567 2.051 Gender (Male/female) −0.534 0.766 0.487 0.485 0.586 0.131 2.629 Group (LC%HCC/CC%CH) 0.257 0.986 0.068 0.794 1.293 0.187 8.928 Genotype (C/B) −0.351 0.83 0.179 0.672 0.704 0.138 3.577 Antiviral Therapy (Treated/untreated) 1.919 0.847 5.138 0.023* 6.814 1.296 35.817 B, regression coefficient; S.E., Standard Error; *, P < 0.05; OR, odds ratio; CI, confidence interval. Further comparison between sample groups also demonstrated that individuals VX-680 mouse with antiviral therapy showed a higher occurrence of deletions compared to the untreated group (P = 0.005, FET, Figure 3). A similar result was seen when the analysis was applied

only to chronic carrier (CC) and chronic hepatitis (CH) patients (P = 0.007, fisher exact test (FET), Figure 3) when the possible contribution of mutant accumulation in advanced liver diseases was removed. When stratifying each deletion hotspot by antiviral therapy, BCP deletions were more common in patients with interferon therapy (P = 0.018,

FET Figure 3), whereas deletions in preS, particularly in the preS2 region, were more likely to be found in cases with nucleotide analog (NA) treatment (P = 0.023, FET, Figure 3). In addition, sequencing data of the preS clones from the second batch of 52 individuals support the full-length analysis results. Of 10 selleck chemicals CH patients containing preS2-deleted viruses detected by clone sequencing, 5 had received NA treatment, while 2 were

treated with Interferon-alpha (IFN-α). Meanwhile, no significant difference in deletion occurrence was found between different genders (P = 0.608, FET) or genotypes (P = 0.450, FET). In addition, two out of three preS2 deletion mutants in the antiviral group had known antiviral resistance mutations, M204I and L180M, respectively. Figure 3 Deletion mutations and antiviral treatments. The profiles of different types of HBV deletions between patients with (+) and without (−) antiviral therapy based on 51 HBV full-length sequences. Upper panel: analysis from all samples of CC, CH, LC, and HCC. Lower panel: analysis without patients of progressive liver diseases. Antiviral medication was grouped as nucleotide analog only (left), IFN only (middle), and either one or both (right). Each deletion and the ratio of wt virus to medroxyprogesterone mutants were labeled under the histogram. Dynamic accumulation of preS deletion mutants in HBV quasispecies during ADV treatment The above results suggest that NAs may contribute to the accumulation of preS deletion mutants in quasispecies of CH patients. To further verify NAs’ selection in this region, we collected blood samples from two CH patients before and after about 3 months of ADV treatment. Serial samples were also collected from additional CH and LC patients, in intervals of 2.5 months and 5 months respectively, with no-antiviral treatment as the control.