Case Report: Acute liver injury with Epstein-Barr virus DNAemia following teplizumab: drug-induced liver injury, viral reactivation, or both?

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.