Clinical Article

Occult Hepatitis B in Patients with Isolated Hepatitis B Core Antibody in a community hospital in the Bronx NY

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Abstract

10.6% of patients who were hepatitis B core alone positive (HBCAP) had occult hepatitis B – 70% of whom were HIV+.  There was documented evidence of prior HBV infection in one third of patients who were HBCAP. This occurred significantly more frequently in HIV+ patients. HBV screening for HIV+ patients should include HBV DNA.

Introduction

At our community hospital in the Bronx, 5% of patients screened for hepatitis B are core antibody alone positive. The aim of this study is to determine if risk factors that are present in our population (drug use, HIV status, HCV status) affect the patients’ HBCAP status and may represent not the loss of HBsurface antibody but the presence of occult HBV, determined by the presence of ongoing HBV replication.

Methods

We retrospectively reviewed data for all patients who were HBCAP from January 2003 to December 2005. Patients with evidence of prior HBV (HBV surface-antigen+, surface-antibody+, HBV e-antibody+ or HBV-DNA positive) were grouped together. The associations between prior HBV infection and HIV, HCV, and substance use were examined by ANOVA and multivariate logistic regression.

Results

We identified 1,571 patients who were HBCAP. Sixty five percent were males, 53% Hispanic and 38% Black.  Sixty two percent had a history of illicit drug or alcohol use. 52% were infected with HCV, and 31% with HIV. The mean CD4 count was 298 (range: 2-1729). 48% of HIV patients had a CD4 below 200, 21% had a CD4 greater than 500.

In this group of core alone positive patients with known HIV and HCV status, 17.0% are HIV and HCV negative, 26.2% are HIV positive but HCV negative, 17.6% are HCV positive but HIV negative,  and 39.2% are HIV and HCV co-infected (p=0.014).

160 patients had data for HBV DNA. 17 patients (10.6%) were HBV DNA positive (figure 1). The mean HBV DNA was 8,221 (range 195-60,113) and 8 had HBV DNA levels greater than 1,000. 12 of the 17 patients (70%) were HIV positive, 8 (47%) were HCV positive and 7 patients (41%) were co-infected with HIV and HCV.

Figure 1
Figure 1

Multiple HBV serologies were completed for 647 patients; 205 (31.7%) had prior serologic or virologic evidence of HBV.  The proportion with evidence of prior HBV infection was higher for HIV+ vs. HIV- (38.3% vs. 25.9%, p=0.01) and lower for HCV+ vs. HCV- (29.1% vs. 41.0%, p=0.02) and for drug users vs. non-users (29.5% vs. 40.4%, p= 0.03) (figure 2). There was no association with alcohol use.

Figure 2

In multivariate analysis controlling for age, sex, and race, associations with HIV+ and no recorded drug use remained significant (p&ln;0.03).

Discussion

In areas of low hepatitis B prevalence, 10 to 20% of patients are core alone positive. In our institution approximately 5% of all patients screened were core alone positive. This increased to 30% in our subpopulation of HIV positive patients 1  who have a much higher exposure to HBV.  The significance of a core alone positive serology is debated. On the one hand, it is known that with time patients lose their hepatitis b surface antibody and remain core alone positive, on the other hand some patients are unable to express hepatitis B surface antigen. In addition, several articles describe an increase prevalence of HBV core alone positivity in HIV HCV co-infected patients. 2 3   This study also showed that co-infected patients make up a higher proportion of core alone positive patients than HIV or HCV alone. The reason for this remains unclear. Weber 4 suggests that there is a possible interference of the expression of HBV surface Ag with HCV infection, and Rodriguez-Guardado 2 note that the presence of isolated HBV core antibody associated with the HCV genotype 4c/4d.

This study separates two groups of patients: one that had past evidence of hepatitis B infection and a second group of patients that despite multiple HBV serologies had no other serological markers of past HBV infection. This later group could have been infected with HBV but was not evident at the time of serologic or virologic testing.

Thirty two percent of patients had evidence of past HBV infection. This finding occurred significantly more frequently in HIV positive patients but not in patients with similar risk factors: IVDU or hepatitis C patients. This could reflect some interaction between HIV and the expression of HBV markers or the interaction of HIV immune status and HBV disease. Of note, our HIV patients had advanced disease: 48% had CD4 below 200.

One spectrum of HBV core alone positivity is highlighted in our finding that 10.6% of our patients have circulating DNA, 70% of whom are HIV positive. Other studies have described a rate of occult hepatitis B ranging from 0 to 37% in HIV patients. 5 6 7 8   This has implications not only for HBV transmission but also for screening and treatment options for HIV patients. Many drugs used to treat HIV also treat HBV. They can induce suppression of HBV, resistance in HBV, and rebound disease when the drugs are discontinued. Therefore, HIV patients who are core alone positive should be screened with HBV DNA.

References

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  2. Rodriquez-Guardado A, Melon S, Rodriquez M, et al. Influence of HCV genotype in isolated presence of antibody to hepatitis B core antigen in patients with HIV coinfection. Acquir Immune Defic Syndr 2006;42:647-9.

  3. Neau D, Winnock M, Galperine T, et al. Isolated antibodies against the core antigen of hepatitis B virus in HIV-infected patients. HIV Med 2004:5:171-3.

  4. Weber B, Melchior W, Gehrke R, et al. Hepatitis B virus markers in anti-HBc only positive individuals. J Med Virology 2001;64:312-9.

  5. Piroth L, Binquet C, Vergne M, et al. The evolution of hepatitis B virus serological patterns and the clinical relevance of isolated antibodies to hepatitis B core antigen in HIV infected patients. J Hepatol 2002;36:681-6.

  6. Hofer M, Joller-Jemelka HI, Grob PJ, et al. Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Swiss HIV cohort study. Eur J Clin Microbiol Infect Dis 1998; 17:6-13.

  7. Gandhi RT, Wurcel A, McGovern B, et al. Low prevalence of ongoing hepatitis B viremia in HIV-positive individuals with isolated antibody to hepatitis B core antigen. J Acquir Immune Defic Syndr 2003;34:439-441.

  8. Neau D, Winnock M, Jouvencel AC, et al. Occult hepatitis B virus infection in HIV-infected patients with isolated antibodies to hepatitis B core antigen: Aquitaine cohort, 2002-2003. Clin Infect Dis 2005;40: 750-3.