LAUSR

BACKGROUND AND AIMS Predicting changes in disease activity and serological endpoints is necessary for management of patients with chronic hepatitis B (CHB). We examined whether HBV RNA and hepatitis B core-related antigen (HBcrAg), two specialized virological markers proposed to reflect activity of covalently closed circular DNA, may improve ability to predict not sustained inactive carrier [IC] phase, spontaneous alanine aminotransferase [ALT] flare, hepatitis B e antigen [HBeAg] loss and hepatitis B surface antigen [HBsAg] loss. METHODS Among eligible participants enrolled in the North American Hepatitis B Research Network Adult Cohort Study, we evaluated demographic, clinical and virologic characteristics, including HBV RNA and HBcrAg, to predict not sustained IC phase, ALT flare, HBeAg loss and HBsAg loss through a series of Cox proportional-hazard or logistic regression models, controlling for antiviral therapy use. RESULTS Among the study population, 54/103 participants experienced not sustained IC phase, 41/1006 had a spontaneous ALT flare, 83/250 lost HBeAg and 54/1127 lost HBsAg. HBV RNA or HBcrAg were predictive of all four events. However, their addition to models of readily available host (age, sex, race/ethnicity), clinical (ALT, use of antiviral therapy) and viral factors (HBV DNA), which had acceptable-excellent accuracy (e.g., area under the curve = 0.72 for ALT flare, 0.92 for HBeAg loss and 0.91 for HBsAg loss), provided only small improvements in predictive ability. CONCLUSION Given the high predictive ability of readily available markers, HBcrAg and HBV RNA have a limited role in improving prediction of key serologic and clinical events in patients with CHB.