Association of Treated and Untreated Chronic Hepatitis C With the Incidence of Active Tuberculosis Disease: A Population-Based Cohort Study

Abstract

Background Hepatitis C virus (HCV) infection causes dysregulation and suppression of immune pathways involved in the control of tuberculosis (TB) infection. However, data on the role of chronic hepatitis C as a risk factor for active TB are lacking. We sought to evaluate the association between HCV infection and the development of active TB. Methods We conducted a cohort study in Georgia among adults tested for HCV antibodies (January 2015 – September 2o2o) and followed longitudinally for the development of newly diagnosed active TB. Data were obtained from the Georgian National programs of hepatitis C and TB. The exposures of interest were untreated and treated HCV infection. Cox proportional hazards model was used to calculate adjusted hazards ratios. Results A total of 1,828,808 adults were included (median follow-up time: 26 months, IQR: 13-39 months). Active TB was diagnosed in 3,163 (0.17%) individuals after a median of 6 months follow-up (IQR: 1-18 months). The incidence rate per 100,000 person-years was 296 among persons with untreated HCV infection, 109 among those with treated HCV infection, and 65 among HCV-negative persons. In multivariable analysis, both untreated (aHR = 2.9, 95%CI: 2.4-3.4) and treated (aHR = 1.6, 95%CI: 1.4-2.0) HCV infection were associated with a higher hazard of active TB, compared to HCV-negative persons. Conclusions Adults with HCV infection, particularly untreated individuals, were at higher risk of developing active TB disease. Screening for latent TB infection and active TB disease should be part of clinical evaluation of people with HCV infection, especially in high TB burden areas.

A scoping review on the risk of tuberculosis in specific population groups: can we expand the World Health Organization recommendations?

“…11 (92%) of the 12 studies used data from high-income countries [ 12 – 20 , 22 , 23 ], while the other used data from Georgia [ 21 ], a lower-middle-income country. There was high heterogeneity of populations, exposure definitions, analytical methods and estimated outcome measures across studies.…”

“…A retrospective cohort study conducted in the Republic of Georgia, which was originally identified as a conference abstract and has been published recently [ 21 ], compared the risk of active TB in adults with HCV infection with the risk in uninfected adults. They estimated an adjusted HR of 2.9 (95% CI 2.4–3.4) comparing adults with untreated HCV infection with uninfected adults and an adjusted HR of 1.6 (95% CI 1.4–2.0) comparing HCV-infected adults who had completed antiviral treatment with uninfected adults.…”

“…Of the 12 included original studies, three were on patients with rheumatoid arthritis [13][14][15], three were on patients with other rheumatic diseases receiving a variety of treatments [16][17][18], one was on patients receiving corticosteroids for any indication [19] and one each were on patients with the following conditions: diabetes mellitus [20], glomerular diseases [12], hepatitis C virus (HCV) infection [21], malignancies [22] and vitamin D deficiency [23]. 11 of the 12 studies were peer-reviewed, while one, on glomerular disease [12] comprised unpublished data shared with us by the authors after our search identified their preliminary findings in a conference abstract.…”

“…There was high heterogeneity of populations, exposure definitions, analytical methods and estimated outcome measures across studies. 10 (83%) of the 12 studies were analyses of data from large administrative health insurance, medical claims or disease surveillance databases [12][13][14][15][16][17][18][19][20][21], while two (17%) used data from individual hospitals [22,23]. Eight (67%) were retrospective cohort studies [12,13,15,17,[20][21][22][23], two (17%) were nested case-control studies [18,19] and two (17%) utilised both designs [14,16].…”

“…10 (83%) of the 12 studies were analyses of data from large administrative health insurance, medical claims or disease surveillance databases [12][13][14][15][16][17][18][19][20][21], while two (17%) used data from individual hospitals [22,23]. Eight (67%) were retrospective cohort studies [12,13,15,17,[20][21][22][23], two (17%) were nested case-control studies [18,19] and two (17%) utilised both designs [14,16]. The main features and findings from the 12 original studies are summarised in table 1.…”