Use of thrombopoietic agents for the thrombocytopenia of liver disease
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Hans L Tillmann1, John G McHutchison
1Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715-7969, USA. hans.tillmann@duke.edu
Thrombocytopenia can be a sign of advanced liver disease. This complicates the management of these patients, as patients with advanced liver disease frequently need therapeutic interventions, which are associated with an increased risk of bleeding. Thrombocytopenia may even be more pronounced in patients with hepatitis C virus (HCV) infection. This can limit current and future treatments for HCV, which remains based on interferon therapy, and this therapy can worsen thrombocytopenia. Thus, the ability to increase platelets to higher and safer levels would be desirable, but no treatment has yet been proven effective and safe in this setting. The small molecule thrombopoietin mimetic, eltrombopag, has demonstrated a dose-response increase in platelet counts in a phase II study in HCV patients without significant side effects, allowing initiation and completion of a 12-week course of pegylated interferon plus ribavirin in 36%, 53%, and 65% of patients receiving 30 mg, 50 mg, or 75 mg eltrombopag daily, respectively, compared to only 6% in the placebo arm. A current phase III study is currently evaluating whether this treatment allows successful outcomes and sustained viral eradication.
Thrombocytopenia can be a sign of advanced liver disease. This complicates the management of these patients, as patients with advanced liver disease frequently need therapeutic interventions, which are associated with an increased risk of bleeding. Thrombocytopenia may even be more pronounced in patients with hepatitis C virus (HCV) infection. This can limit current and future treatments for HCV, which remains based on interferon therapy, and this therapy can worsen thrombocytopenia. Thus, the ability to increase platelets to higher and safer levels would be desirable, but no treatment has yet been proven effective and safe in this setting. The small molecule thrombopoietin mimetic, eltrombopag, has demonstrated a dose-response increase in platelet counts in a phase II study in HCV patients without significant side effects, allowing initiation and completion of a 12-week course of pegylated interferon plus ribavirin in 36%, 53%, and 65% of patients receiving 30 mg, 50 mg, or 75 mg eltrombopag daily, respectively, compared to only 6% in the placebo arm. A current phase III study is currently evaluating whether this treatment allows successful outcomes and sustained viral eradication.
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