Testing and Screening for the Hepatitis B Virus: Recommendations from the Centers for Disease Control and Prevention (CDC) for the United States in the year 2023 Antiviral treatment, monitoring, and liver cancer surveillance can reduce morbidity and mortality, despite the fact that treatment is not considered curative. There are vaccines for hepatitis B that work. The CDC’s previously published Recommendations for Identification and Public Health Management of People with Chronic Hepatitis B Virus Infection (MMWR Recomm Rep 2008;57[No.]) are updated and expanded in this report. RR-8]) concerning HBV infection screening in the United States. Adults under the age of 18 should be screened for hepatitis B using three laboratory tests at least once in their lifetime. Additionally, the following populations, activities, exposures, or conditions are included in the report’s risk-based testing recommendations for HBV infection: individuals currently or previously detained in a jail, prison, or other detention facility; individuals who have had multiple partners or a history of sexually transmitted infections; and individuals who have a history of hepatitis C infection. Additionally, since many people may be reluctant to disclose stigmatizing risks, anyone who requests HBV testing ought to receive it in order to increase access to testing.
Introduction Compared to the general population, people with chronic hepatitis B virus (HBV) infection are 70%–85% more likely to die young (1–4) and have a higher risk of liver cancer and cirrhosis. In the United States, between 580,000 and 2.4 million people are infected with HBV (5,6), and two thirds of these people may not be aware of their condition. People who were born outside of the United States are disproportionately affected by chronic HBV infection; While non-U.S.-born individuals make up 14% of the general population, 69% of Americans have chronic HBV infection (5–7).
HBV is spread through contact with infected blood or body fluids, such as during pregnancy or delivery, sexual activity, or injection drug use (IDU), with perinatal infection posing the greatest risk for long-term infection (Figure 8) Vaccination against hepatitis B (HepB) is highly effective in preventing HBV infection and liver disease; However, as of 2018, 70% of adults in the United States reported not having been vaccinated. Antiviral treatment, monitoring, and liver cancer surveillance can reduce morbidity and mortality, even though treatment is not considered curative (10,11).
The Viral Hepatitis National Strategic Plan for the United States calls for an increase in the proportion of people with HBV infection who are aware of their infection from 32% (2013–2016) to 90% by 2030 in order to provide a framework for achieving the World Health Organization’s viral hepatitis elimination goals (12,13). This report brings the 2008 CDC recommendations for risk-based testing and treatment of Americans with chronic HBV infection up to date in support of this objective (14). Health care professionals, public health officials, and organizations supporting awareness, prevention, and linkage to care can use this report as a resource to learn who to screen for HBV infection and which groups at risk should be tested regularly (Box 1).
Hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) are the three primary serologic markers used to determine HBV infection status (Table 1). Serologic markers shift over commonplace directions of settled intense disease and movement to constant contamination (Figure 1) (15).
HBsAg: Unless it is temporarily positive shortly after a dose of the HepB vaccine (16), the presence of HBsAg indicates either acute or chronic HBV infection. Chronic infection is defined as having HBsAg for at least six months by the American Association for the Study of Liver Diseases (AASLD).
Anti-HBs: Recovery from HBV infection is indicated by the emergence of anti-HBs antibodies following a decrease in HBsAg. Anti-HBs at concentrations of 10 mIU/mL at 1–2 months after completion of a HepB vaccine series indicate immunity in immunocompetent individuals who have never been infected with HBV. Although some individuals may have anti-HB levels of less than 10 mIU/mL following partial vaccination, it is unknown whether this provides long-term protection. Anti-HB levels can drop to less than 10 mIU/mL over time in vaccine responders who completed a series of vaccinations; be that as it may, the greater part are as yet invulnerable and will mount a safe reaction to an immunization challenge ≥35 years after inoculation (17-20). After administration, hepatitis B immune globulin (HBIG) can provide anti-HBs for four to six months; Therefore, a person’s immune status cannot be accurately assessed by testing for anti-HBs less than six months after receiving HBIGs.
Anti-total HBc: All HBV infections, whether past or present, produce total anti-HBc, which typically lasts a lifetime. Anti-HBc does not occur in people who have a vaccine-induced immunity to HBV. Both immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to HBcAg are found in total anti-HBc assays; There is no commercially available test for IgG anti-HBc alone. Total anti-HBc and HBsAg will typically be present throughout the course of a chronic infection, whereas IgM anti-HBc will vanish (Figure 1). When an acute HBV infection is a concern, IgM anti-HBc should only be ordered.
HBV DNA, HBeAg, and anti-HBe are additional markers: A measure of viral load is HBV DNA. HBeAg is a sign of high infectivity and viral replication; Antibody to HBeAg, or anti-HBe, can be used to track treatment response and the progression of chronic HBV infection. Testing for HBeAg, anti-HBe, and HBV DNA can help guide clinical management and provide information on the level of viral replication and infectivity after identifying a person with HBV infection.
(Supplementary Appendix 1, https://stacks.cdc.gov/view/cdc/124432) There is background information on HBV, including the virus’s description, transmission, clinical features, natural history, and HepB vaccination seroprotection and coverage.
Acute HBV Infection Epidemiology and Risk Factors After accounting for underascertainment and underreporting, an estimated 20,700 new infections (95% CI = 11,800–50,800) were found among the 3,192 cases of acute HBV infection reported to the CDC in 2019. The number of acute HBV infection cases reported in the United States remained relatively stable from 2012 to 2019 (22,23).
There are differences across regions, with Florida, Indiana, Kentucky, Maine, Ohio, Tennessee, and West Virginia reporting the highest rates of cases (2.5 per 100,000 people) in 2019 (23). The national rate of acute HBV infections among women of childbearing age remained stable from 2011 to 2017, but it increased in Alabama, Indiana, and Kentucky (from 0% to 0.3%) (24). The opioid crisis may be the cause of geographic differences in the number of new infections; during 2006-2013, expansions in occurrence instances of intense HBV disease in Kentucky, Tennessee, and West Virginia were among people who detailed IDU as a gamble factor (25).
The overall rate of acute infections that were reported in the United States in 2019 was 1.0 per 100,000 people. Since 2006, there have been fewer than 0.1 cases of acute HBV infections reported per 100,000 people, largely due to routine vaccination of children (23). However, adults continue to transmit HBV infection, particularly among older adults for whom vaccine uptake is suboptimal.
Paces of intense HBV contamination were higher among guys (1.3 per 100,000 populace) than females (0.7) and were most elevated among not Hispanic or Latino (non-Hispanic) White (1.0) people and non-Hispanic Dark people (0.9). 35 percent of the 1,780 case reports that included information about the risk of IUD use reported IUD use (23). 23 percent of the 1,042 case reports that included information about sex partners mentioned multiple sex partners. 47% of the 2,009 case reports that contained any information about risks did not identify any risks.
Chronic HBV Infection According to the National Health and Nutrition Examination Survey (NHANES), an estimated 880,000 people had a chronic HBV infection from 2013 to 2018 (95 percent confidence interval (CI) = 580,000–1,170,000)) The 95 percent confidence interval (CI) for the prevalence of either resolved or unresolved HBV infection was 11.7 million people. Since institutionalized populations are not included in NHANES, the prevalence of ethnic minority groups, which are not well represented in the survey, may be underestimated. In a 2018 meta-analysis of prevalence, 0.42 million (range = 0.28–0.67 million) of the estimated 1.89 million chronically infected with HBV in the United States were born in the United States, while 1.47 million (95 percent CI = 1.21–1.73) were not born in the United States (6,26). People born in East Asia, Southeast Asia, the Caribbean, South Central Asia, and West Africa have the highest rates of chronic HBV infection in the United States.
Kentucky, Mississippi, and West Virginia saw increases in the percentage of women of childbearing age who had been tested for chronic HBV infection from 0.2 percent in 2011 to 0.4 percent in 2017 (24). In 2019, adults’ newly reported cases of chronic HBV infection varied by age, with the lowest rate among those aged 0 to 19 years and the highest among those aged 30 to 39 years (11,3 per 100,000 people) (23). An estimated 20,678–21,314 infants were born to HBsAg-positive pregnant women between 2015 and 2017 (27). According to data from the National Perinatal Hepatitis B Prevention Program, only 52.6% of these infants were found through prenatal screening in 2017.
A total of 1,662 HBV-related deaths were recorded on death certificates in the United States in 2019, giving an age-adjusted rate of 0.42 per 100,000 people (95% CI = 0.40–0.44) (23). Asian and other Pacific Islander people had the highest death rates (2.10), followed by males (0.66) and people between the ages of 65 and 74 (1.54). However, it has been discovered that death certificates underreport deaths caused by HBV infection.
Top Methods The CDC’s 2008 recommendations for adults to be screened for hepatitis B are updated and expanded in this report (14). The CDC looked at the addition of a universal adult screening recommendation and tested people who were thought to be at a higher risk for HBV infection but were not included in the testing recommendations from 2008.
To develop the research questions necessary to evaluate the proposed updates, members of the CDC Guidelines Work Group (hereafter referred to as the work group) adhered to CDC guideline development and reporting standards (28). systematically review; assess the evidence’s quality; and look at any existing cost-effectiveness analyses, meta-analyses, and systematic reviews (Supplementary Appendix 2; Tables 1, 4, and 7 (https://stacks.cdc.gov/view/cdc/124432) are additional. For recommendations on 1) expanding screening to all adults (universal screening), 2) periodic testing for HBV infection among people with hepatitis C virus (HCV) infection, and 3) testing for HBV infection among people with a history of incarceration, comprehensive systematic literature reviews were conducted.
CDC librarians conducted literature searches with guidance from subject matter experts for each of the three systematic reviews. Look were led for English-language writing distributed overall in Medline (OVID), Embase (OVID), CINAHL (Ebsco), and Cochrane Library. Endnote (version 20;) was used to identify duplicates and remove them. DistillerSR systematic review software (version 2.35; Clarivate Analytics) Evidence Partners) functions that automatically “find duplicates.”
The Viral Hepatitis Steering Committee of the CDC considered a variety of approaches for assessing the quality of evidence. The Mixed Methods Appraisal Tool (MMAT) was chosen because it has been proven to be effective in evaluating nonrandomized analytic and descriptive studies, which make up the majority of the literature on HBV infection prevalence (29). Each study is rated by MMAT users based on the criteria for methodological quality, and users indicate whether the criteria were met with “Yes,” “No,” or “Can’t Tell.” The tool should not be used to calculate a summary score because presenting a single number does not reveal which aspects of the studies are problematic. Monetary examinations were assessed by surveying whether the review met the Merged Wellbeing Financial Assessment Detailing Guidelines (CHEERS) (30).
The Centers for Disease Control and Prevention (CDC) came to the conclusion that the brand-new recommendations were based on significant scientific data that will have a clear and significant effect on significant decisions regarding public policies and the private sector. As a result, experts in the field who were not involved in the formulation of these recommendations were required to provide peer review under the Information Quality Act. The CDC asked AASLD, the Infectious Disease Society of America, and the American College of Physicians (ACP) for suggestions for reviewers. Structured peer reviews were provided by five physicians with expertise in hepatology, gastroenterology, internal medicine, or infectious diseases (Supplemental Appendices 2 and 3, https://stacks.cdc.gov/view/cdc/124432), and any edits made in response were documented. There were no conflicts of interest reported by CDC staff or external peer reviewers. In addition, a notice in the Federal Register announcing the availability of the draft recommendations for public comment from April 4 to June 3, 2022, was used to solicit feedback from the general public. On the draft document, 28 public comments were submitted by nonprofit/advocacy organizations, providers, industry groups, medical professional organizations, the general public, academic institutions, and a consulting company to the CDC. The work group considered public comments and documented any modifications made in response (Supplemental Appendix 4, https://stacks.cdc.gov/view/cdc/124432).
Additionally, the work group presented these guidelines to the CDC/Health Resources and Services Administration (HRSA) Advisory Committee on HIV, Viral Hepatitis, and STD Prevention and Treatment. However, this advisory committee did not seek to reach a consensus on any decisions. Cost-effectiveness analyses, additional literature, the practicality of implementing guidelines, benefits to public health, subject matter expertise, and feedback from reviewers and the general public were all taken into account by the steering committee.
Methods for a Systematic Review Universal Screening The search period spanned from January 1, 2008 (the year that the most recent CDC screening guidelines were published) to February 8, 2021 (Supplementary Table 2, https://stacks.cdc.gov/view/cdc/124432). Relevant studies found in review article reference lists and newly published studies were added to the search results. The review process was organized using DistillerSR. Two authors (EC and LP) evaluated each article for inclusion. Until a consensus could be reached, disagreements regarding inclusion decisions were discussed. The prevalence or incidence of HBV infection among adults under the age of 18 as well as linkage-to-care data were included in the articles. If the articles were carried out outside of the United States and its territories, they were excluded; only reported data from non-human studies, environmental studies, and technology evaluations; lacked original data, such as reviews, editorials, and modeled data; were reports on cases; or only included the prevalence of self-reported (i.e., unconfirmed) HBV infection (Supplementary Table 3, https://stacks.cdc.gov/view/cdc/124432). Additional exclusion criteria were not evaluated or recorded when a reviewer determined that an article met one or more exclusion criteria. Only the article with the most complete data was included when multiple articles reported data on the same cohort. Two reviewers (EC and LP) independently abstracted the data, and any discrepancies were discussed until a consensus was reached or a third reviewer (NN) resolved them. Lastly, MMAT was used by two independent assessors (LP, JB, or NN) to evaluate the quality of articles used to calculate the general population’s HBV infection prevalence.
People infected with HCV The search was conducted from January 1, 2005, through September 22, 2020 (Supplementary Table 5, https://stacks.cdc.gov/view/cdc/124432). Endnote and DistillerSR were utilized to organize the review process. One reviewer (PS or EC) looked at each title, and only those that were clearly unrelated to the research question were included. Two authors (MH and PS) looked over each article to see if it could be of use. (Supplementary Table 6, https://stacks.cdc.gov/view/cdc/124432) Disagreements regarding inclusion decisions were discussed until consensus was reached. Two reviewers (MH, PS, or EC) independently abstracted data from the full-text articles included. Using MMAT, the articles’ quality was evaluated. If the prevalence of HBV infection was less than one percent, the population was deemed to be at “increased risk.”
People Who Have Been Imprisoned in the Past in a Jail, Prison, or Other Detention Facility The work group consulted previously published articles on HBV and HCV infections in detention and correctional facilities. (Supplementary Table 8, https://stacks.cdc.gov/view/cdc/124432) The search started on January 1, 2000, and ended on March 3, 2021. Two reviewers (AH, LH, JB, OR, or EC) assessed the relevance of the abstracts, and disagreements regarding inclusion were resolved by the first author (EC) or through consensus discussion. In this review (Supplementary Table 9, https://stacks.cdc.gov/view/cdc/124432), only articles containing incidence or prevalence of HBV infection among individuals with a history of incarceration or incarceration as a risk factor for HBV infection were included. Two reviewers (LP and EC) independently abstracted the data from the full-text articles or abstracts that were included, and disagreements were resolved through consensus discussion. The work group included conference abstracts, which are designated as such due to their presumed lower quality, because there is a limited amount of literature on HBV infection in correctional settings. Using MMAT, the articles’ quality was evaluated. If the prevalence of HBV infection was less than one percent, the population was deemed to be at “increased risk.”
Top Universal Screening Systematic Review and Evidence Review Summary Following deduplication, 2,580 records were accessible for the initial title screen; During the title screen, 1,374 articles were excluded. During the abstract review, an additional 1,028 articles were excluded. After review, 136 of the 178 full-text articles did not meet the inclusion criteria; The final evaluation comprised 42 articles (Supplementary Table 11, https://stacks.cdc.gov/view/cdc/124432). Although it was published after the search period, an additional article that met the inclusion criteria was abstracted to add to the systematic search’s evidence.
(Supplementary Table 11, https://stacks.cdc.gov/view/cdc/124432) There was no HBV testing data from the general population in any of the 18 articles (i.e., screening people who were not known to be at increased risk for HBV infection). Risk-based recommendations are made by testing; Even if the study did not explicitly state that there was risk-based testing, studies with convenience samples of people who had already been tested for HBV infection were considered to be biased toward overestimating the prevalence of HBV infection. The remaining 25 articles (n = 25) included individuals with a higher risk of HBV infection who were not thought to be representative of the general population in the United States. There are Supplementary Tables 14 and 15 (https://stacks.cdc.gov/view/cdc/124432) that provide individual MMAT quality ratings.
The First Key Research Questions How would the number and composition of people who test positive for HBV infection change as a result of adult universal hepatitis B testing?
Q1a: What is the commonness of constant HBV disease in the US? by age group in the general population?
Except for one study in which the authors classified patients as having chronic HBV infection without providing a definition, the work group defined patients with chronic HBV infection as those who were HBsAg positive. Included were studies of first-time blood donors, organ donors, pregnant women, NHANES enrollees, and patients seeking care for a condition other than HBV infection. Among these groups, universal screening is already recommended.
