Quantification of serum HBV RNA allows differentiation of disease stages of hepatitis B virus (HBV) infections

Abstract

Introduction: Inactive carriers of HBV infections are distinguished from individuals with active HBV infections by serum levels of HBV DNA. HBV RNA is another surrogate marker of HBV replication which can be quantified from serum. The aim of this study was to explore whether HBV RNA levels permits a better differentiation between the various stages of HBV infection. Methods: Serum samples from 12 patients with acute and 96 with chronic HBV infection (34 inactive HBsAg carrier with HBV DNA < 4 log10 copies/ml and ALT within normal ranges, 34 HBeAg negative and 28 HBeAg positive patients with chronic active hepatitis B (mean age 45.4 ± 15.6 (17 – 77) years, m/w = 73/35, mean ALT 8.7 ± 19.2 (0.22 – 100)µkat/ml, mean HBsAg 4.3 ± 0.9 (0.7 – 6.0) log10 ng/ml) were retrospectively analyzed. HBV DNA was measured by real-time PCR (limit of detection 2.6 log10 copies/ml). HBV-RNA levels were quantified based on a sensitive One-Step-RACE-PCR-Assay which was developed and validated (limit of detection 2.9 log10 copies/ml). Results: HBV RNA could be detected in 9 of 12 patients with acute HBV infection with a mean of 3.4 ± 1.6 (2.0 – 5.9) log10 copies/ml. HBV RNA was detectable in 29 out of 34 HBeAg negative patients and in all 28 patients with HBeAg positive chronic active HBV infection and showed a high correlation with HBV DNA levels (r = 0.93). Mean HBV DNA levels were significantly lower in HBeAg negative as compared to HBeAg positive patients (6.8 ± 1.3 (4.2 – 8.9) vs. 8.2 ± 1.4 (4.5 – 10.5) log10 copies/ml, p < 0.001), and so were mean HBV RNA levels (4.4 ± 1.5 (2.0 – 7.0) vs. 6.8 ± 1.2 (4.3 – 9.1) log10 copies/ml, p < 0.001). In contrast, HBV RNA was detectable in only in 2 out of 34 inactive HBsAg carriers (2.0 ± 0.2 (2.0 – 2.7) log10 copies/ml), while in 28 of those patients HBV DNA was still detectable with a mean of 3.1 ± 0.7 (2.0 – 4.6) log10 copies/ml. Conclusion: Serum levels of HBV RNA show a high correlation with HBV DNA levels in patients with active chronic HBV infection. However, in patients with inactive HBV infections, HBV RNA is less frequently detected than HBV DNA. It needs to be studied whether HBV RNA serum levels can identify patient inactive carrier status that have disease progression. Corresponding author: Krauel, Alexander E-Mail:Alexander.Krauel@medizin.uni-leipzig.de