Fatma KARAKOC OZUDOGRU, Banu KARACA, Nesrin TURKER, Bahar ORMEN, Sezgin VATANSEVER, Huriye ERBAK YILMAZ, Furkan Oguzhan KARALAR, Fulya GUNSAR, Alper SENER
Turkish Journal of Gastroenterology - 2026;37(9):985-994
Background/Aims: The roles of inflammatory and fibrogenic biomarkers in chronic hepatitis B (CHB) infection and hepatitis B virus (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 HBV-related 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.
