Viral and clinical features in association with the four phases of chronic HBV infection.

<p>The analysis was performed using data from a case-cohort study of participants with chronic HBV infection aged 30–65 y at recruitment in 1989–1992 (n = 1112), and followed to 2006. Parameters of viral genetic diversity were measured in 460 subjects with HBV/Ba and 95 with HBV/Ce (GenBank accession numbers KC792648 – KC793202). Data on BCP double mutations were available for 441 subjects with HBV/Ba and 91 with HBV/Ce. There are three trajectory classes for the time trend of viral load: “sustained low”, “steadily high” (consistently in the levels of 5–6 log₁₀ copies/mL), and “extremely high to low” (gradually declining from the levels of 8–9 log₁₀ copies/mL), as defined by our previous longitudinal viral-load study <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0070169#pone.0070169-Sung1" target="_blank">[13]</a>. Disease-free survival rate (i.e. cumulative incidence) and hazard ratio (HR) for hepatocellular carcinoma (HCC) were estimated by the Kaplan-Meier method and Cox regression model, respectively, using the subcohort of 1054 participants. Odds ratios (ORs) and HRs were derived by multivariate models adjusted for age, cigarette smoking, alcohol consumption, and body mass index. ^a<i>P</i><0.0001 for IT/IC vs. LR/ENH. ^b<i>P</i><0.0340 for Ba vs. Ce subgenotype. ^c<i>P_trend</i><0.0210 across phase of HBV-infection, determined by Mantel–Haenszel extension of the χ² test for trend.