Liver Health in Patients with Hemophilia: Residual Risk Factors of Liver-Related Complications after HCV Clearance

Background and Aim: Hepatitis C virus (HCV) is highly prevalent in patients with hemophilia, but today almost all patients achieve a sustained virological response (SVR) to therapy. Unfortunately, other risk factors (e.g. metabolic and/or alcohol) can make chronic hepatitis continue even after SVR and, potentially, evolve to cirrhosis. We herein report data from a prospective hepatological screening program aimed at evaluating any relevant risk factor of liver-related complications after SVR in patients with hemophilia.

Methods: We enrolled 75 HCV-patients (median age: 54; range: 36-80): 68/7 hemophilia A/B, 63% suffering from a severe inherited bleeding disorder. At time of inclusion, 22 patients (29%) had achieved a SVR after successful interferon-based therapies, 48 (64%) after third generation antiviral agents, 5 (7%) had obtained a spontaneous virus clearance. All patients were screened for active etiologic factors of chronic hepatitis, biochemistry, liver stiffness measurement (LSM) and ultrasound-exploration (US) to rule in/out cirrhosis. Invasive diagnostic tests were adopted when appropriate. Data before SVR were available in 44 patients for pre/post-SVR analysis to explore their potential diagnostic accuracy to rule out an advanced chronic liver disease at time of the screening.

Results: Thirty-one patients (41%) presented at least one active risk factor of potential chronic liver damage, metabolic syndrome being the most prevalent (36%). Twenty-nine patients (39%) had also HIV/HBV infection although adequately treated at time of the screening. Steatosis was detected by US in 37 patients (48%). Based on clinical, biochemical and/or morphological criteria 21 patients (28%) had signs cirrhosis. Among them, 4 patients (5%) had esophageal varices needing treatment, 3 (4%) hepatocellular carcinoma (HCC). One HCC was detected in a non-cirrhotic liver but was associated with metabolic comorbidities, 2 were HCC out of transplantation criteria and were addressed to a multi-disciplinary down-staging approach (e.g. surgery, chemoembolization, chemotherapy). Finally 2 of HCC were transplanted. All the non-invasive tests for cirrhosis (e.g. LSM, APRI, Fib4, Forns score) were sensibly reduced after virus clearance (p<0.05). On the contrary typical US-signs of cirrhosis did not significantly change after SVR. Eleven patients had LSM between 6-9 KPa. Interestingly, 3 of them had irregular liver surface, 1 caudate hypertrophic liver lobe, 6 splenomegaly, suggesting that non-invasive tests may not accurately rule out an advanced chronic liver disease after HCV clearance even for low levels of LSM.

Conclusions: A residual risk of chronic liver damage after HCV-clearance is frequently observed. Non-invasive tests of fibrosis dramatically change after SVR and could be inaccurate to rule out cirrhosis. A specific diagnostic work-up is mandatory to preserve liver-health in this clinical setting.

La Mura:Gore: Speakers Bureau; Alfasigma: Speakers Bureau; Sanofi: Other: Travel grant; Biomarin: Other: Travel grant; Takeda: Other: Travel Grant; CSL Behring: Speakers Bureau. Ciavarella:Bayer: Consultancy, Other: Bayer Hemophilia Awards Fellowship. Gualtierotti:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfiser: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Peyvandi:Roche: Honoraria; Takeda: Honoraria; BioMarin: Honoraria; Grifols: Honoraria; Sobi: Honoraria; Sanofi: Honoraria.