7, 8 In addition to being the envelope of infectious HBV particles, HBsAg is also found in the form of noninfectious spheres or filaments, which exceed infectious virions in number by 102 to 105.9 Serum HBsAg appears to correlate with transcriptionally active cccDNA and is considered a surrogate Sorafenib manufacturer marker of infected cells.10-14 Although cccDNA is the most accurate reflection of the number of infected

hepatocytes, it can be assessed in tissue only with complex techniques that are restricted to specialized research centers. This excludes the analysis of cccDNA levels from general clinical applications. The quantitation of HBV DNA by polymerase chain

reaction is now a standard part of the diagnostic workup for CHB. A serum HBV DNA decline reflects a reduction in viral replication. In contrast, a serum HBsAg decline represents a reduction in the translation of messenger RNAs produced from transcriptionally active cccDNA or integrated sequences.14 Thus, HBsAg quantitation provides different but complementary information that may aid us in the characterization of an individual’s infection status. Several cross-sectional studies have compared HBsAg and HBV DNA levels during different phases of CHB (Table BGB324 mouse 1). The results are encouragingly similar, even though the studies were conducted in different patient populations and, therefore, with different genotypes. Both HBsAg and HBV DNA levels vary during the natural course of the infection, and they are highest in the initial immune tolerance phase when the serum alanine aminotransferase (ALT) level is normal with no or minimal hepatitis activity. HBsAg levels become lower during the immune clearance phase and decrease slowly and progressively in those who maintain persistently normal ALT levels after hepatitis B e antigen (HBeAg) seroconversion.10 All groups have observed the lowest levels of HBsAg and HBV

DNA during this check details inactive phase, which is also characterized by the highest HBsAg/HBV DNA ratio.7, 10, 15 A Hong Kong follow-up study of 68 HBeAg-negative patients over a median period of 8 years showed a slow overall decrease in HBsAg levels, and a >1 log10 IU/mL HBsAg decline between the initial and last visits reflected improved immune control, which was associated with a higher HBsAg seroclearance rate and stronger viral suppression.10 Two European studies of inactive HBsAg carriers showed that those with subsequent HBsAg seroclearance had a significantly greater HBsAg decline than those who remained HBsAg-seropositive (0.28-0.29 versus 0.054-0.058 log10 IU/mL/year).