title: Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention.
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.
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Sofie M A
authors.initials: SM
authors.lastname: Walenbergh
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Houben
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Sander S
authors.initials: SS
authors.lastname: Rensen
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Veerle
authors.initials: V
authors.lastname: Bieghs
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Tim
authors.initials: T
authors.lastname: Hendrikx
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: van Gorp
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Oligschlaeger
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Mike L J
authors.initials: ML
authors.lastname: Jeurissen
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Anita C E
authors.initials: AC
authors.lastname: Vreugdenhil
authors.affiliation: Surgery, Atrium Medical Center Parkstad, 6419PC, Heerlen, The Netherlands.
authors.forename: Jan Willem M
authors.initials: JW
authors.lastname: Greve
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Jogchum
authors.initials: J
authors.lastname: Plat
authors.affiliation: Pathology and Medical Biology, Molecular Genetics, Medical Biology Section, University Medical Center Groningen, 9713GZ, Groningen, The Netherlands.
authors.forename: Marten H
authors.initials: MH
authors.lastname: Hofker
authors.affiliation: Pathobiology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Kalhan
authors.affiliation: Clinical Nutrition, University of Eastern Finland, FI-70211 Kuopio, Finland.|Clinical Nutrition and Obesity Center, Kuopio University Hospital, FI-70211 Kuopio, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lindsey
authors.affiliation: Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Ger H
authors.initials: GH
authors.lastname: Koek
authors.affiliation: Molecular Genetics, General Surgery, Paediatrics, Pathology, Population Genetics, Human Biology, Maastricht University Medical Centre, 6200MD, Maastricht, The Netherlands.
authors.forename: Ronit
authors.initials: R
authors.lastname: Shiri-Sverdlov
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002402:Cathepsin D / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D000410:Alanine Transaminase; D002402:Cathepsin D