This study was performed in pretreatment samples of CHB patients who participated in two independent investigator-initiated studies, which were described in detail previously (Takkenberg et al., 2013 (link); de Niet et al., 2017 (link)). From the first cohort, consisting of HBeAg-negative CHB patients with HBV-DNA levels below 20,000 IU/mL, 150 plasma and 97 liver samples were available for analysis. From the second cohort, consisting of HBeAg-positive or -negative patients with HBV DNA levels >17,182 IU/mL, a total of 32 liver samples were available for analysis. Control liver tissue was obtained from 13 HBV negative patients undergoing surgical liver resection and from the resected liver tissue of the non-affected, tumor free margin surrounding the pathology was stored in RNAlater stabilizing solution (Thermo Fisher Scientific, Waltham, MA, United States) (Stelma et al., 2017 (link)). Control plasma samples were obtained from 10 healthy volunteers. Baseline characteristics of all cohorts are shown in Table 1.
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