Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Sofie M. A. Walenbergh, Tom Houben, Sander S. Rensen, Veerle Bieghs, Tim Hendrikx, Patrick J. van Gorp, Yvonne Oligschläger, Mike L. J. Jeurissen, Marion J. J. Gijbels, Wim A. Buurman, Anita C. E. Vreugdenhil, Jan Willem M. Greve, Jogchum Plat, Marten H. Hofker, Satish Kalhan, Jussi Pihlajamaki, Patrick Lindsey, Ger H. Koek, Ronit Shiri-Sverdlov*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Web of Science)

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.
Original languageEnglish
Article number38278
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 6 Dec 2016

Cite this