Quantitative longitudinal evaluations of hepatitis delta virus RNA and hepatitis B virus DNA shows a dynamic, complex replicative profile in chronic hepatitis B and D

Background & Aims

This study presents a real-time reverse-transcription PCR (rt-RT-PCR) assay for hepatitis delta virus (HDV) RNA quantification, designed to clarify the interplay between HDV and hepatitis B virus (HBV) in chronic infection.

Methods

Serum HDV-RNA and HBV-DNA were analysed by rt-RT-PCR in a cross-sectional study of 37 untreated chronic HDV patients, 25 of whom were also longitudinally studied.

Results

In the cross-sectional study, both viruses were active in 15 (40.5%) patients and inactive in 4 (10.8%); HDV alone was active in 12 (32.4%) and HBV in 6 (16.2%). The longitudinal study showed seven replication profiles, with considerable fluctuating activity of one or both viruses, including alternating predominance. In 20% of cases, longitudinal HBV/HDV viral loads differed from cross-sectional results, indicating a risk of misinterpreting HBV/HDV interactions when assessing a single determination. Fluctuating HBV replication only increased in the presence of fluctuating HDV activity. HBsAg levels, stable in HBV single infection, fluctuated in HDV chronic infection. The results of both the cross-sectional and longitudinal study call into question the major suppressor effect of HDV over HBV, revealing an important role of HBV.

Conclusions

Longitudinal evaluation of viremia shows a complex interaction between HBV and HDV and is essential to understand the pathophysiology of chronic HDV infection.

Abbreviations: HDV, hepatitis delta virus, HBV, hepatitis B virus, rt-RT-PCR, real-time reverse-transcription PCR, PCR, polymerase chain reaction, ALT, alanine aminotransferase, HBsAg, HBV surface antigen, HBeAg, hepatitis B e antigen, anti-HBe, antibody against HBeAg, HCC, hepatocellular carcinoma, CHB, chronic hepatitis B, CV, coefficient of variation, KW, Kruskal–Wallis test, CHD, chronic hepatitis D

Keywords: Hepatitis delta virus, Hepatitis B virus, Chronic delta infection, HDV-RNA quantification, Real-time PCR, Dynamic replicative profiles