Nonalcoholic fatty liver disease is increasing in prevalence. It can be subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Five to twenty percent of cases progress from NAFL to NASH. Increased hepatic Th17 cells and IL-17 expression were observed in NASH mice and patients, respectively. We analyzed CD4+ effector T cells and regulatory T cells (Tregs) from peripheral blood and livers of NAFL and NASH patients. A total of 51 NAFL patients, 30 NASH patients, 31 nonalcoholic fatty liver disease patients (without histology), and 43 healthy controls were included. FACS analysis was performed on PBMCs and intrahepatic lymphocytes. Compared with healthy controls, a lower frequency of resting Tregs (rTregs; CD4+CD45RA+CD25++) and higher frequencies of IFN-γ+ and/or IL-4+ cells were detected among CD4+ T cells of peripheral blood in NASH, and to a lesser degree in NAFL. In hepatic tissue, NAFL to NASH progression was marked by an increase in IL-17+ cells among intrahepatic CD4+ T cells. To define immunological parameters in peripheral blood to distinguish NAFL from NASH, we calculated different ratios. Th17/rTreg and Th2/rTreg ratios were significantly increased in NASH versus NAFL. The relevance of our findings for NASH pathogenesis was highlighted by the normalization of all of the changes 1 y after bariatric surgery. In conclusion, our data indicate that NAFL patients show changes in their immune cell profile compared with healthy controls. NAFL to NASH progression is marked by an increased frequency of IL-17+ cells among intrahepatic CD4+ T cells and higher Th17/rTreg and Th2/rTreg ratios in peripheral blood.
The aim of this study was to demonstrate metabolic changes in the small joints of the hand due to rheumatoid arthritis by means of 31-phosphorus spectroscopy. Suitable measurements were developed and 11 normals and 12 patients were then examined during the course of treatment. Relative concentration of low energy phosphorus metabolites was increased in arthritic joints. The phospholipid quotient (phosphomonoester/phosphodiester) and the relationship of inorganic phosphate and beta-nucleoside triphosphate were significant factors during the course of individual treatments.
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