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

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