Stanford
Prevention Policy Modeling Lab

Viral Hepatitis

Research Area

Viral Hepatitis

Click on a project title to learn more about PPML's work in Viral Hepatitis.

Current Projects

Previous efforts toward HCV elimination within state Departments of Corrections have included a combination of guidelines and evidence, as well as legal pressure. To sustain momentum in states where action has been taken and to initiate HCV elimination strategies in other states, it is helpful to estimate, across states, what would be the likely costs and health benefits of universal HCV testing and treatment strategies in prisons. 

Through partnership with California Correctional Health Care Services, this study aims to model health and economic consequences associated with strategies to achieve HCV micro-elimination within California state prisons through the implementation of various interventions, such as universal HCV testing and treatment and substance use disorder treatment.

Directly acting antiviral (DAA) therapies to treat HCV were very expensive when they first came to market. Many state Medicaid programs were concerned that the high cost of HCV treatment could result in fiscal insolvency or inability to provide other urgent healthcare needs. As a result, some states implemented restrictions on who could be treated for HCV in the state Medicaid program. Three of the most common types of treatment restrictions were:

  • Limiting treatment to those with at least a given threshold of fibrosis on biopsy or non-invasive liver staging approach
  • Limiting treatment to those who have demonstrated abstinence from alcohol and/or drugs for a given number of months
  • Limiting the type of provider that could prescribe HCV medications to hepatology and infectious diseases sub-specialists (provider restrictions)

Over time, the HCV drug market become more competitive, and the cost of HCV medications came down. As costs lowered, Medicaid programs around the United States began to gradually loosen treatment restrictions. Each state implemented its own model for treatment restrictions and removed them on its own timeline.

This project estimates the years of life that were saved by lowering treatment restrictions between 2013 and 2023.

Point-of-care (POC) HCV RNA testing is required for diagnosis in non-clinical, high-impact and community-based settings, and to enable single encounter test-and-treat programs. The projected costs of POC HCV RNA testing are currently about twice the cost of POC rapid diagnostic test (RDT) or commercial lab-based HCV antibody testing. Yet, from a societal perspective, investments in POC HCV RNA testing may be cost-effective in settings where high proportions of clients have ongoing risks of infection.

The primary objectives of this project are to assess the cost and cost-effectiveness of POC HCV RNA testing and to model population-level outcomes to estimate the cost-effectiveness of HCV diagnostic approaches among U.S. adults.

Under the National Hepatitis C Elimination Initiative, efforts at state and local health departments would focus on 3 key pillars: 1) prevention, 2) outreach and clinical care, and 3) tracking and response. The prevention role is for health departments to establish a perinatal hepatitis C elimination program. The outreach and clinical care role involves expanding hepatitis C testing and treatment in key populations and high-impact settings and to provide care coordination and navigation for people diagnosed with hepatitis C. Health department roles, around tracking and response, involve strengthening core viral hepatitis surveillance capacity, increasing HCV testing capacity, and expanding outbreak detection and response capabilities.    

This project models the impact of hepatitis C elimination efforts on short-term outputs and longer-term outcomes, with an emphasis on reporting, at the national level.

PPML is supporting an update to the National Vulnerability Assessment for health outcomes associated with injection drug use (IDU). The updated national vulnerability assessment will address the main study question:

  • What factors are associated with unsterile IDU nationally and what areas are most at risk for the negative health outcomes associated with IDU?

PPML will develop and apply a framework for designing and evaluating vulnerability assessments and other surveillance metrics using the analogy of a decision analysis for a diagnostic test. These consequences will highlight the need to connect these assessments and surveillance metrics to specific public health actions that are triggered by positive or negative signals. We have previously developed a related framework and analytic tools for COVID-19 surveillance metrics, which are being adapted for this project in view of the specific assessments and metrics that are the focus.

This project will align the national and state vulnerability assessments to develop a consistent evaluation method.

Hepatitis B mortality has not been decreasing, and it appears that the U.S. will not meet national targets for reducing hepatitis B-related deaths. In this project, we will examine the entire U.S. population with hepatitis B and focus on the impact of applying WHO treatment guidelines to the U.S. population. This project aims to examine the impact of increased diagnosis and treatment of hepatitis B on liver cancer incidence and hepatitis B-related mortality.

This project will utilize simulation modeling to project the potential impact of public health interventions, including screening and treatment on hepatitis B-related mortality in the United States from 2025 through 2035.

Persons who are justice system-involved are more likely to experience risk factors for hepatitis C and sexually transmitted infections (STI), and prevalence of these infections is higher than in the general population. For many incarcerated individuals, correctional health services may be the first or only touchpoint for testing and treatment. CDC recommends comprehensive opt-out testing at intake, treatment for those infected, and linkage to care upon release. Significant barriers exist for facilities to fully implement these recommendations. However, with dedicated resources and leadership support, some state department of corrections, jails, local health departments, and other community services have come together to overcome these barriers and implement successful programs tailored to their local situation.

Successful implementation of the CDC Recommendations for Correctional Settings across the nation could have important impacts on the community prevalence of these diseases and subsequent transmission. Decreasing the prevalence of these diseases among the incarcerated population and their communities could lead to improved population health and economic outcomes as well as safer work environment for correctional staff. Averted costs through reduced transmission could translate to increased funding to support the development and implementation of interventions and strategies to further reduce disparities in health outcomes for incarcerated populations.

This project will estimate the change in hepatitis C and syphilis national prevalence if all U.S. adult jails fully, successfully implemented the CDC Recommendations for Correctional Settings. It also aims to better understand the factors that could increase or decrease the health and economic impact of the CDC Recommendations and their collaboration with health departments.

As health departments face resource constraints and harm reduction services in some areas face social and political pushback, there is a risk of reduced access to these evidence-based services.

The primary goal of this modeling project is to estimate the health and economic consequences of reduced access to and use of SSP and MOUD among people who inject drugs. Utilizing PPML’s previously developed sexual and injection network model, this project will also evaluate the impact of reduced access and use of SSPs and MOUD on HIV and HCV transmission.

Past Projects

Only a fraction of acute hepatitis A, acute hepatitis B, and acute hepatitis C cases are reported through the National Notifiable Disease Surveillance System to CDC. There are several barriers to ascertaining and reporting acute infections, as many people with viral hepatitis:

  • May not develop symptoms
  • May not seek care if they become symptomatic
  • May not be reported to public health authorities if they do receive medical care

Currently, CDC estimates the incidence of viral hepatitis A, B, and C infections using three probabilistic multiplier models. This project updates and improves the methodology used to estimate the incidence of acute viral hepatitis cases.

The most recent CDC hepatitis B virus (HBV) screening recommendations were published in 2008. Since then, additional groups at increased risk have emerged. Cost-effectiveness analyses for hepatitis B testing strategies in populations at increased risk will help inform the next CDC testing recommendations. 

This project estimated the cost-effectiveness of HBV testing in people with a history of or current sexually transmitted infections, a history of or current incarceration, or co-infection with hepatitis C. It also examines the cost-effectiveness of universal screening for people born before 1991, when the universal HBV vaccination recommendation was implemented. For each group, it assesses the cost-effectiveness of different testing algorithms based on various combinations of the three HBV seromarkers, HBsAg, anti-HBs, and anti-HBc.

Associated Publications

CDC and the U.S. Preventive Services Task Force recommend one-time routine hepatitis C virus (HCV) screening for all adults 18 years and older. CDC continues to recommend that people with risk factors be tested regularly, such as people who inject drugs (PWID). However, there is no evidence to inform the optimal testing interval for people at increased risk or the cost and cost-effectiveness of intensive and frequent testing. This project used a previously developed agent-based network model of HCV transmission across injection-drug-using networks to: 

  • Identify the minimum HCV testing frequency needed to achieve HCV elimination among PWID
  • Estimate the cost of such testing and treatment
  • Measure the cost-effectiveness of various testing frequencies

Associated Publications

As an increasing number of states begin to tackle state-wide hepatitis C elimination plans, the success of these initiatives is likely to depend on effectively addressing the high prevalence of HCV infection and its risk factors in correctional populations, including jails and prisons. Previous studies focused on evaluating a range of strategies for HCV testing and treatment in prisons and found that such strategies could provide high value for funds invested. Jails differ from prisons in ways that present logistical and cost challenges for scaling up HCV testing and treatment. Jail sentence durations are typically short, and most people who initiate HCV treatment in jail will need to be linked to a treatment provider in the community upon release. Jails typically do not have available resources to support large-scale HCV treatment or adequate infrastructure for monitoring patients and linking them to community care. 

This project focused on optimizing HCV testing and treatment strategies in jails and the associated clinical and public health benefits of different strategies. This included identifying testing and treatment implementation models that provide good value for the resources invested in scale-up and estimating budgetary impact from the jail perspective.

Persons who inject drugs (PWID) are at high risk for multiple bloodborne and sexually transmitted infections, including hepatitis C virus (HCV) and HIV. National and state-level planning for syringe service programs (SSP) and medication for opioid use disorder (MOUD) relies on the accurate estimation of PWID population size and requires an understanding of how these interventions impact HCV and HIV transmission, in addition to other bloodborne infections. The structure of injection and sexual networks among PWID leads to heterogeneous risks of infection transmission and acquisition. In addition to SSPs and MOUD, many other preventive strategies are available for both HCV and HIV, including biomedical interventions, such as HIV pre-exposure prophylaxis, HIV treatment, HCV treatment, and behavioral interventions, such as promoting safer injection practices and condom use. Interventions can interact and generate synergistic effects on the prevention of HCV and HIV. What determines the optimal intervention package is unknown. 

This project extended PPML’s existing agent-based network model of HCV transmission among PWID by adding the sexual partnership network and transmission dynamics of HIV and other sexually transmitted infections to the existing network of equipment-sharing.

Further expansion of this work integrated detailed clinical and program data from Massachusetts into the agent-based multiplex model and provides insight into specific questions through a partnership with the Massachusetts Department of Public Health.

Moving toward the elimination of HCV infection in the United States will require achieving several targets for the HCV care cascade, such as diagnosing 90% of people living with chronic HCV infection, linking 90% of those diagnosed to care, and treating 80% of those for whom treatment is indicated. 

This project built on previous PPML work using the dynamic network simulation model of HCV transmission through injection equipment sharing to examine strategies for expanding HCV testing and treatment. The analysis compared the health and economic impact of HCV testing expansion in a range of key venues (correctional settings, emergency departments, syringe services programs, opioid treatment programs) and how specific venue features (e.g., percentage of clients who are PWID, access and utilization of the venue among PWID) influence the outcomes to inform decision making on venue utilization for hepatitis C elimination. Additionally, the analysis explores the potential synergy of combining HCV testing and treatment with harm-reduction services.

Despite advances in prevention and treatment, significant disparities exist in rates of sexually transmitted infections (STI), tuberculosis (TB), and viral hepatitis in the United States. Multiple causes, many rooted in social determinants of health, increase risks of exposure, reduce access to preventive services such as testing, and delay linkages to care and treatment for underserved populations. Disparities are expressed in worse health outcomes, and reduced prevention effectiveness also may result in higher care and treatment expenditures. This project evaluated and quantified the potential health and economic impacts of addressing the strategies, goals, and indicators, as defined by the STI, Viral Hepatitis, and TB National Strategic Plans to reduce racial and ethnic disparities.

Limited data and literature describe the cascade of care for HBV infection in the United States. Past studies suggest many people with hepatitis B are not aware of their infection and that those who are eligible are not receiving care and treatment. 

This project collected up-to-date data on the HBV cascade of care and evaluates the cost-effectiveness of improvements. Health system datasets are used to better understand rates, costs, screening, linkage to care, and treatment for those who are eligible. Modeling tools contribute to understanding the current cascade of care for HBV in the United States and evaluate the cost-effectiveness of portfolios of interventions to improve and increase rates of screening, linkage to care, and treatment for those who are eligible.

Associated Publications

Persons who are inactive hepatitis B carriers make up the largest group of persons with chronic hepatitis B virus (CHB) infection. Treatment is not recommended for this group, since there is not enough evidence on whether current antiviral therapy affects HBsAg status in the long-term. Patients transition from inactive to active, becoming eligible for treatment, at a rate of 0.9% – 2.0% annually, depending on their age. Treatment guidelines suggest that inactive CHB should be monitored for ALT and HBV DNA levels. Despite these recommendations, the uptake of lifelong monitoring of ALT and HBV DNA is low. 

This project assessed the cost-effectiveness of a strategy of lifelong monitoring for inactive CHB and treatment of eligible patients in the United States.

Associated Publications

Viral hepatitis is a leading cause of mortality globally with an estimated 1.3 million deaths each year. Most hepatitis-related morbidity and mortality is from CHB infections, affecting an estimated 257 million people worldwide. Childhood hepatitis B vaccination was introduced globally in the 1990s, and coverage reached 84% by 2015. Efforts to accelerate the prevention and treatment of HBV infection globally were made in 2016 with the launch of the Global Health Sector Strategy (GHSS) on viral hepatitis, which calls for the elimination of viral hepatitis as a public health threat by 2030. 

In 2016, nearly 1.2 million people obtained lawful permanent resident status in the United States; approximately 157,000 of whom had refugee/asylee status. This project assessed the impact of preventing and treating HBV infection among immigrants entering the United States to reduce the burden of CHB in the United States and observe potential cost savings for the healthcare system. 

Associated Publication

Hepatitis delta is the most severe form of viral hepatitis, with faster disease progression to cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver-related death. Hepatitis D virus (HDV) needs the hepatitis B surface antigen from HBV to propagate and cause disease. A recent National Health and Nutrition Examination Survey study reported an anti-HDV prevalence of 42% among hepatitis B surface antigen-positive (HBsAg) carriers. Due to the fast disease progression rates and lack of therapy, HDV remains neglected. However, new therapies for HDV may soon become available. The American Association for the Study of Liver Disease recommends testing persons who are HBsAg carriers and at high risk for HDV infection. 

This project aimed to evaluate the estimated effects of universal HDV screening of adult HBsAg-positive persons compared to persons at high-risk (status quo), by calculating costs, quality-adjusted life years, and health outcomes, as well as evaluating potential cost-effectiveness of new therapies.

Associated Publication

Globally, hepatitis B virus (HBV) is most prevalent in Asia and Sub-Saharan Africa; in the United States, HBV disproportionately affects both native and immigrant Asian and Black populations. This project built on previous PPML work to evaluate the HBV care cascade using insurance data, which showed that Asian patients and patients with commercial insurance were more likely to receive monitoring and treatment than other patients. This project evaluated the impact of reducing racial and insurance disparities in the HBV care cascade to inform policymakers on the impact of efforts to improve equity.

There is a high prevalence of HCV in jails and prisons in the United States, but the limited availability and high cost of effective HCV treatments creates a dilemma for departments of corrections. Correctional facilities are constitutionally mandated to provide the “community standard” of medical care, but the cost of treating all HCV-infected patients in a given corrections system could exceed the entire healthcare budget for the system. This double liability has resulted in no clear direction for HCV screening and treatment guidelines.

This project utilized the Hepatitis C Cost-Effectiveness (HEP-CE) Model to compare four HCV screening and three HCV treatment strategies in incarcerated populations, in terms of clinical outcomes, budget impacts, and cost-effectiveness of these interventions. Building on the existing model structure that accommodates the epidemiology, natural history, and cascade of care associated with chronic HCV infection, the structure incorporated movement in and out of correctional facilities. This project provides a more generalizable framework for comparative evaluation of policies in a range of different settings.

Associated Publications

Current guidelines recommend routine HCV screening among individuals born between 1945 and 1964, as routine screening is notably cost-effective given the high HCV prevalence among this population. Yet, there are additional populations with high prevalence and incidence of HCV, but they remain limited in screening coverage and overlooked by current screening guidelines. Youth under the age of 30 have a rising incidence of HCV infection related to the expanding prevalence of injection drug use, but providers often fail to obtain an accurate risk assessment. The population of individuals born in endemic countries but now residing in the United States is also at a higher risk for HCV and should be screened routinely.

This project explored 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.

Associated Publications

High HCV case rates have been reported in primary care settings, such as community health centers in underserved communities. This project investigated the clinical benefits and cost-effectiveness of various models for HCV screening in community health centers, employing the Hepatitis C Cost-Effectiveness (HEP-CE) model to project QALYs, lifetime costs, and incremental cost-effectiveness ratios associated with eight screening strategies. 

Associated Publications

HCV can be vertically transmitted from mother to child, with an incidence of neonatal HCV infection of up to 5%. Antenatal and perinatal care settings provide a venue to identify HCV-infected mothers and their HCV-exposed infants, with an opportunity to link them all to care before they are lost to follow-up.

PPML developed a model to include long-term outcomes and costs of programs to identify and link HCV-infected pregnant women and their infants to HCV care.

Associated Publication

With the advent of highly effective HCV treatments, there is rising interest in the comparative evaluation of strategies that combine HCV prevention, testing, linkage to care, and treatment, toward the end of eventual elimination in the United States. A range of simulation models have been used to examine different HCV policies. PPML developed an integrated model, operationalized as an agent-based simulation model of a network of injection drug users.

Associated Publications

The prevalence of HCV in prisons is high, but the cost of HCV testing and treatment limits access to HCV treatment. Few correctional systems in the United States routinely test for HCV among inmates for fear of generating an unfunded mandate for treating those patients whom they identify as being HCV-infected. Before prisons can realistically plan to expand access to HCV care, they need a better estimate of the cost of doing so. 

PPML utilized its existing simulation of HCV in correctional settings to develop an end-user tool that correctional systems can use to estimate the budgetary impact of HCV testing and treatment in their system.

Associated Publication

The incidence of HCV is rising among those under the age of 40. Efforts to eliminate HCV transmission therefore require strategies to identify and cure infection among younger people. Many women of reproductive age seek routine medical care from their obstetrician and may only contact the care delivery system when they are pregnant and seeking antenatal care, and this setting may be an excellent venue for routine HCV testing.

Although there currently is no means of preventing mother-to-child transmission, identifying HCV-infected mothers and HCV-exposed infants provides an opportunity to link infected women and babies to care and to prevent HCV exposure during future pregnancies. This project developed a decision-analytic model of HCV testing in antenatal care that was used to project clinical outcomes, cost, and cost-effectiveness of routine testing for HCV in antenatal care settings.

Associated Publication