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Volume 17
Issue 6
10.3390/hematolrep17060069
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Background:
Case Report

Ibrutinib-Associated Liver Injury in a Patient with Chronic Lymphocytic Leukemia: Clinical Course and Therapeutic Approach

by
Antonio Frolli
1,2,*,
Guido Parvis
2,
Martina Bullo
2,
Selene Grano
2,
Giovanni Fornari
2,
Valentina Bonuomo
2,
Daniela Cilloni
1,2 and
Carmen Fava
1,2,*
1
Department of Clinical and Biological Sciences, University of Turin, 10124 Turin, Italy
2
Division of Hematology, AO Ordine Mauriziano di Torino, 10128 Turin, Italy
*
Authors to whom correspondence should be addressed.
Hematol. Rep. 2025, 17(6), 69; https://doi.org/10.3390/hematolrep17060069
Submission received: 28 October 2025 / Revised: 27 November 2025 / Accepted: 10 December 2025 / Published: 11 December 2025
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Abstract

Background: Ibrutinib, a Bruton’s tyrosine kinase inhibitor (BTKi), has revolutionized the treatment of Chronic Lymphocytic Leukemia (CLL), yet hepatotoxicity remains a rare and poorly characterized adverse event. Case Presentation: We report the case of a 54-year-old man with progressive CLL and radiologically confirmed hepatic involvement who developed acute hepatocellular injury during ibrutinib monotherapy. Baseline liver tests showed mild abnormalities attributed to hepatic steatosis and leukemic infiltration. After approximately 10–12 weeks of ibrutinib (420 mg/day), transaminases markedly increased (ALT 660 U/L, AST 326 U/L), while bilirubin and synthetic function remained normal. Viral, autoimmune, and obstructive causes were excluded. Stepwise dose reductions to 140 mg/day provided limited benefit. The addition of prednisone (50 mg/day) led to rapid biochemical improvement. Ibrutinib was successfully re-escalated to 280 mg/day alongside venetoclax initiation, maintaining disease control without recurrence of liver injury. Discussion: The temporal relationship, exclusion of alternative causes, and corticosteroid responsiveness suggest an ibrutinib-induced liver injury, possibly exacerbated by pre-existing hepatic steatosis and leukemic infiltration. Conclusions: This case underscores the multifactorial pathogenesis of BTKi-related hepatotoxicity and highlights the potential role of corticosteroids in management. Prompt recognition, stepwise dose adjustment, and corticosteroid therapy may enable continued treatment and sustained disease control in selected patients.
Keywords: ibrutinib; chronic lymphocytic leukemia; BTKi-related hepatotoxicity; ibrutinib-associated hepatotoxicity ibrutinib; chronic lymphocytic leukemia; BTKi-related hepatotoxicity; ibrutinib-associated hepatotoxicity

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MDPI and ACS Style

Frolli, A.; Parvis, G.; Bullo, M.; Grano, S.; Fornari, G.; Bonuomo, V.; Cilloni, D.; Fava, C. Ibrutinib-Associated Liver Injury in a Patient with Chronic Lymphocytic Leukemia: Clinical Course and Therapeutic Approach. Hematol. Rep. 2025, 17, 69. https://doi.org/10.3390/hematolrep17060069

AMA Style

Frolli A, Parvis G, Bullo M, Grano S, Fornari G, Bonuomo V, Cilloni D, Fava C. Ibrutinib-Associated Liver Injury in a Patient with Chronic Lymphocytic Leukemia: Clinical Course and Therapeutic Approach. Hematology Reports. 2025; 17(6):69. https://doi.org/10.3390/hematolrep17060069

Chicago/Turabian Style

Frolli, Antonio, Guido Parvis, Martina Bullo, Selene Grano, Giovanni Fornari, Valentina Bonuomo, Daniela Cilloni, and Carmen Fava. 2025. "Ibrutinib-Associated Liver Injury in a Patient with Chronic Lymphocytic Leukemia: Clinical Course and Therapeutic Approach" Hematology Reports 17, no. 6: 69. https://doi.org/10.3390/hematolrep17060069

APA Style

Frolli, A., Parvis, G., Bullo, M., Grano, S., Fornari, G., Bonuomo, V., Cilloni, D., & Fava, C. (2025). Ibrutinib-Associated Liver Injury in a Patient with Chronic Lymphocytic Leukemia: Clinical Course and Therapeutic Approach. Hematology Reports, 17(6), 69. https://doi.org/10.3390/hematolrep17060069

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