Effectiveness and safety of glecaprevir/pibrentasvir for 8 weeks in the treatment of patients with acute hepatitis C: A single-arm retrospective study.

BACKGROUND AND AIMS: No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection. APPROACH AND RESULTS: This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3-99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P. CONCLUSIONS: Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.

Tools Needed to Support Same-day Diagnosis and Treatment of Current Hepatitis C Infection.

Current HCV prevention efforts and treatment rates must improve for the United States (U.S.) to achieve WHO global elimination targets by 2030[1]. The current multi-day diagnosis and treatment paradigm for hepatitis C (HCV) infection leads to significant loss in the cascade of care, resulting in far fewer patients receiving treatment with direct acting antiviral agents (DAAs) than those diagnosed with HCV infection [2,3]. To achieve HCV elimination, a paradigm shift in access to HCV treatment is needed from current multi-day testing and treatment algorithms to same day diagnosis and treatment. This shift will require new tools, such as FDA-approved, CLIA-waived point-of-care (POC) antigen or nucleic acid tests (NAT) for HCV and HBV and NAT for HIV that do not require venous blood. Such a shift will also require better utilization of existing resources, expanding access to HCV treatment through availability of onsite treatment, removal of payer barriers to approval, adoption of minimal monitoring approaches during treatment, expanded access to available POC tests, and available specialist referral networks for patients who fail initial therapy, have advanced liver fibrosis, or have co-incident HIV or HBV infection. A same-day diagnosis and treatment paradigm will substantially contribute to HCV elimination by improving treatment rates for those diagnosed with HCV infection and expanding access to treatment in settings where patients have brief encounters with healthcare.

Assessing the Feasibility, Acceptability, and Effectiveness of a Pilot Hepatitis C Screening Program at Food Distribution Sites in Cherokee Nation, Oklahoma.

Compared with other racial and ethnic groups in the United States, American Indian and Alaska Native (AI/AN) people experience the highest incidence of acute hepatitis c (HCV). Cherokee Nation Health Services (CNHS) implemented a pilot health screening program from January through May 2019 to assess whether conducting HCV and other preventive health screenings at food distribution sites is a feasible, acceptable, and effective strategy to increase health screening among underserved community members. Data were collected among 340 eligible participants. Most (76%) participants reported being very comfortable receiving health screenings at food distribution sites and that getting screened at food distribution sites is very easy (75.4%). Most (92.1%, n = 313) participants received HCV screening, with 11 (3.5%) individuals testing positive for HCV antibodies. Of the 11 HCV seropositive individuals, six were confirmed to have active HCV infection of which four initiated treatment. Most (55.7%) participants exhibited a body mass index in the obese range, 33.1% exhibited high hemoglobin A1C (> 6.0), 24.5% exhibited high (> 200) cholesterol, 44.6% exhibited high blood pressure ( > = 140/90), and 54.8% did not have a current primary care provider. This project demonstrated that conducting HCV and other health screenings at food distribution sites within Cherokee Nation was an effective strategy to engage AI/AN people in preventive health screenings. Future programs are needed to scale-up preventive health screenings outside of traditional medical facilities as these types of screenings may help to decrease the HCV disparities among AI/AN people.

Addressing racial and ethnic disparities in US liver cancer care.

HCC, the most common form of primary liver cancer, is the fastest rising cause of cancer-related death in the United States. HCC disproportionately affects racial and ethnic minorities in the United States. A practical framework is needed to organize the complex patient, provider, health system, and societal factors that drive these racial and ethnic disparities. In this narrative review, we adapted and applied the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework to the HCC care continuum, as a step toward better understanding and addressing existing HCC-related disparities. We first summarize the literature on HCC-related disparities by race and ethnicity organized by the framework's 5 domains (biological, behavioral, physical/built environment, sociocultural environment, and health care system) and 4 levels (individual, interpersonal, community, and societal) of influence. We then offer strategies to guide future research initiatives toward promotion of health equity in HCC care. Clinicians and researchers may help mitigate further inequities and better address racial and ethnic disparities in HCC care by prioritizing the following in HCC research: (1) increasing racial and ethnic minority representation, (2) collecting and reporting HCC-related data by racial and ethnic subgroups, (3) assessing the patient experience of HCC care by race and ethnicity, and (4) evaluating HCC-specific social determinants of health by race and ethnicity. These 4 priorities will help inform the development of future programs and interventions that are tailored to the unique experiences of each racial and ethnic group.

Evaluation of the Cherokee Nation Hepatitis C Virus Elimination Program - Cherokee Nation, Oklahoma, 2015-2020.

Approximately 2.4 million persons in the United States have hepatitis C virus (HCV) infection, and 66,700 acute HCV infection cases were estimated for 2020 (1,2). American Indian or Alaska Native (AI/AN) persons are disproportionately affected by HCV infection and experienced the highest rates of acute HCV infection (2.1 cases per 100,000 persons) and HCV-associated mortality (10.17 per 100,000 persons) in the United States during 2020 (1). During 2015, Cherokee Nation Health Services (CNHS) in Oklahoma implemented an HCV elimination program, which includes universal HCV screening, primary HCV workforce expansion, and harm reduction services (3). To assess progress 5 years after program initiation, CNHS analyzed deidentified health record data. During November 1, 2015-October 31, 2020, a total of 1,423 persons received a diagnosis of HCV infection. Among these persons, 1,227 (86.2%) were linked to HCV care, and 871 (61.2%) initiated HCV treatment; 702 (49.3%) returned for their 12-week post treatment completion visit, at which time 698 (49.1%) had achieved laboratory-confirmed sustained virologic response (SVR), defined as undetectable HCV RNA at ≥12 weeks after completion of treatment (SVR12). Although CNHS has linked the majority of persons diagnosed with HCV infection to care, and those who returned for the SVR12 visit had high cure rates (99.4%), treatment initiation was lower than expected. Future activities should prioritize addressing gaps in treatment initiation after linkage to care and confirmation of hepatitis C cure with SVR12 testing.

Evaluation of treatment access and scope of a multistate hepatitis C virus Extension for Community Healthcare Outcomes telehealth service in the US Indian Health System, 2017-2021.

PURPOSE: American Indians/Alaska Native (AI/AN) persons are disproportionately affected by hepatitis C virus (HCV). The Northwest Portland Area Indian Health Board Indian Country Extension for Community Healthcare Outcomes (ECHO) telehealth clinic supports primary care providers (PCPs) in treating HCV. We evaluated the extent to which Indian Country ECHO increases access to HCV treatment and holistically serves AI/AN patients. METHODS: We conducted a retrospective descriptive analysis of Indian Country ECHO treatment recommendations from 2017 to 2021. Recommendations were classified into the following categories: HCV treatment with direct-acting antiviral medication, prevention, substance use disorder treatment, lab or imaging orders, pharmacological considerations, behavior changes, other, and referral. Subanalysis of treatment recommendations was completed for patients with cirrhosis. FINDINGS: Of the 776 patients from 77 Indian Health System facilities who presented at Indian Country ECHO, 718 (93%) received treatment recommendations. Most patients (93%) received recommendations for HCV treatment by their PCP; only 3% received a recommendation for referral to a hepatologist or liver transplant center for additional care. Most patients received at least 1 recommendation beyond the scope of HCV treatment provision. Cirrhosis criteria were met by 8% of patients, of which 80% received recommendations for HCV treatment by their PCP and 25% received recommendations for referral to a specialist for additional care. CONCLUSIONS: Most patients presented at the Indian Country ECHO received recommendations for HCV treatment by their PCP, along with recommendations beyond the scope of HCV. Indian Country ECHO telehealth clinic provides comprehensive recommendations to effectively integrate evidence-based HCV treatment with holistic care at the primary care level.

Adapting a Telehealth Network for Emergency COVID-19 Pandemic Response, 2020-2021.

In March 2020, a Tribal telehealth program-the Indian Country Extension for Community Health Outcomes (ECHO)-added emergency COVID-19 to its programming to support the pandemic response. A long-standing relationship with a network of Indian Health Service, Tribal, and urban Indian clinicians supported a rapid launch of the COVID-19 telehealth program. This nationwide service offered primary care clinicians and staff serving American Indian/Alaska Native people access to virtual learning opportunities, expert clinical recommendations, technical assistance, and capacity building. From March 12, 2020, through April 30, 2021, the program provided 85 clinical sessions in 12 months, with an average participation of 120 attendees per clinic (N = 11 710). Attendees could complete a voluntary evaluation form for each session via an online link. A total of 2595 forms were completed. Attendees came from 33 states and 206 unique locations, primarily from the Pacific Northwest (n = 931, 35.9%). Most pharmacists (78.1%), providers (ie, medical doctor, doctor of osteopathy, advanced practice nurse, physician assistant, or clinical nurse midwife; 70.8%), and nurses (59.6%) gave the sessions the highest rating of "very satisfied." The highest proportion of attendees indicating that they planned a change in practice were pharmacists (68.0%), nurses, (64.1%), and providers (61.3%). Most attendees (93.1%) said that the COVID-19 sessions gave them a sense of social support. Lessons learned were that (1) a telehealth platform can be quickly retasked for emergency response with no further delays, (2) a telehealth network can be scaled up quickly with participation from preexisting relationships, and (3) the platform is flexible and adaptable to the needs of participants. An existing telehealth program can be a key part of timely, relevant, large-scale emergency readiness and response efforts.

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

Evaluation of the Cherokee Nation Hepatitis C Virus Elimination Program in the First 22 Months of Implementation.

Importance: In 2019, hepatitis C virus (HCV) infection contributed to more deaths in the US than 60 other notifiable infectious diseases combined. The incidence of and mortality associated with HCV infection are highest among American Indian and Alaska Native individuals. Objective: To evaluate the association of the Cherokee Nation (CN) HCV elimination program with each element of the cascade of care: HCV screening, linkage to care, treatment, and cure. Design, Setting, and Participants: This cohort study used data from the CN Health Services (CNHS), which serves approximately 132 000 American Indian and Alaska Native individuals residing in the 14-county CN reservation in rural northeastern Oklahoma. Data from the first 22 months of implementation (November 1, 2015, to August 31, 2017) of an HCV elimination program were compared with those from the pre-elimination program period (October 1, 2012, to October 31, 2015). The analysis included American Indian and Alaska Native individuals aged 20 to 69 years who accessed care through the CNHS between October 1, 2012, and August 31, 2017. Cure data were recorded through April 15, 2018. Exposure: The CN HCV elimination program. Main Outcomes and Measures: The main outcomes were the proportions of the population screened for HCV, diagnosed with current HCV infection, linked to care, treated, and cured during the initial 22 months of the elimination program period and the pre-elimination program period. Data from electronic health records and an HCV treatment database were analyzed. The cumulative incidence of HCV infection in this population was estimated using bayesian analyses. Results: Among the 74 039 eligible individuals accessing care during the elimination program period, the mean (SD) age was 36.0 (13.5) years and 55.9% were women. From the pre-elimination program period to the elimination program period, first-time HCV screening coverage increased from 20.9% to 38.2%, and identification of current HCV infection and treatment in newly screened individuals increased from a mean (SD) of 170 (40) per year to 244 (4) per year and a mean of 95 (133) per year to 215 (9) per year, respectively. During the implementation period, of the 793 individuals with current HCV infection accessing the CNHS, 664 were evaluated (83.7%), 394 (59.3%) initiated treatment, and 335 (85.0%) had documented cure. In less than 2 years, the 85% 3-year goal was reached for cure (85.0%), and the goal for linkage to care was nearly reached (83.7%), whereas screening (44.1%) and treatment initiation (59.3%) required more time and resources. Conclusions and Relevance: This cohort study found that after 22 months of implementation, the CNHS community-based HCV elimination program was associated with an improved cascade of care. The facilitators and lessons learned in this program may be useful to other organizations planning similar programs.

Telehealth and hepatitis C treatment for indigenous communities in the United States

To the editor: In the United States (US), an estimated 2.4 million persons have chronic infection with hepatitis C virus (HCV). The number of deaths from HCV-related mortality is greater than that of HIV and tuberculosis combined. Treatment with direct-acting antivirals (DAAs), usually 1-3 pills a day for 8 or 12 weeks, can cure over 95% of patients. Successful treatment of HCV has been shown to greatly reduce liver-related as well as all-cause mortality. American Indian and Alaska Native (AI/AN) people have over twice the national rate of HCV-related mortality. The largest health care provider for AI/AN communities is the Indian Health System, a national network of federal (Indian Health Service), tribal, and urban health facilities, comprised mostly of rural primary care clinics. As part of the Indian Health System response to HCV, health facilities have access to tele-mentoring support such as the ECHO (Extension for Community Healthcare Outcomes) model, which has demonstrated excellent outcomes in treating HCV. The program connects rural clinicians (‘spokes’) to a specialist team (‘hub’). These participants meet regularly via low-bandwidth video conference technology. The format of case-based learning, supported by short didactic presentations, aims to scale up clinical capacity across a health network. Patient presentations entail a brief de-identified standardized form with a patient’s clinical history to assess liver disease severity and determine optimal HCV treatment. [...]

Hepatitis C Virus Infection in Indigenous Populations in the United States and Canada.

American Indian/Alaska Native (AI/AN) and Canadian Indigenous people are disproportionally affected by hepatitis C virus (HCV) infection yet are frequently underrepresented in epidemiologic studies and surveys often used to inform public health efforts. We performed a systematic review of published and unpublished literature and summarized our findings on HCV prevalence in these Indigenous populations. We found a disparity of epidemiologic literature of HCV prevalence among AI/AN in the United States and Indigenous people in Canada. The limited data available, which date from 1995, demonstrate a wide range of HCV prevalence in AI/AN (1.49%-67.60%) and Indigenous populations (2.28%-90.24%). The highest HCV prevalence in both countries was reported in studies that either included or specifically targeted people who inject drugs. Lower prevalence was reported in studies of general Indigenous populations, although in Canada, the lowest prevalence was up to 3-fold higher in Aboriginal people compared with general population estimates. The disparity of available data on HCV prevalence and need for consistent and enhanced HCV surveillance and reporting among Indigenous people are highlighted. HCV affects Indigenous peoples to a greater degree than the general population; thus we recommend tribal and community leaders be engaged in enhanced surveillance efforts and that funds benefitting all Indigenous persons be expanded to help prevent and cover health care expenses to help stop this epidemic.

Implementation of Liver Cancer Education Among Health Care Providers and Community Coalitions in the Cherokee Nation.

INTRODUCTION: The Cherokee Nation Comprehensive Cancer Control Program collaborated with the Cherokee Nation Hepatitis C Virus (HCV) Elimination Program within Cherokee Nation's Health Services to plan and implement activities to increase knowledge and awareness of liver cancer prevention among health care providers and the Cherokee Nation community. From August 2017 to April 2018, the 2 programs implemented liver cancer prevention interventions that focused on education of health care providers and community members. We used descriptive statistics to analyze data collected from a brief, retrospective pre-post survey for each intervention. We assessed overall awareness and knowledge of liver cancer and ability and intention to address it on a scale of 1 to 5. Project Extension for Community Healthcare Outcomes didactic sessions resulted in a 1.1-point improvement, provider education workshops resulted in a 1.4-point improvement, and presentations at community coalition meetings resulted in a 1.7-point improvement. Our study shows that HCV interventions can be used by public health and medical professionals interested in controlling HCV and related diseases such as liver cancer.

Retrospective Study Demonstrating High Rates of Sustained Virologic Response After Treatment With Direct-Acting Antivirals Among American Indian/Alaskan Natives.

BACKGROUND: Treatment for chronic hepatitis C virus (HCV) has rapidly evolved to simple, well-tolerated, all-oral regimens of direct-acting antivirals (DAAs). There are few data on the epidemiology of HCV in American Indians/Alaska Natives (AI/ANs), a population disproportionately affected by HCV. METHODS: In this retrospective cohort study, all HCV-infected AI/AN patients treated with DAA therapies between January 1, 2014, and February 24, 2016, in specialty clinics or by primary care clinicians participating in Extension for Community Healthcare Outcomes (ECHO) were included. Demographic, clinical, and virologic data on all patients treated for HCV from pretreatment through sustained virologic response at 12 weeks (SVR12) were collected. RESULTS: Two hundred eighty patients were included; 71.1% of patients (n = 199) were infected with genotype 1 (GT1), 18.2% (n = 51) with GT2, and 10.7% with (n = 30) GT3. At baseline, 26.1% (n = 73) patients had cirrhosis and 22.6% (n = 56) had active substance use disorder; eighty-eight percent (n = 232) of patients achieved SVR12. Among the 165 GT1 patients treated with sofosbuvir (SOF)/ledipasvir for 8, 12, and 24 weeks, SVR12 was achieved by 91.5% (n = 54), 92.2% (n = 71), and 100% (n = 13), respectively. Among GT2 patients, 87.2% (n = 34) and 71.4% (n = 5) treated with 12 and 16 weeks of SOF/ribavirin (RBV) achieved SVR12, respectively. Among GT3 patients, 100% (n = 2) and 83.3% (n = 20) treated with 12 and 24 weeks of SOF/RBV achieved SVR12, respectively. SVR12 rates remained high among patients with active substance use disorder. CONCLUSIONS: DAA therapies are highly efficacious in HCV-infected AI/ANs. SVR12 rates remained high among patients with active substance use disorder. More steps must be taken to increase access to treatment for this underserved, vulnerable population.

An Evaluation of Hepatitis C Virus Telehealth Services Serving Tribal Communities: Patterns of Usage, Evolving Needs, and Barriers.

INTRODUCTION: American Indian/Alaska Native (AI/AN) populations are disproportionately affected by chronic hepatitis C virus (HCV) infection. Federal facilities of the Indian Health Service, in conjunction with Tribally operated and Urban Indian (I/T/U) health care facilities, serve an estimated 2.2 million AI/AN patients. The facilities are mainly rural and have few specialists. To fill the gap in specialists in I/T/U clinics, the Extension for Community Healthcare Outcomes (ECHO) telehealth model was used to support clinicians to treat HCV in primary care. METHODS: Participants in 3 regional HCV ECHO networks serving AI/AN patients were surveyed by e-mail and text message to determine patterns of ECHO usage, usefulness, and barriers to treating patients with HCV at their primary care clinics. RESULTS: From a total of 44 respondents from 72 eligible health care facilities, a majority (61%) stated that they started treating patients with HCV subsequent to participating in the telehealth program. Participants with more telehealth experience sought increasing complexity in patient case presentations. In California, 7 of 8 clinicians who had attended more than 10 ECHO sessions expressed diminishing need for ECHO sessions to manage cases (<25% of patients). All elements of the ECHO sessions (presenting patient cases, listening to patient case presentations, teaching sessions, and sharing of programmatic insights) were considered "extremely useful" by the majority of respondents. The factors most cited as moderate or extensive barriers to providing HCV care were access to HCV direct acting antivirals (60%) and linking patients to care (50%). DISCUSSION: Extension for Community Healthcare Outcomes may play a key role not only in increasing clinical capacity for HCV treatment but also in the inception of HCV services in this sample of I/T/U facilities. Participants with more telehealth experience demonstrated signs of increasing clinical capacity, where they were more likely to seek complex patient case presentations in ECHO sessions. A number of barriers continue to keep AI/ANs from being cured and stop clinicians from ending the epidemic, including access to HCV medications, time to provide HCV clinical services, and linking patients to HCV services.

Assessing Disparities in the Rates of HCV Diagnoses Within American Indian or Alaska Native Populations Served by the U.S. Indian Health Service, 2005-2015.

Hepatitis C virus (HCV) disproportionately affects American Indians/Alaska Natives (AI/AN). The Indian Health Service (IHS), via federal and tribal health facilities provides medical services to an estimated 2.2 million AI/AN people in the United States. HCV diagnoses, defined by International Classification of Diseases 9th Revision, Clinical Modification (ICD-9-CM) codes, were analyzed from 2005 to 2015. Results showed 29,803 patients with an HCV diagnosis; 53.4% were among persons born 1945-1965 and overall HCV burden was higher among males than females. These data will help inform local, regional, and national efforts to address, plan for and carry out a national strategy to provide treatment for HCV infected patients and programs to prevent new HCV infections.