Hepatitis C Virus Treatment Research Articles

Linkage to hepatitis C treatment in two opioid substitution treatment units in Gothenburg, Sweden: a retrospective cohort study

BackgroundChronic infection with the hepatitis C virus (HCV) is common in people with former or current injection drug use. Among the patients in the opioid substitution treatment (OST) program in Gothenburg, Sweden, more than 50% had been infected with HCV. However, many patients did not have any follow-up for their infection and the linkage to treatment could be improved.MethodsA model of care for HCV was introduced at an OST unit in Gothenburg, Sweden, in 2017. The aim was to increase testing and linkage to HCV treatment. A nurse and a medical doctor, both specialized in infectious diseases, performed on-site testing at the OST unit with transient liver elastography (Fibroscan) to evaluate the fibrosis stage and initiated HCV treatment. This study retrospectively reviewed the patients’ medical records to assess information regarding participation in the model of care, hepatitis C status, linkage to treatment and treatment outcome.ResultsAmong the 225 patients enrolled in OST at baseline, 181 were still in the OST program at the end of study (December 31st, 2018). In total, 29 patients, most of whom did not attend the Clinic of Infectious Diseases, were referred to the model of care. By the end of study, 17 patients (100% of those treated) reached sustained virologic response. In parallel, an additional 19 patients got treatment directly at the Clinic of Infectious Diseases.ConclusionIntegrating HCV screening and examination in an OST unit successfully linked patients to treatment. However, not all patients received treatment. To reach the goal of eliminating HCV, different models of care are needed.

Pharmacoinformatics-based strategy in designing and profiling of some Pyrazole analogues as novel hepatitis C virus inhibitors with pharmacokinetic analysis

ABSTRACT Hepatitis C virus (HCV) infection promotes death rates all over the world. Sofosbuvir is a standard drug for the cure of HCV but unfortunately, it receives a lot of attention for its pricing problems. As a result, it is crucial to consider alternative HCV treatments that are both cost-effective and free of side effects. We report how a pharmacoinformatics-based technique was used to generate and profile certain Pyrazole analogues as novel hepatitis C virus inhibitors by exploring the PubChem drug repository for the lead molecule with further optimization. The proposed molecules all interact by filling the protein target’s binding domain to inhibit the receptor. With binding energy of −35.72 kcal/mol, compound 17e was found as a highly potent NS5B inhibitor, exceeding Sofosbuvir, the FDA-approved NS5B inhibitor with a binding energy of −30.34 kcal/mol. Additionally, the ADMET assessment of the selected molecules (17e) shows outstanding quality with a drug score of 0.74 when especially in comparison to Sofosbuvir, which has a drug score of 0.31. Future studies should therefore focus on the molecular dynamics, synthesis, in vivo testing, and in vitro evaluation of these substances to validate our hypothesis.

Modeling the Impacts of Prevention and Treatment Interventions on Hepatitis C Among People Who Inject Drugs in China.

Injection drug use is the main transmission route of hepatitis C virus (HCV) in China. The prevalence of HCV remains high at 40-50% among people who inject drugs (PWID). We developed a mathematical model to predict the impacts of different HCV intervention strategies on the HCV burden in Chinese PWID by 2030. We developed a dynamic deterministic mathematical model to simulate the transmission of HCV among PWID in China between 2016 and 2030, using domestic data based on the real cascade of HCV care. We considered various intervention scenarios, including treatment regimens, harm reduction program (HRP) coverage, enhanced testing and referral for treatment. HCV incidence will exhibit a gradual but slow declining trend from 12,970 in 2016 to 11,761 in 2030 based on current screening and treatment practices among PWID (scenario 1). Scaled-up HCV screening and treatment integrated with HRPs (scenario 8) demonstrated the most substantial reduction in HCV burden, being the only intervention scenario that could achieve the World Health Organization's (WHO's) HCV elimination target. Specifically, the HCV incidence in 2030 is projected to be reduced by 81.42%, and HCV-related deaths are projected to be reduced by 91.94%. Our study indicates that achieving WHO elimination targets is an extremely challenging goal that requires substantial improvements in HCV testing and treatment among PWID (scenario S8). The findings suggest that coordinated improvements in testing, treatment, and harm reduction programs could greatly reduce the HCV burden among PWID in China, and urgent policy changes are needed to integrate HCV testing and treatment into existing HRPs.

A11 NEXT STEPS IN MICRO-ELIMINATION: PEER POINT OF CARE HEPATITIS C TESTING IN VICTORIA, BRITISH COLUMBIA

Abstract Background Canada is currently on target to reach the 2030 WHO goal of hepatitis C virus (HCV) elimination. Continued high rates of treatment initiation are required to meet this goal. People who use drugs (PWUD), account for the majority of new HCV cases in BC and continue to have many barriers to accessing DAA therapies, despite demonstrated high SVR rates in clinical trials. Improved elimination efforts including innovative outreach testing and treatment with this population are essential. Novel models have proven successful to engage PWUD in HCV therapy with a simplified, task-shifted cascade of care. Peer-based testing and support models have been piloted in other communities and may help connect to marginalized populations. People with lived and living experience of HCV treatment and drug use (peers) are seen as trusted sources of knowledge. Peers can vouch for the efficacy, minimal side effects and ease of HCV treatment that now exist in the current DAA era. Purpose The Peer HCV Point of Care (POC) testing project developed within our long standing nurse-led HCV treatment program seeks to determine whether an outreach peer model of HCV POC testing can be successful in Victoria, BC. The peer program focuses on finding populations who use drugs without regular access to primary care still living with HCV. This task shifting approach is the next phase of local micro-elimination efforts and has not been attempted previously. Method Six peers have been trained to provide HCV POC antibody and dried blood spot RNA tests. Our goals are to pilot the program, learn from our experiences, specifically from the direct input of peers to develop effective and supportive testing and treatment strategies. Peers have worked with nursing and research staff in two-hour blocks and are paid $26 per hour for these shifts. They provide testing at local supportive housing, shelters, social service sites and special events. Each client tested is offered a $10 incentive. Our peers are able to offer both POC antibody testing and, for those who have been exposed to HCV (currently infected, treated or cleared), RNA testing by dried blood spot. Serology by nursing from our mobile outreach van is collected as needed. Result(s) Within the first 4 months of the project peers and staff tested 304 people: 251 people with HCV POC antibody tests (227 negative and 24 positive results), 41 people with HCV dried blood spot RNA tests and 28 with nurse RNA serology. To date 12 people tested RNA+ (11 with previously unknown HCV have active RNA that require treatment), 7 people have been started on treatment. Conclusion(s) This innovative and novel approach to HCV therapy in PWUD was able to successfully use a peer-based approach to find people with limited connection to primary health care to test and treat HCV. We still have much to learn from the valuable knowledge, established relationships and novel perspectives of peers in our efforts to reduce barriers and reach PWUD and others who remain untreated. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest T. Barnett Grant / Research support from: AbbVie, Gilead, Merck, M. Selfridge Grant / Research support from: Kirby Institute, AbbVie, Gilead, Merck, ViiV, A. Drost Grant / Research support from: Abbvie, Gilead, Merck, K. Guarasci Grant / Research support from: Gliead, Abbvie, Merck , K. Lundgren Grant / Research support from: Abbvie, Gilead, Merck , C. Fraser Grant / Research support from: Abbvie, Gilead, Merck, Kirby Institute, ViiV, F. Boothman : None Declared

Using Community Paramedicine to Treat Hepatitis C Virus in Upstate South Carolina.

Hepatitis C virus (HCV) is an infection of the liver that can lead to significant liver damage and hepatocellular carcinoma. Individuals born between 1945 and 1965 and individuals with intravenous drug use represent the largest HCV demographics and often experience barriers to treatment. In this case series, we discuss a novel partnership between community paramedics (CPs), HCV care coordinators, and an infectious disease physician to provide HCV treatment to individuals with barriers accessing care. Three patients tested positive for HCV within a large hospital system in the upstate region of South Carolina. All of the patients were contacted to discuss their results and scheduled for treatment by the hospital's HCV care coordination team. Patients who expressed barriers to attending in-person appointments or were lost to follow-up were offered a telehealth appointment facilitated by CPs performing a home visit with the added ability to draw blood and perform a physical assessment guided by the infectious disease physician. All of the patients were eligible for and prescribed treatment. The CPs assisted with follow-up visits, blood draws, and other patient needs. Two of the three patients connected to care had an undetectable HCV viral load following 4 weeks of treatment, whereas the third was undetectable after 8 weeks. Only one patient reported a mild headache that was potentially linked to the medication, whereas the others did not report any adverse effects. This case series highlights the barriers experienced by some HCV-positive patients and a distinctive plan to address impediments to access for HCV treatment.

Barriers and Facilitators to Hepatitis C Virus (HCV) Treatment for Aboriginal and Torres Strait Islander Peoples in Rural South Australia: A Service Providers’ Perspective

This study explored the barriers and facilitators to hepatitis C virus (HCV) treatment for Aboriginal and Torres Strait Islander peoples in rural South Australia as viewed from a healthcare provider perspective in the era of direct acting antivirals (DAAs). Phase 1 was a qualitative systematic review examining the barriers and enablers to diagnosis and treatment amongst Indigenous peoples living with HCV worldwide. Phase 2 was a qualitative descriptive study with healthcare workers from six de-identified rural and regional Aboriginal Community-Controlled Health Services in South Australia. The results from both methods were integrated at the analysis phase to understand how HCV treatment could be improved for rural Aboriginal and Torres Strait Islander peoples. Five main themes emerged: the importance of HCV education, recognizing competing social and cultural demands, the impact of holistic care delivery and client experience, the effect of internal barriers, and overlapping stigma, discrimination, and shame determine how Indigenous peoples navigate the healthcare system and their decision to engage in HCV care. Continued efforts to facilitate the uptake of DAA medications by Aboriginal and Torres Strait peoples in rural areas should utilize a multifaceted approach incorporating education to community and cultural awareness to reduce stigma and discrimination.

Effect of Hepatitis C Treatment on Risk of Developing Cardiovascular Disease and Cardiac Arrhythmias

Background: Chronic hepatitis C virus (HCV) infection affects more than 70 million people worldwide, is a systemic disease and has been implicated as a risk factor for cardiovascular disease (CVD). Objective: We sought to study the association between risk of CVD between 0-12 month and 12-24 months of HCV treatment initiation. Methods: 567,956 Hepatitis C patients without prior history of CVD were identified in the Cerner Health Facts database. Of these, 1446 patients received HCV treatment. We included both demographic and as covariates in the multivariate logistic regression model. To control for baseline differences among treatment and control groups, propensity score matching (PSM) comparative analysis was used to adjust for potential confounding baseline characteristics between these two groups, and finally 2892 patients (1:1 match) (1446 in each group) were enrolled in the final analysis. Results: There was no statistically significant association between CVD and treatment of HCV (at both 0-12 and 12-24 months). The odds of developing CVD for females were 1.52 times greater than males during the first 12 months of treatment. Advanced age was also associated with a high risk of CVD during the initial 12 months (OR 1.05 95% CI 1.03-1.07). HCV patients with HIV were 45% less likely to experience CVD Expanded =0.55, 95% CI: 0.33- 0.91, p<0.05) compared to those without HIV for 12-24 months. Treatment’s association with the development of cardiac arrhythmias was not statistically significant between 0-12 months or 12-24 months. Older age was associated with a higher risk of cardiac arrhythmias following 0-12 months after treatment with OR 1.08 95% CI 1.04-1.12. There was also a significantly high risk of arrhythmias with hypothyroidism for 0-12 months (OR 4.23 95% CI 1.48-12.08) Conclusion: Female sex and advanced age were associated with increased odds of CVD, and advanced age and hypothyroidism were associated with increased odds of arrhythmias development during the first 12 months of treatment. Further studies are needed to explore this in a prospective fashion.

Delays in fibrosis staging reduce the likelihood of achieving hepatitis C treatment and cure

Background Updated 2021 hepatitis C virus (HCV) treatment guidelines no longer recommend fibrosis staging for treatment-naïve patients without cirrhosis; however, numerous US state Medicaid plans continue to restrict initiation of HCV therapy by fibrosis stage. The study objective was to determine whether delays from HCV diagnosis to fibrosis staging impact the likelihood of initiating/completing HCV treatment and achieving sustained virologic response (SVR). Methods A retrospective cohort study was performed among patients diagnosed with chronic HCV by an urban US emergency department who subsequently underwent fibrosis staging. Time elapsed from HCV diagnosis to hepatic fibrosis staging was evaluated on the likelihood of treatment initiation, treatment completion and SVR. Results Among fibrosis staging modalities, hepatic ultrasounds occurred more quickly following HCV diagnosis (3.5 months, IQR = 12.4 months), compared to FibroSure (8.5 months, IQR = 20.4 months) and FibroScan (9.9 months, IQR = 18.0 months) (p<.001). Each six-month delay in fibrosis staging decreased the likelihood of initiating treatment by 5% (adjusted relative risk (aRR)=0.95; 95% confidence interval (CI)=0.91–0.998; p=.04) and the likelihood of SVR by 7% (aRR = 0.93; 95% CI = 0.87–0.995; p=.04) after adjusting for insurance, race/ethnicity and history of HIV testing. Conclusions Delays in hepatitis fibrosis staging were significantly associated with decreased likelihood of HCV treatment initiation and SVR.

Chemical bioinformatics study of Nonadec-7-ene-4-carboxylic acid derivatives via molecular docking, and molecular dynamic simulations to identify novel lead inhibitors of hepatitis c virus NS3/4a protease

One of the most common viruses in the world today is the hepatitis C virus (HCV). It is a virus with a wide range of characteristics, and it reproduces and evolves quickly. The nonstructural proteins (NS3/4a), are responsible for swift multiplication that causes genome variability. Voxilaprevir is a standard drug for the cure of HCV but unfortunately, it receives a lot of attention for its pricing problems. As a result, it is crucial to consider alternative HCV treatments that are both cost-effective and free of side effects. An in-silicon methodology was applied in the current research to virtually search the PubChem database for compounds that are effective against HCV NS3/4a. Molecule 45 (PubChem68792528) was selected based on its lowest binding energy of -44.55 kcal/mol in contrast to the Voxilaprevir with a binding energy of -40.68 kcal/mol. Also Using Voxilaprevir as a guide, the results of MD simulation showed potentially viable lead compounds that could be built into conventional drugs having a high binding energy of -113.724 kj/mol, stable complex, and mechanisms different from the reference compound with a binding energy of -108.132 kj/mol. For the first 10 ns, compound 45′s average RMSD value increased to 0.28 nm, and it stayed there for the remaining 100 ns of the trajectory, fluctuating between 0.26 and 0.28 nm. Comparing these values to the RMSD values of the reference complex over the course of the simulation, compound 45′s structural modeling is shown to be more stable.

Budget impact analysis of two treatment approaches for hepatitis C in Malaysia through the use of voluntary and compulsory licensing options.

A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to sofosbuvir/daclatasvir (SOF/DAC) is available through compulsory licensing, with access to sofosbuvir/velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes but has higher drug acquisition costs compared to SOF/DAC. A stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications. The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years. A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.

Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C.

Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.

Reducing barriers to the hepatitis C care cascade in prison via point-of-care RNA testing: a qualitative exploration of men in prison using an integrated framework.

Hepatitis C virus (HCV) is highly prevalent within the prison setting. Although HCV testing and treatment are available within prisons, system barriers can impede progress along the HCV care cascade for those who are incarcerated. The PIVOT intervention used a 'one-stop-shop' model (i.e. point-of-care HCV RNA testing, Fibroscan-based liver disease assessment and treatment) at a reception prison in New South Wales, Australia. This analysis sought to understand the role of point-of-care HCV RNA testing at intake in reducing barriers to the HCV care cascade within the male prison setting. Qualitative analysis using semi-structured interviews in a reception prison in Australia. Twenty-four men enrolled in the PIVOT study; all participants had undergone HCV point-of-care testing in the intervention arm. Høj's Integrated Framework informed this analysis. Participants widely expressed the view that point-of-care HCV RNA testing on entry was beneficial for care engagement. Point-of-care testing was perceived as timely (compared with standard pathology) and reduced opportunities for adjudication by correctional officers due to fewer clinic visits for testing and results. Adoption of routine opt-out testing at prison intake was regarded as an important strategy for normalising HCV testing (and likely to increase pathways to treatment uptake) and fostered patient candidacy (i.e. self-perceived eligibility to access care). Twenty-four men in prison in New South Wales, Australia, who underwent opt-out point-of-care HCV RNA testing on entry into prison, widely supported the programme as a means of overcoming barriers to HCV testing and treatment in the prison setting, as well as providing public health benefits through early detection of HCV infection among people entering into custody.

Hepatitis C Virus Testing and Care Cascade Among Transgender and Gender Diverse Individuals

Hepatitis C virus (HCV) prevalence among transgender and gender-diverse individuals ranges from 1.8% to 15.7% versus 1% in the general population. Previous HCV studies inclusive of transgender and gender-diverse individuals primarily rely on convenience-based sampling methods or are geographically restricted. The purpose of this study is to compare the prevalence of HCV diagnoses, testing, and care engagement between transgender and gender-diverse and cisgender individuals. Using Optum's de-identified Clinformatics® Data Mart Database, in 2022, the unadjusted prevalence of HCV testing among all adults and people who inject drugs from January 2001 to December 2019 was measured. Multivariable logistic regression was used to compare the adjusted odds of HCV diagnoses and care engagement by gender subgroup. The overall unadjusted frequency of HCV diagnoses among transgender and gender-diverse individuals was approximately 3 times that of cisgender individuals (1.06% vs 0.38%, p<0.001), including among people who inject drugs (6.36% vs 2.36%, p=0.007). Compared with cisgender women, transfeminine/nonbinary individuals had over 5 times the adjusted odds of a HCV diagnosis and approximately 3.5 times the odds of being tested for HCV. In addition, compared with cisgender women, transfeminine/nonbinary individuals had significantly increased odds of having a HCV‒related procedure (e.g., abdominal ultrasounds, liver biopsies, Fibroscans). Cisgender men had significantly increased odds of receiving HCV medication compared with cisgender women. Although testing was higher among transgender and gender-diverse individuals, the higher overall frequency of HCV diagnoses among transgender and gender-diverse than among cisgender individuals signals persistent health disparities. Interventions are warranted to prevent HCV and increase ongoing testing and treatment uptake among transgender and gender-diverse populations.

Strategic information to guide elimination of viral hepatitis

WHO has placed the world on the path towards the elimination of hepatitis B virus (HBV) and hepatitis C virus (HCV). The 2016 adoption of the Global Health Sector Strategy (GHSS) set goals for a 90% reduction in incidence and a 65% reduction in mortality for HBV and HCV by 2030, along with targets for improvements in testing, treatment, and hepatitis B vaccination. 1 WHOGlobal Health Sector Strategy on viral hepatitis, 2016–2021—towards ending viral hepatitis. June 2016.. http://apps.who.int/iris/bitstream/10665/246177/1/WHO-HIV-2016.06-engDate accessed: December 13, 2022 Google Scholar The collection of reliable data for elimination of viral hepatitis is a particular challenge, requiring monitoring of trends in HBV and HCV incidence and mortality. Even when data are available, the development of HBV and HCV sequalae, including severe liver damage and liver cancer, usually occurs decades after infection, making the interpretation of elimination effects complex. Furthermore, given low screening rates and fragile national surveillance systems, new infections and mortality are often under-reported. Global reporting of progress towards elimination of hepatitis B and hepatitis CThere has been notable global progress towards hepatitis elimination. In 2019, 30·4 million (10·3%) people living with hepatitis B knew their infection status, which was slightly higher than in 2015 (22·0 million; 9·0%), and 6·6 million (22·7%) of those diagnosed with hepatitis B received treatment, compared with 1·7 million (8·0%) in 2015. Mortality from hepatitis C has declined since 2019, driven by an increase in HCV treatment ten times that of the strategy baseline. However, an estimated 89·7% of HBV infections and 78·6% of HCV infections remain undiagnosed. Full-Text PDF

Global reporting of progress towards elimination of hepatitis B and hepatitis C

The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination. In 2020, using a questionnaire, we collected empirical, systematic, modelled, or surveyed data-reported by WHO country and WHO regional offices-on indicators of progress towards elimination of viral hepatitis, including burden of infection, incidence, mortality, and the cascade of care, and validated these data. WHO received officially validated country-provided data from 130 countries or territories, and used partner-provided data for 70 countries or territories. We estimated that in 2019, globally, 295·9 million (3·8%) people were living with chronic hepatitis B virus (HBV) infection and 57·8 million (0·8%) people were living with chronic hepatitis C virus (HCV) infection. Globally, there were more than 3·0 million new infections with HBV and HCV and more than 1·1 million deaths due to the viruses in 2019. In 2019, 30·4 million (95% CI 24·3-38·0) individuals living with hepatitis B knew their infection status and 6·6 million (5·3-8·3) people diagnosed with hepatitis B received treatment. Among people with HCV infection, 15·2 million (95% CI 12·1-19·0) had been diagnosed between 2015 and 2019, and 9·4 million (7·5-11·7) people diagnosed with hepatitis C infection were treated with direct-acting antiviral drugs between 2015 and 2019. There has been notable global progress towards hepatitis elimination. In 2019, 30·4 million (10·3%) people living with hepatitis B knew their infection status, which was slightly higher than in 2015 (22·0 million; 9·0%), and 6·6 million (22·7%) of those diagnosed with hepatitis B received treatment, compared with 1·7 million (8·0%) in 2015. Mortality from hepatitis C has declined since 2019, driven by an increase in HCV treatment ten times that of the strategy baseline. However, an estimated 89·7% of HBV infections and 78·6% of HCV infections remain undiagnosed. A new global strategy for 2022-30, based on these new estimates, should be implemented urgently to scale up the screening and treatment of viral hepatitis. World Health Organization.

Effect of Antiviral Therapy for HCV Treatment in the Presence of Hepatocyte Growth Factor

The effect of antiviral therapy during Hepatitis C Virus (HCV) infection is the focus of this study. HCV infection destroys healthy hepatocyte cells in the human liver, causing cirrhosis and hepatocellular carcinoma. We introduce a cell-population model representing the long-term dynamics of HCV infection in response to antiviral drug therapies. The proliferation of existing cells can create hepatocyte cells in the system. Such models are based on the dynamics of susceptible hepatocytes, infected hepatocytes and HCV with interactive dynamics, which can give a complete understanding of the host dynamics of the system in the presence of antiviral drug therapy. Infection-free equilibrium and endemic equilibrium are two equilibrium states in the absence of drugs. The existence and stability conditions for both systems are presented. We also construct an optimal control system to find the optimal control strategy. Numerical results show that the effects of the proliferation rate and infection rate are critical for the changes in the dynamics of the model. The impact of different weight factors on the optimal control problem is analysed through numerical simulation.

HCV prevalence and treatment outcomes among drug users in an outpatient center for drug addiction in Northern Italy.

We aimed at evaluating hepatitis C virus (HCV) prevalence and treatment referral outcomes in a large population of drug users in Northern Italy. Each participant underwent a quick capillary blood test. Positive participants underwent HCV RNA quantification. HCV RNA positive subjects were referred to treatment and evaluated immediately at the end of treatment and at 3 and 6 months after treatment. Of the 636 participants tested, 244 were positive. Intravenous drug use was more frequent among subjects who tested positive for HCV antibodies (99%). Among subjects who tested positive, 68% were HCV-RNA positive while 32% were negative. Among people referred to treatment, nearly 30% did not show up while 70% completed the treatment with success. Over 99% of people who started direct-acting antiviral agent (DAA) have a sustained response. We observed a significant higher prevalence of HCV positive subjects among people who inject drugs (99%) and we observed a high success rate for HCV treatment engagement. Rapid testing for HCV represents a potential tool for HCV screening among high-risk groups.

How the rural risk environment underpins hepatitis C risk: Qualitative findings from rural southern Illinois, United States.

Hepatitis C virus (HCV) infection has increased among persons who inject drugs (PWID) in the United States with disproportionate burden in rural areas. We use the Risk Environment framework to explore potential economic, physical, social, and political determinants of hepatitis C in rural southern Illinois. Nineteen in-depth semi-structured interviews were conducted with PWID from August 2019 through February 2020 (i.e., pre-COVID-19 pandemic) and four with key informants who professionally worked with PWID. Interviews were recorded, professionally transcribed, and coded using qualitative software. We followed a grounded theory approach for coding and analyses. We identify economic, physical, policy, and social factors that may influence HCV transmission risk and serve as barriers to HCV care. Economic instability and lack of economic opportunities, a lack of physically available HCV prevention and treatment services, structural stigma such as policies that criminalize drug use, and social stigma emerged in interviews as potential risks for transmission and barriers to care. The rural risk environment framework acknowledges the importance of community and structural factors that influence HCV infection and other disease transmission and care. We find that larger structural factors produce vulnerabilities and reduce access to resources, which negatively impact hepatitis C disease outcomes.

Genotypes of Hepatitis C Virus and Efficacy of Direct-Acting Antiviral Drugs among Chronic Hepatitis C Patients in a Tertiary Care Hospital.

Hepatitis C virus (HCV) chronic infection is a major causative factor for several chronic liver diseases, including liver cirrhosis, liver cell failure, and hepatocellular carcinoma. The HCV has seven major genotypes. Genotype 4 is the most prevalent genotype in the Middle East, including Saudi Arabia, followed by genotype 1. The HCV genotype affects the response to different HCV treatments and the progression of liver disease. Currently, combinations of direct-acting antiviral drugs (DAAs) approved for the treatment of HCV achieve high cure rates with minimal adverse effects. Because real-world data from Saudi Arabia about the efficacy of DAAs are still limited, this study was conducted to assess the effectiveness of DAAs in treating patients with chronic hepatitis C and to identify the variables related to a sustained virologic response (SVR) in a real-world setting in Saudi Arabia. This prospective cohort study included 200 Saudi patients with chronic HCV who were 18 years of age or older and had been treated with DAAs at King Abdul-Aziz Specialized Hospital in Taif, Saudi Arabia, between September 2018 and March 2021. The response to treatment was assessed by whether or not an SVR had been achieved at week 12 post treatment (SVR12). An SVR12 was reached in 97.5% of patients. SVR12 rates were comparable for patients of different ages, between men and women, and between patients with and without cirrhosis. In addition, the SVR12 rates did not differ according to the infecting HCV genotype. In this study, the presence of cirrhosis and the patient's gender were independent predictors of who would not reach an SVR12 (known here as the non-SVR12 group) according to the results of univariate and multivariate binary logistic regression analyses based on the determinants of SVR12. In this population of patients with chronic HCV infection, all DAA regimens achieved very high SVR12 rates. The patients' gender and the presence of cirrhosis were independent factors of a poor response.

Impact of hepatitis C virus point-of-care RNA viral load testing compared with laboratory-based testing on uptake of RNA testing and treatment, and turnaround times: a systematic review and meta-analysis

Point-of-care (POC) hepatitis C virus (HCV) RNA nucleic acid test viral load assays are being used increasingly as an alternative to centralised, laboratory-based standard-of-care (SOC) viral load assays to reduce loss to follow-up. We aimed to evaluate the impact of using POC compared with SOC approaches on uptake of HCV RNA viral load testing and treatment, and turnaround times from testing to treatment along the HCV care cascade. We searched PubMed, Embase, and Web of Science for studies published in English between Jan 1, 2016, and April 13, 2022. We additionally searched for accepted conference abstracts (2016-20) not identified in the main search. The contacts directory of the WHO Global Hepatitis Programme was also used to solicit additional studies on use of POC RNA assays. We included studies if they evaluated use of POC HCV RNA viral load with or without a comparator laboratory-based SOC assay, and had data on uptake of viral load testing and treatment, and turnaround times between these steps in cascade. We excluded studies with a sample size of ten or fewer participants. The POC studies were categorised according to whether the POC assay was based onsite at the clinic, in a mobile unit, or in a laboratory. Studies using the POC assay or comparator SOC assays were further stratified according to four models of care: whether HCV testing and treatment initiation were performed in the same or different site, and on the same or a different visit. The comparator was centralised, laboratory-based HCV RNA SOC assays. For turnaround times, we calculated the weighted median of medians with 95% CIs. We analysed viral load testing and treatment uptake using random-effects meta-analysis. The quality of evidence was rated using the GRADE framework. This study is registered with PROSPERO, CRD42020218239. We included 45 studies with 64 within-study arms: 28 studies were in people who inject drugs, were homeless, or both; four were in people incarcerated in prison; nine were in the general or mixed (ie, includes high-risk groups) populations; and four were in people living with HIV. All were observational studies. The pooled median turnaround times between HCV antibody test and treatment initiation was shorter with onsite POC assays (19 days [95% CI 14-53], ten arms) than with either laboratory-based POC assays (64 days [64-64], one arm) or laboratory-based SOC assays (67 days [50-67], two arms). Treatment uptake was higher with onsite POC assays (77% [95% CI 72-83], 34 arms) or mobile POC assays (81% [60-97], five arms) than with SOC assays (53% [31-75], 12 arms); onsite and mobile POC assay vs SOC assay p=0·029). For POC and SOC arms, higher RNA viral load testing uptake was seen with the same-site models for testing and treatment than with different-site models (all within-category p≤0·0001). For onsite and mobile POC arms, there was higher treatment uptake for same-site than different-site models (within-category p<0·0001). Four studies had direct within-study POC versus SOC comparisons for RNA viral load testing uptake (pooled relative risk 1·11 [95% CI 0·89-1·38]), and there were ten studies on treatment uptake (1·32 [1·06-1·64]). Overall, the quality of evidence was rated as low. Compared with use of laboratory-based SOC HCV viral load testing, the use of POC assays was associated with reduced time from antibody test to treatment initiation and increased treatment uptake. The effect of POC viral load testing is greatest when positioned within a simplified care model in which testing and treatment are provided at the same site, and, where possible, on the same day. POC HCV RNA viral load testing is now recommended in WHO guidelines as an alternative strategy to laboratory-based viral load testing. Unitaid.