Serum HBV RNA may represent noninvasive marker for HBV progression
medwireNews: Serum hepatitis B virus (HBV) RNA levels correlate with viral transcriptional activity and histologic changes in the livers of patients with chronic HBV who are receiving nucleos(t)ide analog (NA) therapy, Chinese researchers report.
Wenhong Zhang (Fudan University, Shanghai) and co-investigators say that serum HBV RNA levels “could potentially be used as a noninvasive diagnostic biomarker for liver disease progression” because of the difficulties associated with quantifying intrahepatic viral RNA.
Among 47 entecavir-treated patients with undetectable levels of serum HBV DNA, 35 (74.5%) had detectable serum HBV RNA, at levels of 2.33–4.80 log10 copies/mL.
The researchers report that serum HBV RNA levels correlated significantly with serum hepatitis B surface antigen (HBsAg) titers (correlation coefficient [r]=0.665, p<0.001) and intrahepatic viral RNA levels (r=0.725, p<0.001), as well as with the ratio of intrahepatic HBV RNA to covalently closed circular DNA (cccDNA; r=0.584, p=0.001).
“These data suggest that serum HBV-RNA levels reflect the amount of intrahepatic HBV-RNA and levels of cccDNA-directed viral transcriptional activity,” they write.
Furthermore, deep sequencing of serum HBV RNA and corresponding viral RNA and cccDNA from paired serum and liver samples showed that 6–40% of cccDNA variants were missing in the RNA counterparts, which according to Zhang et al indicates that “these cccDNA are transcriptionally inactive.”
Deep sequencing also demonstrated that serum HBV RNA was more like intrahepatic HBV RNA than cccDNA, and that HBV quasispecies varied over time, suggesting that a small part of the virus may continue to evolve and replicate during the course of infection.
In addition, histopathologic analysis showed that serum HBV RNA levels correlated with histopathologic scores for necroinflammation and fibrosis (r=0.665, p<0.001 for grading; r=0.722, p<0.001 for staging), and that HBV RNA-positive hepatocytes tended to cluster in foci, were sporadically distributed across the lobules, and co-localized with HBsAg.
Writing in the Journal of Hepatology, Zhang and team conclude that their study “sheds light on the nature of HBV-RNA in the pathogenesis of chronic HBV infection and has implications for the management of chronic hepatitis B during [NA] therapy.”
They add: “[T]o suppress viral replication completely, it is important to achieve an effective concentration of antiretroviral drugs in sanctuary sites of liver tissue and intensify treatment with a combination of antivirals from various classes.”
By Laura Cowen
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