Dramatic effect of nivolumab against melanoma and immune‐related liver toxicity: A detailed histopathological and immunohistochemical analysis of nivolumab‐induced liver toxicity

Namiki, Takeshi; Nojima, Kohei; Chikazawa, Sakiko; Iwamoto, Yutaro; Otsuki, Yuki; Al-Busani, Hind; Miura, Keiko; Kiyokawa, Yusuke; Asakage, Takahiro; Yokozeki, Hiroo

doi:10.1111/1346-8138.14710

Cited by 4 publications

(4 citation statements)

References 5 publications

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“…After excluding duplicates, 1647 articles remained. Finally, 39 case reports 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 and 36 RCTs 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , ...…”

Section: Resultsunclassified

Incidence rate and treatment strategy of immune checkpoint inhibitor mediated hepatotoxicity: A systematic review

Miao¹,

Ni²

2023

Cancer Pathogenesis and Therapy

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Section: Resultsunclassified

Incidence rate and treatment strategy of immune checkpoint inhibitor mediated hepatotoxicity: A systematic review

Miao¹,

Ni²

2023

Cancer Pathogenesis and Therapy

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“…In addition to the topic of host factors that might induce iCIs-related hepatitis, the characteristics of the liver histology were important for the management of iCIs-related hepatitis 3 – 5 , 19 – 21 . Granulomatous changes, especially large granulomatous changes with necrosis, were significantly increased in patients with ICIs-related hepatitis compared with DILI and AIH patients in this study.…”

Section: Discussionmentioning

confidence: 99%

“…However, the detailed characteristics of iCIs-related hepatitis induced by treatment with anti-PD-1 have not been clarified. Some groups described that a characteristic liver histology could be observed in patients with liver injury during the treatment with iCIs 3 – 5 . An analysis of immune cell subsets such as CD8 positive cells and CD4 positive cells was carried out in iCIs-related liver injury 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Anti-nuclear antibody and a granuloma could be biomarkers for iCIs-related hepatitis by anti-PD-1 treatment

Kondo

Akahira

Morosawa

et al. 2022

Sci Rep

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It has been reported that various kinds of immune checkpoint inhibitors (iCIs) could induce immune-related liver damage. We should focus on the programmed cell death-receptor-1 (PD-1) antibody and non-small cell lung cancer (NSCLC) to analyze the characteristics of hepatitis related to iCIs and find factors that could be useful biomarkers for the diagnosis. A single-center retrospective study of 252 NSCLC patients who received PD-1 antibody (nivolumab or pembrolizumab). Some of the biochemical markers and immunological markers were analyzed during PD-1-antibody treatment with or without ALT elevation. Histopathological features were reviewed by a single expert of hepatic pathology focusing on the following features: fibrosis, portal inflammation, lobular inflammation, lobular necrosis. The formation of macro- and micro-granulomas was also evaluated. The frequency of liver damage induced by nivolumab including grade 1 to 4 (ALT) was 41.9% (78/186 patients). The positive rate of anti-nuclear antibody in the nivolumab group with iCIs-related hepatitis was significantly higher than that in the nivolumab group without iCIs-related hepatitis (p = 0.00112). Granulomatous changes were significantly increased in patients with iCIs-related hepatitis compared with DILI and AIH patients (p < 0.05). The ratios of inflammatory cells CD4/CD8, and CD138/CD3 in ICIs-related hepatitis were significantly lower than those in AIH or DILI patients (p < 0.05). We demonstrated that the pre-existing ANA and characteristic liver histology including CD8+ cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis in the NSCLC with anti-PD-1 therapy.

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“…However, the detailed characteristics of iCIs-related hepatitis induced by treatment with anti-PD-1 have not been clari ed. Some groups described that a characteristic liver histology could be observed in patients with liver injury during the treatment with iCIs [3][4][5] . An analysis of immune cell subsets such as CD8 positive cells and CD4 positive cells was carried out in iCIs-related liver injury 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Anti-nuclear Antibody and a Granuloma Could be Biomarkers for iCIs-related Hepatitis by Anti- PD-1 Treatment

Kondo

Akahira

Morosawa

et al. 2021

Preprint

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Background and AimsIt has been reported that various kinds of immune checkpoint inhibitors (iCIs) could induce immune-related liver damage. We should focus on the programmed cell death-receptor-1 (PD-1) antibody and non-small cell lung cancer (NSCLC) to analyze the characteristics of hepatitis related to iCIs and find the factors that could be useful biomarkers for the diagnosis. MethodsA single-center retrospective study of 252 NSCLC patients who received PD-1 antibody (nivolumab or pembrolizumab). Some of the biochemical markers and immunological markers were analyzed during PD-1-antibody treatment with or without ALT elevation. Histopathological features were reviewed by a single expert of hepatic pathology focusing on the following features: fibrosis, portal inflammation, lobular inflammation, lobular necrosis. The formation of macro- and micro- granulomas was also evaluated. ResultsThe frequency of liver damage induced by nivolumab including grade 1 to 4 (ALT) was 41.9% (78/186 patients). The positive rate of anti-nuclear antibody in the nivolumab group with iCIs-related hepatitis was significantly higher than that in the nivolumab group without iCIs-related hepatitis (p<0.0001). Granulomatous changes were significantly increased in patients with iCIs-related hepatitis compared with DILI and AIH patients (p<0.05). The ratios of inflammatory cells CD4/CD8, and CD138/CD3 in ICIs-related hepatitis were significantly lower than in those of AIH or DILI patients (p<0.05).ConclusionsWe demonstrated that the pre-existing ANA and characteristic liver histology including CD8+ cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis in the NSCLC with anti-PD-1 therapy.

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Dramatic effect of nivolumab against melanoma and immune‐related liver toxicity: A detailed histopathological and immunohistochemical analysis of nivolumab‐induced liver toxicity

Cited by 4 publications

References 5 publications

Incidence rate and treatment strategy of immune checkpoint inhibitor mediated hepatotoxicity: A systematic review

Incidence rate and treatment strategy of immune checkpoint inhibitor mediated hepatotoxicity: A systematic review

Anti-nuclear antibody and a granuloma could be biomarkers for iCIs-related hepatitis by anti-PD-1 treatment

Anti-nuclear Antibody and a Granuloma Could be Biomarkers for iCIs-related Hepatitis by Anti- PD-1 Treatment

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