title: Non-invasive biomarkers of liver fibrosis in haemophilia patients with hepatitis C: can you avoid liver biopsy?
abstract: Liver biopsy remains the gold standard for the evaluation of fibrosis despite its risks and limitations, especially in haemophilia patients. Recently, non-invasive biomarkers have been used to assess histological features. The most thoroughly evaluated biomarker is the FibroTest (FT) (AUROC 0.80 for fibrosis stages F2F3F4 vs. F0F1). To estimate liver fibrosis in haemophilia patients infected with hepatitis C (HCV) using non-invasive biomarkers without liver biopsy. One hundred and thirty-two haemophilia patients (124 male, mean age 38 +/- 14 years) with anti-HCV antibodies were evaluated. These patients were stratified into several groups: patients with features of advanced liver disease - seven, persistently HCV RNA-negative - 21, persistently normal liver function tests (LFTs)- 24, HCV/HIV co-infected - 27. The following biomarkers of fibrosis were used: FT, AST-to-platelet ratio index (APRI), Forns index, age-platelet index and hyaluronic acid. The obtained scores were correlated with the clinical features of the patients. Estimated by the FT, the distribution of the stage of fibrosis in the 132 patients was F0F1 = 65% (86/132), F2 = 5% (7/132), F3 = 13% (17/132) and F4 = 17% (22/132). Using FT, all patients with clinical suspicion of advanced liver disease were classified as F3F4, whereas patients with persistently HCV RNA-negative were all classified as F0F1. Twenty-one per cent (5/24) of the patients with persistently normal LFTs had fibrosis stage F3F4. The proportion of F3F4 among HCV/HIV co-infected patients was significantly higher than among HCV mono-infected (52% vs. 33%; P = 0.05). Concordance of three or more biomarkers was present in 43% (57/132) of the patients. Liver biopsy could be avoided in 70% (92/132) using a practical assumption that if FT is in concordance with APRI and/or Forns, then we may confidently rely on the biomarker. Concordance rate for patients with presumably advanced or minimal liver disease was excellent (100% and 95% respectively). In our HCV-infected haemophilia patients, FT correctly identified clinically advanced or minimal liver disease. Discordance among the various biomarkers of fibrosis was considerate; nevertheless, practical combination of FT, APRI, and Forns may predict stage of fibrosis with accuracy, potentially avoiding liver biopsy in the majority of the patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Sheba Medical Center, Tel-Hashomer, Israel. yaakov@sheba.health.gov.il
authors.forename: Y
authors.initials: Y
authors.lastname: Maor
authors.forename: D
authors.initials: D
authors.lastname: Bashari
authors.forename: G
authors.initials: G
authors.lastname: Kenet
authors.forename: A
authors.initials: A
authors.lastname: Lubetsky
authors.forename: J
authors.initials: J
authors.lastname: Luboshitz
authors.forename: J M
authors.initials: JM
authors.lastname: Schapiro
authors.forename: G
authors.initials: G
authors.lastname: Pénaranda
authors.forename: S
authors.initials: S
authors.lastname: Bar-Meir
authors.forename: U
authors.initials: U
authors.lastname: Martinowitz
authors.forename: P
authors.initials: P
authors.lastname: Halfon
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D025861:Blood Coagulation Disorders, Inherited / Q000150:complications; D000075202:Contraindications; D005260:Female; D006467:Hemophilia A / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers