Direct-acting Antivirals Research Articles

Epidemiology of hepatitis C from 2015 to 2022 in a central Italian region: the OPT-HepaC project

Abstract Background Chronic hepatitis C virus (HCV) infection is a major global public health problem. This study investigated the evolving landscape of HCV in Tuscany (Italy) from 2015 to 2022, considering demographic shifts, clinical profiles, treatment regimens, and outcomes. Methods The study was conducted in order to characterize HCV-positive patients who started treatment between 2015 and 2022 in Tuscan prescribing centers. The study was part of OPT-HepaC, a project funded by Regional Health Service. Data on demographics, clinical history and outcomes were collected. Three different temporal eras were analysed: the period before andfter the universal availability of direct-acting antivirals (DAA) and the COVID-19 era. Treatment’s effectiveness was evaluated by the Sustained Virological Response (SVR12), assessed 12 weeks after the end of treatment. Outcomes included SVR12, non-SVR12 and lost to follow-up (LTFU). ANOVA, Kruskal-Wallis test and multinomial logistic regression were used for statistical analysis. Results 6882 HCV patients (age: 58.88±14.21) were treated by the centres participating at the study. Males (56.4%) and Italian (91.8%) were predominant. Sociodemographic and variable characteristics vary across the time. While the overall SVR12 remained stable over time (χ2(2)=0.357, p = 0.837), the LTFU rate significantly increased during the COVID-19 era. Facilitating factors for the non-SVR12 and LTFU outcomes were male gender (Odds Ratio (OR)=2.134, p = 0.006)/cirrhosis (OR = 1.713, p = 0.040)/HIV co-infection (OR = 3.251, p = 0.005) and DAA treatment of third generation (OR = 4.187, p = 0.006), respectively. Conclusions The study provides a comprehensive view of the HCV landscape, highlighting demographic changes, treatment regimens and outcomes. The COVID-19 pandemic affected service delivery, delaying HCV diagnosis/treatment and influencing the LTFU rate. Despite challenges, the region maintained high SVR12 rates, emphasizing the importance of sustained efforts in HCV care. Key messages • The study highlights the dynamic nature of HCV management in Tuscany. • The study emphasises the need for continuous adaptation to public health challenges, providing insights for future public health strategies.

Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 Mpro from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants.

The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. The main protease (Mpro) has been an important target for the development of SARS-CoV-2 direct-acting antivirals. Nirmatrelvir as a covalent Mpro inhibitor was the first such approved therapy. Although Mpro inhibitors of various chemical classes have been reported, they are generally less active against nirmatrelvir-resistant variants and have limited pan-coronavirus potential, presenting a significant human health risk upon future outbreaks. We here present a novel approach and utilized DNA-encoded chemical library screening to identify the noncovalent Mpro inhibitor 5, which demonstrated a distinct binding mode to nirmatrelvir. A macrocyclization strategy designed to lock the active conformation resulted in lactone 12 with significantly improved antiviral activity. Further optimization led to the potent lactam 26, which demonstrated exceptional potency against nirmatrelvir-resistant variants as well as against a panel of viral main proteases from other coronaviruses.

Predictors of treatment outcomes for Hepatitis C infection in a nationwide elimination program in Iceland: The treatment as prevention for Hepatitis C (TraP HepC) study

BackgroundLimited data exists about treatment outcomes in nationwide hepatitis C virus (HCV) elimination programs where injection drug use (IDU) is the main mode of transmission. In 2016 Iceland initiated the HCV elimination program known as Treatment as Prevention for Hepatitis C (TraP HepC). Factors associated with HCV cure in this population are examined. MethodsUnrestricted access was offered to direct acting antiviral agents (DAAs). Testing and harm reduction was scaled up and re-treatments were offered for those who did not attain cure. Cure rates for the first 36 months were assessed and factors associated with failure to achieve cure analysed using multivariable logistic regression. ResultsTreatment was initiated for 718; 705 consented for the study. Median age was 44 years (IQR 35–56), history of IDU reported by 593 (84.1 %), recent IDU by 234 (33.2 %); 48 (6.8 %) were homeless. Of 705 patients, 635 achieved cure (90.1 %) during the first treatment. A total of 70 (9.9 %) patients initiated two or more treatments, resulting in 673 participants cured (95.5 %). By multivariable analysis, homelessness was the only statistically significant independent factor associated with not achieving cure (OR 2.67, 95 % CI 1.32–5.41) after first treatment attempt. ConclusionBy reengagement in care and prompt retreatment when needed, a cure rate of 95.5 % was achieved. Unstable housing, a potentially actionable factor is associated with poor outcome.

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a primary liver cancer predominantly arising in individuals with chronic liver diseases such as cirrhosis or chronic hepatitis B virus (HBV) infection. Accounting for approximately 75% of primary liver tumors, HCC's global epidemiology is significantly influenced by HBV and hepatitis C virus (HCV) infections, alcohol and tobacco use, metabolic syndrome, diabetes, obesity, and aflatoxin B1 exposure. Preventive measures, including HBV vaccination and direct-acting antivirals for HCV, have reduced incidence rates, particularly in younger populations. Early diagnosis through surveillance in high-risk groups is critical, employing imaging modalities like ultrasound, CT, and MRI, alongside biomarkers such as alpha-fetoprotein (AFP). Prognostic assessments utilize scores like Child-Pugh and ALBI. Treatment strategies for HCC are multifaceted, involving surgical resection, locoregional therapies (e.g., transarterial chemoembolization), and systemic therapies, including targeted and immunotherapies. Despite advancements, treatment efficacy remains a challenge, necessitating ongoing research into novel therapeutic approaches and predictive biomarkers to enhance personalized treatment and improve outcomes for HCC patients.

Loss to follow-up of patients after antiviral treatment as an additional barrier to HCV elimination

BackgroundEliminating hepatitis C virus (HCV) infections is a goal set by the World Health Organization. This has become possible with the introduction of highly effective and safe direct-acting antivirals (DAA) but limitations remain due to undiagnosed HCV infections and loss of patients from the cascade of care at various stages, including those lost to follow-up (LTFU) before the assessment of the effectiveness of the therapy. The aim of our study was to determine the extent of this loss and to establish the characteristics of patients experiencing it.MethodsPatients with chronic HCV infection from the Polish retrospective multicenter EpiTer-2 database who were treated with DAA therapies between 2015 and 2023 were included in the study.ResultsIn the study population of 18,968 patients, 106 had died by the end of the 12-week post-treatment follow-up period, and 509 patients did not report for evaluation of therapy effectiveness while alive and were considered LTFU. Among patients with available assessment of sustained virological response (SVR), the effectiveness of therapy was 97.5%. A significantly higher percentage of men (p<0.0001) and a lower median age (p=0.0001) were documented in LTFU compared to the group with available SVR assessment. In LTFU patients, comorbidities such as alcohol (p<0.0001) and drug addiction (p=0.0005), depression (p=0.0449) or other mental disorders (p<0.0001), and co-infection with human immunodeficiency virus (HIV) (p<0.0001) were significantly more common as compared to those with SVR assessment. They were also significantly more often infected with genotype (GT) 3, less likely to be treatment-experienced and more likely to discontinue DAA therapy.ConclusionsIn a real-world population of nearly 19,000 HCV-infected patients, we documented a 2.7% loss to follow-up rate. Independent predictors of this phenomenon were male gender, GT3 infection, HIV co-infection, alcohol addiction, mental illnesses, lack of prior antiviral treatment and discontinuation of DAA therapy.

The role of artificial intelligence in the management of liver diseases.

Universal neonatal hepatitis B virus (HBV) vaccination and the advent of direct-acting antivirals (DAA) against hepatitis C virus (HCV) have reshaped the epidemiology of chronic liver diseases. However, some aspects of the management of chronic liver diseases remain unresolved. Nucleotide analogs can achieve sustained HBV DNA suppression but rarely lead to a functional cure. Despite the high efficacy of DAAs, successful antiviral therapy does not eliminate the risk of hepatocellular carcinoma (HCC), highlighted the need for cost-effective identification of high-risk populations for HCC surveillance and tailored HCC treatment strategies for these populations. The accessibility of high-throughput genomic data has accelerated the development of precision medicine, and the emergence of artificial intelligence (AI) has led to a new era of precision medicine. AI can learn from complex, non-linear data and identify hidden patterns within real-world datasets. The combination of AI and multi-omics approaches can facilitate disease diagnosis, biomarker discovery, and the prediction of treatment efficacy and prognosis. AI algorithms have been implemented in various aspects, including non-invasive tests, predictive models, image diagnosis, and the interpretation of histopathology findings. AI can support clinicians in decision-making, alleviate clinical burdens, and curtail healthcare expenses. In this review, we introduce the fundamental concepts of machine learning and review the role of AI in the management of chronic liver diseases.

Diversity, geographical distribution and predictive factors of Hepatitis C virus genotypes and subtypes in Rwanda

BackgroundExisting data on the prevalence of hepatitis C virus (HCV) genotypes and subtypes in Rwanda need to be strengthened. The aim of this study was to identify HCV genotypes and subtypes among HCV-infected patients, as well as their geographical distribution in Rwanda, and to identify the social and economic factors that could influence HCV epidemiology which would make it possible to target national preventive and management actions for infected patients. MethodsThis study included 560 patients with confirmed chronic HCV infection. Patients were recruited from various health facilities in the four provinces of Rwanda as well as in the City of Kigali and had never received treatment with direct-acting antiviral (DAAs). HCV viral loads were measured using Cobas® AmpliPrep/Cobas® TaqMan® HCV Quantitative Test, version 2.0. HCV genotyping was performed using an in-house sequencing protocol targeting the NS5B central region. Genotypic HCV prevalence was correlated with patient geographic location, sociodemographic, behavioral, lifestyle, and clinical factors. ResultsHCV genotype 4 was detected in 99.3% of the patients, while genotype 3 was identified in 0.7%. A total of eight (8) HCV subtypes were detected, with 4k being the predominant subtype nationwide (49.5%), followed by subtypes 4r (21.2%), 4q (16.2%), 4v (7.9%), 4b (2.0%), 4l (1.8%), 4c and 3h represent 0.7% each. Our findings reveal subtype distribution variations among provinces. Subtype 4k was prevalent across regions, particularly in Kigali (64.0%) and the Eastern Province (61.6%). Subtype 4q was more common in the northern province (40.7%), 4r in the southern (43.9%) and western provinces (37.1%), and 4v in the eastern province (17.8%). Farmers exhibit a distinct infection profile compared to other occupations, showing a lower prevalence of subtype 4k but a higher prevalence of subtype 4r. ConclusionsOur study revealed that HCV infection is unevenly distributed in Rwanda, dominated by HCV genotype 4, with considerable heterogeneity in the repartition of the different subtypes. We found potential associations between rural/urban lifestyles and HCV subtype profiles. Determined HCV distribution and diversity can serve as basis not only for HCV infection awareness and prevention campaigns, but also success and guidance for personalized treatment.

HCV genotype distribution in Istanbul: Adetailed 7 year epidemiological overview andimpact of Covid-19 pandemic.

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinomaworldwide. HCV has 8 genotypes (GT) and 86 subtypes and distribution of GTs varies based on geographical regions, transmission routes and even in cultural groups. The determination of viral genotype is crucial in choosing antiviral treatment, determining the duration of therapy, and monitoring treatment respose. Since 2014, with the usage of direct-acting antiviral agents (DAAs) in the treatment of HCV infections, a cure rate over 95% could be possible. Epidemiological data are important to combat a chronic HCV infections. Due to its geographical location, Turkey is like a bridge connecting Asia and Europe. Istanbul is the biggest and most crowded city of Turkey and has received immigration from many different countries, especially from Syria, in recent years and immigration still goes on. In addition, the COVID-19 pandemic has had devastating effects in our country. In this study, we determined the HCV genotypes in Health Sciences University Ümraniye Training and Research Hospital, in Istanbul between 2016 and 2022. Of the 322 patients analyzed during this 7-year period, HCV GT1b was the most prevalent GT in 65.2%, followed by GT3 in 15.5%, GT1a in 10.6%. Our data serve as a great mirror for HCV epidemiology in Turkey and contribute to global data.

Experience and challenges delivering hepatitis C virus treatment for people who inject drugs in Kenya.

Despite having a higher risk of hepatitis C virus (HCV) infections, people who inject drugs (PWID) in sub-Saharan Africa (SSA) have limited access to HCV treatment. There is scarce literature on treatment delivery modalities that overcome logistical and financial barriers. We utilized different service delivery modalities to provide direct-acting antivirals (DAAs) to PWIDs infected with HCV through methadone clinics and needle and syringe program (NSP) sites in Kenya. In collaboration with Kenya's National AIDS and STI Control Programme (NASCOP), we enrolled individuals with active HCV infection confirmed by HCV RNA detection from methadone and NSP sites in Nairobi, Mombasa, and Kilifi counties. Liver function and hepatitis B virus (HBV) status were assessed at baseline. Those eligible for treatment were offered ledipasvir-sofosbuvir treatment provided by NASCOP through directly observed therapy (DOT). Participants completed a follow-up visit 12 weeks after completing treatment to measure sustained viral response (SVR-12). Challenges faced while delivering HCV treatment at participating sites included the limited availability and reliability of laboratory assays, and financial constraints faced by PWIDs to attend daily DOT. Based on our experience, strategies to deliver HCV treatment for PWID in Kenya should consider improving the availability of laboratory tests and prioritizing treatment through methadone centers to achieve good outcomes.

Changes in hepatic steatosis before and after direct acting antiviral treatment in people living with HIV and Hepatitis C coinfection.

Both HIV and hepatitis C virus (HCV) infection increase the risk of hepatic steatosis (HS), which in turn contributes to the severity and progression of liver disease. Direct acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear. HS was assessed using the controlled attenuation parameter (CAP) and the hepatic steatosis index (HSI) in participants coinfected with HIV-HCV from the Canadian Coinfection Cohort. Changes in HS, before, during and after successful DAA treatment, were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides and hazardous drinking). 431 participants with at least one measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval (CrI) 1.6, 4.9) before, and 3.9 dB/m (95% CrI: 1.9, 5.9) after DAA treatment, irrespective of pre-treatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI: -0.1, 0.5) before and 0.2 (95% CrI -0.1, 0.5) after, but demonstrated a marked reduction during treatment -4.5 (95% CrI -5.9, -3.1). When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV.

Replication capacity and susceptibility of nirmatrelvir-resistant mutants to next-generation Mpro inhibitors in a SARS-CoV-2 replicon system

There is an ongoing need to expand the anti-SARS-CoV-2 armamentarium to include agents capable of suppressing replication of drug-resistant mutants emerging during monotherapy with approved direct-acting antivirals. Using a subgenomic SARS-CoV-2 replicon system, we studied the RNA replication capacity of nirmatrelvir (NTV)-resistant mutants and their susceptibility to next-generation Mpro inhibitors, including ibuzatrelvir (ITV), ensitrelvir (ETV), and ML2006a4. Our findings revealed that E166V Mpro mutants reduced viral RNA replication, whereas other Mpro mutations retained or increased the replication capacity, suggesting the potential of the latter to dominate under NTV selective pressure. Except for having an advantage against E166A mutants, ITV largely showed the same mutational sensitivity as NTV. ETV was more effective than NTV against E166V mutants but less effective against S144A, E166A, and L167F mutants. ML2006a4 demonstrated the most effective suppression across most mutants (S144A, E166V, S144A + L50F, E166 A/V + L50F, L167F + L50F, and E166A + L167F + L50F). Thus, ML2006a4 represents an attractive investigational candidate against clinically relevant NTV-resistant SARS-CoV-2 mutants.

Improved Outcomes of Liver Transplantation in Patients With Hepatitis C, Following the Introduction of Innovative Antiviral Therapies

BackgroundThe treatment landscape for Hepatitis C virus (HCV) underwent a significant shift with the introduction of direct-acting antiviral (DAA) medications in late 2013. This study aimed to evaluate the impact of DAAs on liver transplantation outcomes, examining both the benefits and any potential drawbacks associated with their use. Methods and materialsA retrospective registry analysis of the United Network for Organ Sharing database was done for liver transplants in patients diagnosed with Hepatitis C, that were performed in the United States from January 2000 to May 2020. ResultsThe study was divided into 2 subgroups, based on the timing of new DAA medication FDA approved. The only significant difference between the two cohorts is the recipient’s age. The data analysis showed a significant overall 5-year graft survival improvement in the 2014-2020 group compared to the 2000-2013 group, from a mean of 64.8% in 2000-2013 to a mean of 76% in 2014-2020 (P<0.001). Interestingly, when we compared the 5-year graft survivals with recipients who had a donor above age 50, the graft survival rate difference was even more significant (74% vs. 56%, P<0.001), as some studies have shown a suboptimal graft outcome, when the donor age is above 40 years old. Not only has the utilization of DCD livers increased significantly after 2014, but the graft survival in this cohort has also been significantly higher.(P<0.001). ConclusionThe emergence of DAAs in 2013 marked a watershed moment in the management of HCV, offering high cure rates, minimal side effects, and shorter treatment durations, to a point that the short- and long-term outcomes of liver transplant for HCV is almost equal to the other causes of liver transplantation.

Serum collagen IV as a predictor for response to direct-acting antivirals hepatitis C therapy

ABSTRACT Althoughchronic hepatitis C (CHC) therapies based on direct-acting antiviral (DAA) agents safely improved treatment effectiveness, some cases do not obtain sustained virological response (SVR) and, thus, evaluating factors that may be related to treatment failure is very important. We aimed to evaluate the association of baseline serum collagen IV with DAA treatment failure in Egyptian patients with CHC. A total of 175 CHC patients (100 responders and 75non-responders tosofosbuvir/daclatasvir) were included. Collagen IV was assessed using sensitive chemiluminescent immunoassay. There was distinctly higher (P < 0.0001) collagen IV in non-responders compared to responder patients as the median (interquartile range) were 19.02 (13.4–25.2) vs.9.7 (7.2–12.3) µg/L, respectively. Collagen IV has a good ability for distinguishing nonresponders from responder patients (AUC = 0.890) with sensitivity of 92%, specificity 72%, PPV 71.1%, NPV 92.3% and accuracy of 80.6%. Collagen IV was correlated (p < 0.05) with decreased albumin (r=-0.266), elevated APRI (r = 0.288), and elevated FIB-4 (r = 0.281) scores. In conclusion,these findings suggested the remarkable role of baseline collagen IV in the prediction of HCV DAAs treatment response. Thus, however further studies are needed, its measurement may improve treatment duration and the disease control.

Characteristics and prognosis of hepatocellular carcinoma patients after direct-acting antiviral hepatitis C virus therapy in a single medical center in Egypt

Objective: Hepatocellular carcinoma (HCC) incidence has increased dramatically over the previous two decades and is anticipated to rise further in some countries, notably the United States, by 2030. HCC is most widespread in Asia and Africa, where hepatitis B and C are ubiquitous and lead to the development of chronic liver disease and, finally, HCC. In this study, we examined changes in the characteristics and prognosis of HCC patients, as well as the risk of developing HCC after direct-acting antiviral (DAA) medication.Methods: The study enrolled all individuals who attended the Clinical Oncology and Nuclear Medicine Department, Suez Canal University Hospital, Ismailia, Egypt, with a proven diagnosis of HCC in the period between January 2020 and December 2021. HCC is diagnosed based on radiographic appearance (arterial enhancement phase and delayed washout phase) or compatible histology.Results: This retrospective cohort included 254 HCC patients, separated into three groups. Kaplan-Meier curves with log-rank analysis revealed that hepatitis C virus (HCV) treatment therapy considerably reduced the time to HCC development following hepatitis diagnosis (p &lt; .001). HCV therapy had a substantial impact on progression-free survival and overall survival in HCC patients (p &lt; .001).Conclusions: The emergence of DAA medication has greatly altered the management of HCV patients in the context of HCC. DAAs have been shown to be both safe and beneficial in these individuals, particularly in terms of lowering the risk of hepatic decompensation. DAAs have been reported to enhance overall survival in patients with cirrhotic HCV-related HCC, most likely due to decreased hepatic decompensation.

DAA treatment for HCV reduce risk of hepatocellular carcinoma: a 10-years follow-up study based on Chinese patients with hepatitis C

The long-term benefits of direct-acting antiviral (DAA) therapy after achieving sustained virological response (SVR) remain uncertain in the Chinese population. This study evaluates the incidence of hepatocellular carcinoma (HCC), hepatic decompensation, and all-cause mortality among Chinese hepatitis C patients treated with DAAs. We included patients diagnosed since 2011 and followed them until November 1, 2022. The primary outcomes were HCC, hepatic decompensation, and mortality. Multivariable proportional hazards model was used to assess the impact of SVR and cirrhosis status. The cohort consisted of 1272 patients with SVR (92.1%) and 109 without SVR (7.9%), with a median follow-up of 61 months. The incidence of HCC was significantly lower in the SVR group (5.1 per 1000 person-years) compared to the no-SVR group (15.0 per 1000 person-years). Achieving SVR was associated with a significantly reduced risk of HCC (adjusted hazard ratio: 0.32; 95% CI 0.16–0.67). Cirrhosis was linked to an increased risk of developing HCC and hepatic decompensation. These findings highlight the importance of early DAA treatment, particularly for patients with cirrhosis.

Efficacy of Direct Acting Antivirals (DAA) therapy in patients with recurrent hepatitis C after liver and kidney transplantation: a cross-sectional study.

Direct-acting antiviral (DAA) agents are now widely used to treat patients with hepatitis C infection (HCV) and effectively increase their sustained virologic response (SVR). However, the literature seems to lack or deficient evidence of DAA efficacy in more complicated patients, especially those with HCV reinfection after liver transplantation (LT) or liver-kidney (hepatorenal) transplantation (LKT). This study aimed to retrospectively evaluate the effectiveness of two different DAA regimens in LT and LKT patients with HCV reinfection. This cross-sectional study was conducted at three hospitals in Tehran, Iran, from 2014 to 2020, enrolling 53 patients with recurrent HCV infection after LT (n = 35) or LKT (n = 18). Patients were treated for 12 weeks with one of two DAA regimens: 37 patients (70%) received Daclatasvir and Sofosbuvir (SOF + DCV), while 16 patients (30%) received Sofosbuvir and Ledipasvir (SOF + LDV). Ribavirin (RBV) was added as an adjunct antiviral in 28 patients (52.8%). To assess the SVR, all patients were followed for 12 weeks after treatment. Both DAA regimens were well-tolerated and effective, with 94.6% (35 of 37) achieving SVR-12 in the SOF + DCV group and 93.8% (15 of 16) in the SOF + LDV group. Additionally, SVR-12 rates were promising across treatment durations, with 93.9% (31 of 33) in the 12-week group and 95% (19 of 20) in the 24-week group achieving undetectable HCV RNA. No significant difference in SVR was observed between the two regimens (p = 0.439). The DAA-based therapeutic regimen was well tolerated and showed significant effectiveness in achieving the virologic response in patients with HCV reinfection after LT or LKT.

Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.

The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.

Racial and Ethnic Disparities in Hepatitis C Care in Reproductive-Aged Women With Opioid Use Disorder.

In the United States, hepatitis C virus (HCV) diagnoses among reproductive-aged women are increasing amidst the ongoing opioid and drug overdose epidemic. While previous studies document racial and ethnic disparities in HCV testing and treatment in largely male populations, to our knowledge no national studies analyze these outcomes in reproductive-aged women with opioid use disorder (OUD). We analyzed data from a cohort of reproductive-aged women (aged 15-44 years) with diagnosed OUD captured in the TriNetX Research Network, a network of electronic health records from across the United States. Using a log-binomial model, we assessed differences in achieving HCV cascade of care stages (HCV antibody testing, HCV infection [positive HCV RNA test result], linkage to care, and HCV treatment) by race and ethnicity. From 2014 to 2022, 44.6% of the cohort were tested for HCV antibody. Asian and black/African American individuals had a lower probability of having an HCV antibody test than white individuals (risk ratio, 0.77 [95% confidence interval, .62-.96] and 0.76 [.63-.92], respectively). Among those with HCV infection, only 9.1% were treated with direct-acting antivirals. Hispanic/Latinx individuals had a higher probability of treatment than non-Hispanic/Latinx individuals (risk ratio, 1.63 [95% confidence interval, 1.01-2.61]). Few reproductive-aged women with OUD are tested or treated for HCV. Disparities by race and ethnicity in HCV testing further exacerbate the risk of perinatal transmission and disease progression among minoritized communities. Interventions are needed to improve overall rates of and equity in HCV screening and treatment for reproductive-aged women.

A-242 Assessing the efficacy of the one-step diagnostic algorithm for Hepatitis C

Abstract Background Hepatitis C virus (HCV) infection can be asymptomatic and may go into spontaneous remission. However, in 60-80% of cases, it becomes chronic and progresses into cirrhosis or hepatocarcinoma. The virus is mainly transmitted parenterally, although cases of sexual and transplacental transmission have also been found. Since the development of direct-acting antiviral (DAA) therapy that can achieve a complete cure in 95% of patients, eradication strategies based on rapid diagnosis and treatment have been promoted. Therefore, the World Health Organization (WHO) has set a goal to eliminate HCV infection as public health threat by 2030. This is a retrospective study on the usefulness and effectiveness of the one-step HCV diagnostic algorithm application from May 2022 to December 2023 in our hospital. Methods The current HCV testing algorithm consists in a reflex HCV RNA testing, in which anti-HCV antibody-positive samples are automatically referred for HCV RNA testing on the same specimen. We used a serological electrochemiluminescence (ECLIA) assay for the detection of anti-HCV antibodies (Cobas e801, Roche Diagnostics®) in serum samples; and then a confirmation of HCV viremia by nucleic acid testing of HCV RNA in plasma samples (Cobas 4800, Roche Diagnostics®). Results A total of 22713 HCV serologies were performed with a total of 221 positive results (1%). Of the HCV cases, 21 patients had a newly diagnosis of active infection (10%) for whom we recommended derivation to the Digestive Service to initiate elimination treatment. 71% were men, with a mean age of 53 years and a standard deviation of 17. The mean age of women was 56 years with a standard deviation of 18. Coinfection with HIV or hepatitis B virus (HBV) was also assessed. Patients with HIV-HCV coinfection represented 9% of cases and were on average 12 years younger than HCV-monoinfected individuals. We did not identify any case of HBV-HCV co-infection. Conclusions The pattern we observed in terms of incidence by age and sex is similar to that reported in the literature, as well as the incidence of new HCV cases. One-step diagnosis enables the laboratory to identify the need for referring to a specialist, reducing the time to treatment for new and known but untreated cases. Therefore, global access to HCV diagnostics will be a keystone to success.

Single-center retrospective review of standard versus minimal monitoring for hepatitis C direct-acting antiviral therapy

BackgroundHighly effective direct-acting antiviral (DAA) therapies have transformed the landscape of hepatitis C virus (HCV) treatment. However, there continues to be limited data regarding the efficacy and safety of required in-person clinic visits (standard monitoring) versus completely telehealth clinic visits (minimal monitoring) during HCV therapy, which could delay practice adoption. ObjectivesThis study aimed to assess the rates of undetectable HCV ribonucleic acid (RNA) in sustained viral load 12 weeks after therapy (SVR12) in standard versus minimal monitoring approaches during DAA. MethodsA 12-month, single-center retrospective cohort study was conducted in treatment-naïve HCV-infected adults who received DAA therapy between May 1, 2020, and April 30, 2021. The standard monitoring group had ≥1 in-person clinic visit with HCV RNA laboratory monitoring during DAA treatment. The minimal monitoring group had entirely telehealth visits without HCV RNA laboratory monitoring during treatment. Both groups received telephonic touchpoints throughout DAA treatment from a clinical pharmacist practitioner and a nurse care coordinator. The primary outcome was SVR12. ResultsFrom May 2020 to April 2021, 133 patients with HCV met inclusion criteria and were treated with DAA (standard, n = 56; minimal, n = 77), with no differences in baseline demographics. Overall, total encounters during DAA treatment remained significantly higher in the standard than minimal monitoring group (standard, 2.1 ± 0.8, vs. minimal, 1.7 ± 0.9; P < .01). Although minimal monitoring had higher loss to follow-up rates (standard, 7.1%, vs. minimal, 18.2%; P = 0.06), the modified intention-to-treat analysis showed no differences in sustained virologic response (SVR) between standard and minimal monitoring approaches (standard, 98.1%, n = 51, vs. minimal, 95.3%, n = 60; P = 0.41). ConclusionsThis single-center retrospective cohort study demonstrated that minimal monitoring during HCV treatment was as effective in achieving SVR cure rates as standard monitoring. Eliminating required in-person clinic visits during DAA therapy alongside a collaborative approach may play a major role in overcoming barriers to HCV care in select patients.