Discriminative Role of Interleukin-6, Neuropilin-1, and Amphiregulin for Cirrhosis in Patients with Chronic Hepatitis B Infection.

Background/Aims: The roles of inflammatory and fibrogenic biomarkers in chronic hepatitis B (CHB) infection and hepatitis B virüs (HBV)-related cirrhosis remain incompletely understood. The current study investigated the diagnostic and discriminative ability of amphiregulin (AREG), interleukin-6 (IL-6), and neuropilin-1 (Nrp-1) as biomarkers of HBV-related cirrhosis. Materials and Methods: This cross-sectional analytical study included 70 patients with CHB (43 without cirrhosis and 27 with HBVrelated cirrhosis) and 60 healthy controls. Clinical and laboratory data were obtained from hospital records. Serum IL-6, Nrp-1, and AREG levels collected during outpatient visits were measured using enzyme-linked immunosorbent assay. Group differences were analyzed using the Kruskal-Wallis test, discriminative performance was evaluated using receiver operating characteristic (ROC) analysis, and factors independently associated with cirrhosis were identified using logistic regression. Results: IL-6 and Nrp-1 levels were higher in patients with noncirrhotic and HBV-related cirrhotic CHB than in healthy controls (P < .001), with no significant difference between the patient subgroups. AREG levels were lower in the overall CHB cohort than in controls (P < .001) but higher in patients with cirrhosis than in those without cirrhosis (P = .001). ROC analysis showed that AREG had moderate discriminative ability for HBV-related cirrhosis (area under the curve (AUC) = 0.749). The optimal Youden-derived cutoff value was 2.29 ng/mL, with a sensitivity of 74% and a specificity of 65%. In logistic regression, AREG was independently associated with HBV-related cirrhosis (P = .012). Addition of ln-transformed AREG to age- and sex-adjusted aspartate aminotransferase-to-platelet ratio index (APRI)- and Fibrosis-4 index (FIB-4)-based models increased the AUC from 0.923 to 0.970 and from 0.938 to 0.980, respectively. Conclusion: AREG may serve as a complementary biomarker with moderate discriminative value for HBV-related cirrhosis but is unlikely to be useful as a standalone diagnostic or prognostic marker. Although IL-6 and Nrp-1 reflected underlying inflammatory activity, their ability to distinguish cirrhosis was limited.