Case Report: Acute liver injury with Epstein-Barr virus DNAemia following teplizumab: drug-induced liver injury, viral reactivation, or both?
- 1Unit of Pediatrics, San Salvatore Hospital
- 2Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila
- 3Dietetics Service, San Salvatore Hospital
Abstract
Background: Teplizumab (anti-CD3) delays progression from stage 2 to stage 3 type 1 diabetes (T1D) but can be associated with laboratory abnormalities and virologic findings, including Epstein-Barr virus (EBV) DNAemia.
Methods: We report a 15-year-old boy with stage 2 T1D who received a standard course of teplizumab and developed a biphasic rise in aminotransferases occurring mainly after the end of infusions, with preserved bilirubin and coagulation parameters.
Results: During treatment, ALT/AST rose to 78/44 U/L (1.90/1.10×ULN). After completion, ALT/AST increased to 292/172 U/L (7.12/4.30×ULN) on post-treatment day +5 and peaked at 428/220 U/L (10.44/5.50×ULN) on day +6, followed by partial improvement and a second flare beginning on day +20 and peaking on day +24 (ALT 293 U/L, 7.15×ULN; AST 118 U/L, 2.95×ULN; GGT 142 U/L), with normal bilirubin. Coagulation parameters remained within the normal range. Work-up for autoimmune hepatitis, hepatitis B/C, CMV, adenovirus, parvovirus B19, and toxoplasmosis was negative. Abdominal ultrasound/Doppler was unremarkable. MRI reported liver size mildly increased/at the upper limit of normal, nonspecific segment IV abnormalities, and reactive abdominal lymph nodes, with interval improvement at follow-up. Pre-treatment VCA IgG was positive and VCA IgM negative. At post-treatment day +10, whole-blood EBV DNA was 538,623 copies/mL, with negative VCA IgM, EA IgG and EBNA IgG, decreasing to <200 copies/mL at 6 months. Liver enzymes normalized spontaneously over follow-up.
Conclusion: This case highlights marked, biphasic liver injury occurring after teplizumab in association with marked EBV DNAemia. The available clinical, serological, virological, and medication-timing data do not permit definitive attribution to teplizumab, EBV-related hepatic involvement, or concomitant medications. Post-treatment monitoring of both liver enzymes and EBV DNA may be helpful.
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BibTeX
@article{zagaroli2026case,
title = {{Case Report: Acute liver injury with Epstein-Barr virus DNAemia following teplizumab: drug-induced liver injury, viral reactivation, or both?}},
author = {Luca Zagaroli and Valentina Cattivera and Federica Guerra and Sabina Zara and Maria Laura Iezzi and Gabriella Bottone and Claudia Caloisi and Cecilia Fabiano and Cristina Gentile and Giulia Iapadre and Giuliana Nanni and Laura Palumbo and Vincenzo Salpietro and Maurizio Delvecchio},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.2008253},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.2008253/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: Acute liver injury with Epstein-Barr virus DNAemia following teplizumab: drug-induced liver injury, viral reactivation, or both?
AU - Luca Zagaroli
AU - Valentina Cattivera
AU - Federica Guerra
AU - Sabina Zara
AU - Maria Laura Iezzi
AU - Gabriella Bottone
AU - Claudia Caloisi
AU - Cecilia Fabiano
AU - Cristina Gentile
AU - Giulia Iapadre
AU - Giuliana Nanni
AU - Laura Palumbo
AU - Vincenzo Salpietro
AU - Maurizio Delvecchio
PY - 2026
DA - 2026/10/29
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.2008253
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.2008253/full
AB - Background: Teplizumab (anti-CD3) delays progression from stage 2 to stage 3 type 1 diabetes (T1D) but can be associated with laboratory abnormalities and virologic findings, including Epstein-Barr virus (EBV) DNAemia. Methods: We report a 15-year-old boy with stage 2 T1D who received a standard course of teplizumab and developed a biphasic rise in aminotransferases occurring mainly after the end of infusions, with preserved bilirubin and coagulation parameters. Results: During treatment, ALT/AST rose to 78/44 U/L (1.90/1.10×ULN). After completion, ALT/AST increased to 292/172 U/L (7.12/4.30×ULN) on post-treatment day +5 and peaked at 428/220 U/L (10.44/5.50×ULN) on day +6, followed by partial improvement and a second flare beginning on day +20 and peaking on day +24 (ALT 293 U/L, 7.15×ULN; AST 118 U/L, 2.95×ULN; GGT 142 U/L), with normal bilirubin. Coagulation parameters remained within the normal range. Work-up for autoimmune hepatitis, hepatitis B/C, CMV, adenovirus, parvovirus B19, and toxoplasmosis was negative. Abdominal ultrasound/Doppler was unremarkable. MRI reported liver size mildly increased/at the upper limit of normal, nonspecific segment IV abnormalities, and reactive abdominal lymph nodes, with interval improvement at follow-up. Pre-treatment VCA IgG was positive and VCA IgM negative. At post-treatment day +10, whole-blood EBV DNA was 538,623 copies/mL, with negative VCA IgM, EA IgG and EBNA IgG, decreasing to <200 copies/mL at 6 months. Liver enzymes normalized spontaneously over follow-up. Conclusion: This case highlights marked, biphasic liver injury occurring after teplizumab in association with marked EBV DNAemia. The available clinical, serological, virological, and medication-timing data do not permit definitive attribution to teplizumab, EBV-related hepatic involvement, or concomitant medications. Post-treatment monitoring of both liver enzymes and EBV DNA may be helpful.
SN - 1664-2392
ER -