Clinical significance of the determination of fecal short-chain fatty acids in patients with nonalcoholic fatty liver disease / 临床肝胆病杂志

ABSTRACT

Objective To investigate the association of the metabolism of intestinal short-chain fatty acids (SCFAs) with the development and progression of the disease spectrum of nonalcoholic fatty liver disease (NAFLD) by determining the content of fecal SCFAs in patients with different NAFLD diseases and the change in the content of fecal SCFAs after treatment in patients at a high risk of nonalcoholic steatohepatitis (NASH). Methods A total of 90 patients who were diagnosed with NAFLD in The Affiliated Hospital of Qinghai University from July 2020 to July 2021 were enrolled and divided into simple nonalcoholic fatty liver (NAFL) group with 30 patients, NASH group with 30 patients, and nonalcoholic fatty liver fibrosis group with 30 patients, and 40 individuals who underwent physical examination during the same period of time were enrolled as control group. Related case data and fecal SCFAs content were collected for the four groups, and related clinical indices and fecal SCFAs content were collected for 10 patients at a high risk of NASH after 3 months of intervention. The analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the paired samples t -test was used for comparison within each group; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the paired samples Wilcoxon signed rank sum test was used for comparison within each group; a Spearman correlation analysis was used to investigate the correlation between variables; the receiver operating characteristic (ROC) curve analysis was used for diagnostic evaluation. Results Compared with the control group, the nonalcoholic fatty liver fibrosis group had significantly higher contents of valeric acid and caproic acid, and the NAFL group had significantly lower contents of valeric acid and caproic acid (all P < 0.05); the nonalcoholic fatty liver fibrosis group had significantly higher contents of valeric acid and caproic acid than the NAFL group ( P < 0.05); the nonalcoholic fatty liver fibrosis group had a significantly higher content of valeric acid than the NASH group ( P < 0.05); the NASH group had a significantly higher content of caproic acid than the NAFL group ( P < 0.05). After treatment, the high-risk patients in the NASH group had significant reductions in HbA1c, fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bile acid (TBA), prothrombin time (PT), uric acid (UA), controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) ( Z =-2.805, -2.703, -2.193, -2.599, -2.805, -2.701, -2.803, -1.988, -2.807, -2.803, -2.803, and -2.668, all P < 0.05); for these patients, the contents of acetic acid and propionic acid after treatment were significantly higher than those before treatment ( Z =-2.803 and -2.803, both P < 0.05), and the content of isobutyric acid after treatment was significantly lower than that before treatment ( Z =-2.803, P < 0.05). In the diagnosis of nonalcoholic fatty liver fibrosis, valeric acid had an area under the ROC curve (AUC) of 0.842, with a sensitivity of 86.7% and a specificity of 70% at the optimal cut-off value of 141.42 μg/g; caproic acid had an AUC of 0.819, with a sensitivity of 70% and a specificity of 85% at the optimal cut-off value of 6.93 μg/g. Conclusion Valeric acid and caproic acid may promote the development of NAFLD disease spectrum. Acetic acid and propionic acid may have a certain protective effect on the liver of NAFLD patients, and isobutyric acid may promote the development and progression of NASH. The protective effect of acetic acid and propionic acid on the liver may further lead to the reductions in HbA1c, FPG, TG, TC, ALT, AST, GGT, TBA, PT, UA, CAP, and LSM. Valeric acid and caproic acid have an inferior diagnostic value to PIIIP N-P and a superior diagnostic value to type IV collagen and hyaluronic acid. Valeric acid with the optimal cut-off value of 141.42 μg/g and caproic acid with the optimal cut-off value of 6.93 μg/g can be used as the auxiliary diagnostic indicators for the early diagnosis of nonalcoholic fatty liver fibrosis.