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

AIKATERINI SKEVA^1*Theocharis Konstantinidis¹Vasileios Papadopoulos²MARIA PANOPOULOU^1*Konstantinos Mimidis^3,4

• ¹Laboratory of Microbiology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
• ²Laboratory of Anatomy, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece
• ³Laboratory for the Study of Gastrointestinal System and Liver, Democritus University of Thrace, Alexandroupolis, Greece
• ⁴First Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece

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; R2reg: 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; R2reg: 0.800). This is a provisional file, not the final typeset article 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.