Frequent delayed spontaneous seroclearance of hepatitis B virus after incident HBV infection among adult high‐risk groups

Abstract

High rates (~25%) of developing chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen (HBsAg)‐positive for > 6 months following infection) have been observed in people who use drugs (PWUD) and men who have sex with men (MSM). We aimed to estimate the frequency of delayed HBsAg seroclearance, along with its determinants, and time to delayed HBsAg seroclearance. Data were used from MSM and PWUD enrolled in the Amsterdam Cohort Studies (1985‐2002) who had anti‐hepatitis B core antibody seroconversion. Potential determinants for standard HBsAg seroclearance, delayed HBsAg seroclearance and chronic HBV were examined using multinominal logistic regression. Time to HBsAg seroclearance was estimated using Kaplan‐Meier curves. A total of 147 incident HBV infections occurred during follow‐up. On initial HBsAg testing after infection (6‐12 months), 42 (29%) were HBsAg‐positive and 105 (71%) were HBsAg‐negative (‘standard HBsAg seroclearance’). Of the 42 initially HBsAg‐positive individuals, 22 subsequently tested HBsAg‐negative (of whom 7 (31.8%) were HBV DNA positive at last visit, suggesting occult HBV). Overall, 15 became HBsAg‐negative and HBV DNA‐negative (‘delayed HBsAg seroclearance’), while 27 remained HBsAg and/or HBV DNA‐positive (‘chronic HBV’). The 5‐year cumulative probability of delayed HBsAg seroclearance was 41.6% for initially HBsAg‐positive individuals. Delayed HBsAg seroclearance and remaining chronically infected were associated with younger age and HIV/hepatitis C virus (HCV)‐co‐infection. In conclusion, delayed HBsAg seroclearance is common in these key adult populations at‐risk for HBV, while proportion developing HBV chronicity (18%) is still higher compared to the general population (~5%). Given the proportion of individuals with occult HBV infection and that HCV direct‐acting antivirals can lead to HBV reactivation, HBV DNA testing in HCV co‐infected MSM/PWUD are warranted prior to treatment initiation.

Incidence and Influencing Factors of New Hepatitis B Infections and Spontaneous Clearance: A Large-Scale, Community-Based Study in China

“…Some other studies appealed opposite findings. For instance a Hong Kong study of 4,568 cohort members and a research of 148 cohort members in Netherlands also found middle-age was associated with developing chronic infection and low HBsAg seroclearance rate compared with aging people ( 25 , 26 ). The confusing result has not been explained clearly and could partly be due to the increasingly complex innate and adaptive immune responses in elder people ( 27 ).…”

Table_1.DOC

“…Our survey showed that the incidence rate of new hepatitis B infection for males was significantly higher than that for females (684.88 vs. 536.68 per 100,000 person-years, p < 0.001), and 31-40, 41-50, 51-60 age groups had lower new infection rate than younger and elder age groups (Table 1). The phenomenon that males were more likely to have been infected with HBV than females reported by many previous studies could mainly be explained by behavioral differences (11,(21)(22)(23)(24)(25)(26)(27). In this research it may relate to the relatively conservative ideology in this county.…”