Characteristics of the early phase of chronicity in acute hepatitis B infection

Abstract

The mechanism of development of chronicity after acute hepatitis B infection has not been elucidated fully. Following a single source outbreak of hepatitis B among 79 adult women, three patients (4%) became chronic carriers of hepatitis B virus (HBV). We compared features of the virus and antibody response of the latter three patients with those of 12 HBeAg-positive cases with resolving infection. The virus genotype was D, antigenic subtype ayw2. Base sequence analysis of S- and C-gene regions revealed no differences between the two groups. During the acute illness the three patients who developed chronicity had a remarkable transient reduction of HBsAg, HBeAg, and HBV DNA levels at 14-20 weeks after infection, the time of HBeAg seroconversion in the patients who cleared the infection. One HBeAg-specific monoclonal antibody (HBOT.95A) used as solid-phase antibody in a sandwich enzyme immunoassay detected an increased HBeAg signal in 2 of the 3 patients that developed chronicity and in 1 of the 12 patients who recovered. The latter patient had an exceptional long period of HBsAg antigenemia. Standard HBeAg assays detected HBeAg in all cases. HBeAg and anti-HBe-positive serum samples from the patients who recovered could inhibit the HBOT.95A response. The results suggest that chronic hepatitis B develops after an interruption of immune clearance. Differentiation of the antibody response to HBeAg may help to find patients with an increased risk for this interrupted immune clearance who might be candidates for an early intervention therapy.

Lack of correlation between HBsAg and HBV DNA levels in blood donors who test positive for HBsAg and anti‐HBc: implications for future HBV screening policy

“…Based on data reported by Sato et al 1 and Biswas et al, 2 the average ratio of HBsAg to DNA for seroconverters during the ramp‐up phase (determined at assay cut‐off values for investigational and licensed HBsAg assays) can be calculated to be about 0.005 to 0.007 HBsAg ng per 100 DNA copies. Post‐ramp‐up ratios of HBsAg to HBV DNA calculated from data presented in other reports show ranges of 0.03 to 0.25 ng HBsAg per 100 DNA copies in the early acute phase (before anti‐HBc IgM positivity) 13 and 0.01 to more than 100 ng HBsAg per 100 DNA copies during late acute infection 14 . In comparison, the ratios in our study ranged from 0.188 to 2.8 × 10 4 HBsAg ng per 100 HBV DNA copies.…”

Influence of hepatitis B virus genotypes on the intra‐ and extracellular expression of viral DNA and antigens†‡

“…44,[46][47][48] Higher levels of HBsAg secretion for subgenotypes Ae and Aa than the others may contradict their low replicative activity, but may be an immune escape mechanism. The mechanism needs to be sought for, by which genotype A can direct the synthesis of HBsAg in high levels out of proportion to viral DNA, core protein and HBeAg.…”

Hepatitis B Virus Genotypes and Variants

“…The newest HBV genotype, J, was identified in the Ryukyu Islands in Japan, and this genotype has a close relationship with gibbon genotypes and human genotype C (Tatematsu et al 2009 (Mayerat et al 1999). In general, the rate of chronicity following acute genotypes A and D infection were reported to be high compared with genotypes B and C (Heijtink et al 1999;Mayerat et al 1999;Kobayashi et al 2004;Leblebicioglu and Eroglu 2004;Suzuki et al 2005;Ito et al 2014). Taken together, the persistence of HBV infection after acute infection may be attributable to the variable strength of host -viral interactions, the modes of transmission as well as the varying distribution of genotypes.…”