Is the periodic repetition of a coagulation check necessary during anti‐hepatitis C virus therapy?

Peginterferon α and ribavirin have become the mainstay of treatment for chronic hepatitis C virus (HCV) infection.¹ However, chronic use of interferon (IFN)‐α has been associated with the development of autoimmune disorders, such as systemic lupus erythematosus, autoimmune haemolytic anaemia, and autoimmune thyroiditis. In particular, some reports have documented the development of acquired factor VIII inhibitors in patients receiving IFN‐α, including those treated for chronic HCV infection.²,³,⁴,⁵,⁶

We report the case of a 49 year old male patient treated for chronic active HCV related cirrhosis. He received a six month course of peginterferon α2a at a dose of 180 μg weekly and ribavirin at a dose of 800 mg daily for three months only, due to a marked decrease in haemoglobin level, obtaining a complete viral response. Before therapy, activated partial thromboplastin time (aPTT) and prothrombin time‐international normalised ratio (PT‐INR) values were in the normal range (aPTT ratio 1.28 and INR 1.11). Due to abnormal bleeding during a routine dental treatment performed at the end of antiviral treatment in September 2005, the patient underwent a coagulation screening which revealed a prolonged aPTT (2.14; normal range 0.85–1.17). Coagulant factor VIII level was reduced (FVIII:C 17%; normal range 50–150%) and a mixing study demonstrated the presence of a low titre inhibitor (1.6 Bethesda units/ml). Response to subcutaneous injection of desmopressin at a dose of 0.3 mg/kg was satisfactory as FVIII:C increased to 70% and aPTT normalised four hours after injection. Recent tests performed three months after the end of antiviral treatment (November 2005) were unchanged.

If our case report provides further evidence in favour of the association between chronic exposure to peginterferon and the development of acquired factor VIII inhibitors, it raises several important questions too. Firstly, what is the real incidence of this phenomenon in patients treated for HCV infection? Are these inhibitors so rare as initially believed or are they misdiagnosed? Are they clinically relevant, what is the natural history of the coagulative alteration (that is, do they require treatment or do they tend to disappear spontaneously), and which is the best treatment? In our opinion, a response to these concerns may be obtained only through a careful coagulation study (especially aPTT ratio) of these patients during and after IFN treatment.