Gut microbiota associated with impaired cognitive function post-LT

CHICAGO — Cognitive function improves in most patients who undergo liver transplantation for cirrhosis, according to a presentation at Digestive Disease Week. However, in those who do not improve, researchers have found an increase in Proteobacteria that could be associated with incomplete brain recovery for select patients.

“It is assumed that cognitive function recovers completely after liver transplant; however, this may be incomplete in some subgroups. Pre-LT gut microbiota, especially phylum Proteobacteria that includes all the bad bugs that we love to hate ... are especially linked with poor outcomes,” Jasmohan S. Bajaj, MD, from the Virginia Commonwealth University, said in his presentation. “In non-cirrhotic patients, gut microbiota abnormalities are associated with changes in brain function ... however, the association of gut microbiota change on post liver transplant cognitive ability in unclear.”

The researchers enrolled 45 patients listed for liver transplantation. Mean patient age was 56 years, 32 were men, 58% had hepatitis C and the mean MELD score was 26. Thirty-two patients received rifaximin and 25 received lactulose. On average, patients underwent LT 6 months from enrollment and were followed for 7 months.

Patients received microbiota and cognitive testing before LT and 6 months post-LT. Researchers compared these results with age-matched healthy controls. The cognitive testing was performed using the Psychometric Hepatic Encephalopathy score (PHES), which ranges from –15 to +14, higher scores representing better cognitive function.

“Persistent cognitive impairment, for us, was defined as a stable or worsening PHES, because we would expect that people who are being listed for transplant are at the worst they have ever been in their lives, so anything that does not improve in considered worsening,” Bajaj said.

Post-LT, two patients developed rejection, four had infection and four required biliary manipulation, which were resolved for more than 3 months before the post-LT clinical visit. At the post-LT visit, all patients were considered alert and oriented and were receiving Bactrim and stable tacrolimus doses. No patients at the post-LT visit had recurrent cirrhosis or hepatic encephalopathy.

Among most of the patients, there was an improvement in the mean PHES score from –5.9 before LT to –1.7 post-LT (P = .001). Thirteen patients did not improve their PHES scores. Among those who did not improve, Proteobacteria abundance was higher post-LT compared with those who did improve (23% vs. 0.1%; P = .01), whereas the reverse occurred in those who improved.

“There is cognitive and quality of life improvement in most patients post-LT, but in those who have post-LT cognitive impairment, there is a higher Proteobacteria relative abundance change,” Bajaj said. “Alteration in gut microbiota related to combination of pre- and post-LT events are associated with the ultimate post-LT cognitive performance. Further studies are required to define if beneficial modulation of gut microbiota, especially in patients with multiple post-LT infections and hospitalizations could benefit the overall cognitive function of liver transplant recipients.” – by Talitha Bennett

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References:

Bajaj JS, et al. Abstract 647. Presented at: Digestive Disease Week; May 6-9, 2017; Chicago.

Disclosure : Bajaj reports no relevant financial disclosures.