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

Front Med (Lausanne). 2025 Nov 12;12:1678116. doi: 10.3389/fmed.2025.1678116. eCollection 2025.

ABSTRACT

AIM: 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.

METHODS: 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.

RESULTS: 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; R 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; R reg 2 : 0.800).

CONCLUSIONS: 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.

PMID:41312475 | PMC:PMC12647073 | DOI:10.3389/fmed.2025.1678116

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