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Observational Study
. 2022 Feb;55(4):455-463.
doi: 10.1111/apt.16708. Epub 2021 Nov 18.

Epstein-Barr virus status and immunosuppression use in paediatric autoimmune liver disease

Jeremy S Nayagam  1   2 , Michael A Heneghan  1 , Marianne Samyn  3 , Deepak Joshi  1
Affiliations
Observational Study

Epstein-Barr virus status and immunosuppression use in paediatric autoimmune liver disease

Jeremy S Nayagam et al. Aliment Pharmacol Ther. 2022 Feb.

Abstract

Background: Since azathioprine is associated with lymphoproliferative disorders in Epstein-Barr virus (EBV)-naïve patients with inflammatory bowel disease, guidelines advise avoidance. No recommendations exist for autoimmune liver disease (AILD).

Aims: To evaluate EBV status and EBV-related complications in paediatric AILD.

Methods: Single-centre, retrospective, observational study of paediatric AILD.

Results: In 245 paediatric patients with AILD, azathioprine was used in 168 (68.6%) and mycophenolate mofetil in 69 (28.2%). EBV status was assessed in 18 (10.7%) prior to azathioprine and 6 (8.7%) MMF. Acute EBV infection was diagnosed in five patients while on immunosuppression, resulting in one transient hepatitis and one persistent hepatitis. There were no cases of lymphoproliferative disorder in native livers. Liver transplantation (LT) was performed in 39 (15.9%) patients, with 8 EBV IgG-negative at LT. Post-LT EBV viraemia developed in 29 (74.4%), first detected at median 26 days (IQR, 13-86). EBV IgG-negative recipients had higher peak viraemia (266 984 IU/mL [IQR, 41108-2429050] v 5333 [IQR, 2036-38770], P = .004) and longer time to peak viraemia (375 days [IQR, 251-884] v 70 [IQR, 21-604], P = .04). Early EBV-associated post-transplant lymphoproliferative disorder (PTLD) was diagnosed in two patients, both EBV-IgG negative with prior azathioprine.

Conclusions: Real-world data demonstrate that EBV serostatus is not routinely checked before immunosuppression for paediatric AILD. Lymphoproliferative disorder was not diagnosed in those with native livers; however, EBV IgG-negative LT recipients receiving EBV IgG-positive donor organs are at risk of early PTLD. Large multicentre studies with longer follow-up are required to further evaluate the risk.

Keywords: Immunosuppression; autoimmune liver disease; inflammatory bowel disease; paediatric gastroenterology; paediatric hepatology; primary sclerosing cholangitis; thiopurines.

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References

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