NEEMA Funded Projects by Topic Area - Viral Hepatitis

The Advisory Committee on Immunization Practices (ACIP) currently recommends that infants born to Hepatitis B-infected mothers, i.e. those who test positive for the Hepatitis B surface antigen (HBsAg), should receive a single-antigen Hepatitis B vaccine and Hepatitis B Immune Globulin (HBIG) ≤ 12 hours of birth, followed by a completion of the vaccination series (second dose at 1-2 months, and third dose at 6 months). Post-vaccination serologic testing on these infants at 9-18 months should identify unprotected infants (anti-HBs levels are <10 mIU/mL) who need to be revaccinated. Current ACIP recommendations for revaccination are to administer another complete 3-dose series followed by post-vaccination serologic testing 1-2 months after the final vaccine dose. Single-dose revaccination has the potential to conserve public health resources by shortening the duration of case management and avoiding unnecessary vaccination. However, the cost-effectiveness of single-dose revaccination in these infants is unknown. In order to address this issue, an analytical decision tree model will be constructed that considers both intended and unintended consequences of each competing decision (e.g. achieving protective levels of anti-HBs vs. failing to achieve protective levels of anti-HBs, developing side effects such as a severe allergic reaction or unusual muscle weakness vs. not developing side effects, getting infected with HBV vs. not getting infected, receiving treatment vs. not receiving treatment, etc.), where associated probabilities and costs will be extracted from the existing literature.

Hepatitis C infection (HCV) is a significant source of morbidity and mortality in the United States. The purpose of this multi-year activity is to develop a mathematical modeling framework that could be used to inform the creation of a national elimination strategy and inform local implementation. The first phase of this effort has sought to clarify definitions and expectations for the forthcoming model development, through key personnel interviews, literature reviews of existing modeling efforts and HCV control activities, in order to identify existing sources of data and data gaps.

Following the 2005 recommendation, vaccinations for HAV increased dramatically for those individuals indicated by the recommendation. However, pockets of unimmunized individuals remain, including individuals born prior to 1997 in the 11 states where HAV was twice the national average, and individuals born prior to 2004 in intermediate and low incidence areas. In this project, a previous economic model of HAV was used to assess the cost-effectiveness of catch-up vaccination campaigns in specific young age groups.

Amid concern over the rapid growth in hepatitis C (HCV) treatment costs, a fundamental issue often overlooked is the cost of not treating HCV. This project serves to estimate the currently unknown economic burden of HCV on the US economy, information that is vital to frame the debate over cost and economic considerations of HCV-related public policy. While understanding the total economic burden of HCV provides important background information for future policy considerations, such an analysis can inform specific policy concerns, such as insurance coverage (including underinsured patients) and varying costs by insurance plan, out-of-pocket costs, and costs that might be averted through treatment. This analysis seeks answers to these questions by estimating the total economic burden of HCV by cost category, by payer, and by patient type.

Prior cost-effectiveness studies concluded HCV treatment could be safely delayed for patients with limited fibrosis, but this result depends upon an assumption of annual biopsy and progression of liver disease from one stage to the next one year at a time. These assumptions are not applicable to clinical settings where progression is monitored using serologic markers such as AST to Platelet Ratio (APRI) or FIB-4. Because many clinicians are relying on non-invasive methods to stage liver disease, we will use EHR data to predict the potential health impacts of hepatitis c (HCV) treatment delay when (APRI) is used to monitor progression.

State-level estimates of prevalence of chronic HCV infection are critical to understanding variation in HCV burden in the United States, and to informing local prevention, treatment, and advocacy efforts. This project is using statistical modeling approaches to synthesize CDC surveillance, census, and other data sources to yield the first systematic estimates of HCV prevalence for each US state and the District of Columbia.

In the era of highly effective oral therapy for HCV, the most cost effective strategy for screening and testing is unknown. This project is exploring the impact and cost-effectiveness of expanding HCV screening recommendations to include the population at large, risk-targeted populations, and settings of differing HCV prevalence. The Hepatitis C Cost-Effectiveness (HEP-CE) Model will be used to compare the current standard of care (screening the US baby boomer cohort) to one-time routine screening strategies by age: age 50 and older (essentially the boomer cohort without an upper age limit), age 40 and older, age 30 and older, and age 20 and older. The goal of this analysis is to determine the threshold of HCV prevalence and/or incidence above which routine screening becomes cost-effective in these key populations. In connection with analysis of alternative options for routine screening, strategies for repeat targeted testing for high-risk populations will also be investigated.

High HCV case rates have been reported in primary care settings such as community health centers in underserved communities. The clinical benefit and cost-effectiveness of screening strategies in primary care in community health centers will be evaluated. This project aims to inform health policy and clinical guidelines by investigating the cost-effectiveness of screening for HCV in community health settings. The HEP-CE model will be used to project QUALYs, life-time costs, and incremental cost-effectiveness ratios associated with 8 screening strategies. The strategies will differ in three ways: 1) Rapid finger stick vs. venipuncture diagnostics; 2) Ordered by physician vs/ counselor/tested using standard orders; 3) Targeted testing of PWID vs. routine one-time testing. All rapid testing results will be available during the visit. The influence of reflex testing, linkage to care strategies such as patient navigation, and insurance claims assistance will also be evaluated. The analysis will be expanded in three ways: 1) Assess optimal frequency of testing among those with known injection drug use; 2) Determine cost-effectiveness of screening when HCV treatment is restricted to those with greater than F2 fibrosis an with at least 12 months of abstinence from substance use; 3) Develop a cost-effectiveness tool that will allow local jurisdictions around the country to enter limited number of parameters based on local data to evaluate the clinical benefit and cost-effectiveness of screening in primary care setting at community health centers.

With the advent of highly effective HCV treatments, there is rising interest in comparative evaluation of strategies that combine HCV prevention, testing, linkage to care, and treatment, toward the end of eventual elimination in the US, motivated by the aim of “getting to zero.” A range of simulation models have been used to examine different HCV policies. Many models have used relatively simple designs and assumptions relating to transmission dynamics, making them poorly suited to estimating treatment effects on incidence; or they have included more detailed characterizations of networks of drug users but adopted relatively short time horizons and limited detail relevant to HCV testing, linkage, and treatment. An integrated model will be developed that combines the advantages of these two distinct emphases in comparable models, operationalized as an agent-based simulation model of a network of injection drug users, linked to our existing simulation of HCV testing, linkage to care, and treatment.

This project aims to estimate the clinical outcomes and budgetary impact of testing for and treating HCV in correctional settings. The Hepatitis C Cost-Effectiveness (HEP-CE) Model will be modified to compare alternative HCV screening and treatment strategies in incarcerated populations, including separate analyses for prisons and jails. Building on the existing model structure that accommodates the epidemiology, natural history and cascade of care associated with chronic HCV infection, the structure will be augmented to incorporate movements in and out of correctional facilities. The model will capture the particular circumstances in specific correctional facilities, as well as to provide a more generalizable framework for comparative evaluation of policies in a range of different settings.

HCV is vertically transmitted from mother to child with an incidence of neonatal HCV infection of 2-5%. Antenatal and perinatal care settings provide a venue to identify HCV-infected mothers and their HCV exposed infants and an opportunity to link them all to care before they are lost to follow-up. A model will be developed that includes the long-term outcomes and costs of programs to identify and link HCV-infected pregnant women and their infants to HCV care. A first step toward that goal is understanding the current cascade of HCV care in the US Boston Medical Center has one of the largest programs in the US for opiate addicted pregnant women and their babies. The Neonatal Addiction Service Project RESPECT maintains an EMR-based registry of over 1100 mother-baby dyads. The data include longitudinal follow-up of all laboratory results and clinic visits. The RESPECT database will be used to investigate and report follow-up along the HCV cascade of care for HCV-infected opiate addicted mothers and their babies.

The most recent NHANES indicates the prevalence of HBV to be 0.3% (0.2%‐0.4%) or 847,000, of which 400,000 were non‐Hispanic Asians. Other evidence suggests that this may drastically underestimated the true prevalence as many HBV‐infected are unaware of their positive status. Foreign born residents account for 47% to 70% of the chronic hepatitis B cases. This project will model the impact, cost, and cost‐effectiveness of a scaled‐up program to control this important disease in the U.S. Individual populations, targeting strategies, and interventions will be the initial focus. Then, these separate analyses will be integrated into a model of a coherent, comprehensive HBV control strategy, taking into account the size of populations needing interventions, the effectiveness and cost of recruitment strategies for the relevant risk populations, the effects of vaccination and treatment, and the aggregate costs and impact of intervening. Data will be obtained on the sizes and geographic concentrations of the populations at risk of HBV and systematically review the effectiveness and cost of recruitment strategies for these populations, in terms of attrition from identification to recruitment, testing, and treatment. The compartmental simulation model will portray the overall health impact and cost of a scaled‐up national HBV strategy. It will portray results for programs at several different scales, defined by percent of population tested and the relative proportions of the important risk populations. It will also calculate annual cost and benefits, overall and by payer, given various targets and time horizons for scale‐up.

A cost-effectiveness model for testing and treating hepatitis B infection in resource poor settings in the United States will be created. Specifically the modelers will specify target strategies by prevalence and setting; design and implement a new cost-effectiveness model; obtain data inputs, including prevalence, treatment efficacy, and costs; and run base case and sensitivity analyses.

Young PWID are at increased risk of HIV and HCV infection, and drug use is increasing in part due to rising rates of prescription opioid abuse. A coordinated effort is needed to reduce prescription opioid misuse, understand transitions to heroin use and injection, and reduce high risk injection and sex practices in PWID. This project is estimating opioid use over the next 10 years in representative rural and urban settings, estimating HIV and HCV infections, and assessing prevention scenarios to reduce transmission of HIV and HCV by 25%.

This project will address three questions: (1) What strategies are most effective for recruitment of PWID and homeless persons into HIV, HCV, and TB prevention and treatment programs? (2) What portion of PWID and homeless persons not-in-care for HIV, HCV, and TB can be identified with novel (e.g., chain-referral) methods? (3) What is the cost per subject contacted, recruited, tested, and treated by population (PWID, Homeless) and recruitment method?