Denosumab-Induced Immune Hepatitis
Denosumab–Prolia®, Xgeva® (Amgen) is a fully human antibody to the receptor activator of the nuclear factor-K ligand (RANKL). Hepatotoxicity is extremely rare, with only one reported case of immune origin. We present a second case of hepatotoxicity resulting from an immune reaction to denosumab. A 4...
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MDPI AG
2021-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/1/76 |
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| author | Viviana Ostrovsky Stephen Malnick Shahar Ish-Shalom Nadya Ziv Sokolowskaia Ady Yosepovich Manuela Neuman |
| author_facet | Viviana Ostrovsky Stephen Malnick Shahar Ish-Shalom Nadya Ziv Sokolowskaia Ady Yosepovich Manuela Neuman |
| author_sort | Viviana Ostrovsky |
| collection | DOAJ |
| description | Denosumab–Prolia®, Xgeva® (Amgen) is a fully human antibody to the receptor activator of the nuclear factor-K ligand (RANKL). Hepatotoxicity is extremely rare, with only one reported case of immune origin. We present a second case of hepatotoxicity resulting from an immune reaction to denosumab. A 43-year-old female was referred to the Endocrinology, Diabetes & Metabolism Department for treatment of low bone mineral density (BMD) following endocrine therapy with letrozole and lucrin because of breast cancer. She developed premature menopause at the age of 36 years when she underwent a left lumpectomy due to an infiltrating duct carcinoma of the breast (T1 NO MO) and was subsequently started on endocrine therapy. Denosumab was started to prevent osteoporosis. On the third year after starting on denosumab and one month after she received the last injection, she became ill. The routine biochemical analysis showed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rose appreciatively to 10 times the upper limit of normal (ULN). The gamma-glutamyl transferase (GGT) level was elevated slightly to 67 U/L (0–38 U/L). The serum gamma-globulin level was elevated to 1.72 g/dL (0.7–1.6 gr/dl), while the total bilirubin (TB) and serum albumin levels were normal. A liver biopsy revealed a moderate to severe chronic inflammatory infiltrate containing MUM-1 positive plasma cells. In addition, numerous CD-3 positive small T lymphocytes and few CD-20 positive B lymphocytes and eosinophils were seen in the portal tracts. Moderate to severe interface hepatitis, bile duct proliferation and mild portal fibrosis were also identified. The results could be consistent with the diagnosis of drug-induced liver injury (DILI). |
| first_indexed | 2024-03-09T04:45:51Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T04:45:51Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-53f75db146f74877b12d946194a43de62023-12-03T13:16:01ZengMDPI AGBiomedicines2227-90592021-01-01917610.3390/biomedicines9010076Denosumab-Induced Immune HepatitisViviana Ostrovsky0Stephen Malnick1Shahar Ish-Shalom2Nadya Ziv Sokolowskaia3Ady Yosepovich4Manuela Neuman5Diabetes, Endocrinology and Metabolic Disease Institute, Kaplan Medical Center, The Faculty of Medicine, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Internal Medicine C. Kaplan Medical Center, The Faculty of Medicine, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Pathology Kaplan Medical Center, The Faculty of Medicine, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Pathology Kaplan Medical Center, The Faculty of Medicine, The Hebrew University of Jerusalem, Rehovot 76100, IsraelDepartment of Pathology Kaplan Medical Center, The Faculty of Medicine, The Hebrew University of Jerusalem, Rehovot 76100, IsraelIn Vitro Drug Safety and Biotechnology and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5G 1L5, CanadaDenosumab–Prolia®, Xgeva® (Amgen) is a fully human antibody to the receptor activator of the nuclear factor-K ligand (RANKL). Hepatotoxicity is extremely rare, with only one reported case of immune origin. We present a second case of hepatotoxicity resulting from an immune reaction to denosumab. A 43-year-old female was referred to the Endocrinology, Diabetes & Metabolism Department for treatment of low bone mineral density (BMD) following endocrine therapy with letrozole and lucrin because of breast cancer. She developed premature menopause at the age of 36 years when she underwent a left lumpectomy due to an infiltrating duct carcinoma of the breast (T1 NO MO) and was subsequently started on endocrine therapy. Denosumab was started to prevent osteoporosis. On the third year after starting on denosumab and one month after she received the last injection, she became ill. The routine biochemical analysis showed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) rose appreciatively to 10 times the upper limit of normal (ULN). The gamma-glutamyl transferase (GGT) level was elevated slightly to 67 U/L (0–38 U/L). The serum gamma-globulin level was elevated to 1.72 g/dL (0.7–1.6 gr/dl), while the total bilirubin (TB) and serum albumin levels were normal. A liver biopsy revealed a moderate to severe chronic inflammatory infiltrate containing MUM-1 positive plasma cells. In addition, numerous CD-3 positive small T lymphocytes and few CD-20 positive B lymphocytes and eosinophils were seen in the portal tracts. Moderate to severe interface hepatitis, bile duct proliferation and mild portal fibrosis were also identified. The results could be consistent with the diagnosis of drug-induced liver injury (DILI).https://www.mdpi.com/2227-9059/9/1/76immune hepatitiscytokinedenosumabdrug-induced hepatotoxicitynecrosisnuclear factor-κB (NFκB) |
| spellingShingle | Viviana Ostrovsky Stephen Malnick Shahar Ish-Shalom Nadya Ziv Sokolowskaia Ady Yosepovich Manuela Neuman Denosumab-Induced Immune Hepatitis Biomedicines immune hepatitis cytokine denosumab drug-induced hepatotoxicity necrosis nuclear factor-κB (NFκB) |
| title | Denosumab-Induced Immune Hepatitis |
| title_full | Denosumab-Induced Immune Hepatitis |
| title_fullStr | Denosumab-Induced Immune Hepatitis |
| title_full_unstemmed | Denosumab-Induced Immune Hepatitis |
| title_short | Denosumab-Induced Immune Hepatitis |
| title_sort | denosumab induced immune hepatitis |
| topic | immune hepatitis cytokine denosumab drug-induced hepatotoxicity necrosis nuclear factor-κB (NFκB) |
| url | https://www.mdpi.com/2227-9059/9/1/76 |
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