Abstract
HBsAg clearance is associated with clinical cure of chronic hepatitis B virus (HBV) infection. Quantification of HBsAg may help to predict HBsAg clearance during the natural course of HBV infection and during antiviral therapy. Most studies investigating quantitative HBsAg were performed in HBV mono-infected patients. However, the immune status is considered to be important for HBsAg decline and subsequent HBsAg loss. HIV co-infection unfavorably influences the course of chronic hepatitis B. In this cross-sectional study we investigated quantitative HBsAg in 173 HBV/HIV co-infected patients from 6 centers and evaluated the importance of immunodeficiency and antiretroviral therapy. We also compared 46 untreated HIV/HBV infected patients with 46 well-matched HBV mono-infected patients. HBsAg levels correlated with CD4 T-cell count and were higher in patients with more advanced HIV CDC stage. Patients on combination antiretroviral therapy (cART) including nucleos(t)ide analogues active against HBV demonstrated significant lower HBsAg levels compared to untreated patients. Importantly, HBsAg levels were significantly lower in patients who had a stronger increase between nadir CD4 and current CD4 T-cell count during cART. Untreated HIV/HBV patients demonstrated higher HBsAg levels than HBV mono-infected patients despite similar HBV DNA levels. In conclusion, HBsAg decline is dependent on an effective immune status. Restoration of CD4 T-cells during treatment with cART including nucleos(t)ide analogues seems to be important for HBsAg decrease and subsequent HBsAg loss.
Highlights
Chronic Hepatitis B virus (HBV) infection affects more than 350 million people worldwide
P-values obtained by U-Mann Whitney and Kruskall-Wallis ANOVA tests. doi:10.1371/journal.pone.0043143.g004. In this retrospective multi-center study we provide data on HBsAg concentrations in a large cohort of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infected patients that further support the important role of the immune status for HBsAg decline
Combination antiretroviral therapy does restore CD4 T-cell counts and inhibits HBV DNA, which both are relevant factors associated with HBsAg levels, especially in HBeAg positive disease [19] (Fig. 1d)
Summary
Chronic Hepatitis B virus (HBV) infection affects more than 350 million people worldwide. HBsAg clearance and anti-HBs seroconversion is associated with the best outcome in patients with HBV infection [1,2]. In the natural course of HBV infection and during antiviral therapy quantification of HBsAg is a useful tool to predict the chances for HBsAg clearance [3]. The decline of HBsAg concentrations may correlate with an effective immune response against HBV and is less dependent on direct viral suppression with HBV polymerase inhibitors. This statement is supported by data that interferon alpha induced stronger HBsAg decline compared to NA therapy [4,5]. Highest HBsAg levels are observed in immunotolerant HBeAg positive patients while lowest are detected in HBsAg carriers [7,8,9]
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