Abstract
BACKGROUND: Chronic hepatitis B (CHB) with positive HBeAg status constitutes a significant contributor to the development of liver cirrhosis and hepatocellular carcinoma. Pegylated interferon-alpha (pegIFNα) is a common treatment, but its response rate remains limited, and the underlying mechanisms are not fully understood. METHODS: Eighty-two HBeAg-positive CHB patients were enrolled. miR-194-5p expression, HBeAg, and HBV DNA levels were detected using qRT-PCR, ELISA, and quantitative PCR, respectively. ROC and logistic regression analyses were performed. Cellular experiments, including dual-luciferase reporter and rescue assays, along with Western blot analysis of JAK-STAT pathway proteins, were conducted to verify targeting and function. RESULTS: Complete response (CR) patients had significantly lower baseline HBV DNA than suboptimal response (SR) patients. After 48 weeks of pegIFNα therapy, miR-194-5p expression decreased notably in the CR group and correlated positively with HBV DNA and HBeAg levels. miR-194-5p predicted treatment response with an AUC of 0.831 and was an independent predictor. Mechanistically, miR-194-5p targeted SOCS2. Functional studies demonstrated that miR-194-5p overexpression enhanced, while SOCS2 supplementation attenuated, pegIFNα-induced phosphorylation of STAT1/STAT2, thereby influencing cell viability and inflammatory factor expression (TNF-α, IL-6, IL-1β). CONCLUSION: miR-194-5p may predict pegIFNα response in HBeAg-positive CHB. It regulates interferon signaling by targeting SOCS2 and modulating the JAK-STAT pathway activation, suggesting the miR-194-5p/SOCS2 axis as a potential therapeutic target.