Clinical course of liver injury induced by immune checkpoint inhibitors in patients with advanced malignancies

2021 ◽  
Author(s):  
Takanori Ito ◽  
Masatoshi Ishigami ◽  
Takafumi Yamamoto ◽  
Kazuyuki Mizuno ◽  
Kenta Yamamoto ◽  
...  
Keyword(s):  
Liver Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Clinical Course ◽  
Checkpoint Inhibitors ◽  
Advanced Malignancies

Clinical Features and Outcomes Based on Liver Injury Patterns in Liver Injury Caused by Immune Checkpoint Inhibitors

2021 ◽  
Author(s):  
Takanori Ito ◽  
Masatoshi Ishigami ◽  
Takafumi Yamamoto ◽  
Kazuyuki Mizuno ◽  
Kenta Yamamoto ◽  
...  
Keyword(s):  
Liver Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Clinical Course ◽  
Checkpoint Inhibitors ◽  
Therapeutic Effects ◽  
Injury Patterns ◽  
Injury Grade ◽  
Grade 3 ◽  
Almost All

Abstract BackgroundThe clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury.MethodsWe evaluated the characteristics and clinical course of immune-related liver injury in 1087 patients treated with ICIs for advanced malignancies between August 2014 and December 2020. ResultsDuring the follow-up period (median, 270 days), 56 patients (5.2%) had immune-related liver injury (≥Grade 3). The liver-injury patterns were hepatocellular (n = 25, 44.6%), mixed (n = 10, 17.9%), or cholestatic (n = 21, 37.5%), and the median time to onset of liver injury was 36, 85, and 53 days, respectively; the hepatocellular pattern occurred earlier than the other types (P = 0.036). Corticosteroids were administered to 29 (51.8%) patients. While liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns (mixed, n = 8; cholestatic, n = 7), and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20. ConclusionThe incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differs according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

Real world data of liver injury induced by immune checkpoint inhibitors in Japanese patients with advanced malignancies

2020 ◽  
Vol 55 (6) ◽  
pp. 653-661 ◽  
Author(s):  
Kazuyuki Mizuno ◽  
Takanori Ito ◽  
Masatoshi Ishigami ◽  
Yoji Ishizu ◽  
Teiji Kuzuya ◽  
...  
Keyword(s):  
Liver Injury ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Japanese Patients ◽  
Real World Data ◽  
World Data ◽  
Advanced Malignancies

FRI-081-Characterisation of severe liver injury induced by immune checkpoint inhibitors

2019 ◽  
Vol 70 (1) ◽  
pp. e420 ◽  
Author(s):  
Yana Davidov ◽  
Afif Yaccob ◽  
Orit Pappo ◽  
Nora Balint-Lahat ◽  
Oranit Cohen-ezra ◽  
...  
Keyword(s):  
Liver Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Severe Liver

Liver injury by immune checkpoint inhibitors in patients with hepatocellular carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 341-341 ◽  
Author(s):  
Nicola Personeni ◽  
Tiziana Pressiani ◽  
Antonio Capogreco ◽  
Arianna Dal Buono ◽  
Antonio D'Alessio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Subsequent Treatment ◽  
Drug Induced ◽  
Increased Risk ◽  
Grade 3

341 Background: In patients with hepatocellular carcinoma (HCC) and baseline liver dysfunction, hepatic immune-related adverse events (HIRAEs) during immunotherapy have not been adequately characterized and their impact on subsequent treatment outcomes is not known. Methods: 40 patients with advanced/unresectable HCC and Child Pugh score A have been enrolled in first and second-line clinical trials of anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs). HCC etiologies were: hepatitis C (32.5%), hepatitis B (7.5%), alcohol abuse (27.5%), other (32.5%). 7 received anti-PD-1 mAbs alone and 33 received combined regimens that included anti-PD-1 mAbs plus either anti-cytotoxic T lymphocyte antigen 4 (30.4%) or tyrosine kinase inhibitors (TKIs) (54.5%), or both (15.1%). We reviewed their liver function tests and HIRAEs onset was related to time to treatment failure (TTF). Results: Overall, 12 patients (30%) developed grade ≥ 3 hepatitis according to Common Toxicity Criteria for Adverse Events v. 4.03, resulting in 4 cases of grade 2 drug-induced liver injury per DILI Working Group criteria. Time between therapy initiation and hepatitis onset was 1.4 months (0.4-2.8) and median peak aminotransferase (AT) level was 258 IU/L (85-869). Out of 6 permanent treatment discontinuations due to adverse events (AEs), 4 were linked to hepatitis. Higher AT median levels at baseline were significantly linked to grade ≥ 3 hepatitis compared with lower grades (95 IU/L vs. 36 IU/L, respectively; p = 0.008). Etiology, age, treatment did not predict HIRAEs onset. TTF in patients in patients with grade ≥ 3 hepatitis was shorter than in the whole cohort (1.4 vs. 3.8 months, p = 0.041), while overall survival did not differ (p = 0.125). Conclusions: We observed a 30% incidence of clinically significant HIRAEs. HIRAEs represent the most frequent AEs leading to treatment discontinuation in patients with HCC undergoing treatments with immune checkpoint inhibitors. Baseline AT levels may identify patients at increased risk of grade ≥ 3 hepatitis.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Koji Imoto ◽  
Motoyuki Kohjima ◽  
Tomonobu Hioki ◽  
Tomoyuki Kurashige ◽  
Miho Kurokawa ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Biopsy ◽  
Clinical Features ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Japanese Patients ◽  
Malignant Neoplasms ◽  
Drug Induced

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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