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CatD may be useful to differentiate pediatric liver inflammation, steatosis

Plasma cathepsin D levels could be used as noninvasive markers for distinguishing pediatric patients with steatosis from those with hepatic inflammation, according to newly published data in The American Journal of Gastroenterology.  

“We hypothesized that cathepsin D (CatD) levels in plasma may be altered in subjects with [nonalcoholic steatohepatitis] compared with subjects without NASH,” the researchers wrote. “Therefore, the aim of this study was to assess plasma levels of CatD in children with different stages of [nonalcoholic fatty liver disease] and to correlate these to histological criteria used for the diagnosis of NASH.”

Researchers analyzed liver biopsies of 96 obese children aged 3 to 12 years with NAFLD according to Kleiner and Brunt’s criteria. Blood was taken from each patient and levels of alanine aminotransferase and cytokeratin-18 (CK-18) were measured in plasma, according to the research. Of the patients, 56 were boys (mean age, 9.3 years) and 40 were girls (mean age, 8.4 years).

Twenty-six children were diagnosed with NASH, 51 were diagnosed with borderline NASH and 19 were diagnosed with steatosis.

Plasma CatD levels were lower in children with liver inflammation compared with children with steatosis. CatD levels were reduced and corresponded with increasing severity of liver inflammation, steatosis, hepatocellular ballooning and NAFLD activity score, as observed by the researchers.

CatD plasma levels correlated with pediatric NAFLD progression stronger than ALT and CK-18 levels. After using plotted receiver operating characteristics (ROC) curves to determine whether CatD could diagnose pediatric NASH, the CatD ROC curve had a greater area under the curve (AUC) of 0.94 compared with the AUC values of ALT and CK-18 (0.59 vs. 0.72). ALT and CK-18 levels had lower sensitivity and specificity, as well as inaccurate positive and negative predictive value percentages for predicting pediatric NASH.

“In short, compared with ALT and CK-18, CatD holds better diagnostic value to predict pediatric NASH and is accurate in making the differentiation between pediatric NASH subjects from those who have steatosis,” the researchers wrote. “Similar to steatosis vs. NASH subjects, CatD also improves the prediction of NASH compared with the combination of steatosis plus borderline NASH, and also compared with borderline NASH separately.”

The researchers concluded: “We have demonstrated for the first time that plasma CatD is significantly decreased in children with NASH compared with children with either steatosis or borderline NASH. Plasma CatD holds high diagnostic value and could be used as a promising noninvasive clinical marker to distinguish pediatric NASH patients from subjects with steatosis, especially upon the addition of CK-18.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.