Kali Zhou1, Abdus S Wahed2, Stewart Cooper3, Adrian M Di Bisceglie4, Robert J Fontana5, Marc G Ghany6, Mandana Khalili1, Anna S Lok5, Robert Perrillo7, William M Lee8, Daryl T Y Lau9, Richard Sterling10, Harry L A Janssen11, Norah A Terrault12. 1. Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California, USA. 2. Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 3. California Pacific Medical Center, San Francisco, California, USA. 4. Saint Louis University, St. Louis, Missouri, USA. 5. Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA. 6. Liver Diseases Branch, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA. 7. Hepatology Division, Baylor University Medical Center, Dallas, Texas, USA. 8. Division of Digestive and Liver Diseases, UT Southwestern Medical Center at Dallas, Dallas, Texas, USA. 9. Liver Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. 10. Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA. 11. University Health Network, Toronto General Hospital, Toronto, Ontario, Canada. 12. Division of GI and Liver Diseases, University of Southern California, Los Angeles, California, USA.
Abstract
INTRODUCTION: Patients with hepatitis B early antigen (HBeAg)-negative chronic hepatitis B (CHB) and low-level viremia are a heterogeneous group. Identifying those at risk of developing active CHB requiring antiviral therapy is important. In this study, we prospectively characterize incidence rates and predictors of transitioning from inactive to active CHB in a North American adult cohort. METHODS: Participants in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis B Research Network cohort who were HBeAg negative with baseline hepatitis B virus (HBV) DNA ≤ 10,000 IU/mL were included in the study. Cox regression models were used to estimate the proportion of individuals in 3 baseline HBV DNA categories (≤100, 101 to ≤2,000, and 2,001 to ≤10,000 IU/mL) who developed phase transition defined by HBV DNA > 10,000 IU/mL and alanine aminotransferase (ALT) > 2× upper limit of normal or initiated treatment during follow-up. RESULTS: Of 970 participants meeting inclusion criteria, 15% experienced phase transition or initiated treatment over a median follow-up of 4 years: 9% of those with baseline HBV DNA ≤ 100 IU/mL, 14% with HBV DNA 101 to ≤2,000 IU/mL, and 24% with HBV DNA 2,001 to ≤10,000 IU/mL (P < 0.001). The overall rate of phase transition or treatment initiation was 7.6 per 100 person-years: 4.6 in those with HBV DNA ≤ 100 IU/mL, 6.8 in those with HBV DNA 101 to ≤2,000 IU/mL, and 12.2 in those with HBV DNA 2,001 to ≤10,000 IU/mL (P < 0.001). Factors independently associated with higher rate of phase transition or treatment initiation included HBV genotype B or C, higher baseline ALT and HBV DNA levels, lower platelet count, quantitative hepatitis B surface antigen > 1,000 IU/mL, and hyperlipidemia. Only higher ALT, higher HBV DNA, and lower platelets were associated with phase transition when patients starting treatment were censored. DISCUSSION: Most adults in this North American cohort with HBeAg-negative CHB and low-level viremia remained inactive and off treatment over 4 years. Transition from inactive to active CHB is infrequent and predominantly associated with viral rather than host factors.
INTRODUCTION:Patients with hepatitis B early antigen (HBeAg)-negative chronic hepatitis B (CHB) and low-level viremia are a heterogeneous group. Identifying those at risk of developing active CHB requiring antiviral therapy is important. In this study, we prospectively characterize incidence rates and predictors of transitioning from inactive to active CHB in a North American adult cohort. METHODS:Participants in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis B Research Network cohort who were HBeAg negative with baseline hepatitis B virus (HBV) DNA ≤ 10,000 IU/mL were included in the study. Cox regression models were used to estimate the proportion of individuals in 3 baseline HBV DNA categories (≤100, 101 to ≤2,000, and 2,001 to ≤10,000 IU/mL) who developed phase transition defined by HBV DNA > 10,000 IU/mL and alanine aminotransferase (ALT) > 2× upper limit of normal or initiated treatment during follow-up. RESULTS: Of 970 participants meeting inclusion criteria, 15% experienced phase transition or initiated treatment over a median follow-up of 4 years: 9% of those with baseline HBV DNA ≤ 100 IU/mL, 14% with HBV DNA 101 to ≤2,000 IU/mL, and 24% with HBV DNA 2,001 to ≤10,000 IU/mL (P < 0.001). The overall rate of phase transition or treatment initiation was 7.6 per 100 person-years: 4.6 in those with HBV DNA ≤ 100 IU/mL, 6.8 in those with HBV DNA 101 to ≤2,000 IU/mL, and 12.2 in those with HBV DNA 2,001 to ≤10,000 IU/mL (P < 0.001). Factors independently associated with higher rate of phase transition or treatment initiation included HBV genotype B or C, higher baseline ALT and HBV DNA levels, lower platelet count, quantitative hepatitis Bsurface antigen > 1,000 IU/mL, and hyperlipidemia. Only higher ALT, higher HBV DNA, and lower platelets were associated with phase transition when patients starting treatment were censored. DISCUSSION: Most adults in this North American cohort with HBeAg-negative CHB and low-level viremia remained inactive and off treatment over 4 years. Transition from inactive to active CHB is infrequent and predominantly associated with viral rather than host factors.