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.

Keywords: antiviral therapy; chronic hepatitis B; gray zone; immune stage; noninvasive model.