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Observational Study
. 2014 Jun;58(11):1625-33.
doi: 10.1093/cid/ciu127. Epub 2014 Mar 5.

Increasing incidence of recent hepatitis D virus infection in HIV-infected patients in an area hyperendemic for hepatitis B virus infection

Chien-Ching Hung  1 , Shih-Min Wu, Pi-Han Lin, Wang-Huei Sheng, Zong-Yu Yang, Hsin-Yun Sun, Mao-Song Tsai, Kuan-Yeh Lee, Ming-Siang Huang, Shu-Fang Chang, Yi-Ching Su, Wen-Chun Liu, Sui-Yuan Chang
Affiliations
Observational Study

Increasing incidence of recent hepatitis D virus infection in HIV-infected patients in an area hyperendemic for hepatitis B virus infection

Chien-Ching Hung et al. Clin Infect Dis. 2014 Jun.

Abstract

Background: Superinfection with hepatitis D virus (HDV) may increase the risk for hepatitis flares and chronic hepatic complications in patients with chronic hepatitis B virus (HBV) infection. This retrospective observational study aimed to examine the incidence of and factors associated with recent HDV superinfection among individuals coinfected with human immunodeficiency virus (HIV) and HBV.

Method: Anti-HDV immunoglobulin G (IgG) was sequentially determined in 375 HIV/HBV-coinfected patients to estimate the HDV incidence between 1992 and 2012. Plasma HDV and HBV loads and HBV surface antigen (HBsAg) levels were determined for the HDV seroconverters. A nested case-control study was conducted to identify the associated factors with HDV seroconversion. Phylogenetic analysis was performed using HDV sequences amplified from HDV seroconverters and HDV-seropositive patients at baseline.

Results: During 1762.4 person-years of follow-up [PYFU], 16 patients seroconverted for HDV, with an overall incidence rate of 9.07 per 1000 PYFU, which increased from 0 in 1992-2001, to 3.91 in 2002-2006, to 13.26 per 1000 PYFU in 2007-2012 (P < .05). Recent HDV infection was associated with elevated aminotransferase and bilirubin levels and elevated rapid plasma reagin titers. Of the 12 patients with HDV viremia, 2 were infected with genotype 2 and 10 with genotype 4. HBsAg levels remained elevated despite a significant decline of plasma HBV DNA load with combination antiretroviral therapy that contained lamivudine and/or tenofovir.

Conclusions: Our findings show that the incidence of recent HDV infection in HIV/HBV-coinfected patients increased significantly from 1992-2001 to 2007-2011, and was associated with hepatitis flares and syphilis.

Keywords: case-control study; seroconversion; seroincidence; sexually transmitted diseases; syphilis.

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Figures

Figure 1.
Figure 1.
Study flow of the incidence of recent hepatitis D virus infection among patients with hepatitis B virus and human immunodeficiency virus coinfection. Abbreviations: HBV, hepatitis B virus; HDV, hepatitis D virus; HIV, human immunodeficiency virus; IDU, injection drug user; IgG, immunoglobulin G; PVL, plasma HIV RNA load.
Figure 2.
Figure 2.
Incidence rate of recent hepatitis D virus infection among patients with hepatitis B virus and human immunodeficiency virus coinfection in 3 study periods, 1992–2012. The incidence rate increased significantly from 0 per 1000 person-years of follow-up (PYFU) between 1992 and 2001 (zero cases for 186.1 PYFU), to 3.91 per 1000 PYFU between 2002 and 2006 (2 cases for 509.7 PYFU), to 13.26 per 1000 PYFU between 2007 and 2012 (14 cases for 1066.6 PYFU).
Figure 3.
Figure 3.
Phylogenetic analysis of hepatitis D virus (HDV) identified from patients with HDV seropositivity at baseline (prevalent HDV infection, open circle, n = 16) and those with HDV seroconversion (incident HDV infection, filled circle, n = 12) during the follow-up. The phylogenetic tree was constructed by the neighbor-joining method based on the Kimura 2-parameter distance matrix listed in MEGA software (version 3.0). The study and reference sequences were aligned using the Clustal W program with minor manual adjustment. The horizontal branch was drawn in accordance with their relative genetic distances. Bootstrap values >700 of 1000 replicates were considered significant and indicated at the nodes of the corresponding branches.
Figure 4.
Figure 4.
Trends of plasma human immunodeficiency virus (HIV) RNA load, hepatitis B virus (HBV) DNA load, hepatitis D virus (HDV) RNA load, and HBV surface antigen (HBsAg) titers in the HDV seroconverters before and after HDV seroconversion. The 13 patients had been diagnosed with HIV/HBV coinfection and were given combination antiretroviral therapy containing lamivudine at enrollment (0.5–1 year before HDV seroconversion). The case number tested for HDV RNA at 0.5–1 year before HDV seroconversion and HDV seronegativity is 12 and 13, respectively. Quantification of HBsAg was determined using the chemiluminescent microparticle immunoassay, the Architect QT, according to the manufacturer's recommendation (Abbott Laboratories, Abbott Park, Illinois).
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