Make platelet count great again: Direct‐acting antiviral agent therapy in patients with chronic hepatitis C

Abstract

Hepatitis C virus (HCV) infection is an endemic disease in Taiwan, which causes adverse liver events, including development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Among the chronic hepatitis C (CHC) patients, sustained virological response (SVR) after antiviral therapy has been shown to be associated with prolonged overall survival and the reduced risks of HCC and liver-related mortality.1 The combination of pegylated interferon (Peg-IFN) plus ribavirin therapy was the standard of care before 2011. However, its use was limited by various disadvantages, including decrease in platelet count during therapy. With the introduction of novel direct-acting antiviral agents (DAAs) targeting the replication process of HCV, this IFN-free therapy has become the standard of care and has higher response rates and fewer side effects. Thrombocytopenia is a common complication of chronic liver diseases, but the pathophysiology of thrombocytopenia in CHC patients is not yet completely understood yet. Regardless of the underlying mechanisms, it has been reported that peripheral platelet count reflects the degree of fibrosis in CHC patients.2 In this study, Hsu et al first investigated the temporal relationship between platelet count and alanine aminotransferase (ALT) level in CHC patients who received DAA therapy. In this retrospective study, the SVR rate at 12 weeks after therapy (SVR12) was 98.7% (77/78). In patients without cirrhosis (n = 70), a 7.5% increase of mean platelet count was noted within 2 weeks after the initiation of DAA therapy. The increased platelet count remained stable throughout the treatment and follow-up periods. In contrast, no obvious changes in platelet count were noted among patients with cirrhosis (n = 8). The underlying mechanism to induce thrombocytopenia in CHC patients is complex. It has been considered that splenic congestion as a consequence of portal hypertension is the major etiology.3 Other possible mechanisms included autoimmune reaction with the production of antiplatelet antibodies, direct bone marrow suppression by HCV, decreased production of thrombopoietin, and endothelial dysfunction.4 This study demonstrated that platelet count increased within 2 weeks after DAA therapy, which has not been observed during Peg-IFN-based therapy as Peg-IFN itself causes thrombocytopenia. Such a rapid recovery could be attributed to the suppression of HCV replication instead of fibrosis regression, which usually takes years to develop. However, we still need more studies to address how suppressed viral replication induces recovery of platelet count. The most challenging issue in the DAA era is how to predict HCC development after SVR12 is achieved. Previous studies have shown that host and liver factors, such as platelet count, are important HCC predictors. Based on this study, the pretreatment platelet count can be affected by viral replication, while the posttreatment platelet count is more stable and can be more representative of the liver fibrosis severity. This also echoes the finding that posttreatment biomarkers, compared to pretreatment biomarkers, serve as better predictors for long-term HCC development in CHC patients treated with curative antivirals.5, 6 Considering all lines of data together, we believe that biomarkers measured after treatment are more appropriate in predicting long-term outcomes than those measured before treatment. There are also some limitations of this study. First, the patient number was small, and there were only eight patients with cirrhosis. The insignificant change of platelet count in cirrhotic patients could be attributed to the small patient number. Second, the study only collected information from baseline to 12 weeks after treatment. It is still unclear whether there is a consistent improvement of platelet count after a long-term follow up, which is more likely to be attributed to liver fibrosis regression. A large-scale study with a long-term follow up is needed to address this issue. In summary, DAA therapy is associated with increased platelet count shortly after suppressing HCV replication in CHC patients without cirrhosis. Further research is needed to assess the long-term effects of DAAs therapy on platelet count and the biological basis for these findings. The authors declare no conflict of interest.