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- W4381487249 abstract "<p>Understanding the mechanisms linking steatosis to fibrosis is needed to establish a promising therapy against nonalcoholic fatty liver disease (NAFLD). This study aims to clarify clinical features and hepatic gene expression signatures that predict and contribute to liver fibrosis development during the long-term real-world histological course of NAFLD subjects with and without diabetes. A pathologist scored 342 serial liver biopsy samples from 118 subjects clinically diagnosed with NAFLD during a 3.8 years (SD 3.45, maximum 15 years) course of clinical treatment (UMIN; Clinical Trials Registry, no. UMIN000035231). At the initial biopsy, 26 subjects had simple fatty liver, and 92 had nonalcoholic steatohepatitis (NASH). In the trend analysis, the Fibrosis-4 index (P < 0.001) and its components at baseline predicted the future fibrosis progression. In the generalized linear mixed model, an increase in HbA1c, but not BMI, was significantly associated with fibrosis progression (0.17 [0.009–0.326]; P = 0.038) for NAFLD subjects with diabetes. In gene set enrichment analyses, the pathways involved in hepatocytes zone 3, central liver sinusoidal endothelial cell (LSEC), stellate cells, and plasma cells were coordinately altered in association with fibrosis progression and HbA1c elevation. Therefore, in NAFLD subjects with diabetes, HbA1c elevation is significantly associated with liver fibrosis progression, independent of weight gain, which may be a valuable therapeutic target to prevent the pathological progression of NASH. Gene expression profiles suggest that diabetes-induced hypoxia and oxidative stress injure LSEC injury in zone 3, which may mediate inflammation and stellate cell activation, leading to liver fibrosis. </p>" @default.
- W4381487249 created "2023-06-22" @default.
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- W4381487249 date "2023-06-21" @default.
- W4381487249 modified "2023-10-16" @default.
- W4381487249 title "<strong>Trajectories of liver fibrosis and gene expression profiles in NAFLD associated with diabetes</strong>" @default.
- W4381487249 doi "https://doi.org/10.2337/figshare.23537514.v1" @default.
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