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Background <p>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.</p> Patients and methods <p>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.</p> Results <p>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 (<i>p</i>-value &lt; 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 (<i>p</i>-value &lt; 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%.</p> Conclusion <p>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.</p>

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Transforming growth factor-βeta and interleukin-1βeta in children with acute liver failure: pathophysiology and outcome perspectives

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月18日

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  • Mohammed Abdel-Salam El-Guindi,
  • Sara Mohammed Abdel Ghafar El Taras,
  • Samar Ebrahim Ghanem,
  • Ahmad Mohamed Sira,
  • Samira Abdel-Wahab Abdel-Aziz

摘要

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.