Is there any role for HBV pgRNA in fibrosis and HCC predisposition?

In this cohort, we aimed to study the evolution of pregenomic RNA (pgRNA) during treatment and compare it with other disease scores such as FIB-4 and PAGE-B.

Eighty-eight HBeAg negative CHB who received long-term treatment with NAs were included. A quantitative HBV S antigen (HBsAg) assay was performed, and viral HBV DNA was quantified by Polymerase Chain Reaction (PCR). Finally, viral RNA levels (pre-core RNA (preC RNA) and pgRNA) were analyzed using the RTPCR protocol. The FIB-4 score was calculated for all patients, depicting the cirrhosis course, while the platelet-related PAGE-B score contributed to the 5-year cumulative prognosis of hepatocellular carcinoma (HCC). Statistical multivariate analysis was performed using the R studio and CATREG SPSS optimal scaling algorithm of SPSS 26.0.0.0.

A total of 18.1% of our sample was positive for HBV pgRNA, delineating a positive correlation with cirrhosis and an apparently negative correlation with therapy duration. HBV pgRNA was not independently correlated with FIB-4 (p = 0.137) after adjustment for aminotransferase/alanine transaminase (AST/ALT)^1/2, (AST)^1/2, 1/platelets (PLT), age, sex, HBsAg, HBV viral load, regimen administered, and therapy duration (ordinal regression ANOVA p < 10^-12; ${\text{R}}_{\text{reg}}^2$ : 0.794). Moreover, HBV pgRNA was not independently correlated with PAGE-B (p = 0.459) after adjustment for age, sex, AST, 1/PLT, duration of therapy, HBsAg, HBV viral load, regimen administered, and the presence of cirrhosis (ordinal regression ANOVA p < 10^-12; ${\text{R}}_{\text{reg}}^2$ : 0.800).

Based on our results, further longitudinal studies are needed to assess the potential usefulness of HBV pgRNA as prognosticator of liver fibrosis and susceptibility to HCC.