1. Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention.
- Author
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Walenbergh SM, Houben T, Rensen SS, Bieghs V, Hendrikx T, van Gorp PJ, Oligschlaeger Y, Jeurissen ML, Gijbels MJ, Buurman WA, Vreugdenhil AC, Greve JW, Plat J, Hofker MH, Kalhan S, Pihlajamäki J, Lindsey P, Koek GH, and Shiri-Sverdlov R
- Subjects
- Adult, Alanine Transaminase blood, Biomarkers blood, Biopsy, Cohort Studies, Female, Humans, Inflammation, Liver pathology, Liver surgery, Male, Middle Aged, Non-alcoholic Fatty Liver Disease pathology, Non-alcoholic Fatty Liver Disease surgery, Severity of Illness Index, Cathepsin D blood, Liver metabolism, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease diagnosis
- Abstract
Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis.
- Published
- 2016
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