IRISH SOCIETY OF GASTROENTEROLOGY SUMMER MEETING 2020
ISG Winter Meeting 2019 Oral Prize - Second Prize
St. James’s University Hospital, Dublin.
No change in circulating or intrahepatic Mucosal Associated Invariant T (MAIT) cells of NAFLD patients following a nutritional weight loss intervention
Dr. Sara Naimimohasses, Philip O’Gorman, Deirdre Ni Fhloinn, Ciara Wright, Mr. Dean Holden, J. Lysaght, Dr. Peter Beddy, Dr. Niall Conlon, Dr. Stephen P Finn, Dr. Margaret R Dunne,Professor Bernadette Moore, Professor Jacintha O'Sullivan, Professor Suzanne Norris
Department of Hepatology, St James' Hospital
MAIT cells are innate-like T lymphocytes that are enriched in the liver and may promote fibrogenesis. Weight loss has been shown to promote histological improvement in NAFLD.
The aim of this study was to assess changes in MAIT cell populations amongst patients with NAFLD following a nutritional weight loss intervention.
20 patients with biopsy proven NAFLD were recruited to the study.15 patients were allocated to a nutritional intervention (NI) group and 5 patients were recruited as controls. Baseline investigations included bloods, fibroscans, DEXAs and these were repeated post NI. The NI consisted of bi-weekly group nutritional education sessions for 12 weeks. Following completion, patients had repeat bloods, fibroscans and DEXAs. 12 patients in the NI with steatohepatitis on their initial liver biopsy had a repeat biopsy to re-assess histological stage. Liver tissue and whole blood samples were stained with antibodies specific for CD45, CD3, CD8, CD161, Vα7.2, CD69 and CD95 and were analysed with multi-colour flow cytometry using a BD FACSCanto II (BD Biosciences) and FlowJo software (Tree Star, Asland, OR). Statistical analysis of paired samples was performed using the Wilcoxon matched pair rank test.
A significant reduction was observed in % body fat-1.3% (-4.2, +2.2%), p=0.0254, HbA1c p=0.0054, ALT p=0.0108 and GGT p=0.0001 in the intervention group. Repeat biopsies showed a significant reduction in NAS score p=0.027. On further analysis, this was due to reductions in hepatic steatosis p=0.0078. No reductions were observed in lobular inflammation, p=0.75, ballooning, p=0.375 or fibrosis, p >0.999. Table 1 shows the characteristics of circulating and intrahepatic MAITs pre and post NI. Pre NI Post NI P value % Circulating MAITs 1.27% 0.97% 0.5305 Circulating MAIT MFI CD69 350 202 0.0479* Circulating MAIT MFI CD95 1690 1622 0.8904 % Intrahepatic MAITs 7.12% 6.56 0.4238 Intrahepatic MAIT MFI CD69 3345 3924 0.4238 Intrahepatic MAIT MFI CD 95 3428 3432 0.7480
No significant changes were observed in peripheral and intrahepatic MAIT cell levels or terminal activation marker expression despite improvements in patients’ metabolic profile and hepatic steatosis. MAIT cells have been shown to promote inflammation and fibrosis through hepatic stellate cell activation. Our study may be limited by the study timeline and because the intervention did not result in fibrosis regression or resolution of steatohepatitis. Given that these are key mechanisms by which MAIT cells are thought to contribute to NAFLD, further studies are required in patients who achieve fibrosis regression.