(Xing et al.
2014).
The Pediatric Acute Liver Failure (PALF) Group reported on an
interferon-gamma (IFN-γ) -related inflammatory activity in patients with
PALF that is associated with survival with native liver. In contrast,
interleukin 6 (IL-6) and IL-8 producing pathways were associated with
patients demise (Xing
et al. 2014). Other groups have found a group of CD8+ T-cells in
patients with I-PALF, proposing this could be a histologic biomarker for
PALF due to immune dysregulation. This study was multicenter, included a
cohort of 37 I-PALF and 18 PALF patients with known etiologies. Both
cohorts had their liver tissue stained for T-cells, B-cell, macrophages,
perforin and tissue resident-memory T cells. CD8+ immunohistochemical
staining was found significantly abundant (82%) in the I-PALF group
compared to the known diagnosis group (7%) with p-value less than
0.0001. In addition, CD8+ cells were positive for perforin (effector
function) and were flagged as CD103-positive (resident memory
phenotype).
Liver tissue from other processes such as autoimmune hepatitis can also
demonstrate ranges of CD8+ dense staining, thus CD8+ staining should not
be considered as pathognomonic of I-PALF, but rather a sign of liver
injury. These findings have led to the use of the newer nomenclature
“activated CD8 T-cell hepatitis.”
Another defining feature of activated I-PALF is age factor. Patients
affected by I-PALF are younger than those with established diagnoses,
inferring that the developing immune system is susceptible to this kind
of immune-mediated injury(Narkewicz et al.
2018).Vodovotz et al. dived into the immune pathways segregating
cohorts of patients by age: infant, toddler, young childhood, older
childhood and adolescent. They found an age-associated maturity of the
immune system that flips patients to a differential of inflammatory
pathways, which could shed light on outcomes of patients with PALF(Vodovotz et al.
2020).