Air Pollution Associated With Mortality Among Chronic Hepatitis B Patients Treated With Nucleotide/Nucleoside Analogues

Abstract

Background and Aims

Air pollution is associated with advanced liver fibrosis in patients with chronic liver diseases, including chronic hepatitis B (CHB). This study aimed to investigate the association between air pollution and mortality in patients with CHB treated with nucleotide/nucleoside analogues.

Methods

We enrolled 697 patients with CHB treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for mortality. Daily air pollutant concentrations were estimated from the year before enrolment.

Results

All-cause mortality showed an annual incidence of 1.1/100 person-years after a follow-up period of 3798.1 person-years. Factors with the strongest association with all-cause mortality were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.95/1.69–9.23; p = 0.02), age ([HR]/CI: 1.07/1.03–1.17, p < 0.001) and pre-treatment gamma-glutamyl transferase (GGT) levels (HR/CI: 1.004/1.001–1.006, p = 0.004). Among patients with cirrhosis, the factors associated with all-cause mortality were age (HR/CI: 1.08/1.04–1.12, p < 0.001), pre-treatment GGT levels (HR/CI: 1.004/1.001–1.008, p = 0.01), platelet count (HR/CI: 0.988/0.977–0.998, p = 0.02) and NO_x concentration (per unit increment, ppb) (1.045/1.001–1.091; p = 0.046). The best NO_x cut-off value for predicting all-cause mortality in patients with cirrhosis was 25.5 ppb (AUROC 0.63; p = 0.03). NO_x levels > 25.5 ppb were associated with a higher incidence of mortality in patients with cirrhosis (HR/CI:2.49/1.03–6.02; p = 0.04).

Conclusions

Air pollution influences all-cause mortality in patients with CHB receiving nucleotide/nucleoside analogue therapy. Long-term NO_x exposure may increase liver-related mortality in patients with chronic hepatitis B and cirrhosis receiving nucleotide/nucleoside analogue treatment.