Stable Liver Function during Long-Term Administration of Eltrombopag, a Thrombopoietin Receptor Agonist, in Patients with Chronic Liver Disease

Abstract

Liver cirrhosis is the end stage of chronic liver disease, but no definitive pharmacological treatment is currently available. It has been reported that thrombopoietin (TPO) promotes liver regeneration and improves liver cirrhosis by increasing platelet count. We have shown the direct effect of platelet transfusion on the improvement of liver function in patients with chronic liver disease. However, platelet transfusion often causes adverse events, such as platelet transfusion refractoriness and pruritus. Therefore, we conducted an exploratory clinical trial and administered eltrombopag, an orally bioavailable, small-molecule, non-peptide TPO receptor agonist that has been approved for the treatment of chronic idiopathic thrombocytopenic purpura. The study included five male patients, aged from 49 to 75 years (57.6 ± 10.4 years), with both chronic liver disease and hepatitis C virus infection, who presented with thrombocytopenia but without cancer. Eltrombopag, ranged from 6.25 to 50 mg/day (18.75 ± 18.22 mg/day), was administrated to the five patients during six months. All of the patients maintained platelet counts between 10 and 15 × 10 10 /L during the study. The indicators of liver function in patients were stable throughout the clinical trial, although we had predicted the same degree of the improvement of liver function, compared to platelet transfusion. Importantly, the liver volumes were also stable, and no cancerous lesions were observed. These results indicate the safety of long-term eltrombopag administration for patients with chronic liver disease and hepatitis C virus infection.

<p>Preoperative aspartate aminotransferase-to-platelet-ratio index as a predictor of posthepatectomy liver failure for resectable hepatocellular carcinoma</p>

“…The AST component of the APRI could be increased because of liver stress or damage caused by liver cirrhosis:20 clearance of AST may have been impaired or HBV replication reactivated,30 with release of AST from injured mitochondria 32. The platelet-count component of the APRI could be decreased because of sequestration and destruction of platelets in the enlarging spleen (portal hypertension)33,34 or progressive liver fibrosis, which could reduce hepatocyte production of thrombopoietin and consequent decreased platelet production 35. Low preoperative platelet counts have been associated with an increased risk of PHLF and mortality after hepatectomy 36…”

A Nomogram Based on Preoperative Inflammatory Indices and ICG-R15 for Prediction of Liver Failure After Hepatectomy in HCC Patients

“…The platelet count could be decreased because of sequestration and destruction of platelets in the enlarging spleen (portal hypertension) (39). And, Thrombopoietin (TPO) synthesis in the liver is reduced because of liver cirrhosis which could stimulate platelet formation (40). These may explain why APRI, not other inflammatory indices could be used to predict PHLF.…”

<p>Clinical Implications of Thrombocytopenia for the Cirrhotic Patient</p>

“…113 Although administration of the thrombopoietin receptor agonist eltrombopag for six months did not result in the improvement of liver function or increase in liver volume in a study of 5 patients with mild to moderate cirrhosis (Child-Pugh scores 8 or less) and thrombocytopenia, administration of 10 units of platelet concentrate once a week for 12 weeks in a series of 10 patients with cirrhosis and thrombocytopenia was associated with significant improvement of serum albumin. 105,114 Platelets play an important role clinically in liver regeneration following living-donor liver transplantation. Among 87 patients undergoing right liver graft, adult-to-adult living-donor liver transplantation, the total amount of platelets transfused is associated with graft regeneration.…”