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

Abstract

ABSTRACT 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 NO 2 (per one‐unit increment, parts per billion; 1.07/1.01–1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO 2 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 NO 2 exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment.