title: Incidence rates of tuberculosis in chronic hepatitis C infected patients with or without interferon based therapy: a population-based cohort study in Taiwan.
abstract: BACKGROUND
  It is debated whether interferon-based therapy (IBT) would affect the incidence of active tuberculosis (TB) among hepatitis C virus (HCV) infected patients. Although some case reports have demonstrated a possible association, the results are currently inconclusive. Therefore, we conducted a nation-wide population study to investigate the incidence of active TB in HCV infected patients receiving IBT in Taiwan.
  
  
  METHODS
  This 9-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 ( >23.7 million). This insurance program covers all citizens in Taiwan. We conducted a retrospective cohort study that identified subjects with HCV infection. IBTs were defined as regimens that included interferon α, peginterferon α2a and peginterferon α2b for at least 2 months. Among them, 621 subjects received IBT, and 2,460 age- and gender-matched subjects were enrolled for analysis. The Cox proportional hazards models were used to estimate the hazard ratio (HR) for active TB, and associated confidence intervals (CIs), comparing IBT cohort and untreated cohort. The endpoint in this study was whether an enrolled subject had a new diagnosis of active TB.
  
  
  RESULTS
  During the 9-year enrollment period, the treated and untreated cohorts were followed for a mean (± SD) duration of 6.97 ± 0.02 years and 8.21 ± 0.01 years, respectively. The cumulative incidence rate of active TB during this study period was 0.150 and 0.151 per 100 person-years in the IBT treated and untreated cohorts, respectively. There was no significant difference in the incidence of active TB in either cohort during a 1-year follow-up (Adjusted Hazard Ratio (AHR): 2.81, 95% Confidence Interval (95% CI): 0.61-12.98) or the long-term follow-up (AHR: 1.02, 95% CI: 0.28-3.78). The Cox proportional hazards model demonstrated that IBT was not a risk factor for active TB . The only risk factor for active TB was the occurrence of hepatic encephalopathy.
  
  
  CONCLUSIONS
  Our results showed that IBT is associated with increased hazard of active TB in HCV infected patients in 1-year follow-up; however, the effect sizes were not statistically significant.
authors.affiliation: Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. amoe616@gmail.com.|School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. amoe616@gmail.com.
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. kmtthidchen@gmail.com.|Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan. kmtthidchen@gmail.com.
authors.forename: Tun-Chieh
authors.initials: TC
authors.lastname: Chen
authors.affiliation: School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. idpaul@gmail.com.|Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan. idpaul@gmail.com.|Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan. idpaul@gmail.com.|Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. idpaul@gmail.com.
authors.forename: Po-Liang
authors.initials: PL
authors.lastname: Lu
authors.affiliation: School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. infectionman@gmail.com.|Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan. infectionman@gmail.com.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan. lwru@mail2000.com.tw.
authors.forename: Wei-Ru
authors.initials: WR
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. yihsya@kmu.edu.tw.|Division of Statistical Analysis, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. yihsya@kmu.edu.tw.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Yang
authors.affiliation: School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. infchen@gmail.com.|Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan. infchen@gmail.com.|Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan. infchen@gmail.com.
authors.forename: Yen-Hsu
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D060085:Coinfection / Q000453:epidemiology; D016208:Databases, Factual; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a