Background: Virus, host factors and their interplay influence Hepatitis B surface Antigen 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 IU/mL, P < 0.001) and in CI than CH (3.48 [2.41/4.38] vs 3.66 [2.57/4.92] log 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 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 IU/mL, P = 0.330] and CH + CI (3.57 [2.67/4.38] vs 3.63 [2.41/4.92] log 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.
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http://dx.doi.org/10.1111/apt.15753 | DOI Listing |
Front Med (Lausanne)
December 2024
Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Objective: To investigate the probability of hepatocellular carcinoma (HCC) in a large number of gray-zone (GZ) patients with chronic hepatitis B (CHB) in clinical practice.
Methods: The patients with CHB who were diagnosed and treated in our hospital from January 2013 to January 2023 were analyzed retrospectively.
Results: According to the different levels of HBeAg, ALT and HBV DNA, GZ patients were divided into four categories: (1) Gray zone A (GZ-A): HBeAg positive, normal ALT level, HBV DNA ≤ 10 IU/ml; (2) Gray zone B (GZ-B): HBeAg positive, ALT>ULN, HBV DNA ≤ 2 × 10 IU/ml; (3) Gray zone C (GZ-C): HBeAg negative, normal ALT level, HBV DNA ≥ 2 × 10 IU/ml; and (4) Gray zone D (GZ-D): HBeAg negative, ALT > ULN, serum HBV DNA ≤ 2 × 10 IU/ml.
Viruses
December 2024
Department of Medicine & State Key Laboratory of Liver Research, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China.
Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, as well as transcripts likely to be derived from dimers of dslDNA, and these differed between HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg-) individuals. HBV transcripts from the last follow-up ~30 months post-ARC-520 treatment were categorized from one HBeAg+ (one of two previously highly viremic patients that became HBeAg- upon treatment and had greatly reduced cccDNA products) and four HBeAg- patients. The previously HBeAg+ patient received a biopsy that revealed that he had 3.
View Article and Find Full Text PDFJ Viral Hepat
February 2025
Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
The exclusion of cirrhosis is important in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT). We aimed to optimise the performance of the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis score based on four factors (FIB-4) to exclude cirrhosis in these patients. Five hundred and eighty four patients with normal ALT who underwent liver biopsy were included in the study.
View Article and Find Full Text PDFEmerg Microbes Infect
January 2025
Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Hepatitis B virus (HBV) DNA integration into the host cell genome is reportedly a major cause of liver cancer, and a source of hepatitis B surface antigen (HBsAg). High HBsAg levels can alter immune responses which therefore contributes to the progression of HBV-related disease. However, to what extent integration leads to the persistent circulating HBsAg is unclear.
View Article and Find Full Text PDFJ Hepatol
December 2024
Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR. Electronic address:
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