title: Serum plant sterols, cholestanol, and cholesterol precursors associate with histological liver injury in pediatric onset intestinal failure.
abstract: BACKGROUND
  Increased serum concentrations of plant sterols, including stigmasterol, during parenteral nutrition (PN) have been linked with serum biochemical signs of intestinal failure-associated liver disease (IFALD), whereas clinical data on their correlation to histologic liver injury have been limited.
  
  
  OBJECTIVE
  We studied interrelations between serum noncholesterol sterols and histologic liver injury in pediatric-onset intestinal failure (IF).
  
  
  METHODS
  Serum plant sterols (stigmasterol, avenasterol, sitosterol, and campesterol), cholestanol, and cholesterol precursors (cholestenol, lathosterol, and desmosterol) were measured in 50 IF patients at a median age 7.3 y and in 86 matched controls. Forty patients underwent liver biopsies. Sixteen patients had been receiving PN for 45 mo, and 34 patients had received PN for 9.1 mo but had not received PN for 5.4 y.
  
  
  RESULTS
  Serum plant sterols were higher in patients who were currently receiving PN than in controls and were related to conjugated bilirubin (r = 0.799-0.541, P < 0.05). During PN, the ratio of serum stigmasterol to cholesterol was 3.3-fold higher in patients with portal inflammation, and the ratio of avenasterol to cholesterol was 3.9-fold higher in patients with cholestasis (P < 0.05 for both). Ratios of stigmasterol and avenasterol to cholesterol were correlated with portal inflammation (r = 0.549-0.510, P < 0.05), cholestasis (r = 0.501-0.491, P = 0.048-0.053), and serum bile acids (r = 0.591-0.608, P < 0.05). The median (IQR) ratio of serum cholestanol to cholesterol was higher during (269 100× μg/mg cholesterol; 203-402 100× μg/mg cholesterol) than after (175 100× μg/mg cholesterol; 156-206 100× μg/mg cholesterol; P < 0.001) weaning off PN and was correlated with cholestasis (r = 0.428), portal inflammation (r = 0.511), and fibrosis (r = 0.323, P < 0.05 for all). After weaning off PN, ratios of cholestenol and lathosterol to cholesterol were >2-fold higher in patients with persistent liver steatosis than in those without steatosis or controls (P < 0.01 for all), whereas lathosterol was correlated with the steatosis grade (r = 0.320, P < 0.050).
  
  
  CONCLUSIONS
  Increased serum stigmasterol and avenasterol concentrations parallel the portal inflammation and cholestasis during PN, thereby reinforcing their contribution to IFALD. A bile acid malabsorption-driven increase in cholesterol synthesis underpins persistent liver steatosis after weaning off PN. Serum cholestanol reflects liver injury in IF patients.
authors.affiliation: From the Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital (AM and MPP), and the Department of Pathology, HUSLAB (JL and PH), Helsinki University Central Hospital, and the Department of Medicine, Division of Gastroenterology and Internal Medicine (MJN and HG), University of Helsinki, Helsinki, Finland.
authors.forename: Annika
authors.initials: A
authors.lastname: Mutanen
authors.affiliation: From the Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital (AM and MPP), and the Department of Pathology, HUSLAB (JL and PH), Helsinki University Central Hospital, and the Department of Medicine, Division of Gastroenterology and Internal Medicine (MJN and HG), University of Helsinki, Helsinki, Finland.
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Nissinen
authors.affiliation: From the Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital (AM and MPP), and the Department of Pathology, HUSLAB (JL and PH), Helsinki University Central Hospital, and the Department of Medicine, Division of Gastroenterology and Internal Medicine (MJN and HG), University of Helsinki, Helsinki, Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Lohi
authors.affiliation: From the Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital (AM and MPP), and the Department of Pathology, HUSLAB (JL and PH), Helsinki University Central Hospital, and the Department of Medicine, Division of Gastroenterology and Internal Medicine (MJN and HG), University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Heikkilä
authors.affiliation: From the Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital (AM and MPP), and the Department of Pathology, HUSLAB (JL and PH), Helsinki University Central Hospital, and the Department of Medicine, Division of Gastroenterology and Internal Medicine (MJN and HG), University of Helsinki, Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
authors.affiliation: From the Section of Pediatric Surgery, Pediatric Liver and Gut Research Group Helsinki, Children's Hospital (AM and MPP), and the Department of Pathology, HUSLAB (JL and PH), Helsinki University Central Hospital, and the Department of Medicine, Division of Gastroenterology and Internal Medicine (MJN and HG), University of Helsinki, Helsinki, Finland.
authors.forename: Mikko P
authors.initials: MP
authors.lastname: Pakarinen
mesh_terms: D000293:Adolescent; D001647:Bile Acids and Salts / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004083:Cholestanol / Q000097:blood*; D002784:Cholesterol / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007410:Intestinal Diseases / Q000097:blood* / Q000150:complications / Q000473:pathology; D007422:Intestines / Q000473:pathology; D008107:Liver Diseases / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D010288:Parenteral Nutrition / Q000009:adverse effects; D010840:Phytosterols / Q000097:blood*; D011446:Prospective Studies; D013265:Stigmasterol / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D010840:Phytosterols; D004083:Cholestanol; D002784:Cholesterol; D013265:Stigmasterol