Egyptian Liver Journal (Mar 2025)
Transforming growth factor-βeta and interleukin-1βeta in children with acute liver failure: pathophysiology and outcome perspectives
Abstract
Abstract Background The exact pathophysiology of acute liver failure (ALF) in children is not well defined. Some animal studies showed increased cytokines as a driving force for its occurrence with defective similar human studies. This study aimed to measure the plasma level of the pro-inflammatory cytokine (IL-1β) and anti-inflammatory cytokine (TGF-β) in children with ALF and assess their relation to the outcome and complications. Patients and methods It is a prospective case–control study that included 25 children with ALF, 20 children with self-limited acute hepatitis A, and 10 healthy children as control groups. Plasma samples were collected at presentation to measure IL-1β and TGF-β levels using the ELISA technique. Results Higher levels of IL-1β and TGF-β were found in ALF than acute hepatitis A group with insignificant differences. TGF-β was significantly higher in ALF and acute hepatitis groups than the healthy control group (p-value < 0.05). Moreover, the TGF-β/IL-1β ratio showed no significant difference among the studied groups despite trending to be higher in ALF. TGF-β and TGF-β/IL-1β ratio were higher in the survived while IL-1β was higher in the deceased cases but all did not reach a significant level. When the TGF-β/IL-1β ratio was ≥ .8, the survival probability in ALF cases was 100%. In the ALF group, IL-1β was significantly higher in those who were complicated with brain edema and circulatory failure (p-value < 0.05). A model score designed of TGF-β/IL-1β ratio, age, encephalopathy, and brain edema can predict mortality in ALF cases at a cutoff value of − 1.2 with a sensitivity of 100%. Conclusion Increased cytokines in ALF with an imbalance between the pro- and anti-inflammatory cytokines could have a role in the pathogenesis and the outcome of ALF. TGF-β/IL-1β ratio is trending to be higher in survived ALF cases and a model score including it can predict the mortality. The baseline level of IL-1β in ALF is significantly higher in those who develop brain edema and circulatory failure, so experimental studies of its targeting are warranted.
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