Long-Term Impact of Direct-Acting Antivirals on Liver Fibrosis and Survival in HCV-Infected Liver Transplant Recipients.

(1) Background: Little is known about the long-term impact of sustained virological response (SVR) on fibrosis progression and patient survival in liver transplantation (LT) recipients treated with direct-acting antivirals (DAAs). We investigated liver fibrosis evolution and patient survival in hepatitis C virus (HCV)-infected patients receiving DAAs after LT. (2) Methods: All consecutive HCV-infected patients treated with DAAs after LT between May 2014 and January 2019 were considered. The clinical and virological features were registered at the baseline and during the follow-up. The liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at the baseline and at least 1 year after the end of treatment (EoT). (3) Results: A total of 136 patients were included. The SVR12 was 78% after the first treatment and 96% after retreatment. After the SVR12, biochemical tests improved at the EoT and remained stable throughout the 3-year follow-up. Liver fibrosis improved after the SVR12 (p < 0.001); nearly half of the patients with advanced liver fibrosis experienced an improvement of an F ≤ 2. The factors associated with lower survival in SVR12 patients were the baseline platelet count (p = 0.04) and creatinine level (p = 0.04). (4) Conclusions: The long-term follow-up data demonstrated that SVR12 was associated with an improvement in hepatic function, liver fibrosis, and post-LT survival, regardless of the baseline liver fibrosis. The presence of portal hypertension before the DAAs has an impact on patient survival, even after SVR12.

Training the healthcare workforce: the global experience with telementorship for hepatitis B and hepatitis C.

BACKGROUND: Telementorship has emerged as an innovative strategy to decentralise medical knowledge and increase healthcare capacity across a wide range of disease processes. We report the global experience with telementorship to support healthcare workers delivering hepatitis B virus (HBV) and hepatitis C virus (HCV) care and treatment. METHODS: In early 2020, we conducted a survey of HBV and HCV telementorship programmes, followed by an in-depth interview with programme leads. Programmes were eligible to participate if they were located outside of the United States (U.S.), focused on support to healthcare workers in management of HBV and/or HCV, and were affiliated with or maintained adherence to the Project ECHO model, a telementorship programme pioneered at the University of New Mexico. One programme in the U.S., focused on HCV treatment in the Native American community, was purposively sampled and invited to participate. Surveys were administered online, and all qualitative interviews were performed remotely. Descriptive statistics were calculated for survey responses, and qualitative interviews were assessed for major themes. RESULTS: Eleven of 18 eligible programmes completed the survey and follow up interview. Sixty-four percent of programmes were located at regional academic medical centers. The majority of programmes (64%) were led by hepatologists. Most programmes (82%) addressed both HBV and HCV, and the remainder focused on HCV only. The median number of participating clinical spoke sites per programme was 22, and most spoke site participants were primary care providers. Most ECHO sessions were held monthly (36%) or bimonthly (27%), with sessions ranging from 45 min to 2 h in length. Programme leaders identified collective learning, empowerment and collaboration to be key strengths of their telementorship programme, while insufficient funding and a lack of protected time for telementorship leaders and participants were identified as major barriers to success. CONCLUSION: The Project ECHO model for telementorship can be successfully implemented across high and low-and-middle-income countries to improve provider knowledge and experience in management of viral hepatitis. There is a tremendous opportunity to further expand upon the existing experience with telementorship to support non-specialist healthcare workers and promote elimination of viral hepatitis.

Qualitative Evaluation of a Program to Integrate Hepatitis C Care Into HIV Care Inclusive of Task Shifting to Nonspecialist Providers.

The treatment and cure of hepatitis C (HCV) in people with HIV is particularly important as progression of their liver disease is quicker compared with those who have HCV monoinfection. Innovative approaches are needed to maximize access to curative HCV treatment. Integration of HCV care into HIV primary care with education and support of nonspecialist providers via telementoring offers a solution to specialist workforce shortages. Using focus group qualitative methodology, health care workers' perspectives regarding this approach, particularly with the Extension for Community Healthcare Outcomes (ECHO) telementoring model, were obtained and are described. Successful integration of HCV care into HIV primary care has demonstrated benefits to patients, including allowing them to remain in their medical home for care. Factors beyond disease that influence their health and wellbeing must also be considered.

"Treated like a Human Being": perspectives of people who inject drugs attending low-threshold HCV treatment at a syringe service program in New York City.

BACKGROUND: Hepatitis C virus (HCV) treatment can effectively cure HCV among people who inject drugs (PWID). Perspectives of PWID treated in innovative models can reveal program features that address barriers to treatment, and guide implementation of similar models. METHODS: We interviewed 29 participants in the intervention arm of a randomized trial. The trial enrolled PWID with HCV in New York City from 2017 to 2020 and tested the effectiveness of a low-threshold HCV treatment model at a syringe services program. Participants were purposively sampled and interviewed in English or Spanish. The interview guide focused on prior experiences with HCV testing and treatment, and experiences during the trial. Interviews were inductively coded and analyzed using thematic analysis. RESULTS: Before enrollment, participants reported being tested for HCV in settings such as prison, drug treatment, and emergency rooms. Treatment was delayed because of not being seen as urgent by providers. Participants reported low self-efficacy, competing priorities, and systemic barriers to treatment such as insurance, waiting lists, and criminal-legal interactions. Stigma was a major factor. Treatment during the trial was facilitated through respect from staff, which overcame stigma. The flexible care model (allowing walk-ins and missed appointments) helped mitigate logistical barriers. The willingness of the staff to address social determinants of health was highly valued. CONCLUSION: Our findings highlight the need for low-threshold programs with nonjudgmental behavior from program staff, and flexibility to adapt to participants' needs. Social determinants of health remain a significant barrier, but programs' efforts to address these factors can engender trust and facilitate treatment. Trial registration NCT03214679.

Combination of Oncolytic Measles Virus and Ursolic Acid Synergistically Induces Oncolysis of Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) remains a difficult-to-treat cancer due to late diagnosis and limited curative treatment options. Developing more effective therapeutic strategies is essential for the management of HCC. Oncolytic virotherapy is a novel treatment modality for cancers, and its combination with small molecules merits further exploration. In this study, we combined oncolytic measles virus (MV) with the natural triterpenoid compound ursolic acid (UA) and evaluated their combination effect against HCC cells, including those harboring hepatitis B virus (HBV) or hepatitis C virus (HCV) replication. We found that the combination of MV and UA synergistically induced more cell death in Huh-7 HCC cells through enhanced apoptosis. In addition, increased oxidative stress and loss of mitochondrial potential were observed in the treated cells, indicating dysregulation of the mitochondria-dependent pathway. Similar synergistic cytotoxic effects were also found in HCC cells harboring HBV or HCV genomes. These findings underscore the potential of oncolytic MV and UA combination for further development as a treatment strategy for HCC.

Above-Standard Survival of Hepatocellular Carcinoma as the Final Outcome of Comprehensive Hepatology Care Programs in a Remote HCV-Endemic Area.

Early detection and prompt linkage to care are critical for hepatocellular carcinoma (HCC) care. Chang Gung Memorial Hospital (CGMH) Yunlin branch, a local hospital in a rural area, undertakes health checkup programs in addition to its routine clinical service. Patients with HCC are referred to CGMH Chiayi branch, a tertiary referral hospital, for treatment. This study enrolled 77 consecutive patients with newly diagnosed HCCs between 2017 and 2022, with a mean age of 65.7 ± 11.1 years. The screening group included HCC patients detected through health checkups, and those detected by routine clinical service served as the control group. Compared to the 24 patients in the control group, the 53 patients in the screening group had more cases with early stage cancer (Barcelona Clinic Liver Cancer or BCLC stage 0 + A 86.8% vs. 62.5%, p = 0.028), better liver reserve (albumin-bilirubin or ALBI grade I 77.3% vs. 50%, p = 0.031) and more prolonged survival (p = 0.036). The median survival rates of the 77 patients were >5 years, 3.3 years, and 0.5 years in the BCLC stages 0 + A, B, and C, respectively, which were above the expectations of the BCLC guideline 2022 for stages 0, A, and B. This study provides a model of HCC screening and referral to high-quality care in remote viral-hepatitis-endemic areas.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Strategies to increase primary care provider capacity for hepatitis C care: The California ECHO-PLUS study.

Expanding capacity to screen and treat those infected with the hepatitis C virus (HCV) is an essential element of the global elimination strategy. We evaluated the hub-and-spoke Project ECHO training versus telementoring models to educate, train and support HCV care by primary care providers in 13 targeted counties in northern California. A novel provider engagement strategy was used. Provider engagement and retention, time to readiness to treat HCV, and knowledge and confidence were the outcomes of interest. 94 participants from 60 unique clinics in the target counties participated in the ECHO-PLUS programme; 39.4% were physicians, 48.9% were advanced practice providers, and 11.7% were nurses. The median (range) participation time was 5 (1-49) hours. Confidence scores (minimum score = 13 and maximum score = 65) increased by a mean of 14.0 (SD:8.2) and 11.4 (SD:12.0) points for the hub-and-spoke and telementoring programmes, respectively (p = .53), with the largest changes in confidence seen in treating patients per guidelines, managing side effects and in serving as a consultant for HCV in their clinic. Among 24 participants with data on time to treatment, median time from beginner to experienced was 8 h (IQR:6-12) for hub-and-spoke and 2 h (IQR:1-2.4) for the telementoring programme (p = .01). A 'boots on the ground' approach to recruiting HCV champions was effective within rural communities. Both tele-ECHO hub-and-spoke and telementoring approaches to training primary care providers yielded increase in knowledge and confidence in HCV care and amplified the number of patients who were screened and treated. Telementoring accelerated the timeline of novice providers being 'ready to treat'.

Logics of control and self-management in narratives of people living with HIV, hepatitis C and hepatitis B.

In Australia, the response to HIV, hepatitis C and hepatitis B has largely been through the constructed category of 'blood borne viruses' which treats these viruses as an interconnected set of conditions with respect to their mode of transmission. In this paper, we explore how people understand their viral infection, and compare the logics underpinning these different understandings. In-depth interviews were conducted with 61 participants who were either living with a blood borne virus or were the family members of people living with them. Our analysis reveals that the viral infection was often described as 'just a condition that needs to be managed', albeit in potentially exhausting ways. This understanding hinged upon a biomedical logic in which viral invasion was seen as causing illness and in turn necessitating biomedical intervention. In contrast, some participants with hepatitis B presented their infection as a condition unintelligible through Western biomedical logics, defined instead by symptomology - in terms of 'liver disease', and/or 'liver inflammation'. This focus on symptomology calls into question the soundness of prevention and management responses to hepatitis B based in biomedical logics and reveals the extent to which living with a virus involves multiple, sometimes incompatible, cultural logics. The different logics underpinning HIV, hepatitis C and hepatitis B reveal shortcomings of framing these viruses together as a coherent single construct.

Experience in managing action research on hepatitis C survey in the prison community. / Experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária.

We aimed to report the experience in managing action research on hepatitis C investigation in the prison community in the Triângulo Mineiro region, Minas Gerais, Brazil. The proposal was developed from March 2019 to March 2020, reaching 240 people to contain the spread of the disease through a survey, testing, and monitoring of positive cases. We adopted intersectoral action with articulation between Universities, Medical Society, Teaching Hospital, and State Secretariat for Justice and Public Security. Strategies for the management of action research are described: study settings and stakeholders, registration and formalization of the activity, application of tests, and management of reagent inmates. We identified difficulties regarding the accommodation of routines among the research team and the proper functioning of the penitentiary, which required extensive training between the parties and managerial articulations. We consider that the report collaborates with the organization of future research aimed at accessing this still invisible population, the prison community when it highlights the strategies adopted to conduct the research.

Objetivou-se relatar a experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária no Triângulo Mineiro, Minas Gerais. A proposta foi desenvolvida entre março de 2019 e março de 2020, alcançando 240 pessoas, com o intuito de conter a disseminação do agravo por meio de inquérito, testagem e acompanhamento dos casos positivos. Adotou-se ação intersetorial, com articulação entre universidades, sociedade médica, hospital de ensino e Secretaria de Estado de Justiça e Segurança Pública. As estratégias para o gerenciamento da pesquisa-ação foram: cenários e atores do estudo, registro e formalização da atividade, aplicação dos testes e manejo dos internos reagentes. Dificuldades foram identificadas quanto à acomodação de rotinas entre equipe de pesquisadores e funcionamento próprio da penitenciária, o que exigiu treinamento ostensivo entre as partes e articulações gerenciais. Considera-se que o relato, quando destaca as estratégias adotadas para a condução da pesquisa, colabora para a organização de investigações futuras que visem acessar essa população ainda invisibilizada.

Stem cells as an ideal carrier for gene therapy: A new approach to the treatment of hepatitis C virus.

BACKGROUND AND AIM: Various chemical drugs have been approved for the treatment of patients with hepatitis C, but most of these treatments are costly, and also have an inadequate response and many side effects. Also, there is no effective vaccine for hepatitis C due to its high genetic diversity. In recent decades, clinical trials have grown dramatically regarding the benefits of stem cell therapy as a modulator of immune system responses and anti-inflammatory drugs. The most promising point in stem cell therapy and similar therapies is that patients with chronic pain and severe injuries are offered drug-free treatment or surgery. In the present study, we examine the various dimensions of the use of stem cells with the approach of gene therapy carriers as a new treatment method in the treatment of Hepatitis C. METHODS: Search terms were including gene carrier, stem cell therapy, gene therapy, liver disorders, hepatitis C virus. At first, 1000 article titles related to the mentioned keywords for different diseases were found. After removing duplicate titles and items that did not match the scope of the research, articles that met the criteria for entering the research and had usable information were selected. All abstracts of selected articles were studied by researchers. In the initial review, articles related to the title were identified and categorized based on the type of challenge. CONCLUSION: Gene therapy, either directly and in vivo or indirectly and in vitro, requires carriers (vectors) to transfer the gene. These carriers are divided into two groups, viral and non-viral. In indirect gene therapy, living cells are isolated from a person's body and genetically modified. Stem cells have the properties to transfer the desired genes to the patient's body, including the ability to proliferate for a long time and differentiate into the tissue cells in which they are located.

Balancing uncertainty and proactivity in care seeking for hepatitis C: qualitative research with participants enrolled in a treatment trial in Ho Chi Minh City, Vietnam.

PURPOSE: Direct acting antiviral treatment to cure hepatitis C virus (HCV) is becoming more accessible yet the experiences of those accessing care and treatment and the contexts under which care seeking takes place are largely unknown in low- and middle-income countries. These experiences are important for insight into the challenges people encounter and the support/structures they utilize. The study objective was to explore the experiences of care seeking and treatment for participants enrolled in a clinical trial in Ho Chi Minh City, Vietnam. METHODS: We used in-depth interviews, home visits, mobile interviews, at both the clinic and in the home as we explored how participants experienced health and illness within their social worlds over time. RESULTS: We enrolled 20 participants, of whom 20 completed the first interview, 16 the second, and 18 completed the last interview. Findings explore four themes: (1) navigating uncertainty, (2) proactivity in the face of challenges, (3) living in fear with faith, and (4) dynamic support systems. CONCLUSIONS: Understanding how participants envision and act upon their lived experiences can help to develop public health programmes that effectively address barriers and promote access to care and treatment for people with HCV in Vietnam.

Strengthening systems of care for people with or at risk for HIV, HCV and opioid use disorder: a call for enhanced data collection.

BACKGROUND: The syndemic between opioid use disorder (OUD), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) results in excessive burdens on the healthcare system. Integrating these siloed systems of care is critical to address all three conditions adequately. In this implementation project, we assessed the data capacity of the health system to measure a cascade of care (COC) across HIV, HCV and OUD services in five states to help guide public health planning. MATERIALS AND METHODS: Data for this study were gathered from publicly available datasets and reports from government (SAMSHA, CMS, HRSA and CDC) sites. We created, where possible, COCs for HIV, HCV, and OUD spanning population estimate, diagnosis, treatment initiation, treatment retention, and patient outcomes for each of five states in the study. RESULTS: The process of data collection showed that baseline COCs examining the intersections of OUD, HIV, and HCV cannot be produced and that there are missing data in all states examined. Collection of specific data points is not consistent across all states. States are better at reporting HIV cascades due to federal requirements. Only gross estimates could be made for OUD cascades in all states because data are separated by payer source, leaving no central point of data collection from all sources. Data for HCV were not publicly available. CONCLUSION: It is difficult to assess the strategies needed or the progress made towards increasing treatment access and decreasing the burden of disease without the ability to construct an accurate baseline. Using integrated COCs with relevant benchmarks can not only guide public health planning, but also provide meaningful targets for intervention.KEY MESSAGESWhile HIV COCs are available for most states at least annually, they are not disaggregated for populations with co-occurring OUD or HCV.Data to calculate HCV COC are not available and data to calculate OUD COC are partially available, but only for specific payers.States do not have systems in place to measure the scope of the syndemic or to identify targets for quality improvement activities.

Viral blood-borne infections testing and linkage to care cascade among persons who experience homelessness in the United States: a systematic review and meta-analysis.

BACKGROUND: Persons who experience homelessness remain at increased risk for three viral blood-borne infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). We assessed the yield of testing and linkage to care programs targeting this population for these infections in the United States (US). METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Central for peer-reviewed articles through August 27, 2020. Additionally, we searched the grey literature. Two individuals independently reviewed all relevant studies to check for eligibility and extracted data for each step in the care cascade. We used random-effects model to generate weighted pooled proportions to assess yield at each step. Cumulative proportions were calculated as products of adjacent-step pooled proportions. We quantitatively synthesized data from the studies that focused on non-drug injecting individuals. RESULTS: We identified 24 studies published between 1996-2019 conducted in 19 US states. Seventeen studies screened for HIV, 12 for HCV, and two screened for HBV. For HIV, 72% of approached were recruited, 64% had valid results, 4% tested positive, 2% were given results, and 1% were referred and attended follow-up. Of positives, 25% were referred to treatment and started care. For HCV, 69% of approached were recruited, 63% had valid results, 16% tested positive, 14% were given results, and 3% attended follow-up. Of positives, 30% were referred for treatment and 19% started care. The yield at each care cascade step differs widely by recruitment strategy (for example, for HIV: 71.6% recruited of reached under service-based with zero yield under healthcare facility-based and outreach). CONCLUSIONS: A very large proportion of this population reached for HIV and HCV care were lost in the follow-up steps and never received treatment. Future programs should examine drop-out reasons and intervene to reduce health disparities in this population.

Peer-facilitated treatment access for hepatitis C: the Live Hep C Free project.

BACKGROUND: This commentary explores the lessons learned during implementation of a peer-facilitated hepatitis C virus (HCV) testing and treatment access project called the Live Hep C Free (LHCF) project in contributing to micro-elimination efforts. CASE PRESENTATION: The LHCF project aims to facilitate access to on-the-spot HCV testing, treatment, and care in priority settings through partnership between a peer worker (PW) and a clinical nurse. Since the start of the project in January 2018, 4515 people were engaged about HCV and encouraged to access on-site HCV health care, and over 1000 people were screened for HCV and liver health, while almost 250 people accessed HCV treatment through the project. This commentary is intended to prompt discussion about incorporating peer-centred HCV health programs into priority sites. HCV care-delivery models such as the LHCF project can continue to contribute to micro-elimination of HCV in key settings to increase treatment uptake amongst high prevalence and/or marginalised populations and support progress toward national elimination targets. CONCLUSIONS: The LHCF project has been able to highlight the benefits of incorporating trustworthy, efficient, and convenient peer-centred health services to engage and support vulnerable populations through HCV testing and treatment, particularly individuals who have historically been disconnected from the health care system. Additional attention is needed to ensure ongoing funding support to sustain the project and deliver at scale and in expanding evaluation data to examine the operation and outcomes of the project in more detail.

Using Health Information Technology to Create Pathways for Hepatitis C Treatment and Cure in West Virginia.

This case study describes use of health information technology for enhanced team-based care and care coordination between primary care providers and infectious disease specialists for curing and eventually eliminating hepatitis C in West Virginia. This program, the West Virginia Hepatitis Academic Mentoring Partnership, aims to improve outcomes of West Virginians with chronic hepatitis C infection by training and supporting primary care providers to screen, diagnose, evaluate, treat, cure, and follow patients in the community rather than referring them to distant specialists with long wait times. This initiative supports health equity by increasing access to quality care in severely under-resourced rural areas. Primary care providers engage with hepatitis C experts in a web-based training and mentoring process, combined with informatics training in use of a customized Research Electronic Data Capture (REDCAP) platform for secure data tracking and bidirectional communication. This use of an informatics platform available to all partners supports shared decision-making between primary care providers and specialists, fostering a primary care learning network for improved hepatitis C care in West Virginia.

HEPATITIS C VIRUS SCREENING AND LINKAGE TO CARE IN MENTAL HEALTH UNITS: AN OPPORTUNITY FOR HCV ELIMINATION.

Hepatitis C Virus (HCV) affects approximately 71 million people infected, with 1.75 million people being diagnosed each year, according to the World Health Organization (WHO) estimates. HCV infection leads to cirrhosis, hepatocellular carcinoma (HCC), liver failure and death.