Globally, spontaneous loss of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B virus (HBV) infection occurs infrequently, and therefore new therapeutic agents are needed for achieving this functional cure, according to a systematic review and meta-analysis of the literature published in the Lancet Gastroenterology & Hepatology.1
Despite the availability of an effective HBV vaccine, morbidity and mortality from chronic HBV infection is still a significant public health concern in endemic regions of the world.2 Reports suggest that there are higher rates of spontaneous HBsAg loss, also known as functional cure, in nonendemic areas of the world compared with endemic areas.3,4 As the loss of HBsAg, rather than viral suppression, becomes the therapeutic end point for new HBV treatment options, a baseline annual rate of spontaneous HBsAg loss is needed to support clinical trials with functional cure as a primary end point.
Thus, researchers systematically determined a pooled annual rate of HBsAg loss in adults with untreated chronic HBV infection and examined the effect of regional endemicity.1 They included 56 studies in their meta-analyses and found that spontaneous HBsAg loss occurred in 3837 (7.8%) of 48,972 patients with a cumulative follow-up of 352,381 person-years. The pooled annual incidence of HBsAg loss was determined to be 1.17%, and the rates did not differ by endemicity (1.19% in endemic areas vs 1.29% in nonendemic areas).
The authors concluded that, “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.”1
- 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-analyses. Lancet Gastroenterol Hepatol. 2019;4:227-238.
- Lemoine M, Eholié S, Lacombe K. Reducing the neglected burden of viral hepatitis in Africa: strategies for a global approach. J Hepatol 2015;62:469-476.
- Sampliner RE, Hamilton FA, Iseri OA, Tabor E, Boitnott J. The liver histology and frequency of clearance of the hepatitis B surface antigen (HBsAg) in chronic carriers. Am J Med Sci 1979;277:17-22.
- Liaw YF, Sheen IS, Chen TJ, Chu CM, Pao CC. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology 1991;13:627-631.