FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnostic efficacy,its sensitivity,specificity,PPV,NPV,and AUROC were 44.2%,92.3%,82.1%,67.4%,and 0.82.The FIB-4 AUROC was 0.76.S index and GPR exhibited almost no diagnostic value for high-risk MASH.CONCLUSION FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI,Forns index,ARR,S index,and GPR;FAST is superior to FIB-4.

Differences of core genes in liver fibrosis and hepatocellular carcinoma:Evidence from integrated bioinformatics and immunohistochemical analysis

BACKGROUND Liver fibrosis and hepatocellular carcinoma(HCC)are common adverse consequences of chronic liver injury.The interaction of various risk factors may cause them to happen.Identification of specific biomarkers is of great significance for understanding the occurrence,development mechanisms,and determining the novel tools for diagnosis and treatment of both liver fibrosis and HCC.AIM To identify liver fibrosis-related core genes,we analyzed the differential expression pattern of core genes in liver fibrosis and HCC.METHODS Gene expression profiles of three datasets,GSE14323,GSE36411,and GSE89377,obtained from the Gene Expression Omnibus(GEO)database,were analyzed,and differentially expressed genes(DEGs)between patients with liver cirrhosis and healthy controls were identified by screening via R software packages and online tool for Venn diagrams.The WebGestalt online tool was used to identify DEGs enriched in biological processes,molecular functions,cellular components,and Kyoto Encyclopedia of Genes and Genomes pathways.The protein–protein interactions of DEGs were visualized using Cytoscape with STRING.Next,the expression pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrachloride(CCl_(4))-induced liver cirrhosis mouse model and in patient liver samples.Finally,Kaplan-Meier curves were constructed using the Kaplan-Meier plotter online server.RESULTS Forty-five DEGs(43 upregulated and 2 downregulated genes)associated with liver cirrhosis were identified from three GEO datasets.Ten hub genes were identified,which were upregulated in liver cirrhosis.Western blot and immunohistochemical analyses of the three core genes,decorin(DCN),dermatopontin(DPT),and SRY-box transcription factor 9(SOX9),revealed that they were highly expressed in the CCl4-induced liver cirrhosis mouse model.The expression levels of DCN and SOX 9 were positively correlated with the degree of fibrosis,and SOX 9 level in HCC patients was significantly higher than that in fibrosis patients.However,high expression of DPT was observed only in patients with liver fibrosis,and its expression in HCC was low.The gene expression profiling interactive analysis server(GEPIA)showed that SOX9 was significantly upregulated whereas DCN and DPT were significantly downregulated in patients with HCC.In addition,the Kaplan-Meier curves showed that HCC patients with higher SOX9 expression had significantly lower 5-year survival rate,while patients with higher expression of DCN or DPT had significantly higher 5-year survival rates.CONCLUSION The expression levels of DCN,DPT,and SOX9 were positively correlated with the degree of liver fibrosis but showed different correlations with the 5-year survival rates of HCC patients.