アテゾリズマブ・ベバシズマブ併用療法後自己免疫性脳炎を発症し，改善後に2次治療に移行した肝細胞癌の1例
68歳，男性．右背部痛を主訴に近医受診，肝腫瘤を指摘され当院紹介．肝細胞癌，多発リンパ節・骨転移と診断し，アテゾリズマブ・ベバシズマブ併用療法（ATZ＋BV）を開始した．投与開始14日目に辻褄の合わない言動と傾眠，16日目にJCS10の意識障害を認めた．血中アンモニア値，頭部MRIに異常なく，髄液検査では僅かな細胞数上昇と蛋白細胞解離を認めた．自己免疫性脳炎を疑い，同日よりステロイドパルス療法を開始した．意識障害は著明に改善し，内服ステロイドに移行後，38日目に後遺症なく自宅退院となった．脳炎の再燃はなく，ATZ＋BV開始60日目に2次治療としてレンバチニブを導入した．肝細胞癌に対するATZ＋...
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| Published in | 肝臓 Vol. 64; no. 11; pp. 559 - 566 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本肝臓学会
01.11.2023
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0451-4203 1881-3593 |
| DOI | 10.2957/kanzo.64.559 |
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| Abstract | 68歳，男性．右背部痛を主訴に近医受診，肝腫瘤を指摘され当院紹介．肝細胞癌，多発リンパ節・骨転移と診断し，アテゾリズマブ・ベバシズマブ併用療法（ATZ＋BV）を開始した．投与開始14日目に辻褄の合わない言動と傾眠，16日目にJCS10の意識障害を認めた．血中アンモニア値，頭部MRIに異常なく，髄液検査では僅かな細胞数上昇と蛋白細胞解離を認めた．自己免疫性脳炎を疑い，同日よりステロイドパルス療法を開始した．意識障害は著明に改善し，内服ステロイドに移行後，38日目に後遺症なく自宅退院となった．脳炎の再燃はなく，ATZ＋BV開始60日目に2次治療としてレンバチニブを導入した．肝細胞癌に対するATZ＋BV後の自己免疫性脳炎は，自験例を含め4例のみ報告されており，初発症状や意識障害出現時期がほぼ一致していた．早期の診断とステロイドパルス療法施行により2次治療へ移行できた症例であると考えられた． |
|---|---|
| AbstractList | 68歳，男性．右背部痛を主訴に近医受診，肝腫瘤を指摘され当院紹介．肝細胞癌，多発リンパ節・骨転移と診断し，アテゾリズマブ・ベバシズマブ併用療法（ATZ＋BV）を開始した．投与開始14日目に辻褄の合わない言動と傾眠，16日目にJCS10の意識障害を認めた．血中アンモニア値，頭部MRIに異常なく，髄液検査では僅かな細胞数上昇と蛋白細胞解離を認めた．自己免疫性脳炎を疑い，同日よりステロイドパルス療法を開始した．意識障害は著明に改善し，内服ステロイドに移行後，38日目に後遺症なく自宅退院となった．脳炎の再燃はなく，ATZ＋BV開始60日目に2次治療としてレンバチニブを導入した．肝細胞癌に対するATZ＋BV後の自己免疫性脳炎は，自験例を含め4例のみ報告されており，初発症状や意識障害出現時期がほぼ一致していた．早期の診断とステロイドパルス療法施行により2次治療へ移行できた症例であると考えられた． |
| Author | 宮西, 浩嗣 田中, 信悟 山本, 彬広 久原, 真 伊藤, 亮 村瀬, 和幸 眞部, 建郎 久保, 智洋 濱口, 孝太 高田, 弘一 大沼, 啓之 加藤, 淳二 大須賀, 崇裕 |
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| Copyright | 2023 一般社団法人 日本肝臓学会 |
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| References | 16) Laserna A, Tummal S, Patel N, et al. Atezolizumab-related encephalitis in the intensive care unit: Case report and review of the literature. SAGE Open Med Case Rep 2018; 6: 2050313X18792422 1) Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76: 681-693 18) Nishijima H, Kon T, Seino Y, et al. Bilateral Thalamic Lesions Associated With Atezolizumab-Induced Encephalitis: A Follow-up Report With Autopsy Findings. Neurology 2022; 98: 204-205 8) Satake T, Maruki Y, Kubo Y, et al. Atezolizumab-induced Encephalitis in a Patient with Hepatocellular Carcinoma: A Case Report and Literature Review. Intern Med 2022; 61: 2619-2623 13) Nader R, Tannoury E, Rizk T, et al. Atezolizumab-induced encephalitis in a patient with metastatic breast cancer: a case report and review of neurological adverse events associated with checkpoint inhibitors. Autops Case Rep 2021; 11: e2021261 15) Robert L, Langner-Lemercier S, Angibaud A, et al. Immune-related Encephalitis in Two Patients Treated With Immune Checkpoint Inhibitor. Clin Lung Cancer 2020; 21: e474-e477 4) 市川弥生子. 免疫チェックポイント阻害薬の副作用～神経領域～. 杏林医会誌 2020; 51: 239-245 7) 平田大氣, 杉本勝俊, 掛川達矢, 他. 肝細胞癌に対するAtezolizumab+Bevacizumab療法導入後に発症した自己免疫性脳炎の1例. 肝臓 2021; 62: 590-592 14) Watanabe S, Yoshizumi K, Moriguchi S, et al. Nivolumab treatment followed by atezolizumab induced encephalitis and neuropathy with antiganglioside antibodies. eNeurologicalSci 2021; 25: 100386 20) Wada S, Iwamoto K, Ozaki N, et al. Atezolizumab, an immune checkpoint inhibitor, caused precedent depressive symptoms related to limbic encephalitis. Psychiatry Clin Neurosci 2022; 76: 125-126 22) Levine JJ, Somer RA, Hosoya H, et al. Atezolizumab-induced Encephalitis in Metastatic Bladder Cancer: A Case Report and Review of the Literature. Clin Genitourin Cancer 2017; 15: e847-849 3) Astaras C, Micheli R, Moura B, et al. Neurological Adverse Events Associated with Immune Checkpoint Inhibitors: Diagnosis and Management. Curr Neurol Neurosci Rep 2018; 18: 3 12) Yamaguchi Y, Nagasawa H, Katagiri Y, et al. Atezolizumab-associated encephalitis in metastatic lung adenocarcinoma: a case report. J Med Case Rep 2020; 14: 88 21) Nakashima K, Demura Y, Kurokawa K, et al. Immune Checkpoint Inhibitor-Induced Limbic Encephalitis during Treatment with Atezolizumab in a Patient with Small-Cell Lung Cancer: A Case Report and Review of the Literature. Case Reports Immunol 2022; 2022: 9290922 24) Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid 2022 (published online June 22. 23) Chen G, Zhang C, Lan J, et al. Atezolizumab-associated encephalitis in metastatic breast cancer: A case report. Oncol Lett 2022; 24: 324 9) Arakawa M, Yamazaki M, Toda Y, et al. Atezolizumab-induced encephalitis in metastatic lung cancer: a case report and literature review. eNeurologicalSci 2018; 14: 49-50 2) Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020; 382: 1894-1905 6) Özdirik B, Jost-Brinkmann F, Savic LJ, et al. Atezolizumab and bevacizumab-induced encephalitis in advanced hepatocellular carcinoma: Case report and literature review. Medicine (Baltimore) 2021; 100: e26377 5) Marini A, Bernardini A, Gigli GL, et al. Neurologic Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review. Neurology 2021; 96: 754-766 17) Kim A, Keam B, Cheun H, et al. Immune-Checkpoint-Inhibitor-Induced Severe Autoimmune Encephalitis Treated by Steroid and Intravenous Immunoglobulin. J Clin Neurol 2019; 15: 259-261 10) 桂 英之, 米田太郎, 木場隼人, 他. ウェブアプリケーションを契機に発見されたアテゾリズマブ単剤による自己免疫性脳炎の1例. 日本病院薬剤師会雑誌 2020; 56: 389-394 19) Sebbag E, Psimaras D, Baloglu S, et al. Immune-Related Cerebellar Ataxia: A Rare Adverse Effect of Checkpoint Inhibitor Therapy. J Neuroimmune Pharmacol 2022; 17: 377-379 11) Chang H, Yong-Won Shin YW, Keam B, et al. HLA-B27 association of autoimmune encephalitis induced by PD-L1 inhibitor. Ann Clin Transl Neurol 2020; 7: 2243-2250 |
| References_xml | – reference: 11) Chang H, Yong-Won Shin YW, Keam B, et al. HLA-B27 association of autoimmune encephalitis induced by PD-L1 inhibitor. Ann Clin Transl Neurol 2020; 7: 2243-2250 – reference: 24) Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid 2022 (published online June 22.) – reference: 4) 市川弥生子. 免疫チェックポイント阻害薬の副作用～神経領域～. 杏林医会誌 2020; 51: 239-245 – reference: 18) Nishijima H, Kon T, Seino Y, et al. Bilateral Thalamic Lesions Associated With Atezolizumab-Induced Encephalitis: A Follow-up Report With Autopsy Findings. Neurology 2022; 98: 204-205 – reference: 6) Özdirik B, Jost-Brinkmann F, Savic LJ, et al. Atezolizumab and bevacizumab-induced encephalitis in advanced hepatocellular carcinoma: Case report and literature review. Medicine (Baltimore) 2021; 100: e26377 – reference: 9) Arakawa M, Yamazaki M, Toda Y, et al. Atezolizumab-induced encephalitis in metastatic lung cancer: a case report and literature review. eNeurologicalSci 2018; 14: 49-50 – reference: 10) 桂 英之, 米田太郎, 木場隼人, 他. ウェブアプリケーションを契機に発見されたアテゾリズマブ単剤による自己免疫性脳炎の1例. 日本病院薬剤師会雑誌 2020; 56: 389-394 – reference: 14) Watanabe S, Yoshizumi K, Moriguchi S, et al. Nivolumab treatment followed by atezolizumab induced encephalitis and neuropathy with antiganglioside antibodies. eNeurologicalSci 2021; 25: 100386 – reference: 22) Levine JJ, Somer RA, Hosoya H, et al. Atezolizumab-induced Encephalitis in Metastatic Bladder Cancer: A Case Report and Review of the Literature. Clin Genitourin Cancer 2017; 15: e847-849 – reference: 1) Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol 2022; 76: 681-693 – reference: 15) Robert L, Langner-Lemercier S, Angibaud A, et al. Immune-related Encephalitis in Two Patients Treated With Immune Checkpoint Inhibitor. Clin Lung Cancer 2020; 21: e474-e477 – reference: 2) Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med 2020; 382: 1894-1905 – reference: 7) 平田大氣, 杉本勝俊, 掛川達矢, 他. 肝細胞癌に対するAtezolizumab+Bevacizumab療法導入後に発症した自己免疫性脳炎の1例. 肝臓 2021; 62: 590-592 – reference: 19) Sebbag E, Psimaras D, Baloglu S, et al. Immune-Related Cerebellar Ataxia: A Rare Adverse Effect of Checkpoint Inhibitor Therapy. J Neuroimmune Pharmacol 2022; 17: 377-379 – reference: 3) Astaras C, Micheli R, Moura B, et al. Neurological Adverse Events Associated with Immune Checkpoint Inhibitors: Diagnosis and Management. Curr Neurol Neurosci Rep 2018; 18: 3 – reference: 16) Laserna A, Tummal S, Patel N, et al. Atezolizumab-related encephalitis in the intensive care unit: Case report and review of the literature. SAGE Open Med Case Rep 2018; 6: 2050313X18792422 – reference: 13) Nader R, Tannoury E, Rizk T, et al. Atezolizumab-induced encephalitis in a patient with metastatic breast cancer: a case report and review of neurological adverse events associated with checkpoint inhibitors. Autops Case Rep 2021; 11: e2021261 – reference: 17) Kim A, Keam B, Cheun H, et al. Immune-Checkpoint-Inhibitor-Induced Severe Autoimmune Encephalitis Treated by Steroid and Intravenous Immunoglobulin. J Clin Neurol 2019; 15: 259-261 – reference: 20) Wada S, Iwamoto K, Ozaki N, et al. Atezolizumab, an immune checkpoint inhibitor, caused precedent depressive symptoms related to limbic encephalitis. Psychiatry Clin Neurosci 2022; 76: 125-126 – reference: 23) Chen G, Zhang C, Lan J, et al. Atezolizumab-associated encephalitis in metastatic breast cancer: A case report. Oncol Lett 2022; 24: 324 – reference: 5) Marini A, Bernardini A, Gigli GL, et al. Neurologic Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review. Neurology 2021; 96: 754-766 – reference: 8) Satake T, Maruki Y, Kubo Y, et al. Atezolizumab-induced Encephalitis in a Patient with Hepatocellular Carcinoma: A Case Report and Literature Review. Intern Med 2022; 61: 2619-2623 – reference: 21) Nakashima K, Demura Y, Kurokawa K, et al. Immune Checkpoint Inhibitor-Induced Limbic Encephalitis during Treatment with Atezolizumab in a Patient with Small-Cell Lung Cancer: A Case Report and Review of the Literature. Case Reports Immunol 2022; 2022: 9290922 – reference: 12) Yamaguchi Y, Nagasawa H, Katagiri Y, et al. Atezolizumab-associated encephalitis in metastatic lung adenocarcinoma: a case report. J Med Case Rep 2020; 14: 88 |
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| Title | アテゾリズマブ・ベバシズマブ併用療法後自己免疫性脳炎を発症し，改善後に2次治療に移行した肝細胞癌の1例 |
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