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Diagnosis of hepatitis C-related liver disease in patients with mild hemophilia

      Following the contamination of blood products with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in the 1970s to 1980s, almost all hemophilia patients who received plasma-derived factor products were infected with HCV prior to the implementation of viral inactivation in 1985. Of these patients, around 20% spontaneously cleared the virus [
      • Franchini M.
      • Tagliaferri A.
      • Rossetti G.
      • et al.
      The natural history of hepatitis C virus infection in hemophiliacs.
      ,
      • Makris M.
      • Konkle B.A.
      Hepatitis C in haemophilia: time for treatment for all.
      ]. The remainder developed chronic hepatitis and around 30% of them cirrhosis and finally hepatocellular carcinoma (HCC) in the absence of treatment [
      • Makris M.
      • Konkle B.A.
      Hepatitis C in haemophilia: time for treatment for all.
      ,
      • Posthouwer D.
      • Makris M.
      • Yee T.T.
      • et al.
      Progression to end-stage liver disease in patients with inherited bleeding disorders and hepatitis C: an international, multicenter cohort study.
      ]. In the nineties and until 2015, treatment with interferon +/- ribavirin, pegylated interferon (PEG-IFN) + ribavirin and PEG-IFN, ribavirin + first generation direct-acting antiviral drugs (DAA) was associated with a limited efficacy and numerous side effects. The absence of treatment as well as the reduced efficacy of these treatments was thus associated with occurrence of cirrhosis and HCC and represents a major cause of morbidity and mortality in hemophilia patients [
      • Makris M.
      • Konkle B.A.
      Hepatitis C in haemophilia: time for treatment for all.
      ]. After 2015, administration of second-generation DAA is associated with a huge efficacy: around 98% of patients are successfully treated, leading to eradication of the virus, and their side effects are very limited. Despite HCV eradication, the risk of HCC occurrence is still present if the patient is treated at the stage of advanced fibrosis [
      • Ioannou G.N.
      • Beste L.A.
      • Green P.K.
      • et al.
      Increased risk for hepatocellular carcinoma persists up to 10 years after HCV eradication in patients with baseline cirrhosis or high FIB-4 scores.
      ]. As follow-up periods for hemophilia patients with chronic hepatitis C are lengthening, the incidence of HCC in hemophilia patients appears to be increasing [
      • Fransen van de Putte D.E.
      • Makris M.
      • Fischer K.
      • et al.
      Long-term follow-up of hepatitis C infection in a large cohort of patients with inherited bleeding disorders.
      ,
      • Thalappillil A.
      • Ragni M.V.
      • Comer D.M.
      • Yabes J.G.
      Incidence and risk factors for hepatocellular cancer in individuals with haemophilia: a national inpatient sample study.
      ].

      Keywords

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