Wednesday, August 5, 2020

Liver Transplant: If No COVID-19 Symptoms, Immunosuppressants OK

Transplant News Sharing // News from Source www.medpagetoday.com

Don’t rush to reduce immunosuppression in post-transplant liver graft patients who are asymptomatic for COVID-19, a small study from Italy suggested.

Published online as a letter in the Lancet Gastroenterology & Hepatology, data from 141 immunosuppressed patients indicated no increased risk of severe COVID-19 disease. This finding is consistent with recent pediatric data, also from Italy, indicating that immunosuppressed children with liver transplants were not at increased risk of pulmonary disease from COVID-19 compared with the general population. That study suggested that the driver of lung damage was not the viral infection but the body’s immune response to it.

In the Milan series, a group led by Vincenzo Mazzaferro, MD, PhD, of the Istituto Nazionale Tumori in Milan, reviewed recent outcomes in 111 long-term liver recipients (>10 years) and 40 short-term recipients (<2 years). Six tested positive -- three in the long-term recipients, all of whom died, and three in the short-term group, "all experiencing an uneventful course of disease," the researchers wrote.

“In keeping with clinical insights from the American Association for the Study of Liver Diseases [AASLD] we suggest that immunosuppression should not be reduced or stopped in asymptomatic liver transplant recipients,” the investigators wrote.

According to AASLD guidance regarding COVID-19 issued April 7, post-transplant immunosuppression was not a risk factor for severe acute respiratory syndrome in 2003-2004 or for Middle East respiratory syndrome in 2012. The AASLD suggested that the immune response itself may be the main driver of pulmonary injury after COVID-19 infection and that some immunosuppression may be protective. It recommended against reducing immunosuppression or stopping mycophenolate mofetil for asymptomatic post-transplant patients without known COVID-19.

In the current Milan study, all three of the fatalities occurred in patients older than 65 years who were receiving antihypertensives and who were overweight, hyperlipidemic, and diabetic. All had tested positive for SARS-CoV-2 by nasopharyngeal swabs. Their post-transplant courses, however, had been uneventful, and their immunosuppressive regimens had been tapered off to very low trough concentrations of calcineurin inhibitors.

All three died after admission for community-acquired pneumonia and had required mechanical ventilation. Death occurred from day 3 to day 12 after the onset of pneumonia.

According to the authors, post-transplant metabolic complications such as arterial hypertension, chronic renal insufficiency, diabetes, hyperlipidemia, and weight gain might outweigh immunosuppression as a risk factor for the development of severe COVID-19 disease in transplant recipients. Recent data from China suggested comorbidities are associated with a worse prognosis.

“Of these metabolic complications, diabetes might be of particular concern, given its high prevalence (20-40%) in patients undergoing solid organ transplantation,” the authors wrote.

Sharing his perspective on the Milan study, Oren K. Fix, MD, MSc, director of the liver transplant program at Swedish Medical Center in Seattle, agreed that no prophylactic reduction in immunosuppression is necessary.

“There was an original knee-jerk reaction when people became aware of COVID that if these patients get this fatal virus, they may be at higher risk so we should reduce immunosuppressives at the outset,” he told MedPage Today. “Now we’re saying, ‘hold off.’ We don’t have the data and theoretically it’s possible the immune reaction itself is killing them and that immunosuppression is protective. Why introduce a new potential complication into a liver transplant patient when we don’t have the information?”

Fix, who is a member of AASLD’s COVID-19 working group that created the guidelines, added that some post-transplant patients may well have a worse outcome after COVID-19 infection, but “we don’t have the data to know which way they’ll go. Don’t anticipate a problem where there isn’t one. Wait and see if they get infected and then it may be okay to lower immunosuppression a bit but not until,” he said.

There has also been a concern that those with rheumatic and autoimmune diseases may be at heightened risk for COVID-19.

Among study limitations, the authors noted the small sample size, the unavailability of the exact number of COVID-19-positive patients, and the associated difficulty in accurately calculating the case-fatality rate.

And since swabbing was done at the Milan facility only for highly symptomatic patients, an accurate comparison of the 3% mortality in the long-term transplant group with Italy’s overall 10% case-fatality rate was not possible. “Nonetheless, given the short observation period (3 weeks) which we report here, the observed death rate is of concern,” Mazzaferro and colleagues wrote, stressing the urgent need for collecting data so that further studies can draw firmer conclusions.

Last Updated April 14, 2020

Disclosures

The authors report having no competing interests.

Fix is a member of the AASLD working group that recently issued Clinical Insights for Hepatology and Liver Transplant Providers during the COVID-19 pandemic. He reported having no conflicts of interest relevant to his comments.

Transplant News Sharing // “Liver Transplants” – Google News from Source www.medpagetoday.com

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