Toward reaching hepatitis B goals: hepatitis B epidemiology and the impact of two decades of vaccination, Georgia, 2021.

BackgroundGeorgia has adopted the World Health Organization European Region's and global goals to eliminate viral hepatitis. A nationwide serosurvey among adults in 2015 showed 2.9% prevalence for hepatitis B virus (HBV) surface antigen (HBsAg) and 25.9% for antibodies against HBV core antigen (anti-HBc). HBV infection prevalence among children had previously not been assessed.AimWe aimed to assess HBV infection prevalence among children and update estimates for adults in Georgia.MethodsThis nationwide cross-sectional serosurvey conducted in 2021 among persons aged ≥ 5 years used multi-stage stratified cluster design. Participants aged 5-20 years were eligible for hepatitis B vaccination as infants. Blood samples were tested for anti-HBc and, if positive, for HBsAg. Weighted proportions and 95% confidence intervals (CI) were calculated for both markers.ResultsAmong 5-17 year-olds (n = 1,473), 0.03% (95% CI: 0-0.19) were HBsAg-positive and 0.7% (95% CI: 0.3-1.6) were anti-HBc-positive. Among adults (n = 7,237), 2.7% (95% CI: 2.3-3.4) were HBsAg-positive and 21.7% (95% CI: 20.4-23.2) anti-HBc-positive; HBsAg prevalence was lowest (0.2%; 95% CI: 0.0-1.5) among 18-23-year-olds and highest (8.6%; 95% CI: 6.1-12.1) among 35-39-year-olds.ConclusionsHepatitis B vaccination in Georgia had remarkable impact. In 2021, HBsAg prevalence among children was well below the 0.5% hepatitis B control target of the European Region and met the ≤ 0.1% HBsAg seroprevalence target for elimination of mother-to-child transmission of HBV. Chronic HBV infection remains a problem among adults born before vaccine introduction. Screening, treatment and preventive interventions among adults, and sustained high immunisation coverage among children, can help eliminate hepatitis B in Georgia by 2030.

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.

Impact of Hepatitis C Virus Infection and Treatment on Mortality in the Country of Georgia, 2015-2020.

BACKGROUND: Mortality related to hepatitis C virus (HCV) infection is a key indicator for elimination. We assessed the impact of HCV infection and treatment on mortality in the country of Georgia during 2015-2020. METHODS: We conducted a population-based cohort study using data from Georgia's national HCV Elimination Program and death registry. We calculated all-cause mortality rates in 6 cohorts: (1) Negative for anti-HCV; (2) anti-HCV positive, unknown viremia status; (3) current HCV infection and untreated; (4) discontinued treatment; (5) completed treatment, no sustained virologic response (SVR) assessment; (6) completed treatment and achieved SVR. Cox proportional hazards models were used to calculate adjusted hazards ratios and confidence intervals. We calculated the cause-specific mortality rates attributable to liver-related causes. RESULTS: After a median follow-up of 743 days, 100 371 (5.7%) of 1 764 324 study participants died. The highest mortality rate was observed among HCV infected patients who discontinued treatment (10.62 deaths per 100 PY, 95% confidence interval [CI]: 9.65, 11.68), and untreated group (10.33 deaths per 100 PY, 95% CI: 9.96, 10.71). In adjusted Cox proportional hazards model, the untreated group had almost 6-times higher hazard of death compared to treated groups with or without documented SVR (adjusted hazard ratio [aHR] = 5.56, 95% CI: 4.89, 6.31). Those who achieved SVR had consistently lower liver-related mortality compared to cohorts with current or past exposure to HCV. CONCLUSIONS: This large population-based cohort study demonstrated the marked beneficial association between hepatitis C treatment and mortality. The high mortality rates observed among HCV infected and untreated persons highlights the need to prioritize linkage to care and treatment to achieve elimination goals.

Nationwide Hepatitis C Serosurvey and Progress Towards Hepatitis C Virus Elimination in the Country of Georgia, 2021.

BACKGROUND: The country of Georgia initiated its hepatitis C virus (HCV) elimination program in 2015, at which point a serosurvey showed the adult prevalence of HCV antibody (anti-HCV) and HCV RNA to be 7.7% and 5.4%, respectively. This analysis reports hepatitis C results of a follow-up serosurvey conducted in 2021, and progress towards elimination. METHODS: The serosurvey used a stratified, multistage cluster design with systematic sampling to include adults and children (aged 5-17 years) providing consent (or assent with parental consent). Blood samples were tested for anti-HCV and if positive, HCV RNA. Weighted proportions and 95% confidence intervals (CI) were compared with 2015 age-adjusted estimates. RESULTS: Overall, 7237 adults and 1473 children were surveyed. Among adults, the prevalence of anti-HCV was 6.8% (95% CI, 5.9-7.7). The HCV RNA prevalence was 1.8% (95% CI, 1.3-2.4), representing a 67% reduction since 2015. HCV RNA prevalence decreased among those reporting risk factors of ever injecting drugs (51.1% to 17.8%), and ever receiving a blood transfusion (13.1% to 3.8%; both P < .001). No children tested positive for anti-HCV or HCV RNA. CONCLUSIONS: These results demonstrate substantial progress made in Georgia since 2015. These findings can inform strategies to meet HCV elimination targets.

Economic evaluation of the Hepatitis C virus elimination program in the country of Georgia, 2015 to 2017.

BACKGROUND AND AIMS: In 2015, the country of Georgia launched an elimination program aiming to reduce the prevalence of Hepatitis C virus (HCV) infection by 90% from 5.4% prevalence (~150 000 people). During the first 2.5 years of the program, 770 832 people were screened, 48 575 were diagnosed with active HCV infection, and 41 483 patients were treated with direct-acting antiviral (DAA)-based regimens, with a >95% cure rate. METHODS: We modelled the incremental cost-effectiveness ratio (ICER) of HCV screening, diagnosis and treatment between April 2015 and November 2017 compared to no treatment, in terms of cost per quality-adjusted life year (QALY) gained in 2017 US dollars, with a 3% discount rate over 25 years. We compared the ICER to willingness-to-pay (WTP) thresholds of US$4357 (GDP) and US$871 (opportunity cost) per QALY gained. RESULTS: The average cost of screening, HCV viremia testing, and treatment per patient treated was $386 to the provider, $225 to the patient and $1042 for generic DAAs. At 3% discount, 0.57 QALYs were gained per patient treated. The ICER from the perspective of the provider including generic DAAs was $2285 per QALY gained, which is cost-effective at the $4357 WTP threshold, while if patient costs are included, it is just above the threshold at $4398/QALY. All other scenarios examined in sensitivity analyses remain cost-effective except for assuming a shorter time horizon to the end of 2025 or including the list price DAA cost. Reducing or excluding DAA costs reduced the ICER below the opportunity-cost WTP threshold. CONCLUSIONS: The Georgian HCV elimination program provides valuable evidence that national programs for scaling up HCV screening and treatment for achieving HCV elimination can be cost-effective.

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

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 2020) 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. A Cox proportional hazards model was used to calculate adjusted hazard ratios (aHRs). 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 3163 (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 infections were associated with a higher hazard of active TB, compared with 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.

Treatment of hepatitis C in primary health care in the country of Georgia.

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Barriers of linkage to HCV viremia testing among people who inject drugs in Georgia.

BACKGROUND: People who inject drugs (PWID) in Georgia have a high prevalence of hepatitis C virus antibody (anti-HCV). Access to care among PWID could be prioritized to meet the country's hepatitis C elimination goals. This study assesses barriers of linkage to HCV viremia testing among PWID in Georgia. METHODS: Study participants were enrolled from 13 harm reduction (HR) centers throughout Georgia. Anti-HCV positive PWID who were tested for viremia (complete diagnosis [CD]), were compared to those not tested for viremia within 90 days of screening anti-HCV positive (not complete diagnosis [NCD]). Convenience samples of CD and NCD individuals recorded at HR centers using beneficiaries' national ID were drawn from the National HCV Elimination Program database. Participants were interviewed about potential barriers to seeking care. RESULTS: A total of 500 PWID were enrolled, 245 CD and 255 NCD. CD and NCD were similar with respect to gender, age, employment status, education, knowledge of anti-HCV status, and confidence/trust in the elimination program (p > 0.05). More NCD (13.0%) than CD (7.4%) stated they were not sufficiently informed what to do after screening anti-HCV positive (p < 0.05). In multivariate analysis, HCV viremia testing was associated with perceived affordability of the elimination program (adjusted prevalence ratio = 8.53; 95% confidence interval: 4.14-17.62). CONCLUSIONS: Post testing counselling and making hepatitis C services affordable could help increase HCV viremia testing among PWID in Georgia.

Door-to-door hepatitis C screening in Georgia: An innovative model to increase testing and linkage to care.

OBJECTIVES: Georgia has a high prevalence of hepatitis C virus (HCV) infection. In 2015 a national HCV elimination program was launched providing free access to screening and treatment. To achieve elimination, innovative approaches to increase screening coverage and linkage to care are needed. This study estimates feasibility, acceptability, and outcomes of the door-to-door pilot HCV testing program in three cities. METHODS: Households were approached by system random sampling and all members were invited for study participation. Researchers used a detailed guide for conducting door-to-door testing and served as case navigators to link anti-HCV-positive individuals to care. RESULTS: Testing acceptance rate was high. In total 4804 individuals were tested and 48 (1.0%) were HCV positive. Among the entire sample of newly and previously tested individuals, overall HCV antibody prevalence was 3.6%. Through case navigation, of 48 newly identified and 26 previously identified anti-HCV-positive individuals, 42 (87.5%) and 17 (65.4%), respectively, were successfully linked to care. CONCLUSIONS: Door-to-door HCV testing has potential to increase testing uptake. Such community-based approaches not only improve testing, but can also serve to increase linkage to care, which is important in achieving the goal of HCV elimination. The study provides a model for high prevalence countries aiming to eliminate hepatitis C.

Feasibility and effectiveness of HCV viraemia testing at harm reduction sites in Georgia: A prospective three-arm study.

BACKGROUND AND AIMS: In 2015, Georgia began a hepatitis C virus (HCV) elimination programme. Although screening programmes have been decentralized for high-risk groups, viraemic testing remains a bottleneck for people who inject drugs. Here, we describe two models of viraemic testing that aimed to address this gap. METHODS: We assigned eight harm reduction sites (HRS) to one of three arms (2,1:1): Xpert HCV viral load testing on-site, blood draw on-site with centralized HCV core antigen testing (HCVcAg), or standard-of-care (SOC) referral with viremia testing performed at treatment centres. RESULTS: 1671 HCV-seropositive participants were enrolled (Xpert, 37.1%; HCVcAg, 29.1%; referral, 33.8%). Participants were predominantly male (95.4%), mean age (IQR) 43 (37, 50) years and 1290 (77.2%) were currently injecting drugs. Significantly higher proportions of participants in the Xpert (100%) and HCVcAg (99.8%) arms received viraemia testing compared with the referral arm (91.3%) (Xpert vs referral, p < 0.0001; HCVcAg vs referral, p < 0.0001). Among viraemic participants, treatment uptake was similar (Xpert, 84.0%; HCVcAg, 79.5%; referral, 88.4%). The time between screening and sample collection for viraemia testing was significantly longer in the referral arm compared with both Xpert and HCVcAg arms (median 1 day compared with 0 days respectively), and the overall time between screening to treatment initiation was longer for the referral arm (median 67 days) compared with both Xpert and HCVcAg arms (median 57 and 50 days respectively). CONCLUSIONS: Point-of-care viraemia testing and blood drawn on-site for HCVcAg testing yielded more HCV-seropositive patients receiving viraemic testing within a shorter timeframe compared with referrals.

Hepatitis C treatment uptake among patients who have received methadone substitution treatment in the Republic of Georgia.

OBJECTIVES: There is a dearth of research on hepatitis C virus (HCV) treatment uptake among people who inject drugs (PWIDs) and receive methadone substitution treatment (MST) in Eastern Europe and Central Asia countries. This study contributed to addressing that gap. We examined and identified factors that may affect HCV treatment uptake among PWID who received MST in the Republic of Georgia. STUDY DESIGN: The design of the study is retrospective cohort study. METHODS: We conducted HCV care cascade analysis by matching the data from the web-based national hepatitis C program registry (ELIM C) and the MST treatment database between January 1, 2015, and December 31, 2018. Using the World Health Organization's (WHO) Consensus HCV cascade of care (CoC) global instrument, we assessed the progress made toward the country's 2020 and WHO's 2030 hepatitis C elimination targets for the subpopulation of MST patients. RESULTS: Overall, 10,498 individuals have been dispensed methadone during the study period. A total of 6828 MST beneficiaries had HCV screening, of whom 5843 (85.6%) tested positive; 5476 (93.7%) were tested for HCV viremia, and 5275 (96.3%) were confirmed with chronic HCV infection. More than 75% (n = 4000) of HCV-infected MST patients initiated HCV treatment, and 3772 (94.3%) completed the treatment. Of those eligible for sustained virologic response assessment, 71.0% (2641/3715) were evaluated, and the reported cure rate was 96.1% (2537). The study found the odds of patients starting HCV treatment differed by the type of facility they were screened at and whether they were registered as PWID at the screening sites. The patients screened at centers with integrated HCV treatment services had higher treatment uptake rates than those screened at other centers. CONCLUSIONS: As the cumulative HCV treatment uptake and cure rates among MST patients with HCV infection are high (75.8% and 96.1%, respectively), the MST patients might become the first microelimination target population in which hepatitis C elimination will be achieved in Georgia. The study found the type of screening facility and whether MST patients registered themselves as PWID or not had significant effects on MST patients starting HCV treatment. At the same time, the study did not find gender and age to be significant predictors of MST patients starting HCV treatment. MST patients used different types of health facilities to get screened for HIV. Many of them did not register themselves as PWID when screened for HIV. The existence of only a few harm reduction sites with integrated HCV treatment services, a high level of stigma, and the criminalization of drug use might have incentivized MST patients to self-navigate across the HCV care continuum with the rest of the population. The implementation of focused, harm reduction, integrated HCV treatment with good peer and professional adherence support at treatment sites could help reach the hepatitis C elimination goals among MST patients.

Assessment of treatment options for patients with hepatitis C virus recombinant form 2k/1b.

AIM: Hepatitis C virus (HCV) intergenotype recombinant form (RF) 2k/1b has been actively circulating in HCV-infected patients, and the prevalence of this RF virus in the Republic of Georgia is one of the highest reported worldwide. The aim of this study was to define the optimal treatment regimen for patients with RF_2k/1b. METHODS: We analyzed the data of 2735 patients who started treatment at the Medical Center Mrcheveli within Georgia's hepatitis C elimination program from May 2015 through December 2019. The patients were treated with sofosbuvir (SOF)-based regimens. For identification of RF_2k/1b variants, refinement of standard (INNO-LiPA) genotyping results for all patient samples assigned the unspecific HCV genotypes (GT) 2a/2c was carried out by sequencing of core and non-structural protein 5B genes. RESULTS: Overall, 444 patients, representing 66% of GT2 and 16% of the total samples, were RF_2k/1b. Treatment of patients with RF_2k/1b with SOF/ledipasvir and SOF/velpatasvir was highly effective and viral cure rates did not differ among genotypes treated with the same regimen: RF_2k/1b, 99% (343/346); GT1, 99% (876/885); GT2, 96% (156/162); and GT3, 99% (545/552). A separate comparison analysis of sustained virologic response rate, treated with SOF plus ribavirin, showed significantly higher sustained virologic response (96%) in patients with confirmed GT2 (by sequencing) compared to unspecified GT2 (by INNO-LiPA) (79%) (P < 0.05). CONCLUSION: Sofosbuvir-based regimens are highly effective for treatment of RF 2k/1b patients, and with availability of new pan-genotypic direct-acting antivirals, genotyping to identify RF 2k/1b patients might not be necessary.

Integration of hepatitis C treatment at harm reduction centers in Georgia-Findings from a patient satisfaction survey.

BACKGROUND: Georgia launched national HCV elimination program in 2015. PWID may experience barriers to accessing HCV care. To improve linkage to care among PWID, pilot program to integrate HCV treatment with HR services at opiate substitution therapy (OST) centers and needle syringe program (NSP) sites was initiated. Our study aimed to assess satisfaction of patients with integrated HCV treatment services at HR centers. METHODS: Survey was conducted among convenience sample of patients receiving HCV treatment at 5 integrated care sites and 4 specialized clinics not providing HR services. Simplified pre-treatment diagnostic algorithm and treatment monitoring procedure was introduced for HCV treatment programs at OST/NSP centers which includes fewer pre-treatment and monitoring tests compared to standard algorithm. RESULTS: In total, 358 patients participated in the survey - 48.6% receiving HCV treatment at the specialized clinics while 51.4% at HR site with integrated treatment. Similar proportions of surveyed patients at HR sites (88.0%) and clinics (84.5%) stated that they did not face any barriers to enrollment in the elimination program. Most patients from HR pilot sites and specialized clinics stated that they received comprehensive information about the treatment (98.4% vs 94.3%; p<0.010). 95% of respondents at both sites were confident that confidentiality was completely protected during treatment. Higher proportion of patients at pilot sites thought that HCV treatment services provided at facility were good compared to those from the specialized clinics (85.3% vs 81.0%). We found significant difference in the time to treatment, measured as average time from viremia testing to administration of first dose of HCV medication: 42.9% of patients at pilot sites vs 4.6% at specialized clinics received the first dose of medication within two weeks. CONCLUSION: Quality of services and perceived satisfaction of patients receiving treatment, suggests that integration of HCV treatment with HR services is feasible.

High sustained viral response among HCV genotype 3 patients with advanced liver fibrosis: real-world data of HCV elimination program in Georgia.

OBJECTIVE: In 2015, Georgia launched HCV elimination program. Initially, patients with advanced liver disease were treated with sofosbuvir-based regimen-the only DAA available for all genotypes. Purpose of the study was assessing real-world data of treatment outcome among patients with HCV GEN3 and advanced liver fibrosis with sofosbuvir-based regimens. RESULTS: Totally 1525 genotype 3 patients were eligible for analysis; most (72.6%) were aged > 45 years, majority were males (95.1%), and all (100%) had advanced liver disease (F3 or F4 by METAVIR score based on elastography). Of those who received sofosbuvir/ribavirin (SOF/RBV) for 24 weeks, 79.3% achieved SVR, while 96.5% who received sofosbuvir/pegylated interferon/ribavirin (SOF/PEG/RBV) for 12 weeks achieved SVR (p < 0.01). Among patients with liver cirrhosis (defined as F4) overall cure rate was 85.7% as opposed to 96.4% for those with F3. Females were more likely to be cured (98.7% vs 89.7%; OR = 8.54). Patients aged 31-45 years had higher likelihood of achieving SVR compared to patients aged 46-60 years (95.7% vs 87.4%; OR = 0.32,). Independent predictors of SVR were treatment with SOF/PEG/RBV (aOR = 6.72) and lower fibrosis stage (F3) (aOR = 4.18). Real-world experience among HCV GEN3 patients with advanced liver fibrosis and treated by sofosbuvir regimen w/o PEGIFN, demonstrated overall high SVR rate.

Blood transfusion safety in the country of Georgia: collateral benefit from a national hepatitis C elimination program.

BACKGROUND: In April 2015, the government of Georgia (country) initiated the world's first national hepatitis C elimination program. An analysis of blood donor infectious screening data was conducted to inform a strategic plan to advance blood transfusion safety in Georgia. STUDY DESIGN AND METHODS: Descriptive analysis of blood donation records (2015-2017) was performed to elucidate differences in demographics, donor type, remuneration status, and seroprevalence for infectious markers (hepatitis C virus antibody [anti-HCV], human immunodeficiency virus [HIV], hepatitis B virus surface antigen [HBsAg], and Treponema pallidum). For regression analysis, final models included all variables associated with the outcome in bivariate analysis (chi-square) with a p value of less than 0.05. RESULTS: During 2015 to 2017, there were 251,428 donations in Georgia, representing 112,093 unique donors; 68.5% were from male donors, and 51.2% of donors were paid or replacement (friends or family of intended recipient). The overall seroprevalence significantly declined from 2015 to 2017 for anti-HCV (2.3%-1.4%), HBsAg (1.5%-1.1%), and T. pallidum (1.1%-0.7%) [p < 0.0001]; the decline was not significant for HIV (0.2%-0.1%). Only 41.0% of anti-HCV seropositive donors underwent additional testing to confirm viremia. Infectious marker seroprevalence varied by age, sex, and geography. In multivariable analysis, first-time and paid donor status were associated with seropositivity for all four infectious markers. CONCLUSION: A decline during the study period in infectious markers suggests improvement in blood safety in Georgia. Areas that need further improvement are donor recruitment, standardization of screening and diagnostic follow-up, quality assurance, and posttransfusion surveillance.

Screening and linkage to care for hepatitis C among inpatients in Georgia's national hospital screening program.

The country of Georgia initiated an ambitious national hepatitis C elimination program. To facilitate elimination, a national hospital hepatitis C screening program was launched in November 2016, offering all inpatients screening for HCV infection. This analysis assesses the effectiveness of the first year of the screening program to identify HCV-infected persons and link them to care. Data from Georgia's electronic Health Management Information System and ELIMINATION-C treatment database were analyzed for patients aged ≥18 years hospitalized from November 1, 2016 to October 31, 2017. We described patient characteristics and screening results and compared linked-to-care patients to those not linked to care, defined as having a test for viremia following an HCV antibody (anti-HCV) positive hospital screening. Of 291,975 adult inpatients, 252,848 (86.6%) were screened. Of them, 4.9% tested positive, with a high of 17.4% among males aged 40-49. Overall, 19.8% of anti-HCV+ patients were linked to care, which differed by sex (20.6% for males vs. 18.4% for females; p = .019), age (23.9% for age 50-59 years vs. 10.7% for age ≥ 70 years; p < .0001), and length of hospitalization (21.8% among patients hospitalized for 1 day vs. 16.1% for those hospitalized 11+ days; p = .023). Redundant screening is a challenge; 15.6% of patients were screened multiple times and 27.6% of anti-HCV+ patients had a prior viremia test. This evaluation demonstrates that hospital-based screening programs can identify large numbers of anti-HCV+ persons, supporting hepatitis C elimination. However, low linkage-to-care rates underscore the need for screening programs to be coupled with effective linkage strategies.

Treatment outcomes of patients with chronic hepatitis C receiving sofosbuvir-based combination therapy within national hepatitis C elimination program in the country of Georgia.

BACKGROUND: Georgia has one of the highest HCV prevalence in the world and launched the world's first national HCV elimination programs in 2015. Georgia set the ambitious target of diagnosing 90% of people living with HCV, treating 95% of those diagnosed and curing 95% of treated patients by 2020. We report outcomes of Sofosbuvir (SOF) based treatment regimens in patients with chronic HCV infection in Georgia. METHODS: Patients with cirrhosis, advanced liver fibrosis and severe extrahepatic manifestations were enrolled in the treatment program. Initial treatment consisted of SOF plus ribavirin (RBV) with or without pegylated interferon (INF). Sustained virologic response (SVR) was defined as undetectable HCV RNA at least 12 weeks after the end of treatment. SVR were calculated using both per-protocol and modified intent-to-treat (mITT) analysis. Results for patients who completed treatment through 31 October 2018 were analyzed. RESULTS: Of the 7342 patients who initiated treatment with SOF-based regimens, 5079 patients were tested for SVR. Total SVR rate was 82.1% in per-protocol analysis and 74.5% in mITT analysis. The lowest response rate was observed among genotype 1 patients (69.5%), intermediate response rate was achieved in genotype 2 patients (81.4%), while the highest response rate was among genotype 3 patients (91.8%). Overall, SOF/RBV regimens achieved lower response rates than IFN/SOF/RBV regimen (72.1% vs 91.3%, P < 0.0001). In multivariate analysis being infected with HCV genotype 2 (RR =1.10, CI [1.05-1.15]) and genotype 3 (RR = 1.14, CI [1.11-1.18]) were associated with higher SVR. Patients with cirrhosis (RR = 0.95, CI [0.93-0.98]), receiving treatment regimens of SOF/RBV 12 weeks, SOF/RBV 20 weeks, SOF/RBV 24 weeks and SOF/RBV 48 weeks (RR = 0.85, CI [0.81-0.91]; RR = 0.86, CI [0.82-0.92]; RR = 0.88, CI [0.85-0.91] and RR = 0.92, CI [0.87-0.98], respectively) were less likely to achieve SVR. CONCLUSIONS: Georgia's real world experience resulted in high overall response rates given that most patients had severe liver damage. Our results provide clear evidence that SOF plus IFN and RBV for 12 weeks can be considered a treatment option for eligible patients with all three HCV genotypes. With introduction of next generation DAAs, significantly improved response rates are expected, paving the way for Georgia to achieve HCV elimination goals.

Progress and challenges of a pioneering hepatitis C elimination program in the country of Georgia.

BACKGROUND & AIMS: Georgia, with a high prevalence of HCV infection, launched the world's first national hepatitis C elimination program in April 2015. A key strategy is the identification, treatment, and cure of the estimated 150,000 HCV-infected people living in the country. We report on progress and key challenges from Georgia's experience. METHODS: We constructed a care cascade by analyzing linked data from the national hepatitis C screening registry and treatment databases during 2015-2018. We assessed the impact of reflex hepatitis C core antigen (HCVcAg) testing on rates of viremia testing and treatment initiation (i.e. linkage to care). RESULTS: As of December 31, 2018, 1,101,530 adults (39.6% of the adult population) were screened for HCV antibody, of whom 98,430 (8.9%) tested positive. Of the individuals who tested positive, 78,484 (79.7%) received viremia testing, of whom 66,916 (85.3%) tested positive for active HCV infection. A total of 52,576 people with active HCV infection initiated treatment and 48,879 completed their course of treatment. Of the 35,035 who were tested for cure (i.e., sustained virologic response [SVR]), 34,513 (98.5%) achieved SVR. Reflex HCVcAg testing, implemented in March 2018, increased rates of monthly viremia testing by 97.5% among those who screened positive for anti-HCV, however, rates of treatment initiation decreased by 60.7% among diagnosed viremic patients. CONCLUSIONS: Over one-third of people living with HCV in Georgia have been detected and linked to care and treatment, however, identification and linkage to care of the remaining individuals with HCV infection is challenging. Novel interventions, such as reflex testing with HCVcAg, can improve rates of viremia testing, but may result in unintended consequences, such as decreased rates of treatment initiation. Linked data systems allow for regular review of the care cascade, allowing for identification of deficiencies and development of corrective actions. LAY SUMMARY: This report describes progress in Georgia's hepatitis C elimination program and highlights efforts to promote hepatitis C virus screening and treatment initiation on a national scale. Georgia has made progress towards eliminating hepatitis C, treating over 50,000 people, approximately one-third of the number infected, and achieving cure for 98.5% of those tested. However, identifying infected individuals and linking them to care remains challenging. Novel approaches to increase diagnostic testing can have unintended consequences further down the care cascade.

Interim effect evaluation of the hepatitis C elimination programme in Georgia: a modelling study.

BACKGROUND: Georgia has a high prevalence of hepatitis C, with 5·4% of adults chronically infected. On April 28, 2015, Georgia launched a national programme to eliminate hepatitis C by 2020 (90% reduction in prevalence) through scaled-up treatment and prevention interventions. We evaluated the interim effect of the programme and feasibility of achieving the elimination goal. METHODS: We developed a transmission model to capture the hepatitis C epidemic in Georgia, calibrated to data from biobehavioural surveys of people who inject drugs (PWID; 1998-2015) and a national survey (2015). We projected the effect of the administration of direct-acting antiviral treatments until Feb 28, 2019, and the effect of continuing current treatment rates until the end of 2020. Effect was estimated in terms of the relative decrease in hepatitis C incidence, prevalence, and mortality relative to 2015 and of the deaths and infections averted compared with a counterfactual of no treatment over the study period. We also estimated treatment rates needed to reach Georgia's elimination target. FINDINGS: From May 1, 2015, to Feb 28, 2019, 54 313 patients were treated, with approximately 1000 patients treated per month since mid 2017. Compared with 2015, our model projects that these treatments have reduced the prevalence of adult chronic hepatitis C by a median 37% (95% credible interval 30-44), the incidence of chronic hepatitis C by 37% (29-44), and chronic hepatitis C mortality by 14% (3-30) and have prevented 3516 (1842-6250) new infections and averted 252 (134-389) deaths related to chronic hepatitis C. Continuing treatment of 1000 patients per month is predicted to reduce prevalence by 51% (42-61) and incidence by 51% (40-62), by the end of 2020. To reach a 90% reduction by 2020, treatment rates must increase to 4144 (2963-5322) patients initiating treatment per month. INTERPRETATION: Georgia's hepatitis C elimination programme has achieved substantial treatment scale-up, which has reduced the burden of chronic hepatitis C. However, the country is unlikely to meet its 2020 elimination target unless treatment scales up considerably. FUNDING: CDC Foundation, National Institute for Health Research, National Institutes of Health.

Three Years of Progress Toward Achieving Hepatitis C Elimination in the Country of Georgia, April 2015-March 2018.

BACKGROUND: In April 2015, in collaboration with the US Centers for Disease Control and Prevention and Gilead Sciences, the country of Georgia embarked on the world's first hepatitis C elimination program. We aimed to assess progress toward elimination targets 3 years after the start of the elimination program. METHODS: We constructed a hepatitis C virus (HCV) care cascade for adults in Georgia, based on the estimated 150 000 persons aged ≥18 years with active HCV infection. All patients who were screened or entered the treatment program during April 2015-March 2018 were included in the analysis. Data on the number of persons screened for HCV were extracted from the national HCV screening database. For the treatment component, we utilized data from the Georgia National HCV treatment program database. Available treatment options included sofosbuvir and ledipasvir/sofosbuvir-based regimens. RESULTS: Since April 2015, a cumulative 974 817 adults were screened for HCV antibodies; 86 624 persons tested positive, of whom 61 925 underwent HCV confirmatory testing. Among the estimated 150 000 adults living with chronic hepatitis C in Georgia, 52 856 (35.1%) were diagnosed, 45 334 (30.2%) initiated treatment with direct-acting antivirals, and 29 090 (19.4%) achieved a sustained virologic response (SVR). Overall, 37 256 persons were eligible for SVR assessment; of these, only 29 620 (79.5%) returned for evaluation. The SVR rate was 98.2% (29 090/29 620) in the per-protocol analysis and 78.1% (29 090/37 256) in the intent-to-treat analysis. CONCLUSIONS: Georgia has made substantial progress in the path toward eliminating hepatitis C. Scaling up of testing and diagnosis, along with effective linkage to treatment services, is needed to achieve the goal of elimination.