Routine hepatitis B virus DNA testing in human immunodeficiency virus–infected patients with positive hepatitis B core antibody but negative hepatitis B surface antigen is not justified by current evidence


  • Potential conflict of interest: Dr. Nuñez received grants from Bristol-Myers Squibb.

Routine Hepatitis B Virus DNA Testing in Human Immunodeficiency Virus–Infected Patients with Positive Hepatitis B Core Antibody but Negative Hepatitis B Surface Antigen is Not Justified by Current Evidence

To the Editor:

In the most recent American Association for the Study of Liver Diseases hepatitis B virus (HBV) guidelines, Drs. Lok and McMahon recommend as “prudent” “to test all human immunodeficiency virus (HIV)-infected persons for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) and if either is positive, to test for HBV DNA”.1 I think that the recommendation of testing for HBV DNA in HIV-infected patients with isolated anti-HBc antibodies should be better supported by clinical evidence. HBV DNA testing is an expensive test, and unless there is a well-defined clinical benefit, it is difficult to justify it. The authors make the recommendation after stating that “patients with HIV infection can have high levels of HBV DNA and hepatic necroinflammation with anti-HBc but not HBsAg, so-called occult HBV”, quoting a manuscript delivered by an international panel in 2005. However, this appears to be a misquotation because that international panel actually considers the “hypothetical” occurrence of such events, but follows saying that “..the prevalence and potential impact of ‘occult’ hepatitis B infections are still unclear in the setting of HIV infection”. There are several studies published that have assessed the presence of “occult HBV” in HIV-infected patients, reporting prevalences as low as 0% and as high as 89.5% depending on the experimental approach. In those cases with detectable HBV DNA, levels rarely reach 350 IU/mL.2–10 Then the question is, what is the clinical relevance of these findings? In one of the most recent series published, alanine aminotransferase levels were not higher in the patients found to have “occult” HBV infection,10 nor were patients reported to have developed liver complications. The same authors also analyzed a possible link between occult infection and cellular immunodeficiency, which has been the claimed reason for a higher frequency of this event in HIV-infected patients, but did not find it. Moreover, the presence of HBV-active drugs within antiretroviral regimens did not have any effect on the presence of “occult” HBV infection. Therefore, identifying patients with detectable HBV DNA is not going to have implications in disease management, because even using an HBV-active highly active antiretroviral therapy regimen seems to not make any difference. I suspect that we are facing a phenomenon of overdiagnosis. This might be a well-recognized finding in clinical research, but with no translation to the clinical care of patients according to current evidence. I have witnessed a fairly high number of HBV DNA testing in “only HBc” HIV-infected patients, which invariably come back reported as undetectable. Because we clinicians use guidelines for guidance in clinical management, unfounded recommendations should be avoided because they have economic repercussions of great relevance in a health care environment increasingly at risk for limited resources.

Marina Núñez M.D., Ph.D.*, * Wake Forest University Health Sciences, Winston Salem, NC.