Clinical features of chronic hepatitis B patients with low hepatitis B surface antigen levels and determinants of hepatitis B surface antigen seroclearance
JGH OPEN
Authors: Taniguchi, Hideaki; Iwasaki, Yoshiaki; Aimi, Masahito; Shimazaki, Gaku; Moriya, Akio
Abstract
Background and Aim: A low hepatitis B surface antigen (HBsAg) level is reported to be predictive of future HBsAg seroclearance. A hospital-based cohort study was conducted to clarify the clinical features of patients with low HBsAg levels and to demonstrate the usefulness of low HBsAg levels for predicting HBsAg seroclearance. Methods: A total of 1459 patients with chronic hepatitis B were included in the study. Of these, 587 had repeated measurements for HBsAg levels and two or more records of HBsAg-positive results. HBsAg levels were measured with a commercially available HBsAg assay. Based on a cut-off index (COI) of 2000, a high HBsAg level was defined as HBsAg >= 2000 COI, and a low HBsAg level was defined as HBsAg <2000 COI. Results: The proportion of patients with low HBsAg levels at baseline tended to increase with age. Patients with low HBsAg levels at baseline had significantly older age, lower transaminase levels, and lower hepatitis B virus (HBV) DNA levels than those with high HBsAg levels. The annual HBsAg seroclearance rate was 1.30%/year. The cumulative incidences of HBsAg seroclearance differed significantly by HBsAg level at baseline (<2000 vs >= 2000 COI), age (>= 50 vs <50 years), and HBV DNA level (<4.0 vs >= 4.0 log copies/mL). Cox proportional hazards regression analyses showed that low HBsAg level (<2000 COI) and low HBV DNA level (<4.0 log copies/mL) were significantly associated with HBsAg seroclearance. Conclusion: Aging was one of the factors affecting HBsAg level. HBsAg seroclearance was significantly associated with low HBsAg level and low HBV DNA level at baseline.
Long-Term TDF-Inclusive ART and Progressive Rates of HBsAg Loss in HIV-HBV Coinfection-Lessons for Functional HBV Cure?
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Authors: Audsley, Jennifer; Avihingsanon, Anchalee; Littlejohn, Margaret; Bowden, Scott; Matthews, Gail, V; Fairley, Christopher K.; Lewin, Sharon R.; Sasadeusz, Joe
Abstract
Background: Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and hepatitis B virus (HBV) replication in HIV-HBV coinfection although HBV DNA can persist in some individuals on TDF-containing antiretroviral therapy (ART). We initiated a prospective longitudinal study to determine durability of HBV virological control and clinical outcomes after prolonged TDF-based ART in HIV-HBV coinfection. Methods: Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing ART from Australia (n = 41) and Thailand (n = 52) were enrolled. Participants were followed 6-monthly for 2 years, then annually to 5 years. Laboratory and clinical assessments and a serum sample were collected at each study visit. These analyses compare follow-up at 2 and 5 years. Results: 12.0% (95% confidence interval 6.8 to 20.2) of total study entry cohort (n = 92) or 15.3% (95% confidence interval: 8.8 to 25.3) of those with data to year 5 (n = 72) lost hepatitis B surface antigen (HBsAg). The only statistically significant association with HBsAg loss was lower study entry quantitative HBsAg. CD4 T-cell count increased by a median 245 cells/mm3 between the preTDF sample and 5 years of follow-up. By year 5, 98.5% of the cohort had undetectable HBV DNA (<15 IU/mL) and 91.4% had undetectable HIV RNA (<20 copies/mL). Conclusions: HBsAg loss was high and ongoing over 5 years of follow-up in HIV-HBV coinfected individuals on TDF-containing ART and undetectable HBV was almost universal. Although the pattern of HBsAg loss temporarily parallels immune reconstitution, we could not identify predictive immune markers. The high rate of HBsAg loss in HIV-HBV coinfection may offer valuable insights into the search for a functional HBV cure.