A Model to Identify Gray Zone Patients With Chronic Hepatitis B Requiring Antiviral Therapy: A Multicenter Retrospective Study

Abstract Background Individuals who do not match any specific immune stage of chronic hepatitis B are classified into the gray zone, and appropriate management for these patients remains unclear. This study aimed to develop and validate a noninvasive model to identify gray zone patients requiring antiviral therapy (AVT). Methods We retrospectively collected data on 200 gray zone patients not requiring AVT, according to assessment by noninvasive parameters from 2010 to 2023 in 6 hospitals, and randomized them into development (n = 140) and validation (n = 60) cohorts. Univariable and multivariable regression analyses were performed to identify independent variables for establishing a nomogram to predict the probability of requiring AVT by liver biopsy. Results Seventy-eight patients (n = 39%) were identified as requiring AVT. The following were identified as independent variables for constructing the nomogram: age (odds ratio [OR], 1.06; 95% CI, 1.01–1.11), alanine aminotransferase (OR, 2.43; 95% CI, 1.08–5.59), lymphocyte percentage (OR, 6.43; 95% CI, 1.23–33.64), platelet count (OR, 0.99; 95% CI, .98–1.00), and international normalized ratio (per 0.01) (OR, 0.99; 95% CI, .98–.1.00). These variables showed good discriminability based on the development data set (area under the curve, 0.755) and validation data set (area under the curve, 0.707), calibration, and clinical applicability. Conclusions Gray zone patients requiring AVT should be identified, and the model developed here is a promising tool. Clinical trials registration ClinicalTrials.gov NCT06041022.