Is there a biomarker that can predict which patients will develop dangerous infectious complications after receiving a liver transplant? Nalu Navarro-Alvarez, MD, assistant professor of plastic and reconstructive surgery in the University of Colorado Department of Surgery, says yes.
Navarro-Alvarez, who began her liver research at her lab in Mexico, has focused much of her recent research on an inflammatory protein called galectin-3, which becomes more highly expressed as patients move from fibrosis to the more serious cirrhosis of the liver.
“My research is trying to understand what this molecule does inside the liver, where it has been useful as a biomarker to determine the progression of the disease of these patients,” says Navarro-Alvarez, who came to the CU Department of Surgery in 2019 and still maintains her Mexico lab. “An interesting finding that came out of this research is that levels of galectin-3 can also predict which patients, after transplant, are going to develop infectious complications. If you know in advance that a patient is on the verge of developing these complications, you may broaden your antibiotic spectrum when applicable, or you might watch them more closely.”
Higher levels in acute cases
Navarro-Alvarez’s findings were borne out in her studies of patients arriving in the emergency room with decompensated cirrhosis, an acute deterioration in liver function that typically requires a transplant. In those patients, galectin-3 is higher than in those with more manageable forms of the disease.
“These patients have a very short-term high mortality,” she says. “Within three months, if these patients don't get transplanted, a very high percentage of them are going to die. When we get these patients in the emergency room, we measure galectin-3, and what we observe is that the patients that have higher levels, some of them develop complications of an infection, and they die of the infection.” The manuscript including these data is being prepared and will be submitted soon.
It's obvious that galectin-3 plays a role in the decline, Navarro-Alvarez says — what still needs to be understood is exactly how this protein is preventing the body from fighting the infection. She first published her research on the role of galectin-3 in severe liver disease in 2022; she is now looking to better understand exactly how the protein affects the immune system.
“If you're not able to fight the infection and you have high levels of the protein in your circulation, it might be doing something to your immune cells,” she says. “The research is trying to understand how galectin-3 is impairing your host immune cells.”
Using patient samples from people who underwent liver transplantation from providers at the CU Department of Surgery, Navarro-Alvarez is looking at how cells behave in the presence of galectin-3, and what type of interventions might be developed to prevent the resulting complications.
“Once we understand exactly what galectin-3 is doing in the immune cells, the obvious thing to do will be to try to block or decrease the circulating galectin-3 levels,” she says. “If we discover and confirm that high galectin-3 levels are changing your immune system, then we have to try to reverse that phenotype that we might find in the immune cells that are impairing their ability to fight the infection.”
One avenue of potential discovery is figuring out where the galectin-3 originates — in the immune cells, or in the liver itself.
“If it’s coming from the immune cells that are getting overactivated, those cells might also fight the graft,” she says and that is not good. “They need to be activated in order to fight the infections that will invade the host, but there needs to be a modulation so they don’t attack the graft. One of the things we observed with the samples here in Colorado is that in patients who develop infectious complications, T cells are decreased. There is evidence in the literature that galectin 3 promotes the death of T cells, so what might be happening is they don't have enough T cells to fight the infection.”
Navarro-Alvarez is applying for a grant to further study the issue, both in the lab and using samples from patients in Colorado.
“I'm excited about this, and I really want to see what we can do to help this population,” she says. “I think eventually this will lead to better outcomes for the patients, which is why we do research. It’s for the good of trying to help patients and understanding mechanisms to develop potential therapies.”