Do the circulating Pre‐S/S quasispecies influence hepatitis B virus surface antigen levels in the HBeAg negative phase of HBV infection?

Abstract

Background: Virus, host factors and their interplay influence Hepatitis B surfaceAntigen serum levels during Hepatitis B Virus (HBV) infection course and treatment. Aim:To study the Pre-S/S circulating quasispecies in a cohort of untreated, HBeAg negative, genotype-D, HBsAg carriers. Methods:We studied 260 carriers: 71 with HBeAg negative infection (ENI; HBV-DNA ≤2000 IU/mL); 42 Grey Zone (GZ; HBV-DNA ≤20 000 IU/mL); 82 chronic hepatitis (CH) and 65 cirrhosis (CI) (HBV-DNA > 20 000 IU/mL). Population sequencing was applied to identify Pre-S/S gene mutations responsible for any amino acid substitution or potential biological/antigenic implications (M-muts) on HBsAg.Results: HBsAg serum levels were lower in ENI + GZ than in CH + CI (2.61 [−1.10/4.06] vs 3.62 [2.41/4.92] log 10 IU/mL, P < 0.001) and in CI than CH (3.48 [2.41/4.38] vs 3.66 [2.57/4.92] log 10 IU/mL, P < 0.001). M-muts were found in 73 (28.1%) cases: 5 (7.0%) ENI, 3 (7.1%) GZ, 26 (31.7%) CH, 39 (60.0%) CI (P < 0.001) and mostly in Pre-S2 (17.6%) than Pre-S1 (5.8%) and Small-S (10.8%; P < 0.001). Overall HBsAg serum levels were higher in carriers with M-muts (3.56 [0.95/4.38] vs 3.17 [−1.10/4.92] log 10 IU/mL, P < 0.001), but comparable in carriers with or without M-mut when considering separately ENI + GZ (2.84 [0.95/3.89] vs 2.61 [−1.10/4.06] log 10 IU/mL, P = 0.330] and CH + CI (3.57 [2.67/4.38] vs 3.63 [2.41/4.92] log 10 IU/mL, P = 0.37). Infection phase (β: 0.422, P < 0.001), age (β: −0.260, P < 0.001), ALT (β: −0.103, P = 0.045), liver stiffness (β: −0.118, P = 0.039) and HBV-DNA (β: 0.384, P < 0.001), but not M-mut were independently associated with HBsAg serum levels. Conclusions: In HBeAg negative, genotype-D, carriers Pre-S/S heterogeneity increases with severity of liver disease, but does not influence HBsAg serum levels, that in low viraemic carriers are associated with an effective control of HBV. | 1407 CAVALLONE Et AL.

Analysis of full-length Hepatitis B Virus Genome From Chronic Hepatitis B-patients With Higher Alanine Aminotransferase Elevation

“…Sueki et al also reported the presence of amino acid substitutions in HBV pre-S1 and pre-S2, may be related to the emergence of lamivudine resistance during chronic HBV infection [28]. In HBeAg-negative and HBV GT-D carriers, pre-S/S heterogeneity increases with severity of liver disease [29]. Next generation sequencing-based platform may provide an improvement of the clinical application of pre-S mutants in serving as predictive and prognostic markers for HBV-related HCC [30].…”

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