There is an association between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis, but the genetic risk of atherosclerosis in NAFLD remains unclear. Here, a single-nucleotide polymorphism (SNP) of the heat shock 70 kDa protein 8 (HSPA8) gene was analyzed in 123 NAFLD patients who had been diagnosed using a liver biopsy, and the NAFLD phenotype including the maximum intima–media thickness (Max-IMT) of the carotid artery was investigated. Patients with the minor allele (A/G or G/G) of rs2236659 showed a lower serum heat shock cognate 71 kDa protein concentration than those with the major A/A allele. Compared with the patients with the major allele, those with the minor allele showed a higher prevalence of hypertension and higher Max-IMT in men. No significant associations between the HSPA8 genotype and hepatic pathological findings were identified. In decision-tree analysis, age, sex, liver fibrosis, and HSPA8 genotype were individually associated with severe carotid artery atherosclerosis (Max-IMT ≥ 1.5 mm). Noncirrhotic men aged ≥ 65 years were most significantly affected by the minor allele of HSPA8. To predict the risk of atherosclerosis and cardiovascular disease, HSPA8 SNP genotyping might be useful, particularly for older male NAFLD patients.

Background/Objectives: We aim to determine if cytokeratin-18 fragment (CK-18F) could be used to diagnose metabolic dysfunction-associated steatohepatitis (MASH). Methods: A total of 289 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled in the analysis. To evaluate the association between CK-18F levels and the histological features of MASH, weighted receiver operating characteristic (ROC) curve analyses were performed. The diagnostic utility of CK-18F was compared with that of the Mac-2 binding protein glycan isomer (M2BPGi). Additionally, we assessed the predictive performance of combining CK-18F with either the FIB-4 index or the FIB-3 index for diagnosing MASH and investigated predictors of future progression to cirrhosis. Results: CK-18F was more useful for MASH diagnosis than M2BPGi and the FIB-4 index in the multivariate analysis, with a sensitivity of 47% and specificity of 80% at a CK-18F cutoff value of 750 U/L. Because CK-18F decreases with advanced liver fibrosis, the combination of the FIB-4 or FIB-3 index with CK-18F was examined to identify cases with cirrhosis. The combination of the CK-18F level and the FIB-3 index better predicted MASH than the combination of the CK-18F level and the FIB-4 index. The FIB-3 index was the most useful predictor of cirrhosis on imaging five years after diagnosis with F2 or less disease. Conclusions: CK-18F is useful for MASH diagnosis, and the diagnostic algorithm combining CK-18F with the FIB-3 index may be more useful than the previously reported MASH diagnostic algorithm that combined it with the FIB-4 index.