Antiprogrammed Cell Death‐1 Immunotherapy‐Related Secondary Sclerosing Cholangitis

Ogawa, Kohei; Kamimura, Kenya; Terai, Shuji

doi:10.1002/hep.30189

Cited by 32 publications

(26 citation statements)

References 5 publications

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“…Although autoimmune hepatitis appears to have a similar reporting frequency, in both anti-CTLA-4 and anti-PD-1/PD-L1 drugs, cholangitis showed higher reporting with anti-PD-1/PD-L1 monoclonal antibodies. This is corroborated by recent case series, and can manifest as 'large duct or small duct cholangitis', and may have different clinical presentations, biochemical evolution, and outcome, including secondary sclerosing cholangitis and vanishing bile duct syndrome, even after discontinuation [64][65][66][67][68][69][70].…”

Section: What's New: Spectrum and Epidemiology Of Immune-related Advesupporting

confidence: 65%

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

et al. 2020

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The advent of immune checkpoint inhibitors (ICIs) caused a paradigm shift both in drug development and clinical practice; however, by virtue of their mechanism of action, the excessively activated immune system results in a multitude of offtarget toxicities, the so-called immune-related adverse events (irAEs), requiring new skills for timely diagnosis and a multidisciplinary approach to successfully manage the patients. In the recent past, a plethora of large-scale pharmacovigilance analyses have characterized various irAEs in terms of spectrum and clinical features in the real world. This review aims to summarize and critically appraise the current landscape of pharmacovigilance studies, thus deriving take-home messages for oncologists. A brief primer to study design, conduction, and data interpretation is also offered. As of February 2020, 30 real-world postmarketing studies have characterized multiple irAEs through international spontaneous reporting systems, namely WHO Vigibase and the US FDA Adverse Event Reporting System. The majority of studies investigated a single irAE and provided new epidemiological evidence about class-specific patterns of irAEs (i.e. anti-cytotoxic T-lymphocyte antigen 4 [CTLA-4] versus anti-programmed cell death 1 [PD-1] receptor, and its ligand [PD-L1]), kinetics of appearance, co-occurrences (overlap) among irAEs, and fatality rate. Oncologists should be aware of both strengths and limitations of these pharmacovigilance analyses, especially in terms of data interpretation. Optimal management (including rechallenge), predictivity of irAEs (as potential biomarkers of effectiveness), and comparative safety of ICIs (also in terms of combination regimens) represent key research priorities for next-generation real-world studies.

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Section: What's New: Spectrum and Epidemiology Of Immune-related Advesupporting

confidence: 65%

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

et al. 2020

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“…Furthermore, cholestatic and mixed-type liver injuries were more frequent than the hepatocellular type, and only one case showed bile duct dilation on imaging tests (Case 4). is result is reasonable because the hepatic irAEs with abnormal image findings in the bile ducts have been reported (acute cholangitis [19][20][21] and primary sclerosing cholangitis [22]), but their incidence is rare. ese findings suggest that the bile duct disorder on the hepatic irAEs might occur at the microscopic level.…”

Section: Clinical Features Of Hepatic Iraementioning

confidence: 87%

Clinical Features of Liver Injury Induced by Immune Checkpoint Inhibitors in Japanese Patients

Imoto

Kohjima

Hioki

et al. 2019

Canadian Journal of Gastroenterology and Hepatology

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Aim. Immune checkpoint inhibitors (ICIs) have improved the survival rate of patients carrying various malignant neoplasms. Despite their efficacy, ICIs occasionally induce liver injury as an immune-related adverse event (irAE). This study aimed to reveal the clinical features of the hepatic irAE in Japanese patients. Methods. Among 387 patients treated with ICIs, those who developed drug-induced liver injury were investigated. We also describe the histological findings and clinical courses of four patients with hepatic irAE who underwent liver biopsy. Results. Among the 56 patients with all-grade liver injury, only 11 (19.6%) showed hepatocellular-type liver injury, which resembled autoimmune hepatitis. Thirty-four patients (60.7%) developed cholestatic or mixed-type liver injury, although only one patient showed abnormal image findings in the bile duct. Most patients with grade ≤2 liver injury improved spontaneously, while two patients with biliary dysfunction required ursodeoxycholic acid or prednisolone. Among eight patients with grade ≥3 liver injury, three required no immunosuppressants and five were treated with prednisolone (three of five patients required other types of immunosuppressants). Four patients in the case series showed diverse clinical features in terms of hepatotoxic pattern, symptoms, and the interval time between the initiation of immunotherapy and the onset of the hepatic irAE. Conclusions. Our findings suggest that ICIs could cause microscopic biliary disorder without any abnormal image finding. Because the hepatic irAE presents diverse clinical features, liver biopsy is recommended to provide appropriate treatments.

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“…Indeed, imbalanced expression of PD-1/PD-L1 has previously been reported in inflamed livers of PBC and AIH patients 41,42 . Moreover, recent case reports on the development of secondary sclerosing cholangitis in patients receiving checkpoint inhibitor treatment highlight the functional importance the PD-L1/PD-1 axis for biliary immune homeostasis 43,44 .…”

Section: Mechanistically Cd8 + T Cell-derived Il-17 Induced the Exprmentioning

confidence: 99%

IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression

Stein

Henze

Poch

et al. 2021

Journal of Hepatology

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Antiprogrammed Cell Death‐1 Immunotherapy‐Related Secondary Sclerosing Cholangitis

Cited by 32 publications

References 5 publications

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

Clinical Features of Liver Injury Induced by Immune Checkpoint Inhibitors in Japanese Patients

IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression

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