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World Transplant Congress 2014

Issue: November 2014

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This year marked the second joint meeting of the American Society of Transplant Surgeons, The Transplantation Society and the American Society of Transplantation, also known as the World Transplant Congress.

The conference brings together experts from around the world to exchange new scientific and clinical information relevant to solid organ and tissue transplantation, including liver transplantation. The 2014 meeting was held in July in San Francisco and drew more than 6,500 attendees.

HCV Next Editorial Board member Catherine T. Frenette, MD, medical director of liver transplantation at Scripps Center for Organ and Cell Transplantation, Scripps Green Hospital, La Jolla, Calif., attended the conference and shared important developments relevant to solid organ transplantation that are important for experts who care for patients with hepatitis C virus infection.

HCV and Solid Organ Transplantation

HCV is an important disease in all solid organ transplant patients. At the 2014 meeting, there were several breakout sessions that focused specifically on HCV in the setting of liver transplantation.

There has been a dramatic increase in the last 5 years of death on the liver transplant waitlist, with almost 3,000 patients dying while on the waitlist each year in the United States. As we treat more patients with HCV, we will decrease the death rates in this population. However, HCV still remains the most common indication for liver transplant, and in some areas of the country 50% of transplant patients are infected with HCV. Treatment of HCV in the post-transplant patient will continue to be an important topic for many years to come. K. Rajender Reddy, MD, Michael Charlton, MD, and Norah Terrault, MD, gave excellent summary talks on HCV treatment in the pre- and post-transplant settings.

Simeprevir, Sofosbuvir After Transplant

Two major abstracts on HCV were presented at the World Transplant Congress. First, the liver transplant team from California Pacific Medical Center presented a case series of post-liver transplant patients treated with simeprevir 150 mg daily (Olysio, Janssen Therapeutics) and sofosbuvir 400 mg daily (Sovaldi, Gilead). Ripper and colleagues included 15 patients who were between 8 and 861 weeks post-transplant (13 men, two women). Four of the patients were within 24 weeks of transplant. Nine patients had HCV genotype 1, four had genotype 1b, one had mixed genotype 1a/1b and one had unknown genotype.

Sixty-seven percent of patients had been previously treated, but none had received a protease inhibitor. Three patients had ribavirin added during their therapy. The primary immunosuppression was tacrolimus in 10 patients, sirolimus in three and cyclosporine in two.

All patients became HCV RNA negative by end of treatment. Of 13 patients that had reached week-4 post-treatment, 69% had achieved an SVR4. There were no additional patients who had relapse between weeks 4 and 12 (eight patients reached 12 weeks post-treatment). Of the four patients with documented relapse, all had Metavir F3 or F4 disease. Three of the four did not become undetectable until week 8 of therapy.

The therapy was well tolerated; headache and fatigue were the main side effects. No patients discontinued therapy and no graft losses or deaths were reported. Two patients developed suspected acute cellular rejection, both of whom responded to increased immunosuppression.

This study suggested that the use of simeprevir plus sofosbuvir was well tolerated in the post-transplant setting, but patients had slower viral kinetics and higher relapse rates than reported in a pre-transplant cohort. It is possible that a longer duration of therapy may be needed to optimize SVR rates in this population.

3D Regimen After Transplant

The second important abstract was presented by Mantry and colleagues, who studied the use of the AbbVie 3D regimen of ABT-450 boosted with ritonavir, ombitasvir and dasabuvir with ribavirin in post-liver transplant patients with recurrent HCV genotype 1 infection (85% with genotype 1a, 15% with genotype 1b). Thirty-four patients were enrolled. The study included only patients with early stage disease (≤F2); 56% had stage F0 or F1 disease and 44% had stage F2 disease. Patients received 24 weeks of therapy in combination with ribavirin. This combination has significant interactions with the immunosuppressant medications, and patients required dose reduction of tacrolimus to 0.5 mg once weekly or 0.2 mg every 3 days and reduction of cyclosporine to one-fifth of the daily pre-treatment dose given once daily.

With this regimen for 24 weeks, the SVR12 was 97.1%. Only one patient had a relapse on post-treatment day 3. This patient was found to have several mutations conveying resistance at relapse, although none of these mutations were present at baseline.

The researchers observed no episodes of acute or chronic rejection, and one patient discontinued therapy due to adverse events. The predominant adverse events included fatigue, headache and cough. Twenty of the 24 patients developed anemia, and five required erythropoietin support. No patients required transfusion.

Catherine T. Frenette

A ribavirin dose of 600 mg to 800 mg daily was the most frequent ribavirin dose both at baseline and end of treatment.

This study suggested that the 3D regimen is effective in the post-transplant setting, but can be difficult to use because of the need for ribavirin as well as the drug-drug interactions with the calcineurin inhibitors.

HCV Effect on Kidney Transplant

Another abstract presented during a plenary session was a review of the United Network for Organ Sharing (UNOS) database of kidney transplant recipients with HIV, HCV or HIV/HCV coinfection. While HCV-positive candidates are often viremic at the time of kidney transplant, most centers require that HIV-positive candidates have no detectable virus.

According to data presented by Sawinski and colleagues, graft and patient survival in HIV-positive kidney transplant recipients did not differ significantly from that of HIV- and HCV-negative recipients; however, HCV-positive recipients had significantly worse graft survival (HR=1.41) and patient survival (HR=1.53).

Now that we have direct-acting antivirals that will soon be able to be used in kidney transplant candidates, the researchers suggested that pre-transplant HCV eradication should be prioritized in this population.

Important Patient Populations

Overall, this meeting was a significant contribution to the literature for patients with solid organ transplant, especially those with HCV. Many other abstracts were significant, but could not be reviewed here, and may be reviewed either in the American Journal of Transplantation or Transplantation. Slide presentations and talks can be viewed online at World Transplant Congress On Demand 2014. This is an exciting time in the world of HCV, and organ transplant candidates and recipients are an important population in which to consider treatment.