Author information

• ¹Senior Investigator, Liver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA.
• ²Graduate School of Public Health University of Pittsburgh, Pittsburgh, PA, USA.
• ³Statistician, Epidemiology department, Graduate School of Public Health University of Pittsburgh, Pittsburgh, PA, USA.
• ⁴Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
• ⁵Washington University School of Medicine and John Cochran VA Medical Center, St. Louis, MO. USA.
• ⁶Director of Hepatology and Liver Center, Massachusetts General Hospital, Boston, MA, USA.
• ⁷Division of Gastrointestinal and Liver Diseases, Keck Medicine of University of Southern California, Los Angeles, CA, USA.
• ⁸Toronto Centre for Liver Disease, University of Toronto, Toronto, Canada.
• ⁹Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, CA, USA.
• ¹⁰Meredith Mosle Chair in Liver Disease, UT Southwestern Medical Center, Dallas, TX, USA.
• ¹¹Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
• ¹²Head of Infectious Disease Research, Abbott Diagnostics, Abbott Park, USA.
• ¹³Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA, USA.

Abstract

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.