Early immunosuppression therapy improves outcomes in CD8+ T-cell activated paediatric acute liver failure and...

Paediatric acute liver failure (PALF) and hepatitis of indeterminate aetiology with distinctive CD8+ T-cell rich liver infiltrates is a recently recognised disorder of immune-mediated dysregulation. We aimed to characterise the clinical phenotype, liver immunohistochemistry, response to immunosuppression (IS) therapy and clinical outcomes up to 24-months in an Australian cohort.

Single-centre retrospective study of patients aged 1-18 years who presented between 2017 and 2022 with hepatitis or acute liver failure with CD8+ rich infiltrates on liver biopsy.

Of the 13 patients identified, 8/13 had CD8+ PALF and 5/13 had CD8+ hepatitis. Median age at presentation was 10.8 years (interquartile range [IQR] 7.8-12.3), and 85% were male. Peripheral lymphopenia was noted in 85% of patients. Corticosteroids (CS) were commenced in 10/13 (77%) patients at a median of 13 days post-illness-onset (IQR 9-14). Maintenance IS was initiated in 7/10 (70%) patients, at a median of 20 days post-illness-onset (IQR 19-37), with tacrolimus commenced in 4/7 (57%) patients. At 24-month follow-up, 100% of patients were alive, 9/13 (69%) survived with native liver (4/8 with PALF; 5/5 with hepatitis), 4/8 (50%) with PALF required liver transplantation and 2/13 (15%) developed aplastic anaemia and recovered without haematopoietic stem cell transplantation. Successful withdrawal of IS was achieved in 50% patients with their native liver.

Evaluation of liver immunohistochemistry and peripheral T-cell subset analysis is essential for identification of patients with PALF and hepatitis with CD8+ T-cell predominant liver injury. Early CS and adjunct IS are safe and effective in achieving favourable outcomes at 24 months.