Give antibiotics before liver transplant improves liver function

A research team led by UCLA found that giving mice antibiotics for 10 days before a liver transplant improves their liver function after surgery.

After concluding the experiment on mice, scientists discovered data from liver transplants performed between October 2013 and August 2015 at the Ronald Reagan UCLA Medical Center, revealing that the same phenomenon seems to occur in humans . Human patient statistics have even shown that people who were in a medical condition before their surgery, but received antibiotics before surgery, came out better after their transplant than patients who were in better health before their surgery. but did not receive antibiotics.

The researchers concluded that antibiotics inhibited the bacteria responsible for inflammation, which could result in rejection of organs. Specifically, they found that in mice and humans, pre-transplant treatment reduces the damage that can occur when blood flow is restored to the liver after a period of time without oxygen; and it has reduced inflammation and cell damage while accelerating the removal of damaged cells. As a result, hepatic function was better than in mice and human patients who had not received antibiotics before a transplant.

Humans carry billions of bacteria, many of which are essential to health, for example to aid the digestion of food. But other bacteria are linked to inflammatory bowel disease, cardiovascular disease, obesity, diabetes and even Parkinson's disease.

The idea is to identify which bacterium is the good guy and which is the bad guy. "

Dr. Jerzy Kupiec-Weglinski, professor of surgery Paul I. Terasaki at David Geffen Medical School of UCLA and lead author of the study

The research is published in the peer-reviewed journal Journal of Clinical Investigation.

Studies conducted in the last four years at the University of Chicago and the University of Maryland have shown that in mice that received antibiotics before a skin or heart transplant, these transplants lasted longer without rejection than in mice that had not received antibiotics before surgery. From these studies, UCLA researchers were able to detect certain bacteria that seemed to help ensure better transplants.

In mice given antibiotics during the 10 days preceding the transplant, the liver showed less damage – deterioration caused by dead cells, for example – than in mice that did not receive antibiotics before to have undergone the same procedure.

"The livers in mice that received antibiotics were protected against graft damage and subsequent rejection because antibiotics modulated their host microbiomes, which in turn stimulated cell protection." said Kupiec-Weglinski.

To confirm the effect of the antibiotics, the researchers then transplanted faeces from untreated mice into those to which the drug had been administered. Mice that received feces grafts suffered inflammatory lesions of the liver, although they received antibiotics earlier in the experiment.

"This has shown that the benefits of antibiotics are clearly linked to the microbiota," said Kupiec-Weglinski.

Data on UCLA patients covered 264 people who had liver transplants – 156 who, because they were sicker before their surgery, received antibiotics for 10 days or more before the transplant and 108 who had antibiotics been administered for less than 10 days, or not at all before surgery.

"To our surprise, the livers worked better after transplantation in very sick patients requiring prolonged antibiotic therapy," said Kupiec-Weglinski.

The researchers then focused their attention on human patients who had been given a specific antibiotic, rifaximin, before transplantation. (To gather a larger sample, the team badyzed the transplant data over a longer period than the initial set of UCLA patients from January 2013 to July 2016.) It found that in patients receiving rifaximin, intestine and has a low risk of inducing bacterial resistance, early liver failure was significantly delayed or stopped.

Although the combination of data from human patients and mice demonstrates the benefits of prolonged antibiotic therapy prior to transplantation, the researchers wrote in the journal that results were collected over a short period of time – barely 10 days after the transplant – and longer-term studies are needed to strengthen the results.

Kupiec-Weglinski also said the study opens the door to further research that could determine which microorganisms protect liver function after a transplant and which bacteria should be "rejected" to limit their negative effects.