To the Editor:
Antibody to hepatitis B core antigen (anti-HBc) is considered a sensitive and specific serum marker of hepatitis B virus (HBV) infection. Patients who have been infected with HBV and have recovered have antibody to hepatitis B surface antigen (anti-HBs), and those who are actively infected have hepatitis B surface antigen. In some patients, anti-HBc is the only marker of HBV infection. This finding could be due to false-positive results of reactivity testing, loss of anti-HBs with time or failure of patients to develop anti-HBs after HBV infection, occult chronic HBV infection with levels of hepatitis B surface antigen below the limits of detection, or a prolonged “window” phase of acute HBV infection. 1,2
Isolated reactivity to anti-HBc is observed relatively frequently in patients with HIV infection. We describe the characteristics of patients with isolated anti-HBc and HIV coinfection. 2–5
The presence of serological markers for HBV and hepatitis C virus (HCV) was investigated in 450 patients with infection by HIV. All patients had undergone testing for anti-HBc and anti-HBs. Patients who were positive for either antibody were evaluated for hepatitis B surface antigen, hepatitis B e antigen, and antibody to hepatitis B e antigen. Isolated anti-HBc was defined as positive results for anti-HBc with all the rest of the markers negative. The tests were done with commercially available kits (AXSYM System; Abbott Laboratories, Abbott Park, IL). Routine tests for determination of liver enzyme levels, CD4+ cell counts, and HIV load were performed simultaneous to serological studies.
Fifty-seven patients positive for anti-HBs and for anti-HBc (group 1) were compared with 47 patients with isolated anti-HBc (group 2). The χ2 test was used for comparing qualitative determinations between the 2 groups, and the Student t test was used for quantitative variables.
The 2 groups did not differ statistically by sex (group 1, 80% men; group 2, 75% men) or age (group 1, 41 ± 7 years; group 2, 40 ± 5 years). There were no statistically significant differences in CD4+ cell count (group 1, 375 ± 257/mm3; group 2, 309 ± 280/mm3; P = 0.387) or HIV load (group 1, 155,579 ± 289,917 copies/mL; group 2, 243,641 ± 581,318 copies/mL; P = 0.2) between the 2 groups. Eighty-nine patients with isolated anti-HBc also had antibodies to HCV versus 47 patients with antibodies to HCV in group 2 (P = 0.0001). Multivariate analysis also showed a significant association between antibodies to HCV and the presence of isolated anti-HBc (P = 0.387). We did not observe statistically significant differences in liver enzyme levels (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase) between the 2 groups (Table 1).
The presence of isolated anti-HBc is observed relatively frequently in immunocompromised patients, intravenous drug users, and patients with HIV or HCV infection. 5,6 Other studies 5 have examined the influence of immunosuppression produced by HIV in the absence of production of or during the loss of anti-HBs. However, our results did not show a relation between CD4+ cell counts carried out simultaneous to serological tests and the presence of isolated anti-HBc. On the other hand, and like other studies, 5–7 our results showed a greater statistical relation between the presence of antibodies to HCV and isolated anti-HBc. Some theories have attributed this fact to the possible interference in hepatitis B surface antigen synthesis by HCV infection, but the real cause is not clear. 7
In conclusion, the presence of isolated anti-HBc is frequent in patients with HIV infection, and it is statistically associated with HCV coinfection. However, its presence is not related to CD4+ cell count in these patients. The clinical significance of this association is not clear.
Azucena Rodríguez Guardado*
Mercedes Rodríguez Pérez†
Jose A. Maradona*
Jose A. Cartón*
*Infectious Diseases Unit, Hospital Central de Asturias, Oviedo, Spain
†Microbiology Unit, Hospital Central de Asturias, Oviedo, Spain
1. Silva AE, McMahon BJ, Parkinson AJ, et al. Hepatitis B virus DNA in persons with isolated antibody to hepatitis B core antigen who subsequently received hepatitis B vaccine. Clin Infect Dis
2. Ghandi RT, Wurcel A, Lee H, et al. Isolated antibody to hepatitis B core antigen in human immunodeficiency virus type-1–infected individuals. Clin Infect Dis
3. Davaro RE, Cheeseman SH, Keroack MA, et al. The significance of isolated antibody to hepatitis B core antigen seropositive in patients infected with human immunodeficiency virus. Clin Infect Dis
4. Vazquez-Vizoso F, Eiroa P, Ledo L, et al. HIV infection and isolated detection of anti-HBc. Gastroenterology
5. Santos EA, Yoshida CFT, Rolla VC, et al. Frequent occult hepatitis B virus infection in patients infected with human immunodeficiency virus type 1. Eur J Clin Microbiol Infect Dis
6. Cacciola I, Pollicino T, Squadrito G, et al. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med
7. Weber B, Melchior W, Gehrke R, et al. Hepatitis B virus markers in anti-HBc only positive individuals. J Med Virol