THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION

Abstract

Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem, and impedes the initiation and continuation of antiviral therapy. The pathophysiology is multifactorial, with auto-immunogenecity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoeitin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. With dose reduction of INF-based treatment recommended for platelet count below 50,000 and complete withdrawal for count below 25,000, the main challenge with thrombocytopenia in chronic HCV infection is in initiating or maintaining anti-viral therapy, particularly in resource-poor setting where INF-based therapy continues to be a major therapeutic approach. The increased risk of bleeding may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity and allow successful initiation and completion of IFN-based anti-HCV treatment without any dose reduction or discontinuation. Other treatment modalities including newer TPO analogues- AMG-51, PEG-TPOmp and AKR-501, recombinant human IL-11 (rhIL-11, Oprelvekin), recombinant human.