Unknown aetiology delays treatment of paediatric acute liver failure

Most cases of paediatric acute liver failure (PALF) in Singapore are still of indeterminate aetiology, according to a recent single-centre study. Given the poor survival prospects of PALF, timely liver transplantation (LT) is critical.

“As the data was derived from the largest tertiary paediatric hospital in Singapore, our findings could be representative of cases of PALF in the country. However, we acknowledge that this is a retrospective, observational study of an uncommon paediatric condition, with inherent limitations of ascertainment and verification bias,” the researchers said.

“Nonetheless, this is the first study on PALF in Singapore, and the findings from this paper will provide useful insights and understanding of the aetiologic spectrum, prognosis and survival outcome in our local population,” they added.

The review included 34 paediatric PALF patients (median age at presentation 10 months, 67.6 percent boys) receiving care at the KK Women’s and Children’s Hospital. Fourteen (41.2 percent) patients were diagnosed with PALF of indeterminate aetiology, while metabolic and infectious factors were deemed to be responsible for nine cases each (26.5 percent). [Singapore Med J 2021;doi:10.11622/smedj.2021138]

Stratifying by age, inborn errors of metabolism as PALF aetiology were predominant among patients <12 months of age (7 of 18; 38.9 percent). These included organic acidaemia (n=3), mitochondrial disorders (n=2), and urea cycle defect (n=2).

In contrast, half of patients diagnosed with PALF >1 year of age had indeterminate aetiology. Only two patients in this age subgroup presented with metabolic disorders.

Sixteen patients died during the study period, yielding an overall mortality rate of 47.1 percent. Fifteen patients died without LT, seven of whom had multiorgan failure. On the other hand, 13 saw spontaneous recovery, corresponding to a rate of 38.2 percent. Transplant-free survival rates were low, with only 22.2 percent and 28.6 percent of PALF patients with metabolic and indeterminate aetiologies, respectively, achieving such endpoint.

Nine patients were referred and underwent workup for LT, but only six patients (17.6 percent) were able to receive the transplants; the remaining three died before the procedure. One-year post-transplant survival was 83.5 percent.

Unadjusted analysis identified serum lactate, international normalized ratio, the need for invasive ventilation, and hepatic encephalopathy as potential correlates of death or the need for LT. None remained significant upon multivariable logistic regression analysis.

“Our data revealed the missed opportunity for LT in at least three patients who were referred for LT assessment but died before LT could be performed,” the researchers said. “Potentially, some of the patients who were considered unsuitable candidates for LT might also have missed the window of opportunity to be assessed for LT prior to the onset of multisystem complications.”

“PALF is universally associated with poor survival rates and is best managed at a dedicated LT unit to ensure seamless and timely transition from supportive management to transplant assessment for patients who will eventually benefit from LT,” they added.