ABSTRACT
Non-invasive biomarkers of non-alcoholic fatty liver disease (NAFLD) supporting diagnosis and monitoring disease progression are urgently needed. The present study aimed to establish a bioinformatics pipeline capable of defining and validating NAFLD biomarker candidates based on paired hepatic global gene expression and plasma bioanalysis from individuals representing different stages of histologically confirmed NAFLD (no/mild, moderate, more advanced NAFLD). Liver secretome gene signatures were generated in a patient cohort of 26 severely obese individuals with the majority having no or mild fibrosis. To this end, global gene expression changes were compared between individuals with no/mild NAFLD and moderate/advanced NAFLD with subsequent filtering for candidate gene products with liver-selective expression and secretion. Four candidate genes, including LPA (lipoprotein A), IGFBP-1 (insulin-like growth factor-binding protein 1), SERPINF2 (serpin family F member 2) and MAT1A (methionine adenosyltransferase 1A), were differentially expressed in moderate/advanced NAFLD, which was confirmed in three independent RNA sequencing datasets from large, publicly available NAFLD studies. The corresponding gene products were quantified in plasma samples but could not discriminate among different grades of NAFLD based on NAFLD activity score. Conclusion: We demonstrate a novel approach based on the liver transcriptome allowing for identification of secreted hepatic gene products as potential circulating diagnostic biomarkers of NAFLD. Using this approach in larger NAFLD patient cohorts may yield potential circulating biomarkers for NAFLD severity.
Subject(s)
Non-alcoholic Fatty Liver Disease , Serpins , Somatomedins , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/genetics , Insulin-Like Growth Factor Binding Protein 1/metabolism , Methionine Adenosyltransferase/genetics , Secretome , Serpins/metabolism , Biomarkers , Somatomedins/metabolism , Lipoprotein(a)/metabolismABSTRACT
INTRODUCTION: The number of procedures involving transabdominal preperitoneal laparoscopic surgery for inguinal hernia (TAPP) has increased in Denmark. Optimized perioperative regimens are needed. MATERIAL AND METHODS: This retrospective, single-institution study included consecutive patients during an eight-year period from 1 January 2002 to 31 December 2007 (period I) and from 1 January 2008 to 31 December 2009 (period II). In period II, perioperative indwelling catheter (Foley catheter) was not used routinely. Furthermore, the surgical technique was adjusted, a small team of dedicated TAPP surgeons was established, and two of the surgeons attended prearranged surgical training programmes. Additionally, period II patients were enrolled into structured patient protocols. The primary endpoint was complications within the first 30 days after surgery, and we also registered the rate of reoperation due to recurrence. RESULTS: A total of 684 patients underwent TAPP surgery for 946 inguinal hernias. From period I to II, the number of TAPP surgeons was reduced to a third and two surgeons received TAPP training. During period I, minor urological complications were observed in 5% (confidence interval (CI) 3.1-6.9%) compared with 1% in period II (0.0-2.5%). The overall morbidity rate was 13%. Serious complications were observed in 3% (CI 3.1-6.9%) of the cases in period I and in 2% (0.0-2.5%) of the cases in period II. For the entire eight-year study period, the cumulative rate of re-operation due to recurrence was 2%. CONCLUSION: TAPP without routine use of an indwelling catheter may reduce the risk of urological complications.
