Cost-effectiveness and economic investment to eliminate chronic hepatitis C in Mexico.

In July 2020, the Mexican Government initiated the National Program for Elimination of Hepatitis C (HCV) under a procurement agreement, securing universal, free access to HCV screening, diagnosis and treatment for 2020-2022. This analysis quantifies the clinical and economic burden of HCV (MXN) under a continuation (or end) to the agreement. A modelling and Delphi approach was used to evaluate the disease burden (2020-2030) and economic impact (2020-2035) of the Historical Base compared to Elimination, assuming the agreement continues (Elimination-Agreement to 2035) or terminates (Elimination-Agreement to 2022). We estimated cumulative costs and the per-patient treatment expenditure needed to achieve net-zero cost (the difference in cumulative costs between the scenario and the base). Elimination is defined as a 90% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage and 65% reduction in mortality by 2030. A viraemic prevalence of 0.55% (0.50-0.60) was estimated on 1st January 2021, corresponding to 745,000 (95% CI 677,000-812,000) viraemic infections in Mexico. The Elimination-Agreement to 2035 would achieve net-zero cost by 2023 and accrue 31.2 billion in cumulative costs. Cumulative costs under the Elimination-Agreement to 2022 are estimated at 74.2 billion. Under Elimination-Agreement to 2022, the per-patient treatment price must decrease to 11,000 to achieve net-zero cost by 2035. The Mexican Government could extend the agreement through 2035 or reduce the cost of HCV treatment to 11,000 to achieve HCV elimination at net-zero cost.

Impact of COVID-19 pandemic on diagnosis and treatment access of patients with viral hepatitis in Turkey.

INTRODUCTION: We aimed to evaluate access to diagnosis, treatment and follow-up in patients with viral hepatitis during the COVID-19 pandemic. METHODOLOGY: Patients who started treatment for hepatitis B and hepatitis C were included in the study and analyzed in two periods: before-pandemic and during-pandemic. Indication for treatment and frequency of laboratory follow-up was obtained from hospital records. A telephone survey was administered to evaluate treatment access and compliance. RESULTS: Four centers with 258 patients were included in the study. Of these 161 (62.4%) were male, median age was 50 years. The number of patients, admitted to outpatient clinics was 134647 in the before-pandemic period and 106548 in the during-pandemic period. Number of patients who started treatment for hepatitis B were significantly high during-pandemic period compared with before-pandemic (78 (0.07%); 73 (0.05%) respectively; p = 0.04). The number who received treatment for hepatitis C was similar in both periods: 43 (0.04%); 64 (0.05%), respectively (p = 0.25). Prophylactic treatment for hepatitis B, due to immunosuppressive agents was significantly higher in during-pandemic period (p = 0.001). In the laboratory follow-ups at 4th, 12th and 24th weeks of treatment, worse adherence was detected in during-pandemic (for all p < 0.05). Access to treatment and compliance of all patients was over 90% and did not differ in the two periods. CONCLUSIONS: During-pandemic, hepatitis patients' access to diagnosis, treatment initiation and follow-up had worsened in Turkey. The health policy implemented during the pandemic had a positive impact on patients' access to and compliance to treatment.

High risk injection drug use and uptake of HIV prevention and treatment services among people who inject drugs in KwaZulu-Natal, South Africa.

We conducted a mixed-methods study to understand current drug use practices and access to healthcare services for people who use injection drugs in KwaZulu-Natal, South Africa. We used respondent-driven sampling to recruit 45 people who used injection drugs within the past 6 months from KwaZulu-Natal, South Africa. We found high rates of practices that increase HIV/viral hepatitis risk including the use of shared needles (43%) and direct blood injections (bluetoothing) (18%). Despite 35% living with HIV, only 40% accessed antiretroviral therapy within the past year, and one accessed PrEP. None of the participants ever tested for Hepatitis C.

TASL, TADE, and DAROC consensus for the screening and management of hepatitis C in patients with diabetes.

Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.

Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review.

Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.

Evaluation of Simplified HCV Diagnostics in HIV/HCV Co-Infected Patients in Myanmar.

To evaluate a decentralised testing model and simplified treatment protocol of hepatitis C virus (HCV) infection to facilitate treatment scale-up in Myanmar, this prospective, observational study recruited HIV-HCV co-infected outpatients receiving sofosbuvir/daclatasvir in Yangon, Myanmar. The study examined the outcomes and factors associated with a sustained virological response (SVR). A decentralised "hub-and-spoke" testing model was evaluated where fingerstick capillary specimens were transported by taxi and processed centrally. The performance of the Xpert HCV VL Fingerstick Assay in detecting HCV RNA was compared to the local standard of care ( plasma HCV RNA collected by venepuncture). Between January 2019 and February 2020, 162 HCV RNA-positive individuals were identified; 154/162 (95%) initiated treatment, and 128/154 (84%) returned for their SVR12 visit. A SVR was achieved in 119/154 (77%) participants in the intent-to-treat population and 119/128 (93%) participants in the modified-intent-to-treat population. Individuals receiving an antiretroviral therapy were more likely to achieve a SVR (with an odds ratio (OR) of 7.16, 95% CI 1.03-49.50), while those with cirrhosis were less likely (OR: 0.26, 95% CI 0.07-0.88). The sensitivity of the Xpert HCV VL Fingerstick Assay was 99.4% (95% CI 96.7-100.0), and the specificity was 99.2% (95% CI 95.9-99.9). A simplified treatment protocol using a hub-and-spoke testing model of fingerstick capillary specimens can achieve an SVR rate in LMIC comparable to well-resourced high-income settings.

Hepatitis C Infection and Treatment among Injecting Drug Users Attending General Practice: A Systematic Review and Meta-Analysis.

BACKGROUND: The care provided in general practice to intravenous drug users (IDUs) with hepatitis C (HCV) extends beyond opioid substitution therapy. An aggregated analysis of HCV service utilization within general practice specifically related to diagnosis and treatment outcomes remains unknown from previous literature. AIMS: This study aims to estimate the prevalence of HCV and analyze data related to the diagnosis and treatment-related outcomes of HCV patients with a history of intravenous drug use in the general practice setting. DESIGN AND SETTING: A systematic review and meta-analysis in general practice. METHODS: This review included studies published in the following databases: EMBASE, PubMed, and Cochrane Central Register of Controlled Trials. Two reviewers independently extracted data in standard forms in Covidence. A meta-analysis was done using a DerSimonian and Laird random-effects model with inverse variance weighting. RESULTS: A total of 20,956 patients from 440 general practices participated in the 18 selected studies. A meta-analysis of 15 studies showed a 46% (95% confidence interval (CI), 26-67%) prevalence rate of hepatitis C amongst IDUs. Genotype information was available in four studies and treatment-related outcomes in 11 studies. Overall, treatment uptake was 9%, with a cure rate of 64% (95% CI, 43-83%). However, relevant information, such as specific treatment regimens, treatment duration and doses, and patient comorbidities, was poorly documented in these studies. CONCLUSION: The prevalence of HCV in IDUs is 46% in general practice. Only ten studies reported HCV-related treatment outcomes; however, the overall uptake rate was below 10%, with a cure rate of 64%. Likewise, the genotypic variants of HCV diagnoses, medication types, and doses were poorly reported, suggesting a need for further research into this aspect of care within this patient group to ensure optimal treatment outcomes.

Collaborative Referral Model for Hepatitis C Screening and Treatment in a Remote Mountainous Region of Taiwan during the COVID-19 Pandemic.

Community-based screening for the hepatitis C virus (HCV) decreased during the COVID-19 pandemic. We developed a collaborative referral model between a primary clinic (Liouguei District Public Health Center, LDPHC) and a tertiary referral center to increase HCV screening and treatment uptake in a mountainous region of Taiwan. Once-in-a-lifetime hepatitis B and C screening services established by the Taiwan National Health Insurance were performed at LDPHC. Antibody-to-HCV (anti-HCV)-seropositive patients received scheduled referrals and took a shuttle bus to E-Da hospital for HCV RNA testing on their first visit. Direct-acting antiviral agents (DAAs) were prescribed for HCV-viremic patients on their second visit. From October 2020 to September 2022, of 3835 residents eligible for HCV screening in Liouguei District, 1879 (49%) received anti-HCV testing at LDPHC. The overall HCV screening coverage rate increased from 40% before referral to 69.4% after referral. Of the 79 anti-HCV-seropositive patients, 70 (88.6%) were successfully referred. Of the 38 HCV-viremic patients, 35 (92.1%) received DAA therapy, and 32 (91.4%) achieved sustained virological response. The collaborative referral model demonstrates a good model for HCV screening and access to care and treatment in a Taiwan mountainous region, even during the COVID-19 pandemic. Sustained referral is possible using this routine referral model.

HCV universal EHR prompt successfully increases screening, highlights potential disparities.

BACKGROUND & OBJECTIVES: Screening for hepatitis C virus is the first critical decision point for preventing morbidity and mortality from HCV cirrhosis and hepatocellular carcinoma and will ultimately contribute to global elimination of a curable disease. This study aims to portray the changes over time in HCV screening rates and the screened population characteristics following the 2020 implementation of an electronic health record (EHR) alert for universal screening in the outpatient setting in a large healthcare system in the US mid-Atlantic region. METHODS: Data was abstracted from the EHR on all outpatients from 1/1/2017 through 10/31/2021, including individual demographics and their HCV antibody (Ab) screening dates. For a limited period centered on the implementation of the HCV alert, mixed effects multivariable regression analyses were performed to compare the timeline and characteristics of those screened and un-screened. The final models included socio-demographic covariates of interest, time period (pre/post) and an interaction term between time period and sex. We also examined a model with time as a monthly variable to look at the potential impact of COVID-19 on screening for HCV. RESULTS: Absolute number of screens and screening rate increased by 103% and 62%, respectively, after adopting the universal EHR alert. Patients with Medicaid were more likely to be screened than private insurance (ORadj 1.10, 95% CI: 1.05, 1.15), while those with Medicare were less likely (ORadj 0.62, 95% CI: 0.62, 0.65); and Black (ORadj 1.59, 95% CI: 1.53, 1.64) race more than White. CONCLUSIONS: Implementation of universal EHR alerts could prove to be a critical next step in HCV elimination. Those with Medicare and Medicaid insurance were not screened proportionately to the national prevalence of HCV in these populations. Our findings support increased screening and re-testing efforts for those at high risk of HCV.

Successful Hepatitis C Birth Cohort Screening and Linkage to Care in a US Community Health System.

CONTEXT: Birth cohort ("baby boomer") screening represents a well-validated strategy for the identification of asymptomatic hepatitis C-infected patients. However, successful linkage of newly diagnosed patients to antiviral therapy has been more difficult to accomplish. OBJECTIVE: To analyze the results of a systemwide birth cohort screening program in a US community health care system. DESIGN: We analyzed the data from an ongoing hepatitis C virus (HCV) screening and treatment program that was established at NorthShore University Health System in 2015. Hepatitis C virus screening by primary care providers was prompted through automated Best Practice and Health Maintenance alerts. Patient visits and screening orders were tracked using a customized HCV dashboard. Virologic, demographic, and treatment data were assessed and compared with those of a cohort of patients with previously established HCV infection. RESULTS: Since program inception, 61 8161 (64.3%) of the entire NorthShore baby boomer population of 96 001 patients have completed HCV antibody testing, and 160 patients (0.26%) were antibody positive. Of 152 antibody-positive patients who underwent HCV RNA testing, 53 (34.2%) were viremic. A total of 39 of 53 patients (73.6%) underwent antiviral therapy and achieved a sustained virologic response. Compared with patients identified through screening, a comparison cohort of patients with previously established HCV had more advanced fibrosis and significantly lower dropout rates. The COVID-19 pandemic was associated with a decrease in the number of outpatient visits of screening-eligible patients and with a reduction in HCV screening rates. CONCLUSION: Our data demonstrate the electronic medical records-assisted systemwide implementation of HCV birth cohort screening and successful linkage to antiviral therapy in a community-based US multihospital system.

SARS-CoV-2 spike mRNA vaccine sequences circulate in blood up to 28 days after COVID-19 vaccination.

In Denmark, vaccination against Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has been with the Pfizer-BioNTech (BTN162b2) or the Moderna (mRNA-1273) mRNA vaccines. Patients with chronic hepatitis C virus (HCV) infection followed in our clinic received mRNA vaccinations according to the Danish roll-out vaccination plan. To monitor HCV infection, RNA was extracted from patient plasma and RNA sequencing was performed on the Illumina platform. In 10 of 108 HCV patient samples, full-length or traces of SARS-CoV-2 spike mRNA vaccine sequences were found in blood up to 28 days after COVID-19 vaccination. Detection of mRNA vaccine sequences in blood after vaccination adds important knowledge regarding this technology and should lead to further research into the design of lipid-nanoparticles and the half-life of these and mRNA vaccines in humans.

Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion.

The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility and correlates of protection against SARS-CoV-2. Exposed seronegative individuals have been reported in patients exposed to the blood-borne pathogens Human Immunodeficiency virus and Hepatitis C virus and the sexually transmitted viruses Hepatitis B virus and Herpes Simplex virus. By comparing the quality of seronegative T-cell responses to SARS-CoV-2 with seronegative cellular immunity to these highly divergent viruses, common patterns emerge that offer insights on the role of cellular immunity against infection. For both SARS-CoV-2 and Hepatitis C, T-cell responses in exposed seronegatives are consistently higher than in unexposed individuals, but lower than in infected, seropositive patients. Durability of T-cell responses to Hepatitis C is dependent upon repeated exposure to antigen - single exposures do not generate long-lived memory T-cells. Finally, exposure to SARS-CoV-2 induces varying degrees of immune activation, suggesting that exposed seronegative individuals represent points on a spectrum rather than a discrete group. Together, these findings paint a complex landscape of the nature of infection but provide clues as to what may be protective early on in SARS-CoV-2 disease course. Further research on this phenomenon, particularly through cohort studies, is warranted.

Viral co-infections in leprosy: a scoping review.

CONTEXT: The most reported viral co-infections in leprosy are human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), and SARS-CoV-2. In co-infections, the burden of an agent can be increased or decreased by the presence of others. To address this issue, we need to fully understand their prevalence, risk factors, immunology, clinical manifestations, and treatment. The purpose of this scoping review is to describe the clinical and epidemiological characteristics of the most reported viral co-infections in leprosy to inform clinicians and guide future research. METHODS: The authors conducted a literature search of five databases for articles on each of the aforementioned co-infections published prior to October 2022. Two independent reviewers conducted the selection process and identified 53 papers meeting the study inclusion criteria. The data extraction process and evidence synthesis were conducted by one reviewer and double-checked by a second one, consistent with best practice recommendations for scoping reviews. RESULTS: For all assessed viruses, most studies reported prevalence rates in leprosy patients higher than the general population. Studies found that HTLV, HBV, and HCV chronic infections were highest in multibacillary leprosy, whereas HIV was mostly found in paucibacillary leprosy, and SARS-Cov-2 affected leprosy subtypes equally. Overall, co-infections were also associated with higher rates of leprosy reactions, except for COVID-19. Forty-six percent of the studies discussed issues related to treatment, which led to favorable outcomes for the most part. CONCLUSIONS: This review summarizes the existing literature on viral co-infections in leprosy patients, generating valuable insights and recommending areas for future research.

Project T-SHARP: study protocol for a multi-site randomized controlled trial of tele-harm reduction for people with HIV who inject drugs.

BACKGROUND: The resurgence of HIV outbreaks and rising prevalence among people who inject drugs (PWID) remain exigent obstacles to Ending the HIV Epidemic in the USA. Adapting a low threshold, comprehensive treatment model for PWID with HIV can leverage syringe services programs (SSPs) to increase availability and accessibility of antiretrovirals (ART), medications for opioid use disorder (MOUD), and hepatitis C cure. We developed Tele-Harm Reduction, a telehealth-enhanced, harm reduction intervention delivered within an SSP venue. METHODS: The T-SHARP trial is an open-label, multi-site, randomized controlled superiority trial with two parallel treatment arms. Participants (n=240) recruited from SSPs in Miami, Ft. Lauderdale, and Tampa, Florida, who are PWID with uncontrolled HIV (i.e., HIV RNA>200) will be randomized to Tele-Harm Reduction or off-site linkage to HIV care. The primary objective is to compare the efficacy of Tele-Harm Reduction for initiation of ART at SSPs vs. off-site linkage to an HIV clinic with respect to viral suppression across follow-up (suppression at 3, 6, and 12 months post randomization). Participants with HIV RNA<200 copies/ml will be considered virally suppressed. The primary trial outcome is time-averaged HIV viral suppression (HIV RNA <200 copies/ml) over 3-, 6-, and 12-month follow-up. Secondary outcomes include initiation of MOUD measured by urine drug screen and HCV cure, defined as achieving 12-week sustained virologic response (negative HCV RNA at 12 weeks post treatment completion). A cost-effectiveness analysis will be performed. DISCUSSION: The T-SHARP Trial will be the first to our knowledge to test the efficacy of an innovative telehealth intervention with PWID with uncontrolled HIV delivered via an SSP to support HIV viral suppression. Tele-Harm Reduction is further facilitated by a peer to support adherence and bridge the digital divide. This innovative, flipped healthcare model sets aside the traditional healthcare system, reduces multi-level barriers to care, and meets PWID where they are. The T-SHARP trial is a pragmatic clinical trial that seeks to transform the way that PWID access HIV care and improve HIV clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05208697. Trial registry name: Tele-Harm Reduction. Registration date: January 26, 2022.

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

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

Characteristics and Treatment Rate of Patients With Hepatitis C Virus Infection in the Direct-Acting Antiviral Era and During the COVID-19 Pandemic in the United States.

Importance: Clinical data on hepatitis C virus (HCV) treatment rates in the United States are sparse. Objective: To evaluate HCV treatment rates in the era of direct-acting antivirals (DAAs). Design, Setting, and Participants: This retrospective cohort study used data from the deidentified Optum Cliniformatics Data Mart Database (2014-2021) on patients with HCV in the DAA and COVID-19 eras. The database includes patients with private health insurance in the US. Main Outcomes and Measures: The treatment rate and changes over time were assessed with adjusted log-binomial regression, and factors associated with treatment were examined using multivariable logistic regression. Results: A total of 133 348 patients with HCV (79 567 [59.7%] men; mean [SD] age, 59.7 [12.3] years; 4448 [3.3%] Asian, 24 662 [18.5%] Black, and 74 750 [56.1%] White individuals) were included; 38 180 (26.8%) had HCV RNA data, and of those, 20 277 (53.1%) had positive HCV RNA. Overall, 13 214 patients with positive HCV RNA tests (65.2%) received DAA treatment; 6456 of 6634 patients treated with DAAs (97.3%) achieved sustained virologic response. After adjusting for age, sex, and race and ethnicity, the treatment rate in 2018 was 0.5 times greater than the rate in 2014 (adjusted prevalence ratio, 1.50; 95% CI, 1.42-1.59) but declined after 2018, decreasing from 64.8% to 61.2%, and especially after 2019, when it decreased to less than 60% (P < .001). The number of patients with viremic HCV identified in between April 2020 and March 2021 also decreased to 496 from 2761 and 3258 in the preceding 2 years. Receiving care from a gastroenterologist or infectious disease specialist with advanced care practitioner (ie, nurse practitioner, physician assistant, or clinical nurse specialist) was independently associated with greater odds of DAA treatment (adjusted odds ratio [aOR], 1.64; 95% CI, 1.07-1.50). Patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) were 31% less likely to receive treatment compared with those without (aOR, 0.69; 95% CI, 0.54-0.90). Conclusions and Relevance: In this cohort study, less than two-thirds of insured patients with viremic HCV received DAA treatment, with declines in both the treatment rate and the number of viremic HCV diagnoses since 2019 and especially during the COVID-19 pandemic. Further efforts are needed to increase HCV diagnosis and treatment, especially for those with cirrhosis and HCC. An urgent call for nationwide actions to improve access to DAA treatment, community outreach programs, and specialists through referral pipelines is needed in the United States to stay on track to meet the World Health Organization goal of reducing the burden of viral hepatitis with the eventual goal to eliminate viral hepatitis.