Lipid and copper metabolism in humans with wilson disease: Enigmatic relationship

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the article by Hamilton et al. published in hepatology, an experimental study highlighting the role of nuclear receptors in a mouse model of Wilson disease (WD).1 Their previous study demonstrated that lipid metabolism was inhibited in response to hepatic copper accumulation in the WD mouse model,2 and this expanded study showed that up‐regulation of the nuclear receptor by liver X receptor agonist administration can increase serum lipid values to normal despite significant hepatic copper overload. These findings seem very convincing and throw light on WD pathogenesis. The only human study describing attenuation in lipid metabolism in WD suggests low cholesterol levels, but the study does not provide correlation of lipids with hepatic copper.3 We had opportunity to retrospectively study serum lipid profiles, liver function tests, and hepatic copper in our WD children (n = 26) seen at King's College Hospital from 2005 to 2015. WD diagnosis was established with ATP7B mutations in all. Serum total cholesterol (TC) and triglyceride (TG) data before starting treatment were collected. Hepatic copper was measured in four explant livers of WD/acute liver failure children and 22 core liver biopsy tissues from WD/non–acute liver failure children. The median age at diagnosis was 10.86 (1.64‐17.26) years, and 62% were female. The median hepatic copper was high (513 [7‐4225] μg/g dry weight liver). Interestingly, the median TC and TG in our study were normal, with values of 4.45 (1.7‐6.3) and 1.3 (0.5‐3.2) mmol/L. Indeed, the median body mass index that might affect the lipid profile level was also normal (19.8 [13.7‐40.7] kg/m2). We further assessed the correlation between serum lipid profiles with hepatic copper and liver function tests. There was no correlation between lipid profiles (TC and TG) and hepatic copper (Fig. 1). TG has no correlation with other parameters, while TC significantly correlates with total bilirubin (r = –0.621, P = 0.001) and alanine aminotransferase (r = 0.422, P = 0.028).Figure 1: The correlation between lipid profiles and hepatic copper content.Our data suggest that low cholesterol in hepatic WD patients might relate to severity of liver disease. Our data on correlation of hepatic copper with cholesterol in children with liver disease are not in keeping with the observation in the animal model. However, we were not able to perform nuclear receptor studies in our patient population, but our finding may be of relevance before applying the data from animal studies to humans.