title: Non-invasive fibrosis score for hepatitis delta.
abstract: Identifying advanced fibrosis in chronic hepatitis delta patients and thus in need of urgent treatment is crucial. To avoid liver biopsy, non-invasive fibrosis scores may be helpful but have not been evaluated for chronic hepatitis delta yet.
  
  
  
  We evaluated eight non-invasive fibrosis scores in 100 HDV RNA-positive patients with available central histological reading. New cut-off values were calculated by using Receiver Operating Characteristics and Youden indexes. Predictors for the presence of ISHAK F3-6 were revealed by t-tests or Mann-Whitney tests.
  
  
  
  None of the tested scores had an area under the curve (AUROC) > 0.8 and performed according to our predefined requirements of a sensitivity of >80% and a positive predictive value (PPV) >90% - even after adaption. However, the ELF score was able to identify advanced fibrosis with a high sensitivity (93%) and PPV (81%), but relies on expensive extracellular matrix markers with bad availability in many endemic regions of HDV. Thus, we developed a novel non-invasive approach and identified low cholinesterase (P=.002), low albumin (P=.041), higher gamma glutamyl transferase, as well as older age (P<.001) as predictors of fibrosis resulting in the Delta Fibrosis Score (DFS). The DFS performed with a sensitivity of 85% and PPV of 93% with an AUROC of 0.87.
  
  
  
  Existing non-invasive fibrosis scores are either impracticable or do not perform well in chronic hepatitis delta patients. However, the new Delta Fibrosis Score is the first non-invasive fibrosis score specifically developed for chronic hepatitis delta and requires only standard parameters.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Gunnar L
authors.initials: GL
authors.lastname: Lutterkort
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Wranke
authors.affiliation: Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
authors.affiliation: Institute for Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Budde
authors.affiliation: Institute for Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Westphal
authors.affiliation: Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Stift
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Bremer
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, HepNet Study-House, Hannover, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Hardtke
authors.affiliation: Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Keskin
authors.affiliation: Department of Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Idilman
authors.affiliation: Institute for Biostatistics, Hannover Medical School, Hannover, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Koch
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, HepNet Study-House, Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Hans P
authors.initials: HP
authors.lastname: Dienes
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, HepNet Study-House, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.|German Center for Infectious Disease Research (DZIF), Partner Site Hannover-Braunschweig, HepNet Study-House, Hannover, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Heidrich
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D005260:Female; D005858:Germany; D019701:Hepatitis D, Chronic / Q000150:complications* / Q000473:pathology; D003698:Hepatitis Delta Virus; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011237:Predictive Value of Tests; D012372:ROC Curve; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D005723:gamma-Glutamyltransferase
keywords: Hepatitis Delta; hepatitis D virus; liver biopsy; non-invasive fibrosis/cirrhosis score