Residual burden of liver disease after HCV clearance in hemophilia: a word of caution in the era of gene therapy.

Ruling out advanced fibrosis/cirrhosis is mandatory for persons with hemophilia (PWH) who are candidate to gene therapy. However, clinical evaluation and non-invasive tests may be inaccurate after HCV clearance. We conducted a prospective hepatological screening to detect advanced fibrosis/cirrhosis in PWH after HCV clearance. Any risk factor of chronic liver damage was registered by using biochemical data, liver stiffness measurement (LSM) and ultrasound (US). A pre/post HCV clearance analysis was prospectively conducted in a subgroup of patients with the measurement of LSM, US and non-invasive tests of fibrosis (NITs). We evaluated 119 patients (median age: 53 years; range: 36-87) with a previous HCV infection (108/11 hemophilia A/B). Ninety-six (81%) presented at least one potential risk factor of chronic liver damage. Metabolic risk factors were the most prevalent, 51 cases (44%) having US steatosis. In 21 cases (18%) clinical, biochemical, liver morphology and/or LSM were suggestive of advanced fibrosis/cirrhosis. Furthermore, 10 cases (8%) had esophageal varices, 3(3%) hepatocellular carcinoma. In 57 cases included in the prospective analysis, LSM and NITs were reduced after HCV-clearance (p<0.05), but US signs specific of cirrhosis remained unchanged. Overall, 23/80(29%) cases with LSM<10KPa had at least one US sign suggestive of advanced fibrosis/cirrhosis. A similar proportion (18%) was observed for LSM<8KPa. Overall, risk factors of chronic liver damage are frequent after HCV clearance, but LSM and NITs changes after clearance may be inaccurate to rule out advanced fibrosis/cirrhosis. A specific diagnostic work-up is warranted to evaluate liver health in PWH in the era of gene therapy.