Factors predicting staging and treatment initiation for patients with chronic hepatitis C infection: insurance a key predictor.

BACKGROUND: Chronic hepatitis C (HCV) infection affects over 2.4 million Americans and accounts for 18 000 deaths per year. Treatment initiation in this population continues to be low even after introduction of highly effective and shorter duration direct-acting antivirals. This study assesses factors that influence key milestones in the HCV care continuum. METHODS: Retrospective time-to-event analyses were performed to assess factors influencing liver fibrosis staging and treatment initiation among individuals confirmed with chronic HCV infection at University of Illinois Hospital and Health Sciences System between 1 August 2015 and 24 October 2016 and followed through 28 January 2018. Cox regression models were utilized for multivariable analyses. RESULTS: Individuals tested at the liver clinic (hazard ratio [HR] = 2.03; 95% confidence interval [CI]: 1.19-3.46) and at the federally qualified health center (HR = 3.51; 95% CI: 2.19-5.64) had higher instantaneous probability of being staged compared with individuals tested at the emergency department (ED) or inpatient setting. And probability of treatment initiation increased with advancing liver fibrosis especially for Medicaid beneficiaries (HR = 1.64; 95% CI: 1.35-1.99). CONCLUSIONS: The study demonstrates a need for improving access for patients with early stages of the disease in order to reduce HCV-related morbidity and mortality, especially those tested at nontraditional care locations such as the ED or the inpatient setting.

Hepatitis C Virus Resistance Testing in Genotype 1: The Changing Role in Clinical Utility.

OBJECTIVE: To review the role and utility of baseline resistance testing with currently available and pipeline genotype 1 hepatitis C virus (HCV) treatment. DATA SOURCES: Authors reviewed liver meeting abstracts for data on currently-available and pipeline genotype 1 retreatment regimens from January 1, 2015, to March 23, 2017. Additional trials were identified from a review of clinicaltrials.gov using the pipeline medication names. STUDY SELECTION AND DATA EXTRACTION: Authors identified reports of current and pipeline genotype 1 retreatment regimens. Seven references were clinical study results presented at the meetings of the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver, and 2 studies were from clinicaltrials.gov . DATA SYNTHESIS: Retreatment trial data of currently available salvage regimens indicate that baseline NS5A resistance-associated substitutions (RASs) may decrease sustained virological response (SVR) rates when retreating with ledipasvir/sofosbuvir but are not affected when using elbasvir/grazoprevir + sofosbuvir + ribavirin, paritaprevir/ritonavir/ombitasvir + dasabuvir + sofosbuvir, or sofosbuvir/velpatasvir + ribavirin. Pipeline data indicate that baseline NS5A RASs do not affect SVR rates when retreating with sofosbuvir/velpatasvir/voxilaprevir or glecaprevir/pibrentasvir. CONCLUSIONS: Baseline resistance testing was used for decisional support for 3 clinical scenarios in patients with HCV genotype 1 infection at the time of manuscript submission. Pending the approval of 2 new direct-acting antiviral regimens in the third quarter of 2017, the rapidly evolving HCV treatment guidelines will likely reflect a decreased clinical utility for resistance testing.

Pharmacist-initiated hepatitis C virus screening in a community pharmacy to increase awareness and link to care at the medical center.

OBJECTIVE: To describe the design and implementation of a pharmacist-led hepatitis C virus (HCV) screening and education program in a community pharmacy with a protocol for linkage to care at the affiliated hepatology clinic for patients born between 1945 and 1965. SETTING: Outpatient pharmacy affiliated with the University of Illinois Hospital and Health Sciences System. PRACTICE DESCRIPTION: The community pharmacist resident conducted the HCV screening at the health system-based community pharmacy. PRACTICE INNOVATION: Community pharmacists provided patients with HCV screening and education while patients waited for their prescriptions to be ready or upon appointment. Patients were given a questionnaire before and after HCV education to assess the impact of pharmacist-provided education on patient knowledge. A protocol was developed to link patients with a positive HCV antibody test result to care with a hepatologist for confirmatory testing at a follow-up appointment at the medical center. EVALUATION: Investigators assessed the feasibility of providing the screening and education, recorded the number of patients screened, and recorded the differences in the questionnaire responses before and after education. RESULTS: Pharmacist-led HCV screening services were implemented successfully at the community pharmacy. All patients had a negative antibody result; therefore, linkage to care at the medical center, although available, was not necessary. The self-reported posttest HCV knowledge scores were significantly higher than pretest scores. CONCLUSION: This article outlines the methodology for providing a multidisciplinary HCV screening, education, and referral program in a community pharmacy affiliated with a medical center. Pharmacist-initiated HCV screening in a community pharmacy can assist with identifying patients at risk for HCV infection and provide patients with linkage to care in the health system. This report may encourage community pharmacists to conduct future prospective trials to evaluate clinical and economic outcomes of community-based HCV screenings.

A cross-sectional survey of viral hepatitis education within pharmacy curricula in the United States.

BACKGROUND: The Viral Hepatitis National Strategic Plan emphasizes the importance of a collaborative provider workforce trained in hepatitis prevention and treatment to eliminate viral hepatitis in the United States by 2030. Although pharmacists play a key role in hepatitis management, literature lacks documentation of the amount of viral hepatitis education provided to pharmacy students. AIM: Our study goal was to describe viral hepatitis education provided at United States pharmacy schools. METHOD: In this cross-sectional survey study, investigators developed a 19-item Qualtrics questionnaire, sent questionnaire links to curricula content experts at 140 accredited pharmacy colleges/schools in May-June 2022, and allotted 28 days for completion. Questions assessed the viral hepatitis instruction provided to students and hepatitis instructors' training/experience. We used descriptive statistics for analysis. RESULTS: Forty-eight pharmacy institutions across 29 states/territories responded; 44% had 50-99 students/class, and 58% used lecture and discussion to provide required hepatitis education. Students received more lecture (average = 3.4 h, range 0.8-1.6 h/hepatitis topic) than discussion (average = 1.7 h, range 0.6-0.9 h/hepatitis topic), with the most time spent on hepatitis C, followed by hepatitis B virus. Respondents reported 93% of their instructors had post-graduate training/certifications and 67% worked in clinical settings with hepatitis patients. CONCLUSION: Survey results demonstrate variability in hepatitis education across United States pharmacy curricula. Data offer stakeholders in hepatitis elimination efforts knowledge about the viral hepatitis education provided to Doctor of Pharmacy students. Future directions include consideration of implementation of minimum hepatitis education standards to further support work toward national hepatitis elimination.

Glecaprevir/pibrentasvir + sofosbuvir for post-liver transplant recurrent hepatitis C virus treatment.

Glecaprevir/pibrentasvir in combination with sofosbuvir may serve as a safe and effective option for treatment of recurrent hepatitis C virus post-liver transplant in patients who previously failed direct-acting antivirals.

Sustained Virologic Response Rates Before and After Removal of Sobriety Restriction for Hepatitis C Virus Treatment Access.

OBJECTIVES: Until November 1, 2018, Illinois Medicaid restricted coverage of hepatitis C virus (HCV) medication to patients with sobriety from alcohol and illicit substances for ≥12 months. This policy limited treatment access for patients with a high risk of HCV transmission, despite clinical trial and real-world data demonstrating high sustained virologic response (SVR) rates among patients with substance use. The objective of this study was to compare HCV SVR rates between patients treated before and after removal of the Illinois Medicaid sobriety restriction. METHODS: We performed a retrospective cohort study of Medicaid-insured patients who completed direct-acting antiviral treatment at an urban, academic medical center in Illinois from January 1, 2014, through October 21, 2020. The primary endpoint was SVR. We compared group characteristics using χ2 or Fisher exact tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. We used logistic regression to compare SVR rates before and after the policy change, adjusting for differences between groups. RESULTS: A total of 496 patients (348 pre-policy change; 148 post-policy change) started treatment; excluding loss to follow-up/early discontinuation, SVR rates were 95.4% (309 of 324) pre-policy change and 97.1% (134 of 138) post-policy change. SVR rates did not differ after adjusting for the use of historic HCV regimens and the higher cirrhosis rate in the pre-policy change group compared with the post-policy change group (odds ratio = 0.98; 95% CI, 0.32-3.67). CONCLUSION: HCV SVR rates were similar before and after removal of the Illinois Medicaid sobriety restriction, regardless of group differences. Results support HCV treatment regardless of documented sobriety to facilitate progress toward HCV elimination.

Practical considerations when treating chronic hepatitis E in solid organ transplant recipients.

Hepatitis E virus (HEV) can lead to chronic infections in immunosuppressed patients. The use of ribavirin to treat chronic HEV has been well-established in case reports and guidelines. However, practical approaches to the use of this antiviral treatment in a post-transplant patient, including drug interactions, dosing adjustments, and monitoring parameters, are lacking. Thus, we present our real-world approach to the use of ribavirin to treat chronic HEV in a solid organ transplant recipient.

Predicting Treatment Failure for Initiators of Hepatitis C Virus Treatment in the era of Direct-Acting Antiviral Therapy.

Introduction: Hepatitis C virus (HCV), the leading cause of advanced liver disease, has enormous economic burden. Identification of patients at risk of treatment failure could lead to interventions that improve cure rates. Objectives: Our goal was to develop and evaluate a prediction model for HCV treatment failure. Methods: We analyzed HCV patients initiating direct-acting antiviral therapy at four United States institutions. Treatment failure was determined by lack of sustained virologic response (SVR) 12 weeks after treatment completion. From 20 patient-level variables collected before treatment initiation, we identified a subset associated with treatment failure in bivariate analyses. In a derivation set, separate predictive models were developed from 100 bootstrap samples using logistic regression. From the 100 models, variables were ranked by frequency of selection as predictors to create four final candidate models, using cutoffs of ≥80%, ≥50%, ≥40%, and all variables. In a validation set, predictive performance was compared across models using area under the receiver operating characteristic curve. Results: In 1,253 HCV patients, overall SVR rate was 86.1% (95% CI = 84.1%, 88.0%). The AUCs of the four final candidate models were: ≥80% = 0.576; ≥50% = 0.605; ≥40% = 0.684; all = 0.681. The best performing model (≥40%) had significantly better predictive ability than the ≥50% (p = 0.03) and ≥80% models (p = 0.02). Strongest predictors of treatment failure were older age, history of hepatocellular carcinoma, and private (vs. government) insurance. Conclusion: This study highlighted baseline factors associated with HCV treatment failure. Treatment failure prediction may facilitate development of data-driven clinical tools to identify patients who would benefit from interventions to improve SVR rates.

Medication therapy management services: definitions and outcomes.

In the US, the Medicare Modernization Act of 2003 required that Medicare Part D insurers provide medication therapy management (MTM) services (MTMS) to selected beneficiaries, with the goals of providing education, improving adherence, or detecting adverse drug events and medication misuse. These broad goals and variety in MTM programmes available make assessment of these programmes difficult. The objectives of this article are to review the definitions of MTMS proposed by various stakeholders, and to summarize and evaluate the outcomes of MTMS consistent with those that may be offered in Medicare Part D or reimbursed by State Medicaid programmes. MTM programmes are approved by the Centers for Medicare and Medicaid Services (CMS). Pharmacy, medical and insurance organizations have provided guidelines and definitions for MTM programmes, distinguishing them from other types of community pharmacy activities. MTM has been distinguished from disease state management because of the focus on medications and multiple conditions. It differs from patient counselling because it is delivered independent of dispensing and involves collaboration with patients and providers. There is no consensus on the recommended mode of delivery (i.e. face-to-face or by telephone) for MTM. A MEDLINE search was conducted to identify articles published after 2000 using the search terms 'medication therapy management' and 'medication management'. Studies with outcomes evaluating community-based programmes consistent with MTMS, regardless of MTMS reimbursement source, were included in the review. Seven publications describing four MTMS were identified. For each of the identified articles, we describe the study design, service setting, inclusion criteria and outcomes. An additional three surveys describing multiple MTMS were identified and are summarized. Finally, ongoing efforts by CMS to evaluate the success of MTMS in the US are described. To date, there are limited outcomes available for MTMS. The wide variety of MTMS offered means that evaluations of individual programmes are necessary. Despite the potential benefits of MTMS, there are numerous challenges to providing MTMS, including reimbursement, justification of the service and stakeholder acceptance of the services. There remains a need for adequately funded, prospective, controlled studies of MTM programmes using strong designs to advance our knowledge of the effectiveness of various interventions and methods of delivery, and for naturalistic studies assessing the impact of CMS approved MTM programmes.

Expanding Hepatitis C Virus Care and Cure: National Experience Using a Clinical Pharmacist-Driven Model.

BACKGROUND: The US National Viral Hepatitis Action Plan depends on additional providers to expand hepatitis C virus (HCV) treatment capacity in order to achieve elimination goals. Clinical pharmacists manage treatment and medication within interdisciplinary teams. The study's objective was to determine sustained virologic response (SVR) rates for clinical pharmacist-delivered HCV therapy in an open medical system. METHODS: Investigators conducted a multicenter retrospective cohort study of patients initiating direct-acting antivirals from January 1, 2014, through March 12, 2018. Data included demographics, comorbidities, treatment, and clinical outcomes. The primary outcome of SVR was determined for patients initiating (intent-to-treat) and those who completed (per-protocol) treatment. Chi-square tests were conducted to identify associations between SVR and adverse reactions, drug-drug interactions, and adherence. RESULTS: A total of 1253 patients initiated treatment; 95 were lost to follow-up, and 24 discontinued therapy. SVR rates were 95.1% (1079/1134) per protocol and 86.1% (1079/1253) intent to treat. The mean age (SD) was 57.4 (10.1) years, the mean body mass index (SD) was 28.7 (6.2) kg/m2, 63.9% were male, 53.7% were black, 40.3% were cirrhotic, 88.4% were genotype 1, and 81.6% were treatment-naïve. Patients missing ≥1 dose had an SVR of 74.9%; full adherence yielded 90% (P < .0001). CONCLUSIONS: HCV treatment by clinical pharmacists in an open medical system resulted in high SVR rates comparable to real-world studies with specialists and nonspecialists. These findings demonstrate the success of a clinical pharmacist-delivered method for HCV treatment expansion and elimination.

Closing the Gap: The Challenges of Treating Hepatitis C Virus Genotype 3 Infection.

The efficacy of hepatitis C virus (HCV) treatment has increased over the last 5 years to nearly 100% for many patient groups. Patients with genotype (GT) 3 HCV infection, however, and specifically cirrhotic or treatment-experienced patients, have lower sustained virologic response (SVR) rates than patients with other GTs. Because GT 3 presents more clinical challenges than other GTs, this review focuses on the evolution and efficacy of direct-acting antiviral (DAA) treatment options for HCV GT 3 infection after the historical standard of care with pegylated interferon and ribavirin. Our objective was to review the SVR rates with available and late-pipeline DAAs for HCV GT 3 infection and discuss challenges with successful GT 3 treatment. Authors performed a literature search of the PubMed/MEDLINE database (inception to March 27, 2017) and narrowed the field to clinical trials published in English. Trials that evaluated alternative treatments, non-DAA historical treatment, and DAAs not currently indicated for HCV were excluded. Trials only involving patients with human immunodeficiency virus/HCV coinfection were also excluded. Additional trials were identified from a review of the ClinicalTrials.gov database. Authors further identified references from a review of literature citations and reviewed annual meeting abstracts from the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver for pipeline and real-world GT 3 data. Phase III trial data were not available to support all GT 3 treatment recommendations found in the guidelines. The SVR rates were lower in treatment-experienced and cirrhotic patients with GT 3 than other HCV populations. Treatment failure was associated with resistance to current treatment regimens. Clinical studies included patients with various levels of advanced liver disease, but few patients with decompensated cirrhosis were represented. Recent advances in pharmacologic treatment with DAAs have greatly increased SVR rates in patients with all HCV GTs, but SVR rates for treatment-experienced cirrhotic patients with GT 3 are lower than for other GTs. Given the limited data and observed SVR rates in this patient population, the optimal therapy for patients with decompensated cirrhotic GT 3 HCV infection is not yet established. Newer agents and recommendations regarding baseline resistance are likely to evolve treatment strategies in the near future.

Elbasvir/Grazoprevir Use in Postliver Transplantation Patients on Hemodialysis.

BACKGROUND: Current national hepatitis C virus (HCV) guidelines do not recommend the use of elbasvir (EBR)/grazoprevir (GZR) in postliver transplantation (LT) patients due to drug-drug interactions with immunosuppression agents. However, recommendations do not address the treatment of HCV in renally impaired post-LT patients. Treatment regimens that are recommended for post-LT patients are not safe in patients with severe renal impairment and patients on dialysis. EBR/GZR is approved for use in patients with renal impairment and patients on dialysis, but not in the post-LT setting. METHODS: Authors reviewed the electronic medical records of 3 treatment-naive HCV genotype 1a male post-LT patients on hemodialysis who were treated with EBR/GZR with or without ribavirin for 12 or 16 weeks. RESULTS: No patients had serious adverse drug events during treatment and no patients stopped treatment early or died. Providers monitored immunosuppression levels; both patients who were taking tacrolimus required immunosuppression dose adjustments during HCV treatment. No patients experienced organ rejection. All patients achieved sustained virologic response. CONCLUSIONS: Current HCV guidelines do not address the treatment options for post-LT patients with severe renal impairment or who are on dialysis, nor do published accounts of use of EBR/GZR in this patient population exist. Clinicians may benefit from exposure to real-world cases of HCV treatment in this historically difficult-to-cure patient population. Providers must address drug-drug interactions with EBR/GZR and monitor for changes in immunosuppression levels to ensure safety with its use in post-LT patients.

Genotype 1 hepatitis C virus and the pharmacist's role in treatment.

PURPOSE: The treatment of hepatitis C virus (HCV) genotype 1 has changed rapidly with recently approved direct-acting antiviral (DAA) regimens. The role of the pharmacist in the management of HCV therapy has increased. SUMMARY: Chronic HCV infection is the main cause of end-stage liver disease and the primary reason for liver transplantation, liver-related death, and hepatocellular carcinoma in the United States. The recent approval of several DAAs has led to improved tolerability, sustained virological response (SVR) rates, and shorter treatment durations compared with treatment with pegylated interferon and ribavirin. Most HCV cases can be treated with the currently available regimens, and expected SVR rates exceed 90%. Several fixed-dose and pangenotypic antiviral regimens are currently in various phases of clinical trials. Pharmacists are well equipped to assist the medical team and patients with comprehensive management of HCV treatment. Pharmacists in various settings can play an instrumental role in access to HCV medications, selection of HCV treatment, detection of drug-drug interactions, and education of patients about potential adverse effects and the importance of adherence and laboratory test monitoring during HCV treatment. However, the high cost of HCV treatment poses challenges for ubiquitous treatment. CONCLUSION: Available DAA regimens have improved HCV treatment outcomes and are selected based on efficacy, potential drug interactions, and the patient's ability to obtain medication coverage. Each of these factors provides an opportunity for pharmacist involvement in HCV management.

Satisfaction With Medication Therapy Management Services at a University Ambulatory Care Clinic.

A survey was issued to patients enrolled in the Medication Therapy Management Clinic (MTMC) at University of Illinois Hospital and Health Sciences (June 2011-January 2012) in order to assess satisfaction with pharmacy services provided by pharmacists. A 23-item survey was offered to 65 patients in the MTMC program before or after clinic visits. Since there is a paucity of data indicating the level of satisfaction with MTM services provided by pharmacists, this survey may contribute to the process of building a greater collaboration between the pharmacist and patient. Sixty-two of 65 patients completed the survey; satisfaction with MTMC pharmacists was demonstrated to be significantly positively correlated with overall satisfaction with the MTMC. Patient satisfaction is not significantly different according to age, gender, ethnicity, or number of disease states. Satisfaction with the pillbox service is not significantly different between younger and older patients. It was also noted that patients taking a greater number of medications had higher levels of satisfaction. Most patients indicated that they were satisfied with the MTMC pharmacists and services; further study linking patient satisfaction with MTM services to improved patient outcomes may allow our MTMC to serve as a model for other pharmacist-managed MTMCs serving similar patient populations.

Development of a specialty medication prior-authorization service at an urban academic medical center.

PURPOSE: The project in which a clinical pharmacist enlisted the help of pharmacy students to create a team responsible for prior-authorization (PA) paperwork associated with hepatitis C virus (HCV) infection treatment is described. SUMMARY: Many insurance companies require completion of a time-consuming PA process for approval of high-cost specialty medications, such as those used in the treatment of HCV infection. A clinical pharmacist at an urban academic medical center recruited pharmacy students to assist with and streamline the HCV medication PA process. After training, the students developed a protocol to increase the efficiency of completing PA requests, appealing denials, obtaining PA extensions, and documenting progress in the electronic medical record to ensure continuity of care. The PA team collaborated with clinicians to document proof of medical need and worked with insurers, pharmacies, and patients to achieve timely approval and receipt of medications. From June 2014 to March 2015, three students spent 240 hours developing the PA protocol and completing 88 PA requests, with an overall medication approval rate of 87.7%; 18 patients were also referred to medication assistance programs. The PA team's work allowed the clinical pharmacist to spend more time on clinical activities and scholarship, while the students increased their knowledge of HCV disease and HCV-targeted therapies and improved their skills in written and verbal communication with patients, providers, and insurance companies. CONCLUSION: Pharmacy students successfully implemented a PA team to manage prescription approval for HCV medications with assistance from a clinical pharmacist.

Therapeutic Advances in HCV Genotype 1 Infection: Insights from the Society of Infectious Diseases Pharmacists.

Hepatitis C virus (HCV) is the most common blood-borne infection in the United States. The high morbidity and mortality due to untreated infection have prompted updated screening recommendations that now include one-time HCV screening for all patients born between 1945 and 1965, in addition to risk factor-based screening. Current guidelines recommend treatment for all patients with chronic HCV. Treatment for HCV genotype 1 has evolved dramatically since the approval of the direct-acting antivirals. The approval of ledipasvir-sofosbuvir, ombitasvir-paritaprevir-ritonavir and dasabuvir, and simeprevir with sofosbuvir has dramatically altered the treatment landscape. High sustained virologic response (SVR) rates favor treatment, yet access to care poses a challenge for patients and providers. Current and emerging data with new therapies indicate high SVR rates in treatment-naïve and treatment-experienced patients, including patients with cirrhosis and in other special populations. Additional data suggest the addition of ribavirin can decrease treatment duration without compromising SVR rates. Resistance is an increasing area of interest in HCV, with baseline mutations identified and the potential for the development of resistance-associate variants in patients undergoing treatment. Due to the rapid evolution of HCV treatment, pharmacists should address challenges and play an integral role in agent selection, dosing, drug interaction screening, adverse effect monitoring, and the coordination of treatment. Clinical application of the latest information will reduce patient risk and improve outcomes.