Stanford
Prevention Policy Modeling Lab
Research Area

Viral Hepatitis

Viral Hepatitis

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

Projects

 

Past Projects

Estimating Acute Viral Hepatitis Infections from Reported Cases

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 in three ways.

  • It upgrades the structural model to a hierarchical framework and includes covariates that can predict variation in each of the three adjustment factors, including probabilities of symptoms, care-seeking, and capture in the surveillance system. 
  • It incorporates time series and stratum-specific estimates of underlying incidence and corresponding case notification data. 
  • It focuses on joint modeling of hepatitis A, B, and C incidence, including ascertainment and reporting, with synthesis of available evidence relevant to each and accounting for shared processes.

Cost-Effectiveness Analysis of Hepatitis B Screening in Various Populations

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 estimates 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

Determining HCV Testing and Treatment Strategies to Eliminate HCV Among People Who Inject Drugs

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 uses 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

Hepatitis C Elimination in a Correctional Jurisdiction

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 focuses on optimizing HCV testing and treatment strategies in jails and the associated clinical and public health benefits of different strategies. This includes 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.

Evaluating SSP and MAT Program Coverage Needed to Reduce HIV and HCV Infections in the United States

PWID are at high risk for multiple bloodborne and sexually transmitted infections, including 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 extends 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, to: 

  • Determine the levels of SSP coverage needed to reduce new HIV and HCV infections among PWID by 25%, 50%, and 90%
  • Compare the population health and economic impacts of different levels of program coverage for opioid use disorder
  • Identify intervention combinations among the different prevention strategies that may produce substantial reductions in HCV and HIV burden among PWID
  • Compare the cost-effectiveness of different intervention packages

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

Hepatitis C Testing and Linkage to Care-Health Department Investment and Potential Savings

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 builds on previous PPML work using the hepatitis C cost-effectiveness simulation model to inform CDC screening guidelines and intervention policies to examine HCV elimination strategies in correctional settings and in the community. This analysis explores a range of different public health strategies that can improve the HCV care cascade, such as enhanced surveillance, expanded screening in key venues (correctional settings, primary care clinics, emergency departments), and integration of programs and services related to the opioid use epidemic. The project evaluates the costs associated with these public health interventions and quantifies the return on investments, in terms of both health and economic outcomes.

Reducing Racial/Ethnic Disparities in Syphilis, TB, Hepatitis C and B in the United States

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 is a cross-cutting project evaluating and quantifying 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. 

Evaluating Interventions to Improve the HBV Cascade of Care

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 collects 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

Cost-Effectiveness of Linking Hepatitis B Patients to Monitoring and Liver Cancer Screening

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

Impact of Global HBV Control Efforts on the Burden of Chronic HBV Infection in the United States

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 assesses 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. 

Cost-Effectiveness of Universal Screening for Hepatitis D Among Adults with Chronic Hepatitis B in the United States

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 aims 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.

Evaluating the Health and Economic Impacts of Reducing Racial and Insurance Disparities in the Hepatitis B Care Cascade

Globally, 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 builds 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 evaluates the impact of reducing racial and insurance disparities in the HBV care cascade to inform policymakers on the impact of efforts to improve equity.

Health and Economic Impact of Universal Hepatitis C Virus Testing and Treatment in Prisons

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, the 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.

Life Years Saved Due to Removing Eligibility Restrictions to Treat Hepatitis C Virus in the United States

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.

The goal of this project is to estimate the years of life that were saved by lowering treatment restrictions between 2013 and 2023.

The Cascade of Care of Chronic Hepatitis B Among Adult Medicaid Beneficiaries in the United States

This project works to understand the cascade of testing, care, and treatment of chronic hepatitis B among Medicaid beneficiaries to inform targeting of interventions. To do so, this project:

  • Analyzes the cascade of testing, care, and treatment of CHB among adult Medicaid beneficiaries in the United States between 2016 and 2021 using the most recent Medicaid claim data 
  • Simulates health outcomes for Medicaid beneficiaries if they received similar levels of follow-up care and treatment as individuals with private insurance

Past Projects

Screening and Treatment for HCV in Correctional Settings

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

Targeting Populations for Routine HCV Screening

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

HCV Screening and Treatment in Community Health Centers

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. 

The strategies differed in three ways:

  • Rapid finger stick vs. venipuncture diagnostics
  • Testing initiated by a physician vs. a dedicated HCV counselor and tester using standing orders
  • Targeted testing of people who inject drugs vs. universal one-time testing

In addition, the analysis expanded to:

  • Assess the optimal frequency of testing among those with known injection drug use
  • Determine the cost-effectiveness of screening when HCV treatment is restricted to those with greater than F2 fibrosis and with at least 12 months of abstinence from substance use
  • Develop a cost-effectiveness tool that allows local jurisdictions around the country to enter a limited number of parameters based on local data to evaluate the clinical benefit and cost-effectiveness of screening in a primary care setting at community health centers

Associated Publications

The Cascade of HCV Care for HCV-infected Pregnant Women and Their Babies

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

HCV Transmission Modeling to Evaluate Long-term Strategies Toward Elimination

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

An End-User Tool to Estimate the Cost of HCV Testing and Treatment for Correctional Settings

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 Publications

Clinical Outcomes and Cost-Effectiveness of Routine HCV Screening in U.S. Prenatal Care Settings

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 Publications