Non-invasive biomarkers of liver fibrosis in haemophilia patients with hepatitis C: Can you avoid liver biopsy?

Introduction: 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). Aim: To estimate liver fibrosis in haemophilia patients infected with hepatitis C (HCV) using noninvasive biomarkers without liver biopsy. Methods: 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, ageplatelet index and hyaluronic acid. The obtained scores were correlated with the clinical features of the patients. Results: Estimated by the FT, the distribution of the stage of fibrosis in the 132 patients was F0F1 1/4 65% (86/132), F2 1/4 5% (7/ 132), F3 1/4 13% (17/132) and F4 1/4 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 1/4 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). Conclusions: 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.