Pediatric Wilson’s Disease Carries Higher Risk of Worse Outcomes

Children with Wilson’s disease (WD) are more likely than are adults to present with acute liver failure or acute-on-chronic liver failure and have lower transplant-free survival, according to data from a large single-center study in India.

These findings underscore the importance of early recognition and genetic evaluation in pediatric patients, and timely consideration of liver transplantation in severe presentations, reported lead author Anand V. Kulkarni, MD, of AIG Hospitals, Hyderabad, India, and colleagues.

“There is a lack of large cohort studies evaluating the clinical presentation of WD, along with a limited understanding of genotype–phenotype correlations in patients with WD presenting with liver disease and the absence of comprehensive comparisons between pediatric and adult outcomes,” the investigators wrote in Gastro Hep Advances (2025 Jun. doi: 10.1016/j.gastha.2025.100717). “Additionally, data on living donor liver transplantation (LDLT) outcomes in WD remain scarce.”

To address these gaps, Kulkarni and colleagues performed a single-center retrospective study of all patients with WD diagnosed and managed at AIG Hospitals between June 2020 and April 2024. 

Diagnosis followed Leipzig criteria, incorporating clinical features, slit-lamp examination for Kayser–Fleischer rings, serum ceruloplasmin, 24-hour urinary copper, hepatic copper when available, and genetic testing when available. 

Patients were stratified by age into pediatric and adult groups. The investigators compared clinical presentation, laboratory parameters, and outcomes across age groups.

Management reflected standard practice at the center: chelation with D-penicillamine or trientine, zinc therapy as monotherapy or adjunctive therapy, plasma exchange for acute liver failure or acute-on-chronic liver failure, and evaluation for living-donor liver transplantation when indicated. Genetic analysis was performed in approximately 70% of the cohort.

The final dataset included 156 patients, with a median age of 19 years (range, 2–57), and an approximately equal split between adult and pediatric groups. 

Presentation differed markedly by age. Among pediatric patients, the most common presentations were acute liver failure (26.7%) and acute-on-chronic liver failure (20%). Adults most frequently presented with decompensated cirrhosis (30.9%). Kayser–Fleischer rings were more prevalent in the pediatric group, consistent with underlying disease despite acute presentation.

Outcomes also varied by age and presentation. On Kaplan–Meier analysis, transplant-free survival was 72% in children and 87.7% in adults after a median follow-up of 1.33 years (P = .01). Overall cohort transplant-free survival at 1.33 years was 80.1%. Thirteen percent of patients underwent LDLT, with 90% 1-year post-transplant survival. Among those who received plasma exchange for acute presentations, transplant-free survival was 40.5%.

Among the patients with genetic data, 54.1% were homozygous or compound heterozygous for combinations of pathogenic variants and variants of uncertain significance in ATP7B. The most frequently observed pathogenic variants were p.Gly977Glu, p.Cys271Ter, and p.Asn1186Ser. Several additional variants, including novel changes, were identified across the cohort. 

No consistent genotype–phenotype correlation was observed. The investigators noted that the center’s focus on liver disease likely enriched the cohort for hepatic presentations, and that some patients were included based on Leipzig scores of 2-3 with supportive clinical response to therapy.

“Further research should focus on identifying structural variants, variants in other genes, and epigenetic modulators of genetic expression,” Kulkarni and colleagues concluded.

The genetic tests were performed with intramural funding support from the Asian Healthcare Foundation, provided to AIG Hospitals Hyderabad. The investigators disclosed no conflicts of interest.