BACKGROUND & AIMS: Long-term outcome data in patients with chronic hepatitis B (CHB) treated with high-genetic-barrier nucleos(t)ide analogues (NAs) beyond year 10 are scarce. We assessed the incidence and predictors of hepatocellular carcinoma (HCC), liver transplantation (LT), all-cause and liver-related death, and HBsAg loss among patients treated with NAs for >10 years. METHODS: The long-term PAGE-B cohort included 1,644 Caucasian patients with CHB treated with entecavir or tenofovir. Cumulative incidence was estimated using Kaplan-Meier methods or cumulative incidence functions accounting for competing events. Incidence rates (IRs) per 100 person-years (/100 PYs) were calculated. RESULTS: Of 1,644 patients, 903 were followed beyond year 10 (mean:14 ± 2 years). The 10- and 15-year cumulative incidences of HCC were 10.9% and 13.2%, respectively. The HCC IR was 1.25 before year 10 and 0.55/100 PYs after year 10 (p <0.001), with similar findings after inverse probability weighting. The IR of death or LT was lower before vs. after year 10 (1.50 vs. 1.95/100 PYs, p = 0.069), whereas the IR was similar for liver-related death/LT between the two periods (0.74 vs. 0.70/100 PYs, p = 0.840). HCC development and baseline platelet count were independently associated with LT-free liver-related or overall survival, which was also associated with older age and diabetes. The 10- and 15-year cumulative incidences of HBsAg loss on NA(s) were 8.3% and 14.3%, respectively; the IR of HBsAg loss increased from 0.94 before year 10 to 1.42/100 PYs after year 10 (p = 0.025). HBsAg loss was independently associated with older age and baseline HBeAg positivity. NA therapy was discontinued in 125 (7.6%) patients who remained HBsAg positive. CONCLUSIONS: Despite >10 years of NA therapy, patients with CHB remain at risk of HCC, although the incidence rate declines significantly. HCC remains the main determinant of mortality. The rate of HBsAg loss increases after year 10 but remains low, occurring more frequently in older patients and those who were initially HBeAg positive. IMPACT AND IMPLICATIONS: Despite more than 10 years of effective nucleos(t)ide analogue therapy, patients with chronic hepatitis B remain at risk of hepatocellular carcinoma, highlighting the need for continued long-term surveillance. Although the incidence of hepatocellular carcinoma declined after year 10, it remained the main determinant of long-term outcomes. These findings reinforce the importance of sustained risk stratification, particularly among patients with lower baseline platelet counts or other risk factors. The gradual increase in hepatitis B surface antigen loss beyond 10 years provides further evidence that prolonged antiviral therapy may offer ongoing benefits, although functional cure remains uncommon and is more likely among older patients and those who were initially HBeAg-positive.

OBJECTIVES: We aimed to evaluate the effect of the implementation of electronic-prescribing protocols for infectious diseases on outpatient antimicrobial prescribing patterns in Greece. METHODS: In 2018-2019, in the context of policies to control antimicrobial use in Greece, electronic-prescribing protocols for acute pharyngitis, community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and urinary tract infection (UTI) were introduced. We conducted a retrospective nationwide Interrupted Time Series analysis of monthly outpatient antimicrobial prescription counts overall and for targeted infectious syndromes during the preintervention and postintervention periods. Data were extracted from the official nationwide electronic prescription database covering July 2017 to December 2021. RESULTS: Overall reductions in median monthly antimicrobial prescription counts between the pre- and postintervention periods were 71.3% (95% CI: -78.5% to -56.4%) for pharyngitis, 90.0% (95% CI: -94.3% to -85.3%) for CAP, 92.6% (95% CI: -94.1% to -87.9%) for AECOPD, 85.8% (95% CI: -86.6% to -83.0%) for UTI. Despite these syndrome-specific reductions, the median monthly number of total outpatient antimicrobial prescriptions did not decrease (417 633 vs. 424 592 prescriptions per month). Before the intervention, the protocol-targeted syndromes collectively accounted for a median of 27.6% of total antimicrobial prescriptions per month, whereas 'other nonprotocol conditions' represented a median of 72.4%. After implementation, these proportions shifted dramatically to a median of 4.5% and 95.5% respectively (p < 0.001 for both changes), indicating a shift in diagnostic coding associated with antimicrobial prescribing. CONCLUSIONS: Although the protocols were designed to promote targeted antimicrobial use, their complex implementation may have inadvertently encouraged suboptimal prescribing practices. Improper coding and inconsistent antimicrobial prescribing data hinder antimicrobial stewardship efforts and should prompt a national health policy action plan.