ABSTRACT
Background: The combined effect of hepatitis B virus infection and metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatocellular carcinoma (HCC) risk remains unclear. The current study sought to elucidate the impact of MASLD on HCC progression in chronic hepatitis B (CHB) patients. Method: This retrospective cohort study included CHB patients who had undergone liver biopsy and abdominal imaging at the Guangdong Provincial Hospital of Chinese Medicine between 2013 and 2019. We investigated the correlation between MASLD and HCC risk, and inverse probability treatment weighting (IPTW) was used to adjust for patient characteristics. Results: A total of 1,613 patients were included, and 483 (29.9%) were diagnosed with MASLD. Over a median follow-up period of 5.02 years, 36 (2.2%) developed HCC, comprising 4.8% (23/483) of those with MASLD and 1.2% (13/1,130) of those without. Those with MASLD had a significantly higher cumulative incidence of HCC than those without (p < 0.001). The presence of MASLD was associated with a higher risk of HCC (adjusted hazard ratio [HR], 3.996; 95% confidence interval [CI], 2.007-7.959; p < 0.001). After adjustment using IPTW, the patients with MASLD retained a higher cumulative incidence of HCC (p < 0.001). Moreover, MASLD was found to be an independent risk factor for the development of HCC (adjusted HR, 10.191; 95% CI, 4.327-24.002; p < 0.001). However, among patients with MASLD, there were no significant differences in the cumulative risk of HCC between patients with and without overweight, between those with <2 and ≥2 cardiometabolic risk factors (CMRFs), between those with <3 and ≥3 CMRFs, or between those with <4 and ≥4 CMRFs (p = 0.110, p = 0.087, p = 0.066, and p = 0.490, respectively). Conclusion: The presence of MASLD is associated with a higher risk of HCC in patients with CHB. Notably, this higher risk is present in patients with MASLD, irrespective of the presence or absence of overweight or the number of CMRFs they have.
ABSTRACT
BACKGROUND: The morbidity of nonalcoholic fatty liver disease (NAFLD) has been rising, but the pathogenesis of NAFLD is still elusive. This study is aimed at determining NAFLD-related hub genes based on weighted gene coexpression network analysis (WGCNA). METHODS: GSE126848 dataset based construction of coexpression networks was performed based on WGCNA. Database for Annotation, Visualization, and Integrated Discovery (DAVID) was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hub genes were identified and validated in independent datasets and mouse model. RESULTS: We found that the steelblue module was most significantly correlated with NAFLD. Total 15 hub genes (NDUFA9, UQCRQ, NDUFB8, COPS5, RPS17, UBL5, PSMA3, PSMA1, SF3B5, MRPL27, RPL26, PDCD5, PFDN6, SNRPD2, PSMB3) were derived from both the coexpression and PPI networks and considered "true" hub genes. Functional enrichment analysis showed that the hub genes were related to NAFLD pathway and oxidative phosphorylation. Independent dataset-based analysis and the establishment of NAFLD mouse model confirmed the involvement of two hub genes NDUFA9 and UQCRQ in the pathogenesis of NAFLD. CONCLUSIONS: Oxidative phosphorylation and NAFLD pathway may be crucially involved in the pathogenesis of NAFLD, and two hub genes NDUFA9 and UQCRQ might be diagnostic biomarkers and therapeutic targets for NAFLD.
