizing the importance of contrast‐enhanced CT and MR scanning in evaluation of these patients.205”
From AASLD practice guidance on drug, herbal, and dietary supplement–induced liver injury (2023) · cites this paper as [205]
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Citations
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Ipilimumab-associated Hepatitis
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Cited by
ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury
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Self-citationACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury
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AASLD practice guidance on drug, herbal, and dietary supplement–induced liver injury
Fontana, R. J., Liou, I., Reuben, A., Suzuki, A., Fiel, M. I., Lee, W., & Navarro, V. (2023) · Hepatology · doi:10.1002/hep.32689 · Cited by 340
Self-citationHepatotoxicity From Immune Checkpoint Inhibitors: A Systematic Review and Management Recommendation
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Metadata
- Authors
- Tsung, I., Dolan, R., Lao, C. D., Fecher, L., Riggenbach, K., Yeboah‐Korang, A., & Fontana, R. J.
- Affiliations
- Department of Internal Medicine University of Michigan Ann Arbor Michigan
- Division of Hematology and Oncology University of Michigan Ann Arbor Michigan
- Division of Gastroenterology and Hepatology University of Michigan Ann Arbor Michigan
- ORCID
- Fontana, Robert J.
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2019-07-15
- Volume
- 50
- Issue
- 7
- Pages
- 800-808
- ISSN
- 0269-2813
- 1365-2036
- Cited by
- 86
- References
- 22
- Language
- en
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