Incidence, risk factors and outcomes of checkpoint inhibitor-induced liver injury: A 10-year real-world retrospective cohort study

Atallah, Edmond; Welsh, Sarah J.; O’Carrigan, Brent; Oshaughnessy, Ana; Dolapo, Igboin; Kerr, Andrew; Kucharczak, Joanna; Lee, Colin Y C; Crooks, Colin J; Hicks, Amy; Chimakurthi, Chenchu; Rao, Ankit; Franks, Hester; Patel, Praneil; Aithal, Guruprasad P.

doi:10.1016/j.jhepr.2023.100851

Cited by 15 publications

(18 citation statements)

References 51 publications

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“…Although 20-30% of patients have a concurrent irAE at ILICI onset (e.g. dermatitis, thyroiditis, or colitis), most patients do not have fever, itching or abdominal pain [7,8]. An hepatocellular injury pattern is seen in 40-50% of ILICI cases while the remaining patients have a mixed or cholestatic pattern which is more common with anti-PD-(L)1 therapy [8,9].…”

Section: Clinical Presentation and Diagnosis Of Immune-mediated Liver...mentioning

confidence: 99%

“…dermatitis, thyroiditis, or colitis), most patients do not have fever, itching or abdominal pain [7,8]. An hepatocellular injury pattern is seen in 40-50% of ILICI cases while the remaining patients have a mixed or cholestatic pattern which is more common with anti-PD-(L)1 therapy [8,9]. In a recent systematic review, the overall incidence of ILICI was 15.3% and the incidence of grade 3/4 ILICI was 5.3% [10].…”

Section: Clinical Presentation and Diagnosis Of Immune-mediated Liver...mentioning

confidence: 99%

“…In a recent systematic review, the overall incidence of ILICI was 15.3% and the incidence of grade 3/4 ILICI was 5.3% [10]. Risk factors for developing irAEs overall and specifically ILICI include age less than 65 years, a higher body mass index, female gender (60%), anti-CTLA-4 therapy, and combination anti-CTLA-4/PD-(L)1 therapy [3,8,9,11,12]. Although patients with autoimmune disorders are excluded from clinical trials, they do appear to be over-represented in postmarketing surveillance studies of irAEs [13,14].…”

Section: Clinical Presentation and Diagnosis Of Immune-mediated Liver...mentioning

confidence: 99%

“…Although patients with autoimmune disorders are excluded from clinical trials, they do appear to be over-represented in postmarketing surveillance studies of irAEs [13,14]. A lower neutrophil-to-lymphocyte ratio has been associated with ILICI [8]. Although hepatic metastases are known to reduce efficacy of ICI's, they have not reliably been associated with ILICI [15,16].…”

Section: Clinical Presentation and Diagnosis Of Immune-mediated Liver...mentioning

confidence: 99%

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Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Likhitsup,

Fontana

2024

Current Opinion in Gastroenterology

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Purpose of review The aim is to summarize the latest data on the incidence, clinical manifestations, and management of immune- mediated liver injury from checkpoint inhibitors (ILICI). Recent findings ILICI develops in 10–15% of oncology patients receiving immunotherapy with most having asymptomatic serum aminotransferase and/or alkaline phosphatase elevations. Most grade 1–2 ILICI patients improve with drug discontinuation and/or short-term oral corticosteroids. In contrast, the 2–3% with grade 3/4 hepatotoxicity frequently require oral or intravenous corticosteroids and some are hospitalized to initiate further immunosuppression with mycophenolate mofetil or azathioprine. Liver biopsy is generally reserved for patients with atypical features or those with severe hepatotoxicity who fail to respond to treatment. Up to 3% of ILICI patients with a cholestatic profile have MRI evidence of intra or extrahepatic cholangitis that responds poorly to immunosuppression. Most ILICI patients improve during follow-up and liver-related death is very uncommon (<1%). Up to 30% of rechallenged ILICI patients develop recurrent hepatotoxicity with a shorter latency. Summary ILICI is increasingly encountered by gastroenterologists evaluating oncology patients with abnormal liver biochemistries. A stepwise approach to exclude viral hepatitis, alcohol, hepatic metastases, and pancreaticobiliary disease is recommended. The majority of ILICI patients fully recover with ICI discontinuation and short-term corticosteroids or a second line immunosuppressant.

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Section: Clinical Presentation and Diagnosis Of Immune-mediated Liver...mentioning

confidence: 99%

Section: Clinical Presentation and Diagnosis Of Immune-mediated Liver...mentioning

confidence: 99%

Section: Clinical Presentation and Diagnosis Of Immune-mediated Liver...mentioning

confidence: 99%

Section: Clinical Presentation and Diagnosis Of Immune-mediated Liver...mentioning

confidence: 99%

See 2 more Smart Citations

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Likhitsup,

Fontana

2024

Current Opinion in Gastroenterology

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“…5 Although this toxicity is normally mild, it can be life-threatening in the case of acute liver failure development. 6,7 As for the rest of severe irAEs, treatment with corticosteroids (CS) is the backbone of therapy for severe ChILI, 8,9 that is grade 3 or grade 4 hepatitis according to the Common Terminology Criteria for Adverse Events (CTCAE) system. However, results from two series of patients with ChILI have shown that some severe cases may not require CS, and liver injury may be resolved with just temporary discontinuation of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor‐induced liver injury

Riveiro‐Barciela,

Barreira‐Díaz,

Salcedo

et al. 2024

Aliment Pharmacol Ther

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SummaryBackgroundThere are few data on corticosteroids (CS)‐sparing strategies for checkpoint inhibitor (ICI)‐induced liver injury (ChILI).AimWe aimed to assess the performance of a 2‐step algorithm for severe ChILI, based on ICI temporary discontinuation (step‐1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step‐2).MethodsProspective study that included all subjects with grade 3/4 ChILI. Peripheral extended immunophenotyping was performed. Indication for CS: severe necroinflammation; mild or moderate necroinflammation with later biochemical worsening.ResultsFrom 111 subjects with increased transaminases (January 2020 to August 2023), 44 were diagnosed with grade 3 (N = 35) or grade 4 (N = 9) ChILI. Main reason for exclusion was alternative diagnosis. Lung cancer (13) and melanoma (12) were the most common malignancies. ICI: 23(52.3%) anti‐PD1, 8(18.2%) anti‐PD‐L1, 3(6.8%) anti‐CTLA‐4, 10(22.7%) combined ICI. Liver injury pattern: hepatocellular (23,52.3%) mixed (12,27.3%) and cholestatic (9,20.5%). 14(32%) presented bilirubin >1.2 mg/dL. Overall, 30(68.2%) patients did not require CS: 22(50.0%) due to ICI discontinuation (step‐1) and 8/22 (36.4%) based on the degree of necroinflammation (step‐2). Biopsy mainly impacted on grade 3 ChILI, sparing CS in 8 out of 15 (53.3%) non‐improvement patients after ICI discontinuation. CD8+ HLA‐DR expression (p = 0.028), central memory (p = 0.046) were lower in CS‐free managed subjects, but effector‐memory cells (p = 0.002) were higher. Time to transaminases normalisation was shorter in those CS‐free managed (overall: p < 0.001, grade 3: p < 0.001). Considering our results, a strategy based on ICI discontinuation and biopsy for grade 3 ChILI is proposed.ConclusionsAn algorithm based on temporary immunotherapy discontinuation and biopsy allows CS avoidance in two thirds of cases of severe ChILI.

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Drug-induced autoimmune-like liver injury

Weber

2024

Innere Medizin

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Incidence, risk factors and outcomes of checkpoint inhibitor-induced liver injury: A 10-year real-world retrospective cohort study

Cited by 15 publications

References 51 publications

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor‐induced liver injury

Drug-induced autoimmune-like liver injury

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