Apolipoprotein H-based prognostic risk correlates with liver lipid metabolism disorder in patients with HBV-related hepatocellular carcinoma.

ABSTRACT

Background: /Aim: Chronic hepatitis B patients often develop concomitant fatty liver disease, which is associated with increased risk of liver cirrhosis and hepatocarcinoma. Our previous studies have shown that apolipoprotein H (APOH) levels are gradually decreased in patients with chronic HBV infection at different stages of disease progression, and APOH deficiency disrupted hepatic lipid metabolism and caused fatty liver. We focus on the relationship between APOH and hepatocellular carcinoma (HCC) in the context of chronic HBV infection. Methods and results: APOH was downregulated at the transcriptional level in HBV-related HCC patients from open-source human liver transcriptome databases, and relatively high expression of APOH might be a favourable prognostic marker in HCC. APOH downregulation was positively associated with tumour grade and HCC subtypes. The analysis result of CHCC-HBV database showed that APOH-associated differential expression genes (DEGs) enriched in lipid metabolic pathways and downregulated APOH correlated with macrophage, neutrophil and CD8 T cell infiltration levels. Next, in vitro experiments were performed and APOH gene was silenced in HepG2.2.15 cells, an HBV producing human HCC cells. Further transcriptomic assay and analysis revealed the DEGs were enriched in cholesterol metabolism. The subsequent RT-qPCR experiments identified that CYP7A1 expression was higher upregulated in APOH silencing HepG2.2.15 cells than vehicle control cells (p < 0.05). Finally, demographic data of patients with HBV-related HCC were enrolled, and serum APOH levels were analysed using ELISA. Serum APOH levels were significantly lower in patients with HCC than in healthy controls (p < 0.05), and positively correlated with triglyceride level in healthy controls (p < 0.05). In HBV-HCC patients, serum APOH levels were positively correlated with albumin levels and negatively correlated with alkaline phosphatase (ALP), total bilirubin, and INR levels (p < 0.05). Conclusion: APOH downregulation disrupted liver lipid metabolism to potentially affect the overall survival in patients with HBV-related HCC.