It was suspected that aristolochic acid-induced mutations may be associated with hepatitis B virus (HBV), playing an important role in liver carcinogenesis. The purpose of this study was to investigate the association between the use of Chinese herbs containing aristolochic acid and the risk of hepatocellular carcinoma (HCC) among HBV-infected patients. We conducted a retrospective, population-based, cohort study on patients older than 18 years who had a diagnosis of HBV infection between January 1, 1997 and December 31, 2010 and had visited traditional Chinese medicine clinics before one year before the diagnosis of HCC or the censor dates. A total of 802,642 HBV-infected patients were identified by using the National Health Insurance Research Database in Taiwan. The use of Chinese herbal products containing aristolochic acid was identified between 1997 and 2003. Each patient was individually tracked from 1997 to 2013 to identify incident cases of HCC since 1999. There were 33,982 HCCs during the follow-up period of 11,643,790 person-years and the overall incidence rate was 291.8 HCCs per 100,000 person-years. The adjusted hazard ratios (HRs) were 1.13 (95% confidence interval [CI], 1.11-1.16), 1.21 (95% CI, 1.13-1.29), 1.37 (95% CI, 1.24-1.50) and 1.61 (95% CI, 1.40-1.84) for estimated aristolochic acid of 1-250, 251-500, 501-1,000 and more than 1,000 mg, respectively, relative to no aristolochic acid exposure. Our study found a significant dose-response relationship between the consumption of aristolochic acid and HCC in patients with HBV infection, suggesting that aristolochic acid which may be associated with HBV plays an important role in the pathogenesis of HCC.

Objective To investigate the association between rheumatoid arthritis (RA) and deep neck infection (DNI). Study Design Retrospective cohort study. Methods Patients newly diagnosed with RA between 2000 and 2011 were identified from the National Health Insurance Research Database in Taiwan. Moreover, patients without RA were randomly selected and matched at a 1:4 ratio by age, sex, urbanization level, income, and diabetes mellitus. The patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of DNI. Results In total, 30,207 patients with RA and 120,828 matched patients without RA were enrolled. Patients with RA had a significantly higher cumulative incidence of DNI than those without RA (P < 0.001). The adjusted Cox proportional hazard model demonstrated that RA was significantly associated with a higher incidence of DNI (hazard ratio: 2.80, 95% confidence interval: 2.26–3.46, P < 0.001). Therapeutic methods (surgical or nonsurgical) did not differ significantly between the patients with RA‐DNI and with non–RA‐DNI. Patients with RA‐DNI had higher rates of tracheostomy, mediastinitis, mediastinitis‐related mortality, and mortality than patients with non–RA‐DNI, although these differences were without statistical significance. RA patients receiving no therapy experienced higher rates of DNI compared with those receiving methotrexate alone, disease‐modifying antirheumatic drugs, or biologic therapies. Conclusion This study is the first to investigate the association between RA and DNI. We conclude RA is an independent predisposing factor for DNI. Level of Evidence 4 Laryngoscope, 130:1402–1407, 2020