Clinical pattern of checkpoint inhibitor-induced liver injury in a multicentre cohort

Hountondji, Lina; Matos, Christophe Ferreira De; Lebossé, Fanny; Quantin, Xavier; Lesage, C.; Palassin, Pascale; Rivet, Valérian; Faure, Stéphanie; Pageaux, Georges‐Philippe; Assenat, Éric; Alric, Laurent; Zahaf, Amel; Larrey, Dominique; Viel, Philine Witkowski Durand; Rivière, Benjamin; Sèlves, Janick; Dalle, Stéphane; Maria, A.; Comont, Thibaut; Meunier, Lucy

doi:10.1016/j.jhepr.2023.100719

Cited by 13 publications

(24 citation statements)

References 40 publications

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“…Subjects who develop an ALT of >1 to 3Â upper limit of normal (ULN) have grade 1, ALT >3-5Â ULN have grade 2, ALT >5-20Â ULN have grade 3, and those with ALT >20Â ULN have grade 4 [18]. However, CTCAE criteria do not correlate well with clinical outcomes or mortality in ILICI [8,19]. The Drug-Induced Liver Injury Network (DILIN) defines DILI severity on a numerical scale of 1-5 with 1 being mild (i.e.…”

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

confidence: 99%

“…A percutaneous liver biopsy is typically reserved for patients with !grade 2 ILICI who fail to improve with drug discontinuation and/or corticosteroid therapy or in those who present with atypical symptoms to exclude an opportunistic infection or metastases [19,23]. Although there are no pathognomonic histological features of ILICI, lobular inflammation, granulomatous hepatitis, central vein endothelitis, and spotty or confluent centrilobular necrosis are frequently reported [26,27].…”

Section: Role Of Liver Biopsymentioning

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: Role Of Liver Biopsymentioning

confidence: 99%

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Likhitsup,

Fontana

2024

Current Opinion in Gastroenterology

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“…Clinical parameters that support a diagnosis of CPI-H include the time of hepatitis onset after CPI administration, the use of combination CPI therapy, and the presence of concurrent irAEs. 51 55…”

Section: Insights Into Checkpoint Inhibitor Hepatitis Clinical Sectionmentioning

confidence: 99%

“…However, initially, the pattern may appear as a mixed cholestatic/hepatocellular picture before evolving into a predominantly hepatocellular pattern at its peak. 51 Anti-PD-1 therapy is more frequently associated with a mixed cholestatic presentation and has been linked to the development of immune-related biliary disease/cholangitis. 52…”

Section: Presentationmentioning

confidence: 99%

“…58 Clinical parameters that support a diagnosis of CPI-H include the time of hepatitis onset after CPI administration, the use of combination CPI therapy, and the presence of concurrent irAEs. 51,55 Histology and Liver Biopsy The role and timing of liver biopsy in CPI-H are still debated, and data on histopathological findings of CPI-H are limited as discussed above. The authors recommend that liver biopsy is considered in patients with grade 3 to 4 CPI-H who prove steroid refractory, in those with atypical features or in whom there is diagnostic doubt.…”

Section: Investigationmentioning

confidence: 99%

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Immune Checkpoint Inhibitor-Induced Liver Injury

Gudd,

Sheth,

Thursz

et al. 2023

Semin Liver Dis

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In recent years cancer treatment has been revolutionized by the development and wide application of checkpoint inhibitor (CPI) drugs, which are a form of immunotherapy. CPI treatment is associated with immune-related adverse events, off-target tissue destructive inflammatory complications, which may affect a range of organs, with liver inflammation (hepatitis) being one of the more commonly noted events. This is a novel form of drug-induced liver injury and a rapidly evolving field, as our understanding of both the basic immunopathology of CPI hepatitis (CPI-H) and optimal clinical management, races to catch up with the increasing application of this form of immunotherapy in clinical practice. In this review, we summarize current evidence and understanding of CPI-H, from fundamental immunology to practical patient management.

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Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma

Gao,

Wu,

Yang

et al. 2023

Invest New Drugs

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Clinical pattern of checkpoint inhibitor-induced liver injury in a multicentre cohort

Cited by 13 publications

References 40 publications

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Immune Checkpoint Inhibitor-Induced Liver Injury

Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma

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