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HBV genotype, antigen status correlate with RNA levels

Factors associated with serum hepatitis B RNA levels include HBV e antigen status, serum alanine aminotransferase, HBV genotype and the presence of basal core promoter mutations, according to recently published data from a multi-ethnic cohort study.

“HBV RNA in serum is a novel and promising marker for [covalently closed circular DNA (cccDNA)] transcriptional activity and could thus be used to monitor response for currently available treatment, but in particular for future HBV treatments targeting the HBV life cycle,” Margo J.H. van Campenhout, MD, from the Erasmus MC University Medical Center, the Netherlands, and colleagues wrote.

van Campenhout and colleagues measured the full-length poly-adenylated HBV RNA levels in serum samples from 366 HBeAg-positive patients and 122 HBeAg-negative patients with chronic HBV. Patients participated in three previous randomized controlled trials and were mostly white (64%) or Asian (31%).

Mean HBV RNA level in the full cohort was 5.9 copies/mL. Mean HBV RNA level among HBeAg-positive patients was 6.5 log c/mL compared with 4.1 log c/mL among those negative for HBeAg (P < .001).

HBV RNA levels correlated with the degree of ALT elevation (r = 0.29; P < .001). Mean HBV RNA level varied by genotype: 6 log c/mL in genotype A and C, 6.5 log c/mL in genotype B, and 5.6 log c/mL in genotype D (P = .003).

Based on multivariable linear regression, factors that correlated significantly with lower HBV RNA included HBeAg-negativity (beta = –0.69; P < .001); HBV genotypes A (beta = –0.13; P = .002), B (beta = –0.07; P = .049) and C (beta = –0.61; P < .001) in comparison to genotype D; presence of any basal core promoter mutation either alone (beta = –0.14; P = .001) or in combination with precore mutation (beta = –0.22; P < .001).

In contrast, higher serum ALT correlated with higher HBV RNA (beta = 0.23; P < .001).

Overall, the researchers found that HBV RNA correlated significantly with HBV DNA (r = 0.85; P < .001), moderately with quantitative HBV surface antigen (r = 0.52; P < .001), and with quantitative HBeAg (r = 0.41; P < .001).

“These factors should be taken into consideration for the interpretation and comparison of HBV RNA serum levels across different infected individuals and in the development of HBV RNA as a potential serum marker for cccDNA transcriptional activity,” the researchers concluded. – by Talitha Bennett

Disclosure: van Campenhout reports no relevant financial disclosures. Please see the full study for the other authors’ relevant financial disclosures.