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BOSTON – After a short preventive period of antivirals, recipients of donors infected with the hepatitis C virus had an "excellent" graft function at 6 and 12 months, with no detectable signs of the disease .
"I would cautiously say that this ability to safely transplant organs from donors infected with hepatitis C to uninfected recipients could increase by about 20% the number of organs available for transplantation." said senior author Ann E. Woolley, MD. theheart.org | Medscape Cardiology.
"However, it's a shifting target because, unfortunately, the epidemic of intravenous drug use is continuing and the percentage of donors with hepatitis C continues to increase, many of them are." 39, with a history of active drug use. "
In a study published online on April 3 in the New England Journal of MedicineWoolley and a team of infectious disease experts, transplant doctors and surgeons from Brigham and Women's Hospital at Harvard Medical School in Boston reported on the results of their open pilot study.
Although donor transplants with hepatitis C virus (HCV) have already been performed, the best approach to start treatment and duration of treatment after transplant, as well as results for heart transplant recipients and of the lung, have not been systematically studied.
A direct-acting antiviral treatment was instituted a few hours after organ transplantation in 44 patients – including 36 grafted lung and 8 heart transplant recipients. No patient has received both organs.
Direct-acting antiviral treatments have revolutionized the field of HCV treatment. Therapeutic regimens are usually administered for 8 to 12 weeks and are expensive. Researchers used a short course of 4 weeks of sofosbuvir 400 mg and velpatasvir 100 mg once daily, all drugs provided for free as part of the study.
In the majority of cases, the viral load dropped to zero in a few days and, in all patients, was undetectable around the two-week mark, Woolley and colleagues said.
HCV is not transmitted by a transplanted organ, but by the blood that comes with this organ. "Even though the organs have been washed, there is still a microscopic amount of blood, and when this blood reaches the liver and settles and begins to reproduce, it is so that the virus is transmitted."
"Since we started treatment at zero hour, as soon as it was safely possible after the transplant, the recipients had a very low viral load and we were able to prevent the virus from reaching the liver. and to reproduce, "said Woolley, adding that their protocol demonstrates a potential for post-exposure prophylaxis of hepatitis C.
The median viral load in HCV-infected donors was 890,000 IU / mL, but the median detectable viral load immediately after transplantation in 42 of the 44 HCV-detectable organ recipients was 1,800 IU / mL. .
Because the elimination of HCV from infected organ recipients is only half of the challenge, the researchers also evaluated the safety of transplanted organs and their longevity.
Of the first 35 patients who completed 6-month follow-up, all were alive and had excellent transplant function and an undetectable HCV load. Of 15 organ recipients with follow-up data after 12 months, the results were similar to those seen in heart and lung recipients of non-HCV-infected donors.
However, there were numerically more cases of acute cell rejection for which treatment was indicated in HCV-infected lung transplant recipients than in patients who received lungs from uninfected donors.
"We did not see that in the hearts, and the difference was not statistically significant, but we wanted to make sure to highlight that result because, of course, we want to make sure that it's not a big deal. no other non-infectious complication can result from the use of this organ source, "Woolley said.
Still much to learn
In an accompanying editorial, Emily A. Blumberg, MD, University of Pennsylvania, Pittsburgh, writes: "The time has come to consider developing the use of non-HCV-compatible transplantation in controlled conditions. "
However, she also stressed the need for many other answers, some of which should be drawn from multicenter trials on a larger scale.
The unmet need is clear: there are currently more than 113,000 people on waiting lists for a transplant in the United States, Blumberg said. In 2018, 36,500 people received a transplant and 12,225 were removed from the waiting list because of a death or progression of an illness that made them too sick for a transplant. transplantation.
Among the questions that remain unanswered is whether the virological response observed at 6 and 12 months will be maintained in the long term, and if there could be an increased risk of cardiovascular disease in the recipients, as had already been reported in HCV positive recipients. organs.
In addition, she suggested that "the patient's consent badumes a level of understanding of HCV infection that may not currently exist".
And then there is the question of costs, with a single 12-week course of sofosbuvir costing about $ 84,000 in the United States. It is difficult to know who will bear the burden of even a shortened treatment.
"The first results are very encouraging, but there is still much to learn," said Blumberg, who, like Woolley, is a specialist in transplanted infectious diseases. She is the current President-Elect of the American Society of Transplantation.
This work was funded in part by the Mendez National Institute of Transplant Foundation, Brigham and Women's Hospital, and grant number 1UL1TR002541-01, the Center for Clinical and Translational Research of Harvard, National Center for the Advancement of Translational Science. Woolley and Blumberg have not reported any conflicts of interest.
N Engl J Med. Posted online 3 April 2019. Abstract, Editorial
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