Introduction: Pediatric Acute Liver Failure (PALF) is a devastating condition that affects previously healthy children, leading to a rapid deterioration and the need of liver transplant (LT). In many cases, the cause of the liver injury cannot be identified. Recent studies hypothesize that liver injury might be due to a hyperinflammatory immune response mediated by activated CD8+ T-cells. Antithymocyte globulin (ATG) has been proposed as a therapeutic option in these cases through depleting T cells and their activation, homing, and cytotoxic activities. The aim of this study is to describe our experience of patients with activated CD8+ PALF treated with ATG.
Methods: We retrospectively report a series of patients with indeterminate PALF treated with ATG. All of them were <18 years old, without previous liver injury and were admitted to our center from July 2023 to February 2025. Common causes for PALF were ruled-out. Suspicious signs of activated CD8+ PALF were lymphopenia, thrombocytopenia, inversion of CD4 to CD8 ratio, high percentage of activated CD8+ T-cells and absence of other etiologies identified. Treatment regimen included rabbit ATG at a dose of 4 mg/kg/day for 4 days, and continued with prednisolone 1 mg/kg/day followed by a gradual taper with discontinuation at 42 days. Prophylaxis for infections with ganciclovir and anidulafungin were used.
Results: 6 patients were included. Median age was 7 years (r: 2-12 yr). Five patients (83%) had a significantly greater percentage of CD8+ T-cells on peripheral blood, with inversion of the CD4 to CD8 ratio. Only 1 patient could not receive the complete treatment, as he died on day 2 due to rapidly evolving liver failure. The remaining 5 patients are alive without a LT, with a median follow up time of 93.5 days (r: 29-514 d). Liver tests have normalized in all 5 cases. No adverse events were observed. Living donors were studied when available and listed for rapid decision making in case of deterioration.
Conclusion: PALF remains a challenge for transplant surgeons and hepatologists worldwide. ATG could be a valid empiric treatment option for activated CD8+ T-cell PALF with good results, and rapidly identifying cases that would benefit from this treatment is of paramount importance.