The pathogenesis of thrombocytopenia in chronic hepatitis C (CHC) conceivably involves autoimmunity; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear. In this study, we examined the changes in the frequency of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells and the levels of plasma B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and interleukin (IL)-21 following treatment of CHC with direct-acting antiviral agents (DAA). We recruited 28 patients with CHC who underwent treatment with DAA for 8-12 weeks and subsequently tested negative for serum hepatitis C virus RNA. Thirty healthy controls were recruited for comparison. Platelet counts increased significantly (p = .016), and the frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly (p = .002) in CHC patients with thrombocytopenia at the end of treatment (EOT) than before DAA treatment (baseline). However, these changes were not observed in CHC patients without thrombocytopenia. Plasma BAFF levels in CHC patients with thrombocytopenia significantly decreased from baseline to EOT (p = .002). Anti-GPIIb/IIIa antibody-producing B cells were positively correlated with plasma BAFF levels in these patients (r = 0.669, p = .039). These results suggest that DAA treatment suppresses the autoimmune response against platelets and improves thrombocytopenia.
Keywords: Anti-GPIIb/IIIa antibody; B-cell-activating factor; direct-acting antiviral agents; hepatitis C; platelets; thrombocytopenia.
What is the context? Production of antiplatelet antibodies is one of the mechanisms underlying thrombocytopenia in patients with chronic hepatitis C.Antiplatelet antibodies against platelet membrane glycoprotein (GP) IIb/IIIa are commonly detected in hepatitis C virus-associated immune thrombocytopenia.Hepatitis C virus elimination by direct-acting antiviral agents (DAA) improves thrombocytopenia in patients with hepatitis C; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear.What is new? In this study, we determined whether DAA treatment can alter the autoimmune response against platelets and improve platelet count.The frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly from the baseline following DAA treatment in chronic hepatitis C patients with thrombocytopenia.DAA treatment reduced the levels of B-cell-activating factor, a cytokine associated with autoantibody production.What is the impact? The study provides evidence that DAA treatment diminishes the autoimmune response to GPIIb/IIIa and, therefore, improves platelet counts in chronic hepatitis C patients with thrombocytopenia.