T‐ and B‐cell responses and previous exposure to hepatitis B virus in ‘anti‐HBc alone’ patients

Abstract

A serologic response to hepatitis B virus (HBV) defined as 'anti-HBc alone' is commonly observed, but its significance remains unclear. This study aimed to define the relationship between 'anti-HBc alone' serostatus and HBV infection, including HBV-specific T- and B-cell memory responses. We enrolled 31 'anti-HBc alone' patients. Total HBV DNA and cccDNA were tested by nested polymerase chain reaction (PCR) analysis in liver samples from 22 'anti-HBc alone' patients vs controls (chronic or resolved HBV infection), followed by HBsAg/HBcAg immunohistochemical (IHC) staining. IFN-γ secretion by HBV-specific T cells was compared in individuals who were 'anti-HBc alone' (n = 27), resolved HBV (n = 21), chronic HBV (n = 24) and 12 healthy controls using enzyme-linked immunospot (ELISpot) assays. An HBsAg-IgG B-cell ELISpot assay was performed in 'anti-HBc alone' patients before and after one dose of recombinant HBsAg vaccine. The majority (23/31, 74.2%) of the 'anti-HBc alone' individuals were co-infected with HCV. Infrequent intrahepatic total HBV DNA (2/22, 9.1%) and cccDNA (1/22, 4.5%) were detected in biopsies; HBsAg and HBcAg IHC staining was negative. HBV-specific T-cell responses were similar between 'anti-HBc alone' individuals and HBV resolvers. Circulating HBV-memory B-cell responses were detected in all 'anti-HBc alone' individuals, consistent with an HBsAg-specific memory pool. After one HBV vaccine dose, increased anti-HBs antibody levels were observed, accompanied by an expansion of HBsAg-specific memory B cells (P = 0.0226). 'Anti-HBc alone' individuals showed HBV-specific T-cell and memory B-cell responses typical of previous viral exposure and protective memory, suggesting a resolved infection.

Characterization of hepatitis B virus (HBV) preS/S gene mutations in blood donors with occult HBV infection in the Baoji area of North China

“…This was approximately three times lower than the data from South China reported by the National Institute of Diagnostics and Vaccine Development in Infectious Diseases of China (1:631), but it was slightly higher than the data from Hong Kong Red Cross Blood Transfusion Service (1:2450) and Shenzhen Blood Center (1:3239) . The reasons for the presence of low HBV DNA levels in the absence of detectable HBsAg among individuals with OBI remains unclear, but it is thought that both host and viral factors are important for suppressing viral replication and maintaining control of the infection . The viral and host factors that contribute to OBI are numerous, complex, and vary between individuals.…”

“…13,14 The reasons for the presence of low HBV DNA levels in the absence of detectable HBsAg among individuals with OBI remains unclear, but it is thought that both host and viral factors are important for suppressing viral replication and maintaining control of the infection. 40 The viral and host factors that contribute to OBI are numerous, complex, and vary between individuals. Possible mechanisms may include low HBsAg production, impaired HBsAg secretion, diminishing HBsAg antigenicity, and elicitation of low-affinity or non-neutralizing antibodies that interfere with detection by the HBsAg reagent.…”

Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV

“…The B cell ELISPOT assay is most widely used to analyze HBV-specific memory B cells, which need to be differentiated in vitro into antibody secreting cells before they can be quantified as spot-forming cells (SFCs). [2][3][4][5] HBsAg B cell ELISPOT assays detect low numbers of anti-HBsAg-antibody (HBsAb)-producing B cells in the blood of patients with CHB, despite the presence of vast amounts of HBsAg in their serum. [4][5][6] Recently, HBsAg-specific B cells could be directly isolated ex vivo from the liver and blood of patients with CHB by using fluorescently labeled HBsAg as baits.…”

Emerging Challenges in Managing Hepatitis B in HIV Patients

“…A single vaccine recall injection may distinguish the three possibilities mentioned above (false positivity, prior immunity with undetectable anti-HBs, or low-level HBV infection). If anti-HBs become positive with high titers 1 month after a shot, an anamnestic response should be suspected, and no further vaccine injections are needed [61,62].…”