Spontaneous Loss of HBsAg Uncommon in Hepatitis B

Hepatitis B virus surface antigen
Hepatitis B virus surface antigen
In adults with chronic HBV infection who have never received treatment, spontaneous loss of hepatitis B surface antigen is infrequent.

In adults with chronic hepatitis B virus (HBV) infection who have never received treatment, spontaneous loss of hepatitis B surface antigen (HBsAg) is infrequent, according to results published in the Lancet Gastroenterology & Hepatology.

These results highlight the importance of developing new treatments that can achieve functional cure for HBV, rather than viral suppression.

In a systematic review and meta-analysis, the researchers searched PubMed and Embase for observational cohort studies and nontreatment groups of randomized controlled trials that reported the proportions of participants with chronic HBV infection that achieved spontaneous HBsAg loss. Studies published up to October 1, 2018, were considered.

The researchers assessed the rate of HBsAg loss and stratified the results by whether the underlying cohort was primarily from an endemic region (prevalence of chronic HBV >2%) or nonendemic region, and also noted demarcations of data for spontaneous conversion in people who tested positive for hepatitis B envelope antigen (HBeAg) vs those who were negative.

In total, the researchers included 67 studies: 11 randomized controlled trials, 39 prospective cohort studies, and 17 retrospective cohort studies. Of these, 56 were included in the meta-analysis after randomized controlled trials were excluded.

The results indicated that 7.8% (3837/48,972) of participants experienced spontaneous HBsAg loss during a cumulative 352,381 person-years of follow-up. Of note, the pooled annual incidence of HBsAg loss was 1.44% (95% CI, 1.12%-1.80%; I²=96%) in cohorts with people who were HBeAg -negative (n=26) and 0.74% (95% CI, 0.11%-1.80%; I²=92%) in cohorts with participants who were HBeAg -positive (n=5). However, when stratified by regional endemicity, researchers reported that these rates were similar.

The researchers calculated a pooled annual incidence of HBsAg loss of 1.17% (95% CI, 0.94%-1.41%; I2=97%). The annual incidence did not differ significantly based on endemicity, with a 1.19% rate for endemic cohorts compared with 1.29% for nonendemic cohorts.

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“The overall low rate of spontaneous functional cure underscores the urgency of developing novel drugs for treatment of chronic HBV with substantially improved efficacy to widen treatment candidacy and support the goal of HBV elimination worldwide,” the researchers wrote.


Zhou K, Contag C, Whitaker E, Terrault N. Spontaneous loss of surface antigen among adults living with chronic hepatitis B virus infection: a systematic review and pooled meta-analysis. Lancet Gastroenterol Hepatol. 2019;4(3):227-238.