Validity of a seven-gene signature as a non-invasive biomarker for cirrhosis: a cross-sectional study in Egyptian patients with HBV infection.

BACKGROUND

Hepatitis B virus (HBV) infection poses a significant public health challenge, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The clinical course of HBV infection is influenced by viral, environmental, and host genetic variants. Recently, a Cirrhosis Risk Score (CRS) based on seven genetic variants has been developed to identify individuals at risk of developing cirrhosis. This study aimed to assess the predictive value of seven gene signatures in Egyptian patients with HBV infection as molecular biomarkers for cirrhosis.

METHODS

In this cross-sectional study, 170 HBV-infected patients exhibiting various degrees of liver fibrosis were recruited. Genotyping for the seven gene SNPs was performed using allelic discrimination assays. Subsequently, the non-invasive scores APRI and FIB-4 were computed and compared with CRS values. Furthermore, an in silico analysis was performed to examine the alterations in gene expression associated with the progression of fibrosis.

RESULTS

The findings revealed a significantly higher prevalence of high CRS scores in late fibrosis (p = 0.006). The mean of CRS was higher in late than in early fibrosis (0.70 vs. 0.60; P = 0.003). However, APRI and FIB-4 scores did not differ significantly across the groups. The ROC analysis indicated that the CRS score can distinguish between patients with early and late fibrosis, with an AUC of 0.63 (p = 0.0034). The risk genotypes in DEGS1 (rs4290029), STXBP5L (rs17740066), and AQP2 (rs2878771) were associated with late fibrosis. According to the in silico analysis, there is a remarkable upregulation of DEGS1 and a downregulation of STXBP5L in late fibrosis as compared to early fibrosis. While the AQP2 showed no significant variation between early and late fibrosis.

CONCLUSION

The CRS score showed a modest predictive ability in HBV-infected Egyptian patients; it can be used in conjunction with imaging and clinical tools to improve risk stratification. Moreover, DEGS1, STXBP5L, and AQP2 genetic variants demonstrated a significant association with cirrhosis risk. However, only the DEGS1 and STXBP5L genes showed dysregulated expression levels, suggesting their potential relevance as diagnostic biomarkers in liver fibrosis.