CDC's New Hepatitis C Virus Testing Recommendations for Perinatally Exposed Infants and Children: A Step Towards Hepatitis C Elimination.

New U.S. Centers for Disease Control and Prevention (CDC) guidelines for hepatitis C virus (HCV) testing of perinatally exposed infants and children released in 2023 recommend a nucleic acid test (NAT) for detection of HCV ribonucleic acid (i.e., NAT for HCV RNA) at 2-6 months of age to facilitate early identification and linkage to care for children with perinatally acquired HCV infection. Untreated hepatitis C can lead to cirrhosis, liver cancer, and premature death and is caused by HCV, a blood-borne virus transmitted most often among adults through injection drug use in the United States. Perinatal exposure from a birth parent with HCV infection is the most frequent mode of HCV transmission among infants and children. New HCV infections have been increasing since 2010, with the highest rates of infection among people aged 20-39 years, leading to an increasing prevalence of HCV infection during pregnancy. In 2020, the CDC recommended one-time HCV screening for all adults aged 18 years and older and for all pregnant persons during each pregnancy. Detecting HCV infection during pregnancy is key for the identification of pregnant persons, linkage to care for postpartum treatment, and identification of infants with perinatal exposure for HCV testing. It was previously recommended that children who were exposed to HCV during pregnancy receive an antibody to HCV (anti-HCV) test at 18 months of age; however, most children were lost to follow-up before testing occurred, leaving children with perinatal infection undiagnosed. The new strategy of testing perinatally exposed children at age 2-6 months was found to be cost-effective in increasing the identification of infants who might develop chronic hepatitis C. This report describes the current perinatal HCV testing recommendations and how they advance national hepatitis C elimination efforts by improving the health of pregnant and postpartum people and their children.

Advancing Diagnosis of Current Hepatitis C Virus Infection: A Key to Hepatitis C Elimination in the United States.

More than 2 million adults have hepatitis C virus (HCV) infection in the United States, and new infections continue to increase. Without treatment, HCV infection can lead to advanced liver disease and death. Treatment is recommended for nearly everyone with hepatitis C, resulting in a cure in >95% of people treated and raising the possibility of hepatitis C elimination. Testing is the first step to accessing life-saving treatment. The Centers for Disease Control and Prevention recommends hepatitis C screening for all adults, all pregnant persons, and anyone with risk; yet about one-third of people with hepatitis C remain unaware of their infection. Testing begins with a hepatitis C antibody test, followed, when reactive, by a nucleic acid test to detect HCV RNA. This antibody-first, 2-step testing strategy misses early infections and can result in incomplete diagnoses. Advancements in hepatitis C diagnostics and the US regulatory landscape have created an opportunity to include viral-first testing strategies and improve hepatitis C diagnosis. This journal supplement features 8 articles detailing challenges and opportunities for improving hepatitis C diagnostics in support of advancing hepatitis C elimination in the United States.

Birth Outcomes Among People with Hepatitis C in Pregnancy - Three U.S. States, 2018-2021.

INTRODUCTION: There are limited and conflicting data regarding the impact of hepatitis C in pregnancy on adverse birth outcomes. METHODS: Using the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET), a large surveillance cohort, we describe birth outcomes among a cohort of people with HCV in pregnancy in total and by reported substance use. RESULTS: Among 1418 infants, 89% were born to people with reported substance use during pregnancy. The proportion born preterm was 20%, 13% were small-for-gestational age and 34% of term infants required intensive care. CONCLUSIONS: Assessments of recent changes to recommendations for HCV screening in pregnancy should evaluate the impact on maternal access to care for both HCV treatment as well as comorbidities such as substance use disorder which may contribute to adverse birth outcomes.

CDC Recommendations for Hepatitis C Testing Among Perinatally Exposed Infants and Children - United States, 2023.

The elimination of hepatitis C is a national priority (https://www.hhs.gov/sites/default/files/Viral-Hepatitis-National-Strategic-Plan-2021-2025.pdf). During 2010-2021, hepatitis C virus (HCV) acute and chronic infections (hereinafter referred to as HCV infections) increased in the United States, consequences of which include cirrhosis, liver cancer, and death. Rates of acute infections more than tripled among reproductive-aged persons during this time (from 0.8 to 2.5 per 100,000 population among persons aged 20-29 years and from 0.6 to 3.5 among persons aged 30-39 years). Because acute HCV infection can lead to chronic infection, this has resulted in increasing rates of HCV infections during pregnancy. Approximately 6%-7% of perinatally exposed (i.e., exposed during pregnancy or delivery) infants and children will acquire HCV infection. Curative direct-acting antiviral therapy is approved by the Food and Drug Administration for persons aged ≥3 years. However, many perinatally infected children are not tested or linked to care. In 2020, because of continued increases in HCV infections in the United States, CDC released universal screening recommendations for adults, which included recommendations for screening for pregnant persons during each pregnancy (Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC recommendations for hepatitis C screening among adults-United States, 2020. MMWR Recomm Rep 2020;69[No. RR-2]:1-17). This report introduces four new CDC recommendations: 1) HCV testing of all perinatally exposed infants with a nucleic acid test (NAT) for detection of HCV RNA at age 2-6 months; 2) consultation with a health care provider with expertise in pediatric hepatitis C management for all infants and children with detectable HCV RNA; 3) perinatally exposed infants and children with an undetectable HCV RNA result at or after age 2 months do not require further follow-up unless clinically warranted; and 4) a NAT for HCV RNA is recommended for perinatally exposed infants and children aged 7-17 months who previously have not been tested, and a hepatitis C virus antibody (anti-HCV) test followed by a reflex NAT for HCV RNA (when anti-HCV is reactive) is recommended for perinatally exposed children aged ≥18 months who previously have not been tested. Proper identification of perinatally infected children, referral to care, and curative treatment are critical to achieving the goal of hepatitis C elimination.

Testing for Hepatitis C During Pregnancy Among Persons With Medicaid and Commercial Insurance: Cohort Study.

BACKGROUND: The reported incidence of acute hepatitis C virus (HCV) infection is increasing among persons of childbearing age in the United States. Infants born to pregnant persons with HCV infection are at risk for perinatal HCV acquisition. In 2020, the United States Preventive Services Task Force and Centers for Disease Control and Prevention recommended that all pregnant persons be screened during each pregnancy for hepatitis C. However, there are limited data on trends in hepatitis C testing during pregnancy. OBJECTIVE: We estimated hepatitis C testing rates in a large cohort of patients with Medicaid and commercial insurance who gave birth during 2015-2019 and described demographic and risk-based factors associated with testing. METHODS: Medicaid and commercial insurance claims for patients aged 15-44 years and who gave birth between 2015 and 2019 were included. Birth claims were identified using procedure and diagnosis codes for vaginal or cesarean delivery. Hepatitis C testing was defined as an insurance claim during the 42 weeks before delivery. Testing rates were calculated among patients who delivered and among the subset of patients who were continuously enrolled for 42 weeks before delivery. We also compared the timing of testing relative to delivery among patients with commercial or Medicaid insurance. Multivariable logistic regression was used to identify factors associated with testing. RESULTS: Among 1,142,770 Medicaid patients and 1,207,132 commercially insured patients, 175,223 (15.3%) and 221,436 (18.3%) were tested for hepatitis C during pregnancy, respectively. Testing rates were 89,730 (21.8%) and 187,819 (21.9%) among continuously enrolled Medicaid and commercially insured patients, respectively. Rates increased from 2015 through 2019 among Medicaid (from 20,758/108,332, 19.2% to 13,971/52,330, 26.8%) and commercially insured patients (from 38,308/211,555, 18.1% to 39,152/139,972, 28%), respectively. Among Medicaid patients, non-Hispanic Black (odds ratio 0.73, 95% CI 0.71-0.74) and Hispanic (odds ratio 0.53, 95% CI 0.51-0.56) race or ethnicity were associated with lower odds of testing. Opioid use disorder, HIV infection, and high-risk pregnancy were associated with higher odds of testing in both Medicaid and commercially insured patients. CONCLUSIONS: Hepatitis C testing during pregnancy increased from 2015 through 2019 among patients with Medicaid and commercial insurance, although tremendous opportunity for improvement remains. Interventions to increase testing among pregnant persons are needed.

Updated Operational Guidance for Implementing CDC's Recommendations on Testing for Hepatitis C Virus Infection.

Current hepatitis C virus (HCV) testing guidance recommends a two-step testing sequence for diagnosis of HCV infection. Performing an HCV RNA test whenever an HCV antibody test is reactive (complete testing) is critical to achieve national HCV elimination goals. When an HCV antibody test is reactive and no HCV RNA test is performed, testing is considered incomplete. Historically, approximately one third of patients have incomplete testing. This update clarifies that all sites performing HCV screening should ensure single-visit sample collection. This approach allows for automatic HCV RNA testing when an HCV antibody test is reactive to avoid incomplete testing. Use of strategies that require multiple visits to collect HCV testing samples should be discontinued. Automatic HCV RNA testing on all HCV antibody reactive samples will increase the percentage of patients with current HCV infection who are linked to care and receive curative antiviral therapy.

Hepatitis C Virus Clearance Cascade - United States, 2013-2022.

Approximately 2.4 million adults were estimated to have hepatitis C virus (HCV) infection in the United States during 2013-2016 (1). Untreated, hepatitis C can lead to advanced liver disease, liver cancer, and death (2). The Viral Hepatitis National Strategic Plan for the United States calls for ≥80% of persons with hepatitis C to achieve viral clearance by 2030 (3). Characterizing the steps that follow a person's progression from testing to viral clearance and subsequent infection (clearance cascade) is critical for monitoring progress toward national elimination goals. Following CDC guidance (4), a simplified national laboratory results-based HCV five-step clearance cascade was developed using longitudinal data from a large national commercial laboratory throughout the decade since highly effective hepatitis C treatments became available. During January 1, 2013-December 31, 2021, a total of 1,719,493 persons were identified as ever having been infected with HCV. During January 1, 2013-December 31, 2022, 88% of those ever infected were classified as having received viral testing; among those who received viral testing, 69% were classified as having initial infection; among those with initial infection, 34% were classified as cured or cleared (treatment-induced or spontaneous); and among those persons, 7% were categorized as having persistent infection or reinfection. Among the 1.0 million persons with evidence of initial infection, approximately one third had evidence of viral clearance (cured or cleared). This simplified national HCV clearance cascade identifies substantial gaps in cure nearly a decade since highly effective direct-acting antiviral (DAA) agents became available and will facilitate the process of monitoring progress toward national elimination goals. It is essential that increased access to diagnosis, treatment, and prevention services for persons with hepatitis C be addressed to prevent progression of disease and ongoing transmission and achieve national hepatitis C elimination goals.

Cost-Effectiveness of Strategies to Identify Children with Perinatally Acquired Hepatitis C Infection.

OBJECTIVE: To determine the optimal testing strategy to identify children with perinatally acquired hepatitis C virus (HCV) infection. STUDY DESIGN: We used a decision-tree framework with a Markov disease progression model to conduct an economic analysis of 4 strategies, based on combinations of type and timing of test: anti-HCV with reflex to HCV RNA at 18 months among children known to be perinatally exposed (ie, baseline comparison strategy); HCV RNA testing at 2-6 months among infants known to be perinatally exposed (test strategy 1); universal anti-HCV with reflex to HCV RNA at 18 months among all children (test strategy 2); and universal HCV RNA testing at 2-6 months among all infants (test strategy 3). We estimated total cost, quality-adjusted life years, and disease sequalae for each strategy. RESULTS: Each of the 3 alternative testing strategies resulted in an increased number of children tested and improved health outcomes. HCV RNA testing at 2-6 months (test strategy 1) was cost-saving and resulted in a population-level difference in cost of $469 671. The 2 universal testing strategies resulted in an increase in quality-adjusted life years and an increase in total costs. CONCLUSIONS: Testing of perinatally exposed infants at age 2-6 months with a single HCV RNA test will reduce costs and improve health outcomes, preventing morbidity and mortality associated with complications from perinatal HCV infections.

Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023.

Chronic hepatitis B virus (HBV) infection can lead to substantial morbidity and mortality. Although treatment is not considered curative, antiviral treatment, monitoring, and liver cancer surveillance can reduce morbidity and mortality. Effective vaccines to prevent hepatitis B are available. This report updates and expands CDC's previously published Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection (MMWR Recomm Rep 2008;57[No. RR-8]) regarding screening for HBV infection in the United States. New recommendations include hepatitis B screening using three laboratory tests at least once during a lifetime for adults aged ≥18 years. The report also expands risk-based testing recommendations to include the following populations, activities, exposures, or conditions associated with increased risk for HBV infection: persons incarcerated or formerly incarcerated in a jail, prison, or other detention setting; persons with a history of sexually transmitted infections or multiple sex partners; and persons with a history of hepatitis C virus infection. In addition, to provide increased access to testing, anyone who requests HBV testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.

Timing of Positive Hepatitis C Virus Test Results During and 1 Year Before Pregnancy.

The incidence of hepatitis C virus (HCV) infection in reproductive-aged adults quadrupled during the past decade. Hepatitis C can progress to advanced liver disease and be transmitted perinatally. Highly effective curative hepatitis C treatment is available but is not recommended in pregnancy. Using the Surveillance for Emerging Threats to Mothers and Babies Network, we describe timing of positive RNA testing among pregnant people with HCV (HCV RNA detected during or within one year prior to pregnancy). Four US jurisdictions reported 1161 pregnancies during 2018-2021 among people with hepatitis C: 75.9% were multiparous; and 21.4% had their first peri-pregnancy HCV RNA detected prior to pregnancy, indicating potential missed treatment opportunities to improve maternal health and prevent perinatal transmission.

Widespread Hepatitis A Outbreaks Associated with Person-to-Person Transmission - United States, 2016-2020.

Hepatitis A is a vaccine-preventable disease typically acquired through fecal-oral transmission. Hepatitis A virus (HAV) infection rates in the United States declined approximately 97% during 1995-2015 after the introduction and widespread pediatric use of hepatitis A vaccines (1). Since 2016, hepatitis A outbreaks have been reported in 37 states, involving approximately 44,650 cases, 27,250 hospitalizations, and 415 deaths as of September 23, 2022 (2). A report describing early outbreaks in four states during 2017 noted that most infections occurred among persons reporting injection or noninjection drug use or experiencing homelessness; this finding signaled a shift in HAV infection epidemiology from point-source outbreaks associated with contaminated food to large community outbreaks associated with person-to-person transmission (3). CDC analyzed interim data from 33 outbreak-affected states to characterize demographic, risk factor, and clinical outcome data from 37,553 outbreak-associated hepatitis A cases reported during August 1, 2016-December 31, 2020. Among persons with available risk factor or clinical outcome information, 56% reported drug use, 14% reported experiencing homelessness, and 61% had been hospitalized; 380 outbreak-associated deaths were reported. The most effective means to prevent and control hepatitis A outbreaks is through hepatitis A vaccination, particularly for persons at increased risk for HAV infection (4). The epidemiologic shifts identified during these outbreaks led to a 2019 recommendation by the Advisory Committee on Immunization Practices (ACIP) for vaccination of persons experiencing homelessness and reinforcement of existing vaccination recommendations for persons who use drugs (4). Substantial progress in the prevention and control of hepatitis A has been made; the number of outbreak-affected states has been reduced from 37 to 13 (2). Increased hepatitis A vaccination coverage, particularly through implementation of successful, nontraditional vaccination strategies among disproportionately affected populations (5), is needed to continue progress in halting current outbreaks and preventing similar outbreaks in the future.

Vital Signs: Hepatitis C Treatment Among Insured Adults - United States, 2019-2020.

INTRODUCTION: Over 2 million adults in the United States have hepatitis C virus (HCV) infection, and it contributes to approximately 14,000 deaths a year. Eight to 12 weeks of highly effective direct-acting antiviral (DAA) treatment, which can cure ≥95% of cases, is recommended for persons with hepatitis C. METHODS: Data from HealthVerity, an administrative claims and encounters database, were used to construct a cohort of adults aged 18-69 years with HCV infection diagnosed during January 30, 2019-October 31, 2020, who were continuously enrolled in insurance for ≥60 days before and ≥360 days after diagnosis (47,687). Multivariable logistic regression was used to assess the association between initiation of DAA treatment and sex, age, race, payor, and Medicaid restriction status; adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The prevalence of DAA treatment initiation within 360 days of the first positive HCV RNA test result among Medicaid, Medicare, and private insurance recipients was 23%, 28%, and 35%, respectively; among those treated, 75%, 77%, and 84%, respectively, initiated treatment within 180 days of diagnosis. Adjusted odds of treatment initiation were lower among those with Medicaid (aOR = 0.54; 95% CI = 0.51-0.57) and Medicare (aOR = 0.62; 95% CI = 0.56-0.68) than among those with private insurance. After adjusting for insurance type, treatment initiation was lowest among adults aged 18-29 and 30-39 years with Medicaid or private insurance, compared with those aged 50-59 years. Among Medicaid recipients, lower odds of treatment initiation were found among persons in states with Medicaid treatment restrictions (aOR = 0.77; 95% CI = 0.74-0.81) than among those in states without restrictions, and among persons whose race was coded as Black or African American (Black) (aOR = 0.93; 95% CI = 0.88-0.99) or other race (aOR = 0.73; 95% CI = 0.62-0.88) than those whose race was coded as White. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Few insured persons with diagnosed hepatitis C receive timely DAA treatment, and disparities in treatment exist. Unrestricted access to timely DAA treatment is critical to reducing viral hepatitis-related mortality, disparities, and transmission. Treatment saves lives, prevents transmission, and is cost saving.

Hepatitis C Virus Testing During Pregnancy After Universal Screening Recommendations.

The study evaluates the effect of the 2020 Centers for Disease Control and Prevention and U.S. Preventive Services Task Force recommendations on hepatitis C virus (HCV) screening among pregnant persons nationally and by health insurance type. The study included 5,048,428 pregnant persons aged 15-44 years with either Medicaid or commercial health insurance who had obstetric panel testing performed by Quest Diagnostics, January 2011-June 2021. Antibody screening for HCV infection increased before and accelerated after the updated recommendations in early 2020. Disparities in HCV testing by health insurance status were substantial over the entire study period. Despite substantial progress in the proportion of pregnant persons screened for HCV infection, current testing rates fall short of universal recommendations.

Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

Hepatitis B (HepB) vaccines have demonstrated safety, immunogenicity, and efficacy during the past 4 decades (1,2). However, vaccination coverage among adults has been suboptimal, limiting further reduction in hepatitis B virus (HBV) infections in the United States. This Advisory Committee on Immunization Practices (ACIP) recommendation expands the indicated age range for universal HepB vaccination to now include adults aged 19-59 years. Removing the risk factor assessment previously recommended to determine vaccine eligibility in this adult age group (2) could increase vaccination coverage and decrease hepatitis B cases.

Individual, community, and structural factors associated with linkage to HIV care among people diagnosed with HIV in Tennessee.

OBJECTIVE: We assessed trends and identified individual- and county-level factors associated with individual linkage to HIV care in Tennessee (TN). METHODS: TN residents diagnosed with HIV from 2012-2016 were included in the analysis (n = 3,751). Individuals were assigned county-level factors based on county of residence at the time of diagnosis. Linkage was defined by the first CD4 or HIV RNA test date after HIV diagnosis. We used modified Poisson regression to estimate probability of 30-day linkage to care at the individual-level and the contribution of individual and county-level factors to this outcome. RESULTS: Both MSM (aRR 1.23, 95%CI 0.98-1.55) and women who reported heterosexual sex risk factors (aRR 1.39, 95%CI 1.18-1.65) were more likely to link to care within 30-days than heterosexual males. Non-Hispanic Black individuals had poorer linkage than White individuals (aRR 0.77, 95%CI 0.71-0.83). County-level mentally unhealthy days were negatively associated with linkage (aRR 0.63, 95%CI: 0.40-0.99). CONCLUSIONS: Racial disparities in linkage to care persist at both individual and county levels, even when adjusting for county-level social determinants of health. These findings suggest a need for structural interventions to address both structural racism and mental health needs to improve linkage to care and minimize racial disparities in HIV outcomes.

Who Is Not Linking to HIV Care in Tennessee - the Benefits of an Intersectional Approach.

INTRODUCTION: Guided by an intersectional approach, we assessed the association between social categories (individual and combined) on time to linkage to HIV care in Tennessee. METHODS: Tennessee residents diagnosed with HIV from 2012-2016 were included in the analysis (n=3750). Linkage was defined by the first CD4 or HIV RNA test date after HIV diagnosis. We used Cox proportional hazards models to assess the association of time to linkage with individual-level variables. We modeled interactions between race, age, gender, and HIV acquisition risk factor (RF), to understand how these variables jointly influence linkage to care. RESULTS: Age, race, and gender/RF weAima A. Ahonkhaire strong individual (p < 0.001 for each) and joint predictors of time to linkage to HIV care (p < 0.001 for interaction). Older individuals were more likely to link to care (aHR comparing 40 vs. 30 years, 1.20, 95%CI 1.11-1.29). Blacks were less likely to link to care than Whites (aHR= 0.73, 95% CI: 0.67-0.79). Men who have sex with men (MSM) (aHR = 1.18, 95%CI: 1.03-1.34) and heterosexually active females (females) (aHR = 1.32, 95%CI: 1.14-1.53) were more likely to link to care than heterosexually active males. The three-way interaction between age, race, and gender/RF showed that Black males overall and young, heterosexually active Black males in particular were least likely to establish care. CONCLUSIONS: Racial disparities persist in establishing HIV care in Tennessee, but data highlighting the combined influence of age, race, gender, and sexual orientation suggest that heterosexually active Black males should be an important focus of targeted interventions for linkage to HIV care.

Using Public Health Surveillance Data to Determine Hepatitis C Virus Exposure Among Live-Born Infants in Tennessee, 2013-2017.

OBJECTIVE: Maternal hepatitis C virus (HCV) infection reported on birth certificates has been shown to underestimate HCV infection. We sought to determine the usefulness of HCV surveillance data for (1) quantifying the number of HCV-positive reproductive-aged women with a live birth, (2) comparing maternal HCV surveillance data with reported HCV infection status on birth certificates, and (3) delineating past versus current maternal infection to identify true perinatal exposures. METHODS: We extracted data from January 1, 2013, through December 31, 2017, on birth certificate indication of HCV exposure from the Tennessee Birth Statistical File, and we ascertained indication of HCV exposure by using laboratory data from the Tennessee National Electronic Disease Surveillance System (NEDSS) Base System (NBS). We conducted a sensitivity analysis comparing birth certificate indication of HCV exposure with HCV laboratory data to determine whether true perinatal exposure had occurred. RESULTS: During the study period, 6731 mothers with live births in Tennessee reported having HCV infection during pregnancy: 3295 (49.0%) had both laboratory and birth certificate indication of HCV infection, 2130 (31.6%) had indication of HCV infection on the laboratory report only, and 1306 (19.4%) had indication of HCV infection on the birth certificate only. CONCLUSIONS: Using data from a public health HCV surveillance system with birth certificate data may improve the identification of HCV-infected pregnant women and perinatally exposed infants. Surveillance systems that include complete reporting of all HCV RNA results can be used to distinguish past from present maternal HCV infection to focus limited public health resources on currently infected mothers and their exposed infants.