Correspondence

Viral Hepatitis in HIV Infection

N Engl J Med 2007; 357:90-91July 5, 2007

Article

To the Editor:

Koziel and Peters (April 5 issue)1 suggest a list of tests for viral hepatitis in patients with human immunodeficiency virus (HIV) infection. There was, however, no mention of hepatitis delta virus (HDV) infection in association with hepatitis B virus (HBV). Worldwide, 15 million people are infected with HDV,2 and thus it remains an important cause of liver-related illness and death. HDV suppresses HBV replication, so most patients with HDV infection have low levels of HBV DNA2; therefore, clinicians may underestimate disease severity in the absence of liver histologic findings. Furthermore, only interferon-based therapy is currently effective in the treatment of HDV infection.3-5 Patients coinfected with HIV and HBV should be tested for anti-HDV antibodies (anti-HDV IgG and anti-HDV IgM antibodies), particularly if they are from an area where HDV is endemic or from a country where routine immunization against HBV is not practiced. The HDV RNA level should be measured in patients who are positive for HDV, and a liver biopsy should be performed to assess histologic damage and the need for antiviral treatment.

Timothy J.S. Cross, B.Med.Sci., M.B., B.S.
Chris B. Taylor, M.D., F.R.C.P.
Philip M. Harrison, M.D., Ph.D.
King's College Hospital, London SE5 9RS, United Kingdom
tjscross@hotmail.com

5 References

1. 1

   Koziel MJ, Peters MG. Viral hepatitis in HIV infection. N Engl J Med 2007;356:1445-1454
   Full Text | Web of Science | Medline

2. 2

   Farci P. Delta hepatitis: an update. J Hepatol 2003;39:Suppl 1:S212-S219
   CrossRef | Web of Science | Medline

3. 3

   Farci P, Mandas A, Coiana A, et al. Treatment of chronic hepatitis D with interferon alfa-2a. N Engl J Med 1994;330:88-94
   Full Text | Web of Science | Medline

4. 4

   Castelnau C, Le Gal F, Ripault MP, et al. Efficacy of peginterferon alpha-2b in chronic hepatitis delta: relevance of quantitative RT-PCR for follow-up. Hepatology 2006;44:728-735
   CrossRef | Web of Science | Medline

5. 5

   Niro GA, Ciancio A, Gaeta GB, et al. Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology 2006;44:713-720
   CrossRef | Web of Science | Medline

To the Editor:

Koziel and Peters suggest testing for HBV DNA in HIV-infected patients with so-called occult HBV infection, defined as those in whom antibodies against hepatitis B core antigen (anti-HBc) are the only serologic markers present. This testing may be premature. HBV DNA has also been detected in patients with antibodies against hepatitis B surface antigen (HBsAg)1 and even in patients whose test results are negative for all HBV markers.2 Test results for HBV DNA may vary between negative and positive in patients who have anti-HBc,3 so a single negative result might not be meaningful. The test itself is expensive; commercial laboratories may charge more than $300. Thus, HBV DNA testing should be restricted to research settings for now. An important question is how many cases of HBV-associated cirrhosis or hepatocellular carcinoma have ever been reported among patients with HIV whose test results are negative for HBsAg. If none have been seen, the issue of occult HBV infection might be moot.

Steven Leiner, N.P.
Mission Neighborhood Health Center, San Francisco, CA 94110
stevenleiner@hotmail.com

3 References

1. 1

   Re VL, Frank I, Gross R, et al. Prevalence, risk factors, and outcomes for occult hepatitis B virus infection among HIV-infected patients. J Acquir Immune Defic Syndr 2007;44:315-320
   CrossRef | Web of Science | Medline

2. 2

   Shire NJ, Rouster SD, Stanford SD, et al. The prevalence and significance of occult hepatitis B virus in a prospective cohort of HIV-infected patients. J Acquir Immune Defic Syndr 2007;44:309-314
   CrossRef | Web of Science | Medline

3. 3

   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;17:6-13
   CrossRef | Web of Science | Medline

To the Editor:

The review by Koziel and Peters on viral hepatitis in patients infected with HIV deals with factors that could influence the mortality rate in this setting. There is a high prevalence of GB virus C (GBV-C) infection among patients with HIV, particularly among those with HIV and hepatitis C virus (HCV) coinfection.1,2 Furthermore, the GBV-C infection may significantly influence the mortality rate among patients with HIV, as do the CD4+ cell count and the progression to AIDS.3,4 The potential benefit of HIV and GBV-C coinfection has been demonstrated both in and before the era of highly active antiretroviral treatment.3 Should we consider the coinfection with GBV-C virus as a factor influencing the risk of death among patients with HIV and HCV coinfection?

Domenico Rendina, M.D.
Giuseppe Mossetti, M.D.
Federico II University, 80131 Naples, Italy

Gianpaolo De Filippo, M.D.
Gaetano Rummo Hospital, 82100 Benevento, Italy
gianpaolo.defilippo@ao-rummo.it

4 References

1. 1

   Rendina D, Vigorita E, Bonavolta R, et al. HCV and GBV-c/HGV infection in HIV positive patients in southern Italy. Eur J Epidemiol 2001;17:801-807
   CrossRef | Web of Science | Medline

2. 2

   Schwarze-Zander C, Blackard JT, Zheng H, et al. GB virus C (GBV-C) infection in hepatitis C virus (HCV)/HIV-coinfected patients receiving HCV treatment: importance of the GBV-C genotype. J Infect Dis 2006;194:410-419
   CrossRef | Web of Science | Medline

3. 3

   Berzsenyi MD, Bowden DS, Roberts SK. GB virus C: insights into co-infection. J Clin Virol 2005;33:257-266
   CrossRef | Web of Science | Medline

4. 4

   Weber R, Sabin CA, Friis-Moller N, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med 2006;166:1632-1641
   CrossRef | Web of Science | Medline

Author/Editor Response

Cross and colleagues call attention to an important issue in chronic HBV infection — namely, coinfection with HDV and HIV. In certain regions, particularly among intravenous drug users, HDV and HIV coinfection is common. Although the exact prevalence of HBV and HDV and the impact of HDV on outcomes in the setting of HIV are unclear, the authors raise important concerns about both the diagnosis and the management of HBV and HDV.1

In reply to Leiner, the treatment of patients who have isolated anti-HBc is controversial. There is a wide variation in the prevalence of HBV DNA in the serum of HIV-positive persons with isolated anti-HBc; however, given the implications of choosing antiretroviral therapies that might include a single agent with activity against HBV,2 we feel it is prudent for clinicians to check HBV DNA levels and not restrict this test to research settings.

With respect to testing for GBV-C (also called hepatitis G in older literature), there is no indication that GBV causes hepatitis or liver disease, and there is no effect of GBV-C on the natural history of HCV infection.3 The recent study4 cited by Rendina et al. showed no effect on CD4 counts after clearance of GBV-C infection during treatment with interferon and ribavirin in patients with HIV and HCV coinfection. It has been suggested that GBV-C is a favorable prognostic factor in HIV infection; thus, with higher CD4 counts, by extension, the progression of liver disease would be expected to be slower. However, this has not been proved. Moreover, studies of GBV-C and HIV coinfection have been equivocal with respect to the effect of GBV-C on the natural history of HIV infection.5

Margaret James Koziel, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215
mkoziel@bidmc.harvard.edu

Marion G. Peters, M.D.
University of California at San Francisco, San Francisco, CA 94143

5 References

1. 1

   Sheng WH, Hung CC, Kao JH, et al. Impact of hepatitis D virus infection on the long-term outcomes of patients with hepatitis B virus and HIV coinfection in the era of highly active antiretroviral therapy: a matched cohort study. Clin Infect Dis 2007;44:988-995
   CrossRef | Web of Science | Medline

2. 2

   Filippini P, Coppola N, Pisapia R, et al. Impact of occult hepatitis B virus infection in HIV patients naive for antiretroviral therapy. AIDS 2006;20:1253-1260
   CrossRef | Web of Science | Medline

3. 3

   Stapleton JT. GB virus type C/hepatitis G virus. Semin Liver Dis 2003;23:137-148
   CrossRef | Web of Science | Medline

4. 4

   Schwarze-Zander C, Blackard JT, Zheng H, et al. GB virus C (GBV-C) infection in hepatitis C virus (HCV)/HIV-coinfected patients receiving HCV treatment: importance of the GBV-C genotype. J Infect Dis 2006;194:410-419
   CrossRef | Web of Science | Medline

5. 5

   Bjorkman P, Flamholc L, Naucler A, Molnegren V, Wallmark E, Widell A. GB virus C during the natural course of HIV-1 infection: viremia at diagnosis does not predict mortality. AIDS 2004;18:877-886
   CrossRef | Web of Science | Medline

Citing Articles (1)

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   Maria Cássia Mendes-Correa, Michele S. Gomes-Gouvêa, Mónica V. Alvarado-Mora, Mariliza H. Da Silva, Carolina Lázari, Norma C.S. Cavalcanti, Flaviane K. Alonso, Cátia C. Carpinelli, David E. Uip, João R.R. Pinho. (2011) Hepatitis delta in HIV/HBV co-infected patients in Brazil: is it important?. International Journal of Infectious Diseases 15:12, e828-e832
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