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. Recovery from HBV infection is associated with the presence of antibody to hepatitis B surface antigen (anti-HBs), and active infection shows hepatitis B surface antigen (HBsAg). In some patients, the anti-HBc is the only marker of HBV infection.1,2 A higher frequency of isolated reactivity to anti-HBc is observed in patients with HIV infection and hepatitis C virus (HCV) coinfection.1-6 In this study, we describe the influence of HCV viral load and its genotypes in the development of isolated anti-HBc in a group of patients with HIV coinfection.
The presence of HBV and HCV serological markers was investigated in 450 patients with HIV infection. All patients had undergone testing for anti-HBc and anti-HBs. Patients who were positive for any of the 2 were tested for HBsAg, HbeAg, and anti-HBe. Isolated anti-HBc was defined as positive anti-HBc with all the rest of the markers negative. The test was done with commercially available kits (AXSYM System; Abbott Laboratories, Abbott Park, IL). In addition to this, we realized HCV viral load and genotypes in all patients with HCV infection (COBAS AMPLICOR HCV MONITOR System, Roche Laboratories, Indiana, IN). Routine testing was used to detect liver enzyme, CD4+ cell count, and HIV viral load at the time of serology. Continuous values were expressed as mean and compared using Student t test or U of Mann-Whitney. Categorical values were expressed as absolute and relative frequencies and were compared using Fisher exact test or χ2 test. A P value less than 0.05 was considered statistically significant. A binary logistic regression analysis using a stepwise (Wald) was realized.
We have chosen 94 patients with HIV and HCV coinfection, 36 of them had anti-HBs+ and anti-HBc+ (group 1) who were compared with 58 patients with isolated anti-HBc+ (group 2). The groups did not statistically differ in sex (group 1, 83% were men; and group 2, 73% were men) or mean age (group 1, 30 ± 6 years; and group 2, 30 ± 5 years). There are no statistically significant differences in CD4+ cell count between the groups (group 1, 361 ± 261 cells/mm3; and group 2, 286 ± 222 cells/mm3) or in the HIV viral load (group 1, 143,017 ± 324,200 RNA copies/mL; group 2, 150,805 ± 226,500 RNA copies/mL). We have not observed statistically significant differences between the groups with regard to the liver enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase (Table 1). All patients have positive viremia to HCV. The mean HCV viral load was 1,243,599 UI/mL in group 1 and 1,417,840 UI/mL in group 2 without statistically significant differences in the U of Mann-Whitney test. The distribution of genotypes were as follows, in group 1: 3a, 28%; 1b, 30%; 1a, 23%; 1a/1b, 8.3%; 2a/2c, 0%; and 4c/4d, 0%; and in group 2: 1a, 29%; 3a, 26%; 1b, 20.5%; 4c/4d, 17.2%; 1a/1b, 1.7%; and 2a/2c, 1.7%. The presence of genotype 4c/4d was associated with the presence of isolated anti-HBc+ (P = 0.012, odds ratio = 1208 [1074-1359]). Multivariate analysis also showed a significant association between genotypes 4c/4d and the presence of isolated anti-HBc+ (P = 0.0001).
A higher frequency of isolated anti-HBc has been demonstrated in HIV patients associated with coinfection with HCV.6-9 Previous studies6 done by our working group and other authors5-9 showed a greater statistical relation between the presence of antibodies to HCV and the isolated anti-HBc+. Only a few studies8 distinguish between HCV-viremic patients and HCV RNA-negative patients but did not show a relation between different genotypes of HCV and the presence of isolated anti-HBc+. However, our study showed that the anti-HBc+ alone phenotype was significantly associated with the presence of genotype 4c/4d but not with the HCV viral load. Some theories have attributed the relation between HCV infection and presence of anti-HBc+ alone to the possible interference in HbsAg synthesis in HCV infection.8,9 Our results showed that this interference would be greater in patients with genotype 4c/4d.
In conclusion, the presence of isolated anti-HBc is statistically associated with the presence of genotype 4c/4d in patients with HIV and HCV coinfection. However, its presence is not related to HCV viral load counts in these patients. Although the clinical significance of this association is not clear, these findings represent new information about the relations between these viruses, and future studies will be needed to clarify the detailed mechanisms how the HCV genotypes influence HbsAg or anti-HBs production in patients with HIV infection.
1. Neau D, Winnnock M, Galperine T, et al, Groupe d'Epidemiologie Clinique du Sida en Aquitaine (GECSA). Isolated antibodies against the core antigen of hepatitis B virus in HIV-infected patients. HIV Med
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. Vázquez-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. Guardado AR, Pérez MR, Maradona JA, et al. Isolated presence of antibody to hepatitis B core antigen in patients coinfected with HIV. J Acquir Immune Defic Syndr
7. Greub G, Frei PC. Isolated antibody to hepatitis B core is associated with hepatitis C virus co-infection. Clin Microbiol Infect
8. Wedemeyer H, Cornberg M, Tegtmeyer B, et al. Isolated anti-HBV core phenotype in anti-HCV patients is associated with hepatitis C virus replication. Clin Microbiol Infect
9. Weber B, Melchior W, Gehrke R, et al. Hepatitis B virus markers in anti-HBc only positive individuals. J Med Virol