DAA-Ezetimibe Tx: ‘Transformational’ for Organ Transplant?

DAA-Ezetimibe Tx: ‘Transformational’ for Organ Transplant?

Mavyret plus Zetia thwarted hepatitis C virus infection from HCV-infected organs

BOSTON — A shorter course of direct-acting antiviral therapy (DAA), plus a well-known cholesterol-lowering drug, prevented hepatitis C virus infection in recipients of HCV-infected organs, a researcher said here.

A small group of patients who were given glecaprevir/pibrentasvir (Mavyret) plus ezetimibe (Zetia) for one dose before, and 7 days, after transplant from an HCV-positive donor did not acquire HCV infection, and patients were able to complete their course of treatment prior to being discharged from the hospital, reported Jordan Feld, MD, MPH, of the Toronto Center for Liver Disease.

During a press conference at the Liver Meeting, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), Victor Navarro, MD, of Albert Einstein Healthcare Network in Philadelphia, seemed to chastise reporters for their lack of enthusiasm about the study results.

“I’m surprised you people aren’t on your chairs,” said Navarro, who was not involved in the study. “For somebody who runs a large transplant program, this is really transformational. This will save the cost of treatment, as well as testing [and] probably hospitalization.”

AASLD press conference moderator Meena Bansal, MD, of Mount Sinai Health System in New York City, separately characterized the results as “groundbreaking” to MedPage Today, and said that being able to use HCV-positive organs could “potentially be quite game-changing.”

“Expanding the donor pool is the big thing, and…the fact that you can cure hepatitis C with 1 week of treatment while in the hospital…it’s paradigm-shifting, if it bears out,” she said.

Feld said that a number of studies have looked at using organs from donors with HCV. In those studies, kidney, lung, and heart transplant patients who received organs from HCV-infected donors were treated shortly after transplantation.

But Feld and colleagues wanted to examine if HCV transmission could be prevented entirely, noting that sometimes there have been significant delays in getting patients on treatment, in part due to payers who are “reluctant to approve” treatment for a patient who has acquired an infection through transplantation.

Previous approaches included treating the organ prior to transplantation, as well as using ultraviolet light in lung transplantation, which was able to reduce the levels of virus. However, it could not completely prevent transmission in most patients, he said.

Feld and colleagues tried a different approach using glecaprevir/pibrentasvir, which they described as a potent pan-genotypic regimen that was safe in patients with renal failure and had limited drug interactions. They added that ezetimibe is a well-tolerated, inexpensive drug that had shown potential to block entry of HCV into hepatocytes, Feld said.

Ezetimibe may have been the key, researchers suggested, as they compared their results to a similar study out of Massachusetts General Hospital. Both groups of patients received glecaprevir/pibrentasvir prior to transplant, but Feld’s group had lower peak recipient HCV RNA, though researchers said that may reflect residual donor virus.

HCV-negative transplant patients received donor heart, lungs, kidney, or pancreas from donors that tested positive for HCV via nucleic acid testing (NAT). Patients had HCV RNA testing daily for 14 days, and then weekly out to 12 weeks. The primary outcome of the study was prevention of HCV infection in the recipient (or undetectable serum RNA 12 weeks after transplantation).

Overall, 25 patients received a transplant. They were a mean age of 61, most were white, and most received lung or heart transplants. There were 16 donors (mean age 36) with multiple HCV genotypes, the most common being 1a and 3.

In the 25 patients, there were no virologic failures. There were 18 patients who achieved sustained virologic remission at 12 weeks, and seven who had sustained virologic remission at 6 weeks. The researchers noted that of the three patients with detectable HCV RNA post-treatment, all have cleared the virus.

Feld said the treatment was well-tolerated, with no increase in serious or other adverse events beyond those of a typical transplant population. There were two deaths among lung transplant recipients (one due to sepsis, one due to sub-arachnoid hemorrhage), and neither patient was ever HCV viremic.

Bansal stated that the extent of liver disease in donors may not be known, so doctors will have to assess that, such as whether or not there was significant fibrosis in the donor organ.

Feld said he would like to see if other centers can replicate these results of this prevention strategy.

Originally published on medpagetoday.com


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