Hepatitis C care cascade among patients with and without tuberculosis: Nationwide observational cohort study in the country of Georgia, 2015–2020

Background The Eastern European country of Georgia initiated a nationwide hepatitis C virus (HCV) elimination program in 2015 to address a high burden of infection. Screening for HCV infection through antibody testing was integrated into multiple existing programs, including the National Tuberculosis Program (NTP). We sought to compare the hepatitis C care cascade among patients with and without tuberculosis (TB) diagnosis in Georgia between 2015 and 2019 and to identify factors associated with loss to follow-up (LTFU) in hepatitis C care among patients with TB. Methods and findings Using national ID numbers, we merged databases of the HCV elimination program, NTP, and national death registry from January 1, 2015 to September 30, 2020. The study population included 11,985 adults (aged ≥18 years) diagnosed with active TB from January 1, 2015 through December 31, 2019, and 1,849,820 adults tested for HCV antibodies between January 1, 2015 and September 30, 2020, who were not diagnosed with TB during that time. We estimated the proportion of patients with and without TB who were LTFU at each step of the HCV care cascade and explored temporal changes. Among 11,985 patients with active TB, 9,065 (76%) patients without prior hepatitis C treatment were tested for HCV antibodies, of which 1,665 (18%) had a positive result; LTFU from hepatitis C care was common, with 316 of 1,557 (20%) patients with a positive antibody test not undergoing viremia testing and 443 of 1,025 (43%) patients with viremia not starting treatment for hepatitis C. Overall, among persons with confirmed viremic HCV infection, due to LTFU at various stages of the care cascade only 28% of patients with TB had a documented cure from HCV infection, compared to 55% among patients without TB. LTFU after positive antibody testing substantially decreased in the last 3 years, from 32% among patients diagnosed with TB in 2017 to 12% among those diagnosed in 2019. After a positive HCV antibody test, patients without TB had viremia testing sooner than patients with TB (hazards ratio [HR] = 1.46, 95% confidence intervals [CI] [1.39, 1.54], p < 0.001). After a positive viremia test, patients without TB started hepatitis C treatment sooner than patients with TB (HR = 2.05, 95% CI [1.87, 2.25], p < 0.001). In the risk factor analysis adjusted for age, sex, and case definition (new versus previously treated), multidrug-resistant (MDR) TB was associated with an increased risk of LTFU after a positive HCV antibody test (adjusted risk ratio [aRR] = 1.41, 95% CI [1.12, 1.76], p = 0.003). The main limitation of this study was that due to the reliance on existing electronic databases, we were unable to account for the impact of all confounding factors in some of the analyses. Conclusions LTFU from hepatitis C care after a positive antibody or viremia test was high and more common among patients with TB than in those without TB. Better integration of TB and hepatitis C care systems can potentially reduce LTFU and improve patient outcomes both in Georgia and other countries that are initiating or scaling up their nationwide hepatitis C control efforts and striving to provide personalized TB treatment.

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Enter: The author(s) received no specific funding for this work.  tbcenter@tbgeo.ge. We confirm that others researchers who meet the criteria for access to confidential data will be able to access these data in the same manner as the authors. The authors did not have any special access privileges that others would not have.

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The data underlying the results presented in the study are available from (include the name of the third party and contact information or URL). This text is appropriate if the data are owned by a third party and authors do not have permission to share the data.     relationship between these two infectious diseases has not been well described.

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Specifically, it has not been well characterized how often patients with current or past TB 77 are offered and provided with hepatitis C testing and treatment services.

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Study design and setting 130 We analyzed the hepatitis C care cascade among patients diagnosed with active TB disease 131 and compared it to the care cascade among people with HCV without active TB disease.       those with TB were also less likely to complete hepatitis C treatment (89% vs 94%) and 253 SVR assessment (59% vs 76%) than those without TB. However, among those who 254 completed hepatitis C treatment and were tested for SVR, the cure rate was comparable 255 to those without TB (98.3% vs. 98.9%) (Figures 2a, 2b). Overall, among patients with   In this study of two large-scale public health programs in the country of Georgia, we found 297 that LTFU from the hepatitis C care cascade was high overall, but substantially more  as a useful approach for achieving the overall elimination goals [48].

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Our study has several limitations. First, due to missing national ID numbers, we had to 376 exclude 6% of observations from the NTP database. Second, the limited number of 377 variables in the hepatitis C screening registry and differences in variables available in 378 hepatitis C and TB databases did not allow us to conduct a more in-depth analysis to 379 adjust for potential confounders. For that reason, our time-to-event analyses are limited 380 to the crude comparison of cumulative incidence curves and crude hazards ratios between 381 patients with and without TB, rather than trying to explore any causal associations that 382 would require confounding adjustment. Third, we excluded patients with DR TB from the 383 risk factor analysis of LTFU before HCV treatment initiation due to high heterogeneity in 384 terms of when individual patients with DR TB become eligible for hepatitis C treatment. In conclusion, we found that LTFU from hepatitis C care after positive HCV antibody and 386 viremia testing is more common among patients with TB than those without TB. Existing 387 large-scale public health programs for both TB and hepatitis C in Georgia create a unique 388 opportunity for integrated care of these two infectious diseases, which could potentially 389 reduce LTFU. Though our study was not designed to identify effective interventions for