Role of Air Pollution in Development of Hepatocellular Carcinoma Among Chronic Hepatitis B Patients Treated With Nucleotide/Nucleoside Analogues

Background and Aims: To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues. Methods: We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date. Results: The annual incidence of HCC was 2.1/100 person-years after a follow-up period of over 4840.5 person-years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55–5.81; p = 0.001), male sex (2.98/1.51–5.90; p = 0.02), body mass index (1.11/1.04–1.18; p = 0.002) and age (1.06/1.04–1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00–4.25; p = 0.04) and NO₂ (per one-unit increment, parts per billion; 1.07/1.01–1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO₂ exposure had more than a three-fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34–7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79–19.23; p = 0.004), age (1.12/1.07–1.17; p < 0.001) and platelet count (0.99/0.98–1.00; p = 0.04). Conclusions: Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long-term NO₂ exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment.