Published online Dec 14, 2018. doi: 10.3748/wjg.v24.i46.5271
Peer-review started: September 12, 2018
First decision: October 14, 2018
Revised: October 20, 2018
Accepted: November 9, 2018
Article in press: November 9, 2018
Published online: December 14, 2018
Processing time: 92 Days and 15.6 Hours
Lusutrombopag is an oral, small-molecule thrombopoietin (TPO) receptor agonist (TPO-RA) used for the treatment of thrombocytopenic patients with chronic liver diseases. TPO in the peripheral blood in advanced-stage liver disease was been reduced severely. Therefore, patients with inadequate TPO production due to chronic liver disease are the principal targets of lusutrombopag.
The response to lusutrombopag is unpredictable, assuming that the drug exerts more dramatic effects in thrombocytopenia associated with severe liver disease prior to invasive surgery.
The study aimed to assess the correlation between the clinical characteristics of patients with chronic liver disease and the efficacy of lusutrombopag treatment.
This multicenter retrospective study was conducted at four locations in Japan. This study enrolled thrombocytopenic patients who received oral lusutrombopag. We evaluated the response to lusutrombopag compared to baseline clinical characteristics in patients with chronic liver disease.
Splenic volume and body weight were lower in the responder group than in the non-responder group. Using a logistic regression model to assess the relationship between response to lusutrombopag and clinical characteristics, multivariate analysis confirmed that splenic volume was an independent factor that predicted the response of platelet counts (P = 0.025, odds ratio: 11.2; 95%CI: 1.354-103.0). Splenic volume was negatively correlated to changes in platelet count (r = -0.524, P = 0.001).
Splenic volume influences change in platelet counts after administration of lusutrombopag in patients with chronic liver disease. Larger spleen size appears to reduce the effect of lusutrombopag in terms of platelet count. Splenic volume should be taken into consideration when administering lusutrombopag to ensure that patients receive the optimal treatment. This is the first report to assess the factors that affect the response to lusutrombopag in patients with chronic liver disease. There are multiple factors which can cause thrombocytopenia in patients with chronic liver disease. These factors include anti-platelet antibodies, levels or activity of thrombopoietin, and bone marrow suppression of thrombopoiesis due to myelodysplastic syndromes and/or direct myelosuppressive effects of HCV infection. In this study, the evaluation of influences of these factors was lacking. Therefore, further studies are warranted.
Splenic volume should be taken into consideration when administering lusutrombopag to ensure that patients receive optimal treatment. It is not clear whether or not the combination therapy improves the long-term prognosis of these patients. Therefore, future long-term observational studies are warranted. Further studies are desired to assess multiple factors include anti-platelet antibodies, levels or activity of thrombopoietin, and bone marrow suppression of thrombopoiesis due to myelodysplastic syndromes and/or direct myelosuppressive effects of HCV infection.