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.

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.

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.

Progress in Testing for and Treatment of Hepatitis C Virus Infection Among Persons Who Inject Drugs - Georgia, 2018.

In April 2015, the country of Georgia, with a high prevalence of hepatitis C virus (HCV) infection (5.4% of the adult population, approximately 150,000 persons), embarked on the world's first national elimination program (1,2). Nearly 40% of these infections are attributed to injection drug use, and an estimated 2% of the adult population currently inject drugs, among the highest prevalence of injection drug use in the world (3,4). Since 2006, needle and syringe programs (NSPs) have been offering HCV antibody testing to persons who inject drugs and, since 2015, referring clients with positive test results to the national treatment program. This report summarizes the results of these efforts. Following implementation of the elimination program, the number of HCV antibody tests conducted at NSPs increased from an average of 3,638 per year during 2006-2014 to an average of 21,551 during 2015-2018. In 2017, to enable tracking of clinical outcomes among persons who inject drugs, NSPs began encouraging clients to voluntarily provide their national identification number (NIN), which all citizens must use to access health care treatment services. During 2017-2018, a total of 2,780 NSP clients with positive test results for HCV antibody were identified in the treatment database by their NIN. Of 494 who completed treatment and were tested for HCV RNA ≥12 weeks after completing treatment, 482 (97.6%) were cured of HCV infection. Following the launch of the elimination program, Georgia has made much progress in hepatitis C screening among persons who inject drugs; recent data demonstrate high cure rates achieved in this population. Testing at NSPs is an effective strategy for identifying persons with HCV infection. Tracking clients referred from NSPs through treatment completion allows for monitoring the effectiveness of linkage to care and treatment outcomes in this population at high risk, a key to achieving hepatitis C elimination in Georgia. The program in Georgia might serve as a model for other countries.

Identification of hepatitis C virus 2k/1b intergenotypic recombinants in Georgia.

BACKGROUND AND AIMS: This study aimed to evaluate the prevalence of the hepatitis C virus intergenotype recombinant strain RF1_2k/1b in Georgia, confirm viral recombination by full genome sequencing, and determine a genetic relationship with previously described recombinant hepatitis C viruses. METHODS: We retrospectively analysed data from 1421 Georgian patients with chronic hepatitis C. Genotyping was performed with the INNO-LiPA VERSANT HCV Genotype 2.0 Assay. RESULTS: Virus isolates were assigned to nonspecific hepatitis C genotypes 2a/2c (n = 387) as performed by sequencing of core and NS5B genes. Subsequently, sequencing results classified the core region as genotype 2k and the NS5B region as genotype 1b for 72% (n = 280) of genotype 2 patients, corresponding to 19.7% of hepatitis C patients in Georgia. Eight samples were randomly selected for full genome sequencing which was successful in 7 of 8 samples. Analysis of the generated consensus sequences confirmed that all 7 viruses were 2k/1b recombinants, with the recombination breakpoint located within 73-77 amino acids before the NS2-NS3 junction, similar to the previously described RF1_2k/1b virus. Phylogenetic analysis revealed clustering of the Georgian 2k/1b viruses and RF1_2k/1b, suggesting that they are genetically related. CONCLUSIONS: The 19.7% prevalence of RF1_2k/1b in Georgia patients is far higher than has generally been reported to date worldwide. Identification of recombinants in low income countries with a high prevalence of HCV infection might be reasonable for choosing the most cost-effective treatment regimens.

Assessment of Viral and Clinical Characteristics Among Patients With Chronic Hepatitis B Virus Infection in Georgia.

Background: Hepatitis B virus infection (HBV) is one of the major healthcare problems in Georgia. To achieve viral hepatitis elimination, gaps in diagnosis and management of chronic HBV infection need to be addressed. The aim of our study was to collect data on clinical and viral characteristics of patients with chronic HBV infection to estimate the proportion of patients who may need antiviral treatment. Methods: All relevant deidentified data about demographic, clinical, and viral characteristics were extracted from patients' medical records. Descriptive statistical analyses were done for univariate assessment of demographic, virologic, and clinical characteristics. Chi-square test was used to assess the associations between HBV-DNA level, HBeAg, alanine aminotransferase (ALT), and liver fibrosis. Results: In total, 96% (124/129) of patients with chronic HBV infection are HBeAg-negative; 84% (145/173) had no or mild fibrosis, and 3% (6/162) had advanced liver fibrosis/cirrhosis. Sixty-five out of 126 (51%) patients were classified as HBeAg-positive or HBeAg-negative chronic HBV infection (without hepatitis); 11 (9%) as chronic hepatitis B; 46 (37%) had not classified in any of the known HBV phases, while 30 of them (24% out of total) had high viral load and normal ALT. Statistically significant association was seen between high HBV-DNA and HBeAg-positivity (P = .043). High ALT level was also associated with liver fibrosis (P = .015). Significant positive correlation between age and the presence of moderate or advanced liver fibrosis was observed (P = .002). Conclusion: This is the first study about the clinical and viral characteristics of patients with chronic HBV infection in Georgia. The vast majority were HBeAg-negative, only 3% had advanced liver diseases; about half of patients had inactive diseases. However, one out of four patients had a high viral load but normal ALT. By the evaluation of HBV phases, we estimated that 12%-36% of patients with chronic HBV monoinfection require antiviral treatment.