Evaluation of Knowledge, Attitudes and Practices for Hepatitis B Virus Infection Among Primary Healthcare Physicians in Georgia.

A nationwide serosurvey among adults in 2021 showed a 2.7% (95% confidence interval [CI]: 2.3%-3.4%) prevalence of hepatitis B. Our analysis evaluates knowledge, attitudes and practices (KAP) for hepatitis B virus (HBV) infection among primary healthcare physicians (PHPs) in Georgia. We randomly selected 550 PHPs from medical facilities in Georgia's six largest cities. Using bivariate ordinal regression, we assessed the association of socio-demographic factors with an ordinal knowledge score (low/middle/high). Multivariable logistic regression was performed to calculate adjusted odds ratios (aOR) and 95% CI to determine associations between HBV knowledge score and practices. Of 550 selected PHPs, 506 (92.0%) agreed to participate. Among them, 62.8% scored in the medium or high knowledge tertiles, 72.7% were confident in diagnosing HBV infection, 37.3% were confident in managing patients with hepatitis B; 47.4% reported being screened for and 26.2% reported being vaccinated against HBV infection. Compared to those with low knowledge scores, PHPs with a high score were less likely to recommend activities not supported by evidence, such as: the use of 'hepatoprotective' medications (aOR 0.43, 95% CI 0.25-0.73), caesarean sections (aOR 0.47, 95% CI 0.27-0.82) and withholding breastfeeding (aOR 0.57, 95% CI 0.34-0.96) to prevent HBV transmission. The majority of PHPs were confident in diagnosing HBV infection, but only one in three were confident in managing patients with hepatitis B. PHPs with higher HBV knowledge were less likely to provide inaccurate instructions to their patients. These findings will help to develop awareness and education campaigns supporting HBV elimination in Georgia.

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.

Retreatment of Chronic Hepatitis C Infection: Real-World Regimens and Outcomes From National Treatment Programs in Three Low- and Middle-Income Countries.

Access to recommended second-line treatments is limited for patients who fail initial hepatitis C virus (HCV) therapy in low- and middle-income countries. Alternative regimens and associated outcomes are not well understood. Through a pooled analysis of national program data in Egypt, Georgia, and Myanmar, we observed SVR rates >90% for alternative retreatment regimens.

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.

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.

Emergence of Hepatitis C Virus Genotype Recombinant Forms 2k/1b in Georgia.

BACKGROUND: Hepatitis C virus (HCV) evolution is thought to proceed by mutations within the six major genotypes. Studies of HCV recombinant genotypes in different parts of the world have recently been initiated. Only a few cases of recombination have been identified worldwide, predominantly in Eastern Europe and Asia. In 2011 we detected the recombinant form (RF) of a HCV genotype RF_2k/1b in Georgia. Therefore, we reviewed HCV genotyping data of 491 patients with chronic hepatitis C virus infections of our center in Tbilisi over a period of two years. METHODS: Initially all genotyping analyses were performed with the VERSANT HCV genotype assay (Siemens, LiPA). In a second analysis, parts of the core and the NS5B region were sequenced for all HCV genotypes 2a/2c. RESULTS: Approximately 2/3 of genotype 2 cases were identified as the recombinant form HCV-RF 2k/1b. Overall, this type represented 19% of all HCV patients who underwent genotyping. CONCLUSIONS: We can conclude that almost 20% of HCV infected Georgian patients are infected with HCVRF_2k/ 1b.

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.

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.

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.