Pediatric Wilson Disease Presenting as Acute Liver Failure

Abstract

Objectives: Wilson disease (WD) presenting as acute liver failure (ALF) is rare and typically fatal without liver transplantation (LT). Its rarity has hindered comprehensive studies. We undertook an individual patient data meta-analysis to characterize a cohort of pediatric patients presenting with ALF whose final diagnosis was WD to examine outcomes and identify predictors of poor outcomes. Methods: Database searches were conducted in PubMed, ScienceDirect, and Google Scholar, restricted to English-language articles published between January 1984 and May 2018. Articles were excluded if pediatric (<18 years old) data were not extractable or if LT was not readily available at reporting institutions. Extracted data included clinical and biochemical characteristics, genotype, treatment, and outcome. Results: Data were available on 249 subjects from 52 articles, plus 7 additional subjects identified from our institution's WD database (N = 256). Females represented 69% (n = 170/245). Median age at presentation was 13.4 years (n = 204, range 4.0–17.9). Of the total 256 subjects, 87% underwent LT, 11% achieved spontaneous recovery and 2% died before LT. International normalized ratio >2.0 at presentation was a predictor of LT/death (odds ratio 7.6, 95% confidence interval 1.5–28), with a trend observed for hepatic encephalopathy (HE) (odds ratio 4.18, 95% confidence interval 0.99–18). Arithmetic diagnostic scores proved inferior in the pediatric age-bracket compared to adults. Conclusions: This large international pediatric cohort has permitted an individual patient data analysis of WD presenting as ALF. Notably, 11% of subjects achieved spontaneous survival; the rest required LT. Coagulopathy (international normalized ratio >2:0) and HE at presentation heralded poor outcomes. Further prospective studies may identify additional early predictors of outcomes.

Screening for Wilson’s disease in acute liver failure: A new scoring system in children

“…In addition, some patients with ALF-WD are absence of KF ring. A meta-analysis of 256 children with ALF-WD showed that K-F rings were present in about 74% of these children ( 20 ). In addition, some patients are unable to undergo slit lamp examinations because of their critical condition.…”

“…In general, the level of ceruloplasmin in most children with WD is less than 20 mg/dL ( 22 , 23 ). In children with ALF-WD, a meta-analysis that included 256 cases showed that the average level of serum ceruloplasmin was 11 mg/dL ( 20 ). However, in both WD and other causes of ALF, ceruloplasmin greatly fluctuates, and it can be normal or elevated.…”

“…Increased urinary copper excretion is an important feature of WD, and some studies have shown a significant increase in 24-h urinary copper levels in children with ALF-WD ( 12 , 20 , 25 ). However, it is worth noting that 24-h urinary copper also increases significantly in other related liver diseases that are characterized by a large number of hepatocyte necrosis, so there may be a large overlap between ALF-WD and ALF with other etiology.…”

Hepatic ultrastructural features distinguish paediatric Wilson disease from NAFLD and autoimmune hepatitis

“…7,8 The Korman score for acute liver failure may not apply reliably to the paediatric age-bracket. 9 Thus, information gained from liver biopsy can be critically important. Histopathological changes in WD are diverse and nonspecific.…”

“…Modifications for paediatric WD have been suggested 7,8 . The Korman score for acute liver failure may not apply reliably to the paediatric age‐bracket 9 . Thus, information gained from liver biopsy can be critically important.…”