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Lusutrombopag found safe, effective for severe thrombocytopenia in patients with hepatocellular carcinoma

Key clinical point: For patients with severe thrombocytopenia and chronic liver disease, including hepatocellular carcinoma, the thrombopoietin receptor agonist lusutrombopag significantly reduced the need for platelet transfusions prior to invasive procedures, without increasing the need for rescue treatments for bleeding or the rate of thromboembolic events.

Major finding: A significantly higher proportion of lusutrombopag recipients met the primary efficacy endpoint, including patients with HCC (68.0% vs. 8.9%; P < .0001) and without HCC (77.0% vs. 21/6%; P < .0001).

Study details: An integrated post hoc analysis of data from 270 patients with chronic liver disease and severe thrombocytopenia in two randomized, double-blind, placebo-controlled, phase 3 trials.

Disclosures: Shionogi makes lusutrombopag and sponsored the study. Dr. Alkhouri reported an advisory relationship with Shionogi and Dova Pharma. Two coinvestigators reported being employed by Shionogi. Three coinvestigators also disclosed ties to Shionogi and to several other pharmaceutical companies.


Alkhouri N et al. Clin Gastroenterol Hepatol. 2020 Mar 20. doi: 10.1016/j.cgh.2020.03.032.


Thrombocytopenia is of clinical concern in patients with cirrhosis, as it complicates routine patient care and results in delayed or canceled procedures due to concern for risk of bleeding. In the last few years, availability of thrombopoietin (TPO) receptor agonists have facilitated the performance of elective invasive procedures in cirrhotic patients with severe thrombocytopenia.

These agents have reduced the risk of procedure related bleeding and need for platelet transfusions. However, thrombotic events remain a key safety concern with the use of TPO receptor agonist, particularly in patients with hepatocellular carcinoma, who are at increased risk for spontaneous thrombosis.

In this integrated analysis of data from two phase 3 studies, Alkhouri et al. demonstrated the efficacy of a novel TPO receptor agonist, lusutrombopag, in reducing bleeding events and need for platelet transfusion in cirrhotic patients undergoing invasive procedures. The risk for thrombosis-related adverse events was not increased in lusutrombopag recipients with or without HCC. Previous studies with another TPO, eltrombopag, resulted in high rate of symptomatic portal vein thrombosis. Avatrombopag, a recently approved TPO receptor agonist reported few thrombotic symptomatic events but no prospective imaging for evaluation of thrombotic events was included in the protocol. A unique strength of this study was inclusion of prospective imaging for evaluation of portal vein thrombosis. Strategic scheduling is required with use of TPO agonists. Lusutrombopag can be given orally in convenient daily doses and provides a 7-10-day procedural window for scheduling and performing elective invasive procedures. However, because of several days of lag period for platelet production, these agents cannot be used for emergent cases.

Gagan K. Sood, MD, AGAF, FAASLD, is an associate professor of medicine and surgery, division of gastroenterology and hepatology and division of abdominal transplantation, Baylor College of Medicine, Houston. He has no conflicts of interest.