Clinical And Laboratory Analysis Of The Effect Of Nonalcoholic Fatty Liver Disease On The Prognosis Of Tuberculosis Patients

Objective: Tuberculosis(TB)is a systemic chronic infectious disease caused by the respiratory transmission of Mycobacterium tuberculosis(MTB).Tuberculosis is the most common disease.When TB patients suffer from other chronic diseases,the prognosis is often poor.Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in the world.It is closely related to metabolic disorders such as central obesity,dyslipidemia,hypertension,hyperglycemia,abnormal liver function,and can lead to cirrhosis,liver failure,hepatocellular carcinoma and other severe end-stage liver diseases.At present,whether the clinical prognosis of TB patients is affected by NAFLD remains unclear.This study plans to explore the influence of NAFLD on the prognosis of TB by means of bioinformatics analysis,clinical case analysis and serum sample detection.Methods: In this study,48 patients with TB complicated with NAFLD and 47 patients with simple TB admitted to Taizhou people’s hospital from August 2015 to June 2022 were collected,and according to the sputum smear conversion time,they were divided into a group of 50 patients with no prolonged sputum smear conversion(sputum smear conversion time ≤2months)and a group of 45 patients with prolonged sputum smear conversion time > 2 months),SPSS26.0 software was used for statistical analysis of the clinical baseline data and laboratory examination of patients.The independent risk factors of sputum smear turning negative in TB patients were analyzed by Logistics regression.At the same time,two gene data sets of GSE54992 and GSE89632 were downloaded from GEO database,and the two groups of data were differentially analyzed to obtain the common differential genes in the two data sets.KEGG enrichment analysis was performed on the common differential genes,and protein-protein interaction(PPI)network was constructed to screen the key genes.Finally,combined with macrophage-related inflammatory cytokines,11 patients with TB complicated with NAFLD and 11 patients with simple TB admitted to Taizhou people’s hospital from June 2022 to December 2022 were recollected.Their baseline clinical data were statistically analyzed and the serum of patients were collected.The expression of cytokines in serum was detected by ELISA and the results were analyzed.Results:Gender,body mass index(BMI),NAFLD,neutrophil granulocyte(NEU),lymphocyte(LYM),monocyte(MON),alanine aminotransferase(Alt)between the group without prolonged sputum smear conversion and the group with prolonged sputum smear conversion(ALT),aspartate aminotransferase(AST)and urea nitrogen(BUN)were significantly different(P<0.05).Multivariate logistic regression analysis showed that NAFLD was an independent risk factor for sputum smear conversion time in TB patients(β=4.243,OR=6.634,95%CI: 1.365-26.664,P<0.001).Forty-nine shared genes were obtained from GSE54992 and GSE89632,and identified by KEGG Pathway,GO Biological Processes,Reactome Gene Sets,Canonical Pathways,CORUM and Wiki Pathways enriched shared genes,These genes are mainly enriched in "negative regulation of cysteine-type endopeptidase activity involved in the apoptotic process",inflammatory response and Interleukin-10 signaling.At the same time,PPI network was constructed and hub genes were screened by four algorithms(MCC,MNC,EPC,Degree).The top three genes with scores were interleukin-6(IL-6),interleukin-1β(IL-1β)and interleukin-10(IL-10).Serum IL-6 levels in TB group and TB+NAFLD group were 1.16(0.36-4.19)ng/ml and 0.26(0.06-1.64)ng/ml,respectively.IL-6 level in TB group was significantly higher than that in TB+NAFLD group,and the difference was statistically significant(P<0.05).Serum IL-10 levels in TB group and TB+NAFLD group were 8.24(7.73-9.60)ng/ml and 14.25(9.87-18.66)ng/ml.IL-10 level in TB group was significantly lower than that in TB+NAFLD group,and the difference was statistically significant(P<0.05).Serum IL-1β levels in TB group and TB+NAFLD group were60.78(53.87-71.62)ng/ml and 53.51(45.00-72.38)ng/ml,respectively,and there was no significant difference between the two groups(P>0.05).Conclusion: Nonalcoholic fatty liver is an independent risk factor for prolonged sputum smear conversion time in tuberculosis patients.The different expression levels of serum cytokines IL-6 and IL-10 in patients with TB and NAFLD suggest that patients with NAFLD may affect the progression and prognosis of TB by regulating the levels of inflammatory cytokines.