Patient profiled data for treatment decision-making: valuable as an add-on to hepatitis C clinical guidelines?

BACKGROUND AND AIMS: Systematic reviews and medical guidelines are widely used in clinical practice. However, these are often not up-to-date and focussed on the average patient. We therefore aimed to evaluate a guideline add-on, TherapySelector (TS), which is based on monthly updated data of all available high-quality studies, classified in specific patient profiles. METHODS: We evaluated the TS for the treatment of hepatitis C (HCV) in an international cohort of patients treated with direct-acting antivirals between 2015 and 2020. The primary outcome was the number of patients receiving one of the two preferred treatment options of the HCV TS, based on the highest level of evidence, cure rate, absence of ribavirin-associated adverse effects, and treatment duration. RESULTS: We enrolled 567 patients. The number of patients treated with one of the two preferred treatment options according to the HCV TS ranged between 27% (2015) and 60% (2020; p < 0.001). Most of the patients received a regimen with a longer treatment-duration (up to 34%) and/or addition of ribavirin (up to 14%). The effect on the expected cure-rate was minimal (1-6% higher) when the first preferred TherapySelector option was given compared to the actual treatment. CONCLUSIONS: Medical decision-making can be optimised by a guideline add-on; in HCV its use appears to minimise adverse effects and cost. The use of such an add-on might have a greater impact in diseases with suboptimal cure-rates, high costs or adverse effects, for which treatment options rely on specific patient characteristics.

[Hepatitis C: From diagnosis to global virus elimination]. / Hepatitis C: von der Diagnose zur weltweiten Virus-Elimination.

Chronic infection with hepatitis C virus (HCV) is a common cause of complications such as liver cirrhosis and hepatocellular carcinoma (HCC). It is one of the most significant infectious diseases worldwide, posing a substantial health burden. Since the introduction of direct-acting antiviral agents (DAAs), the treatment landscape has undergone a revolution. HCV infection is curable, and the treatment is safe and well tolerated. Due to the availability of this effective therapeutic option, the World Health Organization (WHO) set an ambitious goal in 2015 to eliminate Hepatitis C by 2030, a goal that the German government also embraced in 2016. The key tasks involve identifying previously undiagnosed cases and ensuring they receive antiviral treatment. Addressing at-risk populations through specific measures, including micro-elimination projects and population-wide campaigns, is essential to achieving the WHO's target both in Germany and globally.

Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (the QuickStart Study): a cluster randomised cross-over trial protocol.

INTRODUCTION: Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia's hepatitis C elimination targets. METHODS AND ANALYSIS: A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models. ETHICS AND DISSEMINATION: The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05016609. TRIAL PROGRESSION: The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.

[Change in intraperitoneal shunt after DAA treatment for hepatitis C].

Improvement and worsening of portal hypertension after direct acting antiviral agent (DAA) treatment for hepatitis C virus-related cirrhosis have been reported, and a consensus remains elusive. In this study, we underscored on the intraperitoneal shunt formed via portal hypertension and examined how the shunt system confirmed by computed tomography (CT) changes before and after treatment in cases in which sustained virological response (SVR) was attained with DAAs. Of the cases in which we achieved an SVR of 24 with DAA treatment for hepatitis C virus-related cirrhosis at our hospital, 83 cases in which CT images were taken before and after treatment were investigated. If the intraperitoneal shunt diameter changed by 20% or more, it was analyzed as an increase or decrease. In 29 patients, intraperitoneal shunt enlargement was noted. When examining factors related to the increase, multivariate analysis detected the FIB4 index at the end of the DAA treatment. Conversely, only four cases were observed in which the size decreased. At the end of treatment, the FIB4 index was the most important factor in increasing the intraperitoneal shunt after DAA treatment for hepatitis C virus-related cirrhosis, and fibrosis was believed to be an influencing factor.

Provider reported implementation barriers to hepatitis C elimination in Washington State.

BACKGROUND: Despite curative treatment options since 2014, only 12% of individuals in Washington State diagnosed with Hepatitis C (HCV) received treatment in 2018. Washington State agencies launched an elimination plan in 2019 to promote access to and delivery of HCV screening and treatment. The purpose of this study is to evaluate provider and health system barriers to successful implementation of HCV screening and treatment across Washington State. METHODS: This is a cross-sectional online survey of 547 physicians, nurse practitioners, physician assistants, and clinical pharmacists who provide care to adult patients in Washington State conducted in 2022. Providers were eligible if they worked in a primary care, infectious disease, gastroenterology, or community health settings. Questions assessed HCV screening and treating practices, implementation barriers, provider knowledge, observed stigma, and willingness to co-manage HCV and substance use disorder. Chi-squared or fishers exact tests compared characteristics of those who did and did not screen or treat. RESULTS: Provider adoption of screening for HCV was high across the state (96%), with minimal barriers identified. Fewer providers reported treating HCV themselves (28%); most (71%) referred their patients to another provider. Barriers identified by those not treating HCV included knowledge deficit (64%) and lack of organizational support (24%). The barrier most identified in those treating HCV was a lack of treating clinicians (18%). There were few (< 10%) reports of observed stigma in settings of HCV treatment. Most clinicians (95%) were willing to prescribe medication for substance use disorders to those that were using drugs including alcohol. CONCLUSION: Despite widespread screening efforts, there remain barriers to implementing HCV treatment in Washington State. Lack of treating clinicians and clinician knowledge deficit were the most frequently identified barriers to treating HCV. To achieve elimination of HCV by 2030, there is a need to grow and educate the clinician workforce treating HCV.

Prevalence and Modes of Transmission of Hepatitis C Virus Infection: A Historical Worldwide Review.

Hepatitis C virus infection affects over 58 million individuals and is responsible for 290,000 annual deaths. The infection spread in the past via blood transfusion and iatrogenic transmission due to the use of non-sterilized glass syringes mostly in developing countries (Cameroon, Central Africa Republic, Egypt) but even in Italy. High-income countries have achieved successful results in preventing certain modes of transmission, particularly in ensuring the safety of blood and blood products, and to a lesser extent, reducing iatrogenic exposure. Conversely, in low-income countries, unscreened blood transfusions and non-sterile injection practices continue to play major roles, highlighting the stark inequalities between these regions. Currently, injection drug use is a major worldwide risk factor, with a growing trend even in low- and middle-income countries (LMICs). Emerging high-risk groups include men who have sex with men (MSM), individuals exposed to tattoo practices, and newborns of HCV-infected pregnant women. The World Health Organization (WHO) has proposed direct-acting antiviral (DAA) therapy as a tool to eliminate infection by interrupting viral transmission from infected to susceptible individuals. However, the feasibility of this ambitious and overly optimistic program generates concern about the need for universal screening, diagnosis, linkage to care, and access to affordable DAA regimens. These goals are very hard to reach, especially in LMICs, due to the cost and availability of drugs, as well as the logistical complexities involved. Globally, only a small proportion of individuals infected with HCV have been tested, and an even smaller fraction of those have initiated DAA therapy. The absence of an effective vaccine is a major barrier to controlling HCV infection. Without a vaccine, the WHO project may remain merely an illusion.

Medicaid Expansion and Restriction Policies for Hepatitis C Treatment.

Importance: Hepatitis C can be cured with direct-acting antivirals (DAAs), but Medicaid programs have implemented fibrosis, sobriety, and prescriber restrictions to control costs. Although restrictions are easing, understanding their association with hepatitis C treatment rates is crucial to inform policies that increase access to lifesaving treatment. Objective: To estimate the association of jurisdictional (50 states and Washington, DC) DAA restrictions and Medicaid expansion with the number of Medicaid recipients with filled prescriptions for DAAs. Design, Setting, and Participants: This cross-sectional study used publicly available Medicaid documents and claims data from January 1, 2014, to December 31, 2021, to compare the number of unique Medicaid recipients treated with DAAs in each jurisdiction year with Medicaid expansion status and categories of fibrosis, sobriety, and prescriber restrictions. Medicaid recipients from all 50 states and Washington, DC, during the study period were included. Multilevel Poisson regression was used to estimate the association between Medicaid expansion and DAA restrictive policies on jurisdictional Medicaid DAA prescription fills. Data were analyzed initially from August 15 to November 15, 2023, and subsequently from April 15 to May 9, 2024. Exposures: Jurisdictional Medicaid expansion status and fibrosis, sobriety, and prescriber DAA restrictions. Main Outcomes and Measures: Number of people treated with DAAs per 100 000 Medicaid recipients per year. Results: A total of 381 373 Medicaid recipients filled DAA prescriptions during the study period (57.3% aged 45-64 years; 58.7% men; 15.2% non-Hispanic Black and 52.2% non-Hispanic White). Medicaid nonexpansion jurisdictions had fewer filled DAA prescriptions per 100 000 Medicaid recipients per year than expansion jurisdictions (38.6 vs 86.6; adjusted relative risk [ARR], 0.56 [95% CI, 0.52-0.61]). Jurisdictions with F3 to F4 (34.0 per 100 000 Medicaid recipients per year; ARR, 0.39 [95% CI, 0.37-0.66]) or F1 to F2 fibrosis restrictions (61.9 per 100 000 Medicaid recipients per year; ARR, 0.62 [95% CI, 0.59-0.66]) had lower treatment rates than jurisdictions without fibrosis restrictions (94.8 per 100 000 Medicaid recipients per year). Compared with no sobriety restrictions (113.5 per 100 000 Medicaid recipients per year), 6 to 12 months of sobriety (38.3 per 100 000 Medicaid recipients per year; ARR, 0.65 [95% CI, 0.61-0.71]) and screening and counseling requirements (84.7 per 100 000 Medicaid recipients per year; ARR, 0.87 [95% CI, 0.83-0.92]) were associated with reduced treatment rates, while 1 to 5 months of sobriety was not statistically significantly different. Compared with no prescriber restrictions (97.8 per 100 000 Medicaid recipients per year), specialist consult restrictions was associated with increased treatment (66.2 per 100 000 Medicaid recipients per year; ARR, 1.05 [95% CI, 1.00-1.10]), while specialist required restrictions were not statistically significant. Conclusions and Relevance: In this cross-sectional study, Medicaid nonexpansion status, fibrosis, and sobriety restrictions were associated with a reduction in the number of people with Medicaid who were treated for hepatitis C. Removing DAA restrictions might facilitate treatment of more people diagnosed with hepatitis C.

After the Storm: Persistent Molecular Alterations Following HCV Cure.

The development of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has revolutionized the management of this pathology, as their use allows viral elimination in a large majority of patients. Nonetheless, HCV remains a major public health problem due to the multiple challenges associated with its diagnosis, treatment availability and development of a prophylactic vaccine. Moreover, HCV-cured patients still present an increased risk of developing hepatic complications such as hepatocellular carcinoma. In the present review, we aim to summarize the impact that HCV infection has on a wide variety of peripheral and intrahepatic cell populations, the alterations that remain following DAA treatment and the potential molecular mechanisms implicated in their long-term persistence. Finally, we consider how recent developments in single-cell multiomics could refine our understanding of this disease in each specific intrahepatic cell population and drive the field to explore new directions for the development of chemo-preventive strategies.

Evaluation of alcohol use behavior among patients cured through HCV elimination program in Georgia.

OBJECTIVE: The objective of the study was to understand the role of self-reported drinking behavior on liver health after achieving sustained viral response (SVR) among HCV patients. RESULTS: The study was conducted in HCV treatment provider clinics in three cities in Georgia: Tbilisi, Batumi, and Telavi. Face-to-face interviews were conducted using a questionnaire developed specifically for this study. 9.5% considered themselves heavy drinkers, while 94.2% were aware that heavy alcohol consumption can progress liver fibrosis. During treatment, 97.8% abstained from alcohol, while 76.6% reported resuming drinking after achieving SVR. Additionally, 52.1% believed that moderate alcohol intake is normal for individuals with low fibrosis scores. Liver fibrosis improvement was more prevalent among individuals who abstained from alcohol after HCV diagnosis (85.4% vs. 71.4%, p < 0.01) and after achieving SVR (87.5% vs. 74.7% of those who resumed drinking after achieving SVR, p < 0.02). In conclusion, the majority of HCV patients abstain from alcohol during treatment but resume drinking after achieving SVR. Those who abstain from alcohol intake after HCV cure have a higher chance of liver fibrosis improvement.

Interferon-free hepatitis C treatment increases a surrogate of atherosclerotic cardiovascular disease risk in Black veterans living with HIV.

Veterans living with HIV (VLWH) and hepatitis C virus (HCV) co-infection have an exacerbated risk of cardiovascular disease (CVD). It is unknown if HCV cure reduces CVD risk in this population. We evaluated changes in low-density lipoprotein (LDL), as a surrogate of CVD risk, 18 months after HCV cure in VLWH. We found significant increases in LDL in VLWH with advanced fibrosis, potentially increasing CVD risk. Lower LDL thresholds to initiate lipid-lowering therapies in VLWH after HCV cure may be warranted.

Hepatitis C (HCV) Reinfection and Risk Factors among Clients of a Low-Threshold Primary Healthcare Service for People Who Inject Drugs in Sydney, Australia.

Hepatitis C (HCV) reinfection studies have not focused on primary healthcare services in Australia, where priority populations including people who inject drugs (PWID) typically engage in healthcare. We aimed to describe the incidence of HCV reinfection and associated risk factors in a cohort of people most at risk of reinfection in a real-world community setting. We conducted a secondary analysis of routinely collected HCV testing and treatment data from treatment episodes initiated with direct-acting antiviral (DAA) therapy between October 2015 and June 2021. The overall proportion of clients (N = 413) reinfected was 9% (N = 37), and the overall incidence rate of HCV reinfection was 9.5/100PY (95% CI: 6.3-14.3). Reinfection incidence rates varied by sub-group and were highest for Aboriginal and/or Torres Strait Islander people (20.4/100PY; 95% CI: 12.1-34.4). Among PWID (N= 321), only Aboriginality was significantly associated with reinfection (AOR: 2.73, 95% CI: 1.33-5.60, p = 0.006). High rates of HCV reinfection in populations with multiple vulnerabilities and continued drug use, especially among Aboriginal and Torres Strait Islander people, highlight the need for ongoing regular HCV testing and retreatment in order to achieve HCV elimination. A priority is resourcing testing and treatment for Aboriginal and/or Torres Strait Islander people. Our findings support the need for novel and holistic healthcare strategies for PWID and the upscaling of Indigenous cultural approaches and interventions.

Virologic Response and Reinfection Following HCV Treatment among Hospitalized People Who Inject Drugs: Follow-Up Data from the OPPORTUNI-C Trial.

Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response (SVR) and reinfection, and to validate complete pharmacy dispensation as a proxy for cure among PWID enrolled in a trial of opportunistic HCV treatment. Data were obtained by reviewing the electronic patient files and supplemented by outreach HCV RNA testing. Reinfection was defined based on clinical, behavioral, and virological data. Intention to treat SVR ≥ 4 within 2 years after enrolment was accomplished by 59 of 98 (60% [95% CI 50-70]) during intervention conditions (opportunistic treatment) and by 57 of 102 (56% [95% CI 46-66]) during control conditions (outpatient treatment). The time to end of treatment response (ETR) or SVR ≥ 4 was shorter among intervention participants (HR 1.55 [1.08-2.22]; p = 0.016). Of participants with complete dispensation, 132 of 145 (91%) achieved ETR or SVR > 4 (OR 12.7 [95% CI 4.3-37.8]; p < 0.001). Four cases of reinfection were identified (incidence 3.8/100 PY [95% CI 1.0-9.7]). Although SVR was similar, the time to virologic cure was shorter among intervention participants. Complete dispensation is a valid correlate for cure among individuals at risk of loss to follow-up. Reinfection following successful treatment remains a concern.

HCV Cascade of Care in HIV/HCV Co-Infected Individuals: Missed Opportunities for Micro-Elimination.

People living with HIV-HCV co-infection comprise a target group for HCV-micro-elimination. We conducted an HCV cascade of care (CoC) for HIV-HCV co-infected individuals living in Greece and investigated factors associated with different HCV-CoC stages. We analyzed data from 1213 participants from the Athens Multicenter AIDS Cohort Study. A seven-stage CoC, overall and by subgroup (people who inject drugs (PWID), men having sex with men (MSM), men having sex with women (MSW), and migrants], was constructed, spanning from HCV diagnosis to sustained virologic response (SVR). Logistic/Cox regression models were employed to identify factors associated with passing through each CoC step. Among 1213 anti-HCV-positive individuals, 9.2% died before direct-acting antiviral (DAA) availability. PWID exhibited higher mortality rates than MSM. Of 1101 survivors, 72.2% remained in care and underwent HCV-RNA testing. Migrants and PWID showed the lowest retention rates. HCV-RNA was available for 79.2% of those in care, with 77.8% diagnosed with chronic HCV. Subsequently, 71% initiated DAAs, with individuals with very low CD4 counts (<100 cells/µL) exhibiting lower odds of DAA initiation. SVR testing was available for 203 individuals, with 85.7% achieving SVR. The SVR rates did not differ across risk groups. In 2023, significant gaps and between-group differences persisted in HCV-CoC among HIV-HCV co-infected individuals in Greece.

The potential impact of the Comprehensive and Progressive Agreement for Prans-Pacific Partnership on Thailand's hepatitis C treatment program.

BACKGROUND: Thailand has expressed interest in joining the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), a twelve-country plurilateral trade agreement whose original incarnation included the United States of America (USA). When the USA withdrew from this agreement, key intellectual property clauses relevant to pharmaceuticals were suspended. These could be reinstated should the CPTPP Parties decide to do so. METHODS: This study uses two scenarios to cost the impact the CPTPP would have had on Thailand's 2020 hepatitis C treatment regime if Thailand joined the CPTPP and suspended clauses were reinstated. RESULTS: Joining the CPTPP could have increased the cost more than tenfold if suspended CPTPP clauses were reinstated and Thailand was not willing or able to issue compulsory licenses. Based on the 2020 budget, the price for this possible scenario could have reduced hepatitis C treatment coverage by 90%. CONCLUSIONS: Acceding to trade agreements such as the CPTPP that require increasing intellectual property protection, could compromise Thailand's hepatitis C program and other national treatment programs reliant on affordable generic medicines. The CPTPP could also prevent Thailand from relying on its own pharmaceutical capabilities to manufacture medicines needed to sustain its treatment programs.

Care Integration for Hepatitis C Virus Treatment Through Facilitated Telemedicine Within Opioid Treatment Programs: Qualitative Study.

BACKGROUND: Telemedicine has the potential to remove geographic and temporal obstacles to health care access. Whether and how telemedicine can increase health care access for underserved populations remains an open question. To address this issue, we integrated facilitated telemedicine encounters for the management of hepatitis C virus (HCV), a highly prevalent condition among people with opioid use disorder (OUD), into opioid treatment programs (OTPs). In New York State, OTPs are methadone-dispensing centers that provide patient-centered, evidence-based treatment for OUD. We investigated the integration and impact of facilitated telemedicine into OTP workflows in these settings. OBJECTIVE: This study aims to understand OTP staff experiences with integrating facilitated telemedicine for HCV treatment into OTPs, including best practices and lessons learned. METHODS: We conducted semistructured interviews with 45 OTP staff members (13 clinical, 12 administrative, 6 physicians, and 14 support staff members) at least one year after the implementation of facilitated telemedicine for HCV management. We used hermeneutic phenomenological analysis to understand OTP staff experiences. RESULTS: We identified 4 overarching themes illustrating the successful integration of facilitated telemedicine for HCV care into OTPs. First, integration requires an understanding of the challenges, goals, and values of the OTP. As OTP staff learned about new, highly effective HCV therapies, they valued an HCV cure as a "win" for their patients and were excited about the potential to eliminate a highly prevalent infectious disease. Second, the integration of facilitated telemedicine into OTPs fosters social support and reinforces relationships between patients and OTP staff. OTP staff appreciated the ability to have "eyes on" patients during telemedicine encounters to assess body language, a necessary component of OUD management. Third, participants described high levels of interprofessional collaboration as a care team that included the blurring of lines between disciplines working toward a common goal of improving patient care. Study case managers were integrated into OTP workflows and established communication channels to improve patient outcomes. Fourth, administrators endorsed the sustained and future expansion of facilitated telemedicine to address comorbidities. CONCLUSIONS: OTP staff were highly enthusiastic about facilitated telemedicine for an underserved population. They described high levels of collaboration and integration comparable to relevant integrative frameworks. When situated within OTPs, facilitated telemedicine is a high-value application of telemedicine that provides support for underserved populations necessary for high-quality health care. These experiences support sustaining and scaling facilitated telemedicine in comparable settings and evaluating its ability to address other comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov NCT02933970; https://clinicaltrials.gov/study/NCT02933970.

Treatment with Antihistamines and the Risk of Liver Cancer in Patients with Viral Hepatitis: A Multi-Center Cohort Study.

Background: The effects of antihistamines on cancer risk and prognosis have been inconsistent across cancers. The aim of this multi-center cohort study was to investigate the association between antihistamine use and the risk of liver cancer in individuals with viral hepatitis. Methods: This multi-center cohort study included individuals diagnosed with hepatitis B or hepatitis C between January 2008 and March 2022. For antihistamine-treated patients, the index date was the date of antihistamine prescription, and for non-users, it was the date of hepatitis diagnosis. Participants were followed for five years, with the primary outcome of interest being new-onset liver cancer. The incidence rate and the adjusted hazard ratio (aHR) along with its 95% confidence interval (CI) of the outcome were calculated. Subgroup analyses were conducted, stratified by types of viral hepatitis including hepatitis C and hepatitis B. An additional validation study was performed. Results: The study included a total of 7748 patients with viral hepatitis. The incidence rate was 12.58 per 1000 person-years in patients with viral hepatitis on antihistamines, compared to 3.88 per 1000 person-years in those without antihistamine use. After adjusting for factors including age, sex, body mass index (BMI), comorbidities, laboratory data of liver function tests, comedications, and the use of antiviral therapies, the risk of new-onset liver cancer was significantly higher in patients on antihistamines (aHR = 1.83, 95% CI, 1.28-2.60). In patients with hepatitis C, the incidence rate in the antihistamine group was 15.73 per 1000 person-years, while non-users had a rate of 4.79 per 1000 person-years. Patients with hepatitis C on antihistamines had a significantly higher risk of developing liver cancer (aHR = 3.24, 95% CI, 2.16-4.86). Conclusions: This multi-center cohort study reported an increased risk of liver cancer in patients with hepatitis B or hepatitis C treated with antihistamines. Long-term follow-up studies are warranted to validate the findings.

Hepatitis C virus diversity and treatment outcomes in Benin: a prospective cohort study.

BACKGROUND: 10 million people are chronically infected with the hepatitis C virus (HCV) in sub-Saharan Africa. The assessment of viral genotypes and treatment response in this region is necessary to achieve the WHO target of worldwide elimination of viral hepatitis by 2030. We aimed to investigate the prevalence of HCV genotypes and outcomes of treatment with direct-acting antiviral agents in Benin, a country with a national HCV seroprevalence of 4%. METHODS: This prospective cohort study was conducted at two referral hospitals in Benin. Individuals were eligible for inclusion if they were seropositive for HCV and willing to consent to participation in the study; exclusion criteria were an inability to give consent or incarceration. Viraemia was confirmed by PCR. The primary outcomes were to identify HCV genotypes and measure sustained virological response rates 12 weeks after completion of treatment (SVR12) with a 12-week course of sofosbuvir-velpatasvir or sofosbuvir-ledipasvir, with or without ribavirin. We conducted phylogenetic and resistance analyses after the next-generation sequencing of samples with a cycle threshold (Ct) value of 30 or fewer cycles. The in-vitro efficacy of NS5A inhibitors was tested using a subgenomic replicon assay. FINDINGS: Between June 2, 2019, and Dec 30, 2020, 148 individuals were screened for eligibility, of whom 100 were recruited prospectively to the study. Plasma samples from 79 (79%) of the 100 participants were positive for HCV by PCR. At the time of the study, 52 (66%) of 79 patients had completed treatment, with an SVR12 rate of 94% (49 of 52). 57 (72%) of 79 samples had a Ct value of 30 or fewer cycles and were suitable for whole-genome sequencing, from which we characterised 29 (51%) samples as genotype 1 and 28 (49%) as genotype 2. Three new genotype 1 subtypes (1q, 1r, and 1s) and one new genotype 2 subtype (2xa) were identified. The most commonly detected subtype was 2d (12 [21%] of 57 samples), followed by 1s (eight [14%]), 1r (five [9%]), 1b (four [7%]), 1q (three [5%]), 2xa (three [5%]), and 2b (two [3%]). 20 samples (11 genotype 2 and nine genotype 1) were unassigned new singleton lineages. 53 (93%) of 57 sequenced samples had at least two resistance-associated substitutions within the NS5A gene. Subtype 2d was associated with a lower-than-expected SVR12 rate (eight [80%] of ten patients). For one patient, with subtype 2b, treatment was not successful. INTERPRETATION: This study revealed a high SVR rate in Benin among individuals treated for HCV with sofosbuvir-velpatasvir, including those with highly diverse viral genotypes. Further studies of treatment effectiveness in genotypes 2d and 2b are indicated. FUNDING: Medical Research Council, Wellcome, Global Challenges Research Fund, Academy of Medical Sciences, and PHARMBIOTRAC.

Applying a stigma and time framework to facilitate equitable access to hepatitis C care among women who inject drugs: The ETHOS Engage Study.

BACKGROUND: Women who inject drugs are significantly less likely to initiate hepatitis C virus (HCV) treatment than men. Concerted efforts are needed to minimise gender-based inequalities in care. The study aim was to use a stigma and time framework to investigate how women who inject drugs experienced HCV care in healthcare settings. METHODS: Semi-structured, in-depth interviews were conducted with 34 participants from the ETHOS Engage Cohort (n = 1,443) in Australia. Inclusion criteria were aged ≥18 years, history of injection drug use, and persons who injected in the prior six months or were currently receiving opioid agonist treatment. Drawing on the original qualitative dataset (n = 34), we conducted a secondary analysis focused on women participants' experiences of receiving HCV related care (n = 21/34). Utilising thematic analysis, we applied Earnshaw's theoretical framework, which incorporates time into stigma and health research via three "timescales" - historical context, human development, and status course. RESULTS: Among the 21 women interviewed (mean age 42 years, 5 are Aboriginal, 11 received HCV treatment), the majority were currently receiving opioid agonist treatment and over half injected drugs in the past month. For historical context, most participants were diagnosed with HCV during the interferon era (1990s-2014). Participants had to navigate a sociomedical landscape not only largely bereft of adequate HCV medical knowledge, appropriate support, and adequate treatments, but were also generally assessed as "unsuitable" for treatment based on their perceived personhood as people who inject drugs. For human development, many participants reported encountering overlapping stigmatizing experiences (layered stigma) while receiving their HCV diagnosis in prenatal care and early postpartum. Under status course, participants acutely recognised the intersection of HCV infection, injection drug use, and gender, and reported concerns about being judged more harshly from healthcare providers as a result. CONCLUSION: A stigma and time framework illuminated multiple overlapping stigmatizing experiences for women who inject drugs in HCV care and in turn, can help to inform tools and interventions to counter their impact.

High incidence of hepatocarcinoma in patients with advanced fibrosis treated with direct-acting antiviral agents for hepatitis C: A real-world retrospective study.

BACKGROUND: Patients treated with direct-acting antivirals for hepatitis C exhibit high cure rates and improved survival. However, there is limited knowledge on their long-term clinical evolution. AIMS: In this study, we aimed to analyse the risk of hepatocarcinoma and hepatic decompensation in patients treated with direct-acting antivirals. METHODS: We conducted a retrospective single-centre study of Portuguese patients with advanced fibrosis treated with direct-acting antiviral agents between 2015 and 2022 at a tertiary hospital. RESULTS: Out of 460 patients, 50 (10.9 %) developed hepatocarcinoma and 36 (7.8 %) experienced hepatic decompensation. The risk for hepatocarcinoma was higher in patients aged over 55 (HR 4.87, 95 % CI 2.34-10.13, p < 0.001), with signs of portal hypertension (HR 3.83, 95 % CI 2.05-7.13, p < 0.001) and arterial hypertension (HR 1.98, 95 % CI 1.09-3.58, p = 0.024). Alcohol consumption (HR 3.30, 95 % CI 1.22-8.94, p = 0.019), signs of portal hypertension (HR 4.56, 95 % CI 2.19-9.48, p < 0.001) and hepatocarcinoma (HR 3.47, 95 % CI 1.69-7.10, p < 0.001) increased the risk of hepatic decompensation. CONCLUSION: Our study found a high incidence of hepatocarcinoma and hepatic decompensation, along with high mortality, in patients with advanced fibrosis treated with direct-acting antivirals. We identified risk factors such as arterial hypertension, alcohol consumption, and signs of portal hypertension, highlighting their role in clinical management and patient monitoring.