Time to seroconversion of HBsAg to anti-HBs in individuals who lost HBsAg during follow-up

Abstract

To determine the time to appearance of antibody against hepatitis B surface antigen (anti-HBs) after clearance of hepatitis B surface antigen (HBsAg) in chronically infected individuals, we followed up 3963 cases with positive antibody against hepatitis B e antigen (anti-HBe) from 1991 to 2014. Of these, 101 (67 males, 34 females) lost HBsAg. These serocleared cases were checked every 6-month interval regarding HBsAg, anti-HBs, liver function tests, and liver sonography. Hepatitis B virus DNA was assessed at the time of seroclearance or the appearance of anti-HBs. The mean age of these patients at entry to this study was 34·4 ± 13 years. The mean follow-up duration until seroclearance of HBsAg was 6·6 ± 4·3 years. After the mean follow-up of 43·7 ± 45 months, anti-HBs appeared in 64 (63·4%) cases. The cumulative probabilities of anti-HBs appearance for 2, 5 and 10 years were 24·3%, 58% and 78·2%, respectively. The appearance of anti-HBs was associated with age ⩾35 years and seroclearance of HBsAg (hazard ratio 1·96, 95% confidence interval 1·32-3·38, P = 0·016) but not with sex. The results show that anti-HBs may develop in 78·2% of cases within 10 years of HBsAg clearance. Age ⩾35 years at HBsAg loss was associated with earlier development of anti-HBs.

Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance and seroconversion in hepatitis B e antigen‐negative chronic infection patients: A population‐based prospective cohort

“…In the subjects who cleared HBsAg, the majority of patients had persistently undetectable HBV DNA levels during follow‐up; however, we revealed low levels of HBV DNA in 34 (11.2%) patients at the last time of follow‐up and 23 (7.0%) patients had HBV DNA detectable levels at the time of HBsAg clearance (Table ). The HBV DNA detected rate in our study was relatively lower than that of Roushan et al, in which, HBV DNA was detected in 16 (15.8%) out of 101 cases at the time of seroclearance. Other studies found that up to 13.4% of cases had detectable HBV DNA with low viral loads .…”

“…By univariate Cox analysis, we found that HBsAg seroclearance rates were higher in male gender, which was in keeping with a previous study . However, it was an interesting finding that female patients were more likely to produce anti‐HBs than males, which was different with an Iranian study of 101 HBsAg seroclearance patients . In that observation study, the appearance of anti‐HBs was not associated with sex.…”

“…The present study may be the largest sample size report showing the trait of anti‐HBs appearance following HBsAg lost in a population‐based cohort study. Anti‐HBs developed in 37.3% of these patients after seroclearance of HBsAg in the cohort after the mean follow‐up of 3.5 ± 1.2 years, which was similar with the observation results of a previous Iranian study . In our cohort, by using logistic regression model, we found that the appearance of anti‐HBs was associated with gender but not with age at baseline or age at time of HBsAg clearance (Table ), which was not consistent with the Iranian study.…”

Durability of Hepatitis B Surface Antigen Loss With Nucleotide Analogue and Peginterferon Therapy in Patients With Chronic Hepatitis B

“…Long intervals between HBsAg loss and anti-HBs seroconversion have been reported. (20)(21)(22) Roushan et al (20) reported the cumulative probabilities of anti-HBs seroconversion after HBsAg loss at 1, 2, 3, 4, and 5 years were 8.7%, 24.3%, 37%, 49.1%, and 58%, respectively, in inactive CHB carriers with spontaneous HBsAg loss. Yip et al (21) also reported an increasing proportion of patients with spontaneous or NUC-induced HBsAg loss over time; detectable anti-HBs seroconversion occurred in 37.6% of patients at the time of HBsAg loss, 42.6% within 1 year of HBsAg loss, and 53.1% at any time during follow-up.…”

Use of ELISpot assay to study HBs-specific B cell responses in vaccinated and HBV infected humans

“…However, only very small percentage of CHB patients cleared HBsAg, with or without treatment 13 , 25 . A promising clinical observation is that, for patients who experienced the complete loss of HBsAg after decades of anti-viral treatment, they could generate decent levels of HBsAb 26 , indicating that B cells from HBV patients may still maintain the potential to produce HBsAb. In contrast, it was reported that diminished HBsAg-specific B-cell responses were correlated with HBV persistence 27 .…”