Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy

Gastroenterology. 2014 Feb;146(2):442-52.e1. doi: 10.1053/j.gastro.2013.10.012. Epub 2013 Oct 12.


Background & aims: Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV.

Methods: Patients with HCV infection and thrombocytopenia (platelet count <75,000/μL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients whose platelet counts reached the predefined minimal threshold for the initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were assigned randomly (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary end point was sustained virologic response (SVR) 24 weeks after completion of antiviral therapy.

Results: More patients who received eltrombopag than placebo achieved SVRs (ENABLE-1: eltrombopag, 23%; placebo, 14%; P = .0064; ENABLE-2: eltrombopag, 19%; placebo, 13%; P = .0202). PEG was administered at higher doses, with fewer dose reductions, in the eltrombopag groups of each study compared with the placebo groups. More patients who received eltrombopag than placebo maintained platelet counts of 50,000/μL or higher throughout antiviral treatment (ENABLE-1, 69% vs 15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%) and thromboembolic events, which were more common in the eltrombopag group of ENABLE-2.

Conclusions: Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise ineligible or marginal patients to begin and maintain antiviral therapy, leading to significantly increased rates of SVR. Clinical trial no: NCT00516321, NCT00529568.

Keywords: AE; Blood Clot; CI; Complication; ENABLE; ETR; EVR; Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease; HCC; HCV; Liver Disease; PEG; PVT; PY; Portal Hypertension; RBV; RVR; SAE; SVR; TCP; TEE; adverse event; confidence interval; early virologic response; end-of-treatment response; hepatitis C virus; hepatocellular carcinoma; patient-year; peginterferon alfa; portal vein thrombosis; rapid virologic response; ribavirin; serious adverse event; sustained virologic response; thrombocytopenia; thromboembolic event.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use*
  • Benzoates / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Hematologic Agents / therapeutic use*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Hydrazines / therapeutic use*
  • Induction Chemotherapy
  • Intention to Treat Analysis
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / virology
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Platelet Count
  • Polyethylene Glycols / therapeutic use
  • Pyrazoles / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Thrombocytopenia / blood
  • Thrombocytopenia / drug therapy*
  • Thrombocytopenia / virology
  • Treatment Outcome
  • Young Adult


  • Antiviral Agents
  • Benzoates
  • Hematologic Agents
  • Hydrazines
  • Interferon alpha-2
  • Interferon-alpha
  • Pyrazoles
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b
  • peginterferon alfa-2a
  • eltrombopag

Associated data

  • ClinicalTrials.gov/NCT00516321
  • ClinicalTrials.gov/NCT00529568