Pediatric Wilson disease presenting as acute liver failure: Prognostic indices

ARTICLE HIGHLIGHTS

Research background

Wilson disease (WD) with acute liver failure (ALF) (WDALF) classically has a high mortality. Many WDALF patients need emergent liver transplantation (LT); however, some WDALF patients do survive without LT. Several prognostic models have been developed to predict ALF or WD mortality, but with varying or contradictory conclusions.

Research motivation

Distinguish WDALF patients who can be spared LT from those in whom LT will be required.

Research objectives

Determine the recent rates in China of mortality and of LT in pediatric WDALF (diagnosis in most patients confirmed genetically) and assess how accurately different prognostic models performed in these patients.

Research methods

Medical records of pediatric WDALF patients in one center over 6 years were retrospectively collected and reviewed. WDALF was confirmed by ATP7B sequencing in most patients. Seven different prognostic models were assessed in these WDALF patients (King’s College Hospital criteria for end-stage liver disease and for pediatric end-stage liver disease; Liver Injury Unit (LIU) model using prothrombin time (PT) or international normalized ratio (INR); admission LIU model using PT or INR; and Devarbhavi model. Results were evaluated statistically for significance.

Research results

Among 41 Han Chinese patients, WDALF was confirmed in 36 by demonstrating at least two ATP7B variants. In the other 5, the diagnosis of WDALF was established by identifying Kayser-Fleischer rings and Coombs-negative hemolytic anemia. In all, 3 died within 15 d of admission, 3 underwent LT within 1 mo of admission, and 3 survived without LT (follow-up 44.6 ± 21.9 mo). Treatment included enteral D-penicillamine and zinc-salt therapy (Zn) with or without urgent plasmapheresis. Eleven underwent plasma exchange (PE), at the same time (2 died, 2 underwent LT, and 7 survived). The other 30 patients did not undergo PE (1 died, 1 underwent LT, and 28 survived). Encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels were significantly correlated with mortality, but the correlations disappeared on logistic regression analysis. No association between ATP7B variant category and clinical characteristics or outcomes was found. Area under the receiver operating curves of the individual models varied from 0.981 to 0.748 with positive predictive values (PPVs) from 0.214 to 0.429.

Research conclusions

Our pediatric WDALF patients, most of whom were found to harbor ATP7B variants, exhibited an overall mortality of 7.3%, showing that pediatric patients with WDALF can survive and recover well without LT after D-penicillamine and Zn therapy with or without PE. This is not a novel finding, but it is based on a larger cohort of WDALF patients than reported in any previous study, and the diagnosis of WDALF in these patients–thanks to genetic studies–is more firmly established than in any previous study. Among seven different prognostic scoring systems, all had good sensitivity but varied in specificity, and PPV was optimal in none.

Research perspectives

WDALF with higher scores assigned using various models can be managed initially with administration of chelators and Zn with or without PE, and patients may recover from ALF even when disease is so severe as to warrant listing for LT. However, ours was a retrospective study; prospective studies or prospective cohort studies in pediatric WDALF are underway to reinforce this conclusion. Biomarkers not previously examined can be assessed in these prospective studies to learn if their inclusion improves model performance.