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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.

References

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  • 1
    Lok ASF, McMahon B. Chronic hepatitis B: Update 2009. HEPATOLOGY 2009; 50: 661662.
  • 2
    Núñez M, Ríos P, Pérez-Olmeda M, Soriano V. Lack of ‘occult’ hepatitis B virus infection in HIV-infected patients AIDS 2002; 16: 20992101.
  • 3
    Neau D, Winnock M, Jouvencel AC, Faure M, Castéra L, Legrand E, 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: 750753.
  • 4
    Rodríguez-Torres M, Gonzales-Garcia J, Bräu N, Solá R, Moreno S, Rockstroh J, et al. APRICOT Investigators Occult Hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection: clinically relevant or a diagnostic problem? J Med Virol 2007; 79: 694700.
  • 5
    Shire NJ, Rouster SD, Rajicic N, Sherman KE. Occult hepatitis B in HIV-infected patients. J Acquir Immune Defic Syndr 2004; 36: 869875.
  • 6
    Lo Re VL 3rd, Frank I, Gross R, Reddy KR, Mounzer K, Zemel BS, et al. Prevalence, risk factors, and outcomes of occult hepatitis B virus infection among HIV-infected patients. J Acquir Immune Defic Syndr 2007; 44: 315320.
  • 7
    Pogany K, Zaajier HL, Prins JM, Wit FW, Lange JM, Beld MG. Occult hepatitis B virus infection before and 1 year after start of HAART in HIV type-1 positive patients. AIDS Res Hum Retroviruses 2005; 21: 922926.
  • 8
    Hofer M, Joller-Jemelka HI, Grob PJ, Luthy R, Opravil M. 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: 613.
  • 9
    Piroth L, Binquet C, Vergne M, Minello A, Livry C, Bour JB, 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: 681686.
  • 10
    Morsica G, Ancarani F, Bagaglio S, Maracci M, Cicconi P, Cozzi AL, et al. Occult hepatitis B virus infection in a cohort of HIV-positive patients: correlation with hepatitis C virus coinfection, virological and immunological features. Infection 2009; 37: 445449.

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