Serologic testing for hepatitis B surface antigen (HBsAg) is the primary way to identify persons with chronic hepatitis B virus (HBV) infection. Testing has been recommended previously for pregnant women, infants born to HBsAg-positive mothers, house hold contacts and sex partners of HBV-infected persons, persons born in countries with HBsAg prevalence of >8%, persons who are the source of blood or body fluid exposures that might warrant postexposure prophylaxis (e.g., needlestick injury to a healthcare worker or sexual assault), and persons infected with human immunodeficiency virus. This report updates and expands previous CDC guidelines for HBsAg testing and includes new recommendations for public health evaluation and management for chronically infected persons and their contacts. Routine testing for HBsAg now is recommended for additional populations with HBsAg prevalence of >2%: persons born in geographic regions with HBsAg prevalence of >2%, men who have sex with men, and injection-drug users. Implementation of these recommendations will require expertise and resources to integrate HBsAg screening in prevention and care settings serving populations recommended for HBsAg testing. This report is intended to serve as a resource for public health officials, organizations, and health-care professionals involved in the development, delivery, and evaluation of prevention and clinical services.# Introduction
United States. Persons with chronic HBV infection can remain asymptomatic for years, unaware of their infections Chronic infection with hepatitis B virus (HBV) is a com and of their risks for transmitting the virus to others and for mon cause of death associated with liver failure, cirrhosis, and having serious liver disease later in life. Early identification of liver cancer. Worldwide, approximately 350 million persons persons with chronic HBV infection permits the identifica have chronic HBV infection, and an estimated 620,000 per tion and vaccination of susceptible household contacts and sons die annually from HBV-related liver disease (1,2). Hepa sex partners, thereby interrupting ongoing transmission. titis B vaccination is highly effective in preventing infection All persons with chronic HBV infection need medical manwith HBV and consequent acute and chronic liver disease. In agement to monitor the onset and progression of liver disease the United States, the number of newly acquired HBV infec and liver cancer. Safe and effective antiviral agents now are tions has declined substantially as the result of the implemen available to treat chronic hepatitis B, providing a greater tation of a comprehensive national immunization program imperative to identify persons who might benefit from medi (3)(4)(5). However, the prevalence of chronic HBV infection cal evaluation, management, and antiviral therapy and other remains high; in 2006, approximately 800,000-1.4 million treatment when indicated. The majority of the medications U.S. residents were living with chronic HBV infection now in use for hepatitis B treatment were approved by the (Table 1), and hepatitis B is the underlying cause of an esti-Food and Drug Administration (FDA) in 2002 or later; two mated 2,000-4,000 deaths each year in the United States (6).
forms of alfa 2 interferon and five oral nucleoside/nucleotide Improving the identification and public health management analogues have been approved, and other medications are in of persons with chronic HBV infection can help prevent seri clinical trials. ous sequelae of chronic liver disease and complement immu-Serologic testing for hepatitis B surface antigen (HBsAg) is nization strategies to eliminate HBV transmission in the the primary way to identify persons with chronic HBV infec tion. Because of the availability of effective vaccine and
The material in this report originated in the National Center for HIV/ postexposure prophylaxis, CDC previously recommended AIDS, Viral Hepatitis, STD, and TB Prevention, Kevin Fenton, MD, HBsAg testing for pregnant women, infants born to HBsAg-Director, and the Division of Viral Hepatitis, John Ward, MD, Director.
positive mothers, household contacts and sex partners of HBV-phylaxis (e.g., needlestick injury to a health-care worker or HBV endemicity, and 3) the increasing benefits of care and sexual assault), and persons infected with human immunode-opportunities for prevention for infected persons and their ficiency virus (HIV) (4,5,(7)(8)(9)(10)(11). This report updates and contacts. On the basis of this discussion, CDC determined expands these multiple previous CDC guidelines for HBsAg that reconsideration of current guidelines was warranted. This testing and includes new recommendations for public health report summarizes current HBsAg testing recommendations evaluation and management of chronically infected persons published previously by CDC, expands CDC recommenda and their contacts. Routine HBsAg testing now is recom-tions to increase the identification of chronically infected mended for persons born in geographic regions in which persons in the United States, and defines the components HBsAg prevalence is >2%, men who have sex with men of programs needed to identify HBV-infected persons (MSM), and injection-drug users (IDUs).
successfully.

# Methods

# Clinical Features and Natural
During February 7-8, 2007, CDC convened a meeting of

# History of HBV Infection
researchers, physicians, state and local public health profes-HBV is a 42-nm DNA virus in the Hepadnaviridae family. sionals, and other persons in the public and private sectors After a susceptible person is exposed, the virus is transported with expertise in the prevention, care, and treatment of chronic by the bloodstream to the liver, which is the primary site of hepatitis B. These consultants reviewed available published HBV replication. HBV infection can produce either asymp and unpublished epidemiologic and treatment data, consid tomatic or symptomatic infection. When clinical manifesta ered whether to recommend testing specific new populations tions of acute disease occur, illness typically begins 2-3 months for HBV infection, and discussed how best to implement new after HBV exposure (range: 6 weeks-6 months). Infants, chil and existing testing strategies. Topics discussed included dren aged 5 years have clinical signs or symp related morbidity and mortality among persons infected as toms of acute disease after infection. Symptoms of acute infants and young children in countries with high levels of hepatitis B include fatigue, poor appetite, nausea, vomiting, abdominal pain, low-grade fever, jaundice, dark urine, and light stool color. Clinical signs include jaundice, liver tender ness, and possibly hepatomegaly or splenomegaly. Fatigue and loss of appetite typically precede jaundice by 1-2 weeks. Acute illness typically lasts 2-4 months. The case-fatality rate among persons with reported cases of acute hepatitis B is approxi mately 1%, with the highest rates occurring in adults aged >60 years (12). Primary HBV infection can be self-limited, with elimina tion of virus from blood and subsequent lasting immunity against reinfection, or it can progress to chronic infection with continuing viral replication in the liver and persistent vire mia. Resolved primary infection is not a risk factor for subse quent occurrence of chronic liver disease or hepatocellular carcinoma (HCC). However, patients with resolved infection who become immunosuppressed (e.g., from chemotherapy or medication) might, albeit rarely, experience reactivation of hepatitis B with symptoms of acute illness (13)(14)(15). HBV DNA has been detected in the livers of persons without serologic markers of chronic infection after resolution of acute infec tion (13,(16)(17)(18)(19). The risk for progression to chronic infec tion is related inversely to age at the time of infection. HBV infection becomes chronic in >90% of infants, approximately 25%-50% of children aged 1-5 years, and <5% of older chil dren and adults) (13,(20)(21)(22)(23). Immunosuppressed persons (e.g., hemodialysis patients and persons with HIV infection) are at increased risk for chronic infection (22). Once chronic HBV infection is established, 0.5% of infected persons spontane ously resolve infection annually (indicated by the loss of detectable HBsAg and serum HBV DNA and normalization of serum alanine aminotransferase  levels); resolution is rarer among children than among adults (13,24,25).
Persons with chronic HBV infection can be asymptomatic and have no evidence of liver disease, or they can have a spec trum of disease, ranging from chronic hepatitis to cirrhosis or liver cancer. Chronic infection is responsible for the majority of cases of HBV-related morbidity and mortality; follow-up studies have demonstrated that approximately 25% of per sons infected with HBV as infants or young children and 15% of those infected at older ages died of cirrhosis or liver cancer. The majority remained asymptomatic until onset of cirrhosis or end-stage liver disease (26). Persons with histologic evi dence of chronic hepatitis B (e.g., hepatic inflammation and fibrosis) are at higher risk for HCC than HBV-infected per sons without such evidence (27). Potential extrahepatic com plications of chronic HBV infection include polyarteritis nodosa (28,29), membranous glomerulonephritis, and mem branoproliferative glomerulonephritis (30).

# Serologic Markers of HBV Infection
The serologic patterns of chronic HBV infection are varied and complex. Antigens and antibodies associated with HBV infection include HBsAg and antibody to HBsAg (anti-HBs), hepatitis B core antigen (HBcAg) and antibody to HBcAg (anti-HBc), and hepatitis B e antigen (HBeAg) and antibody to HBeAg (anti-HBe). Testing also can be performed to assess the presence and concentration of circulating HBV DNA. At least one serologic marker is present during each of the differ ent phases of HBV infection (Figures 1 and 2) (31). Serologic assays are available commercially for all markers except HBcAg, because no free HBcAg circulates in blood. No rapid or oral fluid tests are licensed in the United States to test for any HBV markers.
Three phases of chronic HBV infection have been recog nized: the immune tolerant phase (HBeAg-positive, with high levels of HBV DNA but absence of liver disease), the immune active or chronic hepatitis phase (HBeAg-positive, HBeAg negative, or anti-HBe-positive, with high levels of HBV DNA and active liver inflammation), and the inactive phase (anti-HBe positive, normal liver aminotransferase levels, and low or absent levels of HBV DNA) (32). Patients can evolve through these phases or revert from inactive hepatitis B back to immune active infection at any time.
The serologic markers typically used to differentiate among acute, resolving, and chronic infection are HBsAg, IgM anti-HBc, and anti-HBs (  the presence of anti-HBe usually indicates decreased or unde tectable HBV DNA and lower levels of viral replication.

# FIGURE 2. Typical serologic course of acute hepatitis B virus (HBV) infection with progression to chronic HBV infection
In newly infected persons, HBsAg is the only serologic marker detected during the first 3-5 weeks after infection. The average time from exposure to detection of HBsAg is 30 days (range: 6-60 days) (31,33). Highly sensitive single-sample nucleic acid tests can detect HBV DNA in the serum of an infected person 10-20 days before detection of HBsAg (34). Transient HBsAg positivity has been reported for up to 18 days after hepatitis B vaccination and is clinically insignifi cant (35,36).
Anti-HBc appears at the onset of symptoms or liver-test abnormalities in acute HBV infection and persists for life in the majority of persons. Acute or recently acquired infection can be distinguished from chronic infection by the presence of the immunoglobulin M (IgM) class of anti-HBc, which is detected at the onset of acute hepatitis B and persists for up to 6 months if the infection resolves. In patients with chronic HBV infection, IgM anti-HBc can persist during viral repli cation at low levels that typically are not detectable by the assays used in the United States. However, persons with exac erbations of chronic infection can test positive for IgM anti-HBc (37). Because the positive predictive value of this test is low in asymptomatic persons, IgM anti-HBc testing for diag nosis of acute hepatitis B should be limited to persons with clinical evidence of acute hepatitis or an epidemiologic link to a person with HBV infection.
In persons who recover from HBV infection, HBsAg and HBV DNA usually are eliminated from the blood, and anti-HBs appears. In persons who become chronically infected, HBsAg and HBV DNA persist. In persons in whom chronic infection resolves, HBsAg becomes undetectable; anti-HBc persists and anti-HBs will occur in the majority of these per sons (38,39).
In certain persons, total anti-HBc is the only detectable HBV serologic marker. Isolated anti-HBc positivity can represent 1) resolved HBV infection in persons who have recovered but whose anti-HBs levels have waned, most commonly in highprevalence populations; 2) chronic infection in which circu lating HBsAg is not detectable by commercial serology, most commonly in high-prevalence populations and among per sons with HIV or HCV infection (40) (HBV DNA has been isolated from the blood in <5% of persons with isolated anti-HBc) (40,41); or 3) false-positive reaction. In low-prevalence populations, isolated anti-HBc may be found in 10%-20% of persons with serologic markers of HBV infection, most of whom will demonstrate a primary response after hepatitis B vaccination (42,43). Persons positive only for anti-HBc are unlikely to be infectious except under unusual circumstances in which they are the source for direct percutaneous exposure of susceptible recipients to substantial quantities of virus (e.g., blood transfusion or organ transplant) (44).
HBeAg can be detected in the serum of persons with acute or chronic HBV infection. In the majority of those with

# Epidemiology of HBV Infection in the United States Transmission
HBV is transmitted by percutaneous and mucosal exposure to infectious blood or body fluids. The highest concentra tions of virus are found in blood; however, semen and saliva also have been demonstrated to be infectious (50). HBV remains viable and infectious in the environment for at least 7 days and can be present in high concentrations on inanimate objects, even in the absence of visible blood (13,51). Persons with chronic HBV infection are the major source of new infections, and the primary routes of HBV transmission are sexual contact, percutaneous exposure to infectious body flu ids (such as occurs through needle sharing by IDUs or needlestick injuries in health-care settings), perinatal expo sure to an infected mother, and prolonged, close personal con tact with an infected person (e.g., via contact with exudates from dermatologic lesions, contact with contaminated sur faces, or sharing toothbrushes or razors), as occurs in house hold contact (5,52). No evidence exists of transmission of HBV by casual contact in the workplace, and transmission occurs rarely in childcare settings (4). Few cases have been reported in which health-care workers have transmitted infection to patients, particularly since implementation of standard universal infection control precautions (53).

# Incidence of HBV Infection
During 1985-2006, incidence of acute hepatitis B in the United States declined substantially, from 11.5 cases per 100,000 population in 1985 to 1.6 in 2006 (12). The actual incidence of new HBV infections is estimated to be approxi mately tenfold higher than the reported incidence of acute hepatitis B, after adjustment for underreporting of cases and asymptomatic infections. In 2006, an estimated 46,000 per sons were newly infected with HBV (54). The greatest declines in incidence of acute disease have occurred in the cohorts of children for whom infant and adolescent catch-up vaccination was recommended (12). Among children aged 20 years had the highest incidence of acute HBV infection, reflecting low hepatitis B vaccination coverage among adults with behavioral risks for HBV infection (e.g., MSM, IDUs, persons with multiple sex partners, and persons whose sex partners are infected with HBV) (12).

# Prevalence of HBV Infection and Its Sequelae
U.S. mortality data for 2000-2003 indicated that HBV infection was the underlying cause of an estimated 2,000-4,000 deaths annually. The majority of these deaths resulted from cirrhosis and liver cancer (6;CDC, unpublished data, 2000CDC, unpublished data, -2003.
The burden of chronic HBV infection in the United States is greater among certain populations as a result of earlier age at infection, immune suppression, or higher levels of circulat ing infection. These include persons born in geographic regions with high (>8%) or intermediate (2%-7%) prevalence of chronic HBV infection, HIV-positive persons (who might have additional risk factors) (56)(57)(58), and certain adult popu lations for whom hepatitis B vaccination has been recom mended because of behavioral risks (e.g., MSM and IDUs). An accurate estimate of the prevalence of chronic HBV infec tion in the United States must be derived from multiple sources of data to account for the disproportionate contributions of persons of foreign birth, members of certain ethnic minority populations, and persons with certain medical conditions (Table 1). For the U.S.-born civilian noninstitutionalized population, prevalence estimates can be obtained from the most recent National Health and Nutrition Examination Sur vey (NHANES), which was conducted during 1999-2004 (available at ). Because data from studies of foreign-born U.S. residents indicate that HBsAg seroprevalence corresponds to HBV endemicity in the country of origin (5), for the foreign-born population resid ing in the United States, HBV prevalence estimates were derived by applying country-specific prevalence estimates gath ered from the scientific literature and the World Health Organization (2) to the number of foreign-born U.S. resi dents by their country of birth as reported by the 2006 U.S. Census American Community Survey (59). Other popula tions for which estimates were calculated included those in correctional institutions and the homeless. Together, these sources indicated that an estimated 800,000-1.4 million per sons in the United States have chronic HBV infection. Approximately 0.3%-0.5% of U.S. residents are chronically infected with HBV; 47%-70% of these persons were born in other countries (Table 1).

# Global Variation in Prevalence of HBV Infection
HBV transmission patterns and the seroprevalence of chronic HBV infection vary markedly worldwide, although seroprevalence studies in many countries are limited, and the epidemiology of hepatitis B is changing. Approximately 45% of persons worldwide live in regions in which HBV is highly endemic (i.e., where prevalence of chronic HBV infection is >8% among adults and that of resolved or chronic infection  is >60%) (2) (Figure 3). Histori cally, >90% of new infections occurred among infants and young children as the result of perinatal or household trans mission during early childhood (26). Infant immunization programs in many countries have led to marked decreases in incidence and prevalence among younger, vaccinated mem bers of these populations (60)(61)(62)(63). Countries of intermediate HBV endemicity (i.e., HBsAg prevalence of 2%-7%) account for approximately 43% of the world's population; in these countries, multiple modes of transmission (i.e., perinatal, household, sexual, injection-drug use, and health-care-related) contribute to the infection burden. Regions of the world with high or intermediate prevalence of HBsAg include much of Eastern Europe, Asia, Africa, the Middle East, and the Pacific Islands (2,4) (Figure 3 and Table 3). In countries of low ende micity (i.e., HBsAg prevalence of <2%), the majority of new infections occur among adolescents and adults and are attrib utable to sexual and injection-drug-use exposures. However, in certain areas of low HBV endemicity, prevalence of chronic HBV infection is high among indigenous populations born before routine infant immunization (Table 3).  Ecuador, Guyana, Suriname, Venezuela, and Amazonian areas of Bolivia, Brazil, Columbia, and Peru Caribbean Antigua-Barbuda, Dominica, Grenada, Haiti, Jamaica, St. Kitts-Nevis, St. Lucia, and Turks and Caicos Islands - A complete list of countries in each region is available at .
 Estimates of prevalence of HBsAg, a marker of chronic hepatitis B virus infection, are based on limited data and might not reflect current prevalence in countries that have implemented childhood hepatitis B vaccination. In addition, HBsAg prevalence might vary within countries by subpopulation and locality.  Asia includes three regions: Southeast Asia, East Asia, and Northern Asia.
In the United States, marked decreases in the prevalence of chronic HBV infection among younger, vaccinated foreignborn U.S. residents have been observed, most likely as a result of infant immunization programs globally (64). However, the rate of liver cancer deaths in the United States continues to be high among certain foreign-born U.S. populations. For example, the rate of liver cancer deaths is highest among Asians/ Pacific Islanders, reflecting the high prevalence of chronic hepatitis B in this population (65,66). Globally, other regions with HBsAg prevalence of >2% also have identified high lev els of HBV-associated HCC (67,68).

# Household Contacts and Sex Partners of Persons With Chronic HBV Infection
Serologic testing and hepatitis B vaccination has been rec ommended since 1982 (69) for household contacts and sex partners of persons with chronic HBV infection because pre vious studies have determined that 14%-60% of persons liv ing in households with persons with chronic HBV infection have serologic evidence indicating resolved HBV infection, and 3%-20% have evidence indicating chronic infection. The risk for infection is highest among unvaccinated children liv ing with a person with chronic HBV infection in a household or in an extended family setting and among sex partners of chronically infected persons (70)(71)(72)(73)(74)(75)(76)(77).

# Men Who Have Sex With Men
During 1994-2000, studies of MSM aged <30 years iden tified chronic infection in 1.1% of MSM aged 18-24 years (95% confidence interval  = 0-2.2%) (78), 2.1% (95% CI = 1.6%-2.6%) of MSM aged 15-21 years (79), and 2.3% (95% CI = 1.7%-2.8%) of MSM aged 22-29 years (80). In these studies, prevalence was higher (7.4%; 95% CI = 5.3%-9.6%) among young MSM who were HIV-positive than it was among those who were HIV-negative (1.5%; 95% CI = 1.2%-1.9%) (CDC, unpublished data, 2007). Before the introduction of the hepatitis B vaccine in 1982, prevalence of chronic HBV infection among MSM was 4.6%-6.1% (81)(82)(83). In recent studies, prevalence of past infection increased with increasing age, suggesting that chronic infection might still be more prevalent among older MSM (79,80).

# Injection-Drug Users
Chronic HBV infection has been identified in 2.7%-11.0% of IDUs in a variety of settings (84)(85)(86)(87)(88)(89)(90)(91); HBsAg prevalence of 7.1% (95% CI = 6.3%-7.8%) has been described among IDUs with HIV coinfection (92). IDUs contribute disproportion ately to the burden of infection in the United States: in chronic HBV infection registries, 4%-12% of reported chronically infected persons had a history of injection-drug use (93). Preva lence of resolved or chronic HBV infection among IDUs increases with the number of years of drug use and is associ ated with frequency of injection and with sharing of drugpreparation equipment (e.g., cottons, cookers, and rinse water), independent of syringe sharing (94,95).

# HIV-Positive Persons
As life expectancies for HIV-infected persons have increased with use of highly active antiretroviral therapy, liver disease, much of it related to HBV and HCV infections, has become the most common non-AIDS-related cause of death among this population (56,57,96,97). Chronic HBV infection has been identified in 6%-15% of HIV-positive persons from Western Europe and the United States, including 9%-17% of MSM; 7%-10% of IDUs; 4%-6% of heterosexuals; and 1.5% of pregnant women (58,98,99). This high level of chronic infection reflects both common routes of transmis sion for HIV and HBV and a higher risk of chronicity after HBV infection in an immunocompromised host (100)(101)(102).

# MMWR September 19, 2008

# Persons With Selected Medical Conditions
Although population-level studies are lacking to determine HBsAg prevalence among populations with other medical conditions, persons with chronic HBV infection who initiate cytotoxic or immunosuppressive therapy (e.g., chemotherapy for malignant diseases, immunosuppression related to organ transplantation, and immunosuppression for rheumatologic and gastroenterologic disorders) are at risk for HBV reactiva tion and associated morbidity and mortality (32,101,102). Prophylactic antiviral therapy can prevent reactivation and possible fulminant hepatitis in HBsAg positive patients (13,101).

# Rationale for Testing to Identify Persons With Chronic HBV Infection
Although limited data are available regarding the number of persons with chronic HBV infection in the United States who are unaware of their infection status, studies of programs con ducting HBsAg testing among Asian-born persons living in the United States indicated that approximately one third of infected persons were unaware of their HBV infection (5,(103)(104)(105). Published studies for other populations are lacking. Prompt identification of chronic infection with HBV is essential to ensure that infected persons receive necessary care to prevent or delay onset of liver disease and services to prevent transmission to others. Treatment guidelines for chronic hepatitis B have been issued (13,106,107), and multiple medications have been approved for treatment of adults with chronic HBV infection. With recent advances in hepatitis B treatment and detection of liver cancer, identification of an HBV-infected person permits the implementation of important interventions to reduce mor bidity and mortality, including
- clinical evaluations to detect onset and progression of HBV-related liver disease; - antiviral treatment for chronic HBV infection, which can delay or reverse the progression of liver disease (13); - baseline AFP measurement and periodic ultrasound sur veillance to detect HCC at a potentially treatable stage because early intervention to ablate small localized tumors, resect, or transplant has resulted in long-term tumor-free survival (108); and - interventions designed to reduce progression of liver injury, including vaccination against hepatitis A and counseling to avoid excessive alcohol use. Morbidity and mortality from hepatitis A are increased in the presence of chronic liver disease (109); alcohol use of >25mL-30mL/day is associated with progression of HBV-related liver disease (110,111).
Identification of infected persons also allows for primary prevention of ongoing HBV transmission by enabling per sons with chronic infection to adopt behaviors that reduce the risk of transmission to others and by permitting identifi cation of close contacts who require testing and subsequent vaccination (if identified as susceptible) or medical manage ment (if identified as having chronic HBV infection). Appro priate HBsAg testing and counseling also help prevent health-care-associated transmission in dialysis settings by allowing for cohorting of infected patients (112). Testing donated blood and donors of organs and tissues prevents infectious materials from being used and allows unvaccinated persons exposed to needlesticks to receive additional postexposure prophylaxis if the source of the exposure was HBV-infected (113).
Testing for chronic HBV infection meets established public health screening criteria (114). Screening is a basic public health tool used to identify unrecognized health conditions so treatment can be offered before symptoms occur and, for communicable diseases, so interventions can be implemented to reduce the likelihood of continued transmission (114). Screening for chronic HBV infection is consistent with the main generally accepted public health screening criteria: 1) chronic hepatitis B is a serious health disorder that can be diagnosed before symptoms occur; 2) it can be detected by reliable, inexpensive, and minimally invasive screening tests; 3) chronically infected patients have years of life to gain if medical evaluation and/or treatment is initiated early, before symptoms occur; and 4) the costs of screening are reasonable in relation to the anticipated benefits (114) ).
To prevent HBV transmission, previous guidelines have rec ommended HBsAg testing for hemodialysis patients, preg nant women, and persons known or suspected of having been exposed to HBV (i.e., infants born to HBV-infected mothers, household contacts and sex partners of infected persons, and persons with known occupational or other exposures to infec tious blood or body fluids) (3,112). HBsAg testing also is required for donors of blood, organs, and tissues (113). To guide immunization efforts and identify infected persons, testing also has been recommended previously for persons born in regions with high HBV endemicity (4,121). Finally, testing has been recommended for HIV-positive persons on the basis of their high prevalence of HBV coinfection and their increased risk for HBV-associated morbidity and mortality (122).
Because persons with chronic HBV infection serve as the reservoir for new HBV infections in the United States, identi fication of these persons will complement vaccination strate gies for elimination of HBV transmission. With the availability of effective treatments for chronic hepatitis B, the infected person, once identified, can benefit from testing as well. Thus, CDC recommends expanding HBV testing to include all per sons born in regions with HBsAg prevalence of >2% (high and intermediate endemicity). CDC also recommends HBsAg testing in addition to vaccination for MSM and IDUs because of their higher-than-population prevalence and their ongoing risk for infection. Finally, to prevent adverse medical outcomes among persons who might be seeking medical care for other reasons, recommendations also are made to test per sons with ALT elevations of unknown etiology and candi dates for immunosuppressive therapies.

# Recommendations
Persons who are most likely to be actively infected with HBV should be tested for chronic HBV infection. Testing should include a serologic assay for HBsAg offered as a part of rou tine care and be accompanied by appropriate counseling and referral for recommended clinical evaluation and care. Laboratories that provide HBsAg testing should use an FDAlicensed or FDA-approved HBsAg test and should perform testing according to the manufacturer's labeling, including test ing of initially reactive specimens with a licensed, neutralizing confirmatory test. A confirmed HBsAg-positive result indi cates active HBV infection, either acute or chronic; chronic infection is confirmed by the absence of IgM anti-HBc or by the persistence of HBsAg or HBV DNA for at least 6 months. All HBsAg-positive persons should be considered infectious.
Recommendations and federal mandates related to routine testing for chronic HBV infection have been summarized (Table 4). To determine susceptibility among persons who are at ongoing risk for infection and recommended for vaccina tion, total anti-HBc or anti-HBs also should be tested at the time of serologic testing for chronic HBV infection. New populations recommended for testing are the following:
- Persons born in geographic regions with HBsAg preva lence of >2%. All persons born in geographic regions with HBsAg prevalence of >2% (e.g., much of Eastern Europe, Asia, Africa, the Middle East, and the Pacific Islands) (Figure 3 and Table 3) and certain indigenous populations from countries with overall low HBV endemicity (<2%) (Table 3) should be tested for chronic HBV infection. This includes immigrants, refugees, asylum seekers, and inter nationally adopted children born in these regions, regard less of vaccination status in their country of origin (123).  - Testing for HBsAg should be performed along with other examination and laboratory testing in the context of medical evaluation.
- To prevent transmission to recipients, HBsAg, anti-HBc, and HBV-DNA testing are required.
- Serologic testing should test for all markers of HBV infection (HBsAg, anti-HBc, and anti-HBs) on admission. - To prevent transmission in dialysis settings, hemodialysis patients should be vaccinated against hepatitis B and revaccinated when serum anti-HBs titer falls below 10mIU/mL. - HBsAg-positive hemodialysis patients should be cohorted.
- Vaccine nonresponders should be tested monthly for HBsAg.
- Women should be tested for HBsAg during each pregnancy, preferably in the first trimester. - If an HBsAg test result is not available or if the mother was at risk for infection during pregnancy, testing should be performed at the time of admission for delivery. - To prevent perinatal transmission, infants of HBsAg-positive mothers and unknown HBsAg status mothers should receive vaccination and postexposure immunoprophylaxis in accordance with recommendations within 12 hours of delivery.
- Testing for HBsAg and anti-HBs should be performed 1-2 mos after completion of at least 3 doses of a licensed hepatitis B vaccine series (i.e., at age 9-18 months, generally at the next well-child visit) to assess the effectiveness of postexposure immunoprophylaxis. Testing should not be performed before age 9 months or within 1 month of the most recent vaccine dose. - Maternal and infant medical records should be reviewed to determine whether infant received hepatitis B immune globulin and vaccine in accordance with recommendations.

# ACCREDITATION

# Continuing Medical Education (CME).
CDC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. CDC designates this educational activity for a maximum of 2.5 hours in category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity.

# Continuing Education Unit (CEU). CDC has been reviewed and approved as an

# Goal and Ojectives
This report updates and expands previous CDC guidelines for hepatitis B surface antigen (HBsAg) testing to identify persons with chronic hepatitis B virus (HBV) infection. The report recommends new populations for HBsAg testing and provides new guidelines regarding evaluation and public health management of chronically infected persons. The goal of this report is to guide health-care professionals and public health officials in identifying persons with chronic HBV infection and ensuring appropriate public health management of these persons and their contacts. Upon completion of this educational activity, the reader should be able to 1) identify populations for whom routine HBsAg testing is recommended, 2) identify geographic regions with intermediate or high endemicity of HBV infection, 3) describe components of public health management for HBsAg-positive persons, and 4) describe strategies to increase implementation of HBsAg testing recommendations.
To receive continuing education credit, please answer all of the following questions.   Unless an established patient-provider relation can ensure that the patient will return for serologic test results and that vaccination can be initiated at that time if the patient is susceptible.  Antibody to hepatitis B core antigen.  Antibody to HBsAg.   Persons lacking immunity, either vaccine-induced or following resolved infection, to HBV infection.   ALT = alanine aminotransferase; AST = aspartate aminotransferase.

# For which of the following populations is routine
- Persons with liver disease of unknown eiology. All per sons with persistently elevated ALT or aspartate amino transferase (AST) levels of unknown etiology should be tested for HBsAg as part of the medical evaluation of these abnormal laboratory values.

# Testing Persons With a History of Vaccination
Because some persons might have been infected with HBV before they received hepatitis B vaccination, HBsAg testing is recommended regardless of vaccination history for the following populations:
- Persons born in geographic regions with HBV preva lence of >2%. The majority of these persons were born either before full implementation of routine infant hepa titis B vaccination in their countries of origin or during a period when newborn vaccination programs were in the early stages of implementation. Because of the difficulty in verifying the vaccination status of foreign-born per sons and the high rate of perinatal and early childhood HBV transmission before implementation of routine infant hepatitis B vaccination programs, HBsAg testing is recommended for all persons born in regions with high or intermediate endemicity of HBV infection even if they were vaccinated in their country of origin.
- U.S.

# Management of Persons Tested for Chronic HBV Infection Vaccination at the Time of Testing
Persons to be tested who have been recommended to receive hepatitis B vaccination, including those in settings in which universal vaccination is recommended (i.e., sexually September 19, 2008  HBV infection unless the person has signs or symptoms of receive the first dose of vaccine at the same medical visit after acute hepatitis. All HBsAg-positive laboratory results should blood is drawn for testing unless an established patientbe reported to the state or local health department, in accor provider relation can ensure that the patient will return for dance with state requirements for reporting of acute and serologic test results and that vaccination can be initiated at chronic HBV infection. Chronic HBV infection can be conthat time if the patient is susceptible. In venues where vacci firmed by verifying the presence of HBsAg in a serum sample nation is recommended and testing is not feasible, vaccina taken at least 6 months after the first test, or by the absence of tion still should be provided for all populations for whom it is IgM anti-HBc in the original specimen. Standard case defini recommended.
tions for the classification of reportable cases of HBV infec tion have been published previously (124).

# Contact Management
Sex partners and household and needle-sharing contacts of HBsAg-positive persons should be identified. Unvaccinated past and present sex partners and household and needlesharing contacts should be tested for HBsAg and for anti-HBc and/or anti-HBs and should receive the first dose of hepatitis B vaccine as soon as the blood sample for serologic testing has been collected. Susceptible persons should com plete the vaccine series using an age-appropriate vaccine dose and schedule. Those who have not been vaccinated fully should complete the vaccine series. Contacts determined to be HBsAg positive should be referred for medical care.
Health-care providers and public health authorities treat ing persons with chronic HBV infection should obtain the names of their sex contacts and household members and a history of drug use. Providers then can help to arrange for evaluation and vaccination of contacts, either directly or with assistance from state and local health departments. Con tact notification is well-established in public STD programs; these programs have the expertise to reach identified contacts of HBsAg-positive patients and might be able to provide guid ance on procedures and best practices, or in programs with sufficient capacity, offer assistance to other providers to reach identified contacts. With sufficient resources, identification of contacts should be accompanied by health counseling and include referral of patients and their contacts for other services when appropriate.
The success of contact management for hepatitis B has var ied widely, depending on local resources. One study deter mined that approximately half of providers caring for patients with chronic HBV infection recommended contact vaccina tion, and <20% of contacts initiated vaccination (125). In the national perinatal hepatitis B prevention program, approxi mately 26% of all persons identified as contacts by HBsAg positive women were tested and evaluated for vaccination by public health departments (CDC, unpublished data, 2005). In several state and local programs with targeted efforts for adult hepatitis B prevention, up to 85% of identified contacts have been evaluated (CDC, unpublished data, 2005); how ever, many states and cities have no contact identification pro grams outside the perinatal hepatitis B prevention program. Given the potential for contact notification to disrupt net works of HBV transmission and reduce disease incidence, health-care providers should encourage patients with HBV infection to notify their sex partners, household members, and injection-drug-sharing contacts and urge them to seek medi cal evaluation, testing, and vaccination.

# Patient Education
Medical providers should advise patients identified as HBsAg positive regarding measures they can take to prevent trans mission to others and protect their health or refer patients for counseling if needed. Patient education should be conducted in a culturally sensitive manner in the patient's primary lan guage (both written and oral whenever possible). Ideally bilingual, bicultural, medically trained interpreters should be used when indicated.
- To prevent or reduce the risk for transmission to others, HBsAg-positive persons should be advised to -notify their household, sex, and needle-sharing con tacts that they should be tested for markers of HBV infection, vaccinated against hepatitis B, and, if sus ceptible, complete the hepatitis B vaccine series; -use methods (e.g., condoms) to protect nonimmune sex partners from acquiring HBV infection from sexual activity until the sex partners can be vaccinated and their immunity documented (HBsAg-positive persons should be made aware that use of condoms and other prevention methods also might reduce their risks for HIV infection and other STDs); -cover cuts and skin lesions to prevent the spread of infectious secretions or blood; -clean blood spills with bleach solution (126); -refrain from donating blood, plasma, tissue, or semen; -refrain from sharing household articles (e.g., tooth brushes, razors, or personal injection equipment) that could become contaminated with blood; and -dispose of blood and body fluids and medical waste properly. - HBsAg-positive pregnant women should be advised of the need for their newborns to receive hepatitis B vaccine and hepatitis B immune globulin beginning at birth and to complete the hepatitis B vaccine series according to the recommended immunization schedule. - To protect the liver from further harm, HBsAg-positive persons should be advised to -seek health-care services from a provider experienced in the management of hepatitis B; -avoid or limit alcohol consumption because of the effects of alcohol on the liver, with referral to care pro vided for persons needing evaluation or treatment for alcohol abuse; and -obtain vaccination against hepatitis A (2 doses, 6-18 months apart) if chronic liver disease is present.

# Medical Management of Chronic Hepatitis B
Because 15%-25% of persons with chronic HBV infection are at risk for premature death from cirrhosis and liver cancer, persons with chronic HBV infection should be evaluated soon after infection is identified by referral to or in consultation with a physician experienced in the management of chronic liver disease. When assessing chronic HBV infection, the phy sician must consider the level of HBV replication and the degree of liver injury. Injury is assessed using serial tests of serum aminotransferases (ALT and AST), and, when needed, liver biopsy (histologic activity and fibrosis scores).
Initial evaluation of patients with chronic HBV infection should include a thorough history and physical examination, with special emphasis on risk factors for coinfection with HIV and HCV, alcohol use, and family history of HBV infection and liver cancer. Laboratory testing should assess for indica tors of liver disease (complete blood count and liver panel), markers of HBV replication (HBeAg, anti-HBe, HBV DNA), coinfection with HCV, HDV, and HIV, and antibody to hepa titis A virus (HAV) (if local HAV prevalence makes prevac cination testing cost effective) (109). Where testing is available, schistosomiasis (S. mansoni or S. japonicum) also should be assessed for persons from endemic areas (129) because schis tosomiasis might increase progression to cirrhosis or HCC in the presence of HBV infection (130,131). Persons with chronic HBV infection who are not known to be immune to HAV should receive 2 doses of hepatitis A vaccine 6-18 months apart. Baseline alfa fetoprotein assay (AFP) is used to assess - Disagreement exists internationally about best practices for avoiding transmission of HBV from health-care worker to patient (53).
for evidence of HCC at initial diagnosis of HBV infection, and ultrasound in patients at risk of HCC (i.e., Asian men aged >40 years, Asian women aged >50 years, persons with cir rhosis, persons with a family history of HCC, Africans aged >20 years, and HBV-infected persons aged >40 years with per sistent or intermittent ALT elevation and/or high HBV DNA) (13,108). Liver biopsy (or, ideally, noninvasive markers) can be used to assess inflammation and fibrosis if initial laboratory assays suggest liver damage, as per published practice guide lines for liver biopsy in chronic HBV infection (13).
Following an initial evaluation, all patients with chronic HBV infection, even those with normal aminotransferase lev els, should receive lifelong monitoring to assess progression of liver disease, development of HCC, need for treatment, and response to treatment. Frequency of monitoring depends on several factors, including family history, age, and the condi tion of the patient; monitoring schedules have been recom mended by several authorities (13,106,107,132).
Therapy for hepatitis B is a rapidly changing area of clinical practice. Seven therapies have been approved by FDA for the treatment of chronic HBV infection: interferon alfa-2b, peginterferon alfa-2a, lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate (13,106,132,133). In addition, at least two other FDA-approved oral anti viral medications for HIV (clevudine and emtricitabine) are undergoing phase-3 trials for HBV treatment and might be approved soon for chronic hepatitis B. Treatment decisions are made on the basis of HBeAg status, HBV DNA viral load, ALT, stage of liver disease, age of patient, and other factors (13,32,134).
Coinfection with HIV complicates the management of patients with chronic hepatitis B. When selecting antiretrovirals for HIV treatment, the provider must consider the patient's HBsAg status to avoid liver-associated complications and development of antiviral resistance. Management of these patients has been described elsewhere (135).
Serologic endpoints of antiviral therapy are loss of HBeAg, HBeAg seroconversion in persons initially HBeAg positive, suppression of HBV DNA to undetectable levels by sensitive PCR-based assays in patients who are HBeAg-negative and anti-HBe positive, and loss of HBsAg. Optimal duration of therapy has not been established. For HBeAg-positive patients, treatment should be continued for at least 6 months after loss of HBeAg and appearance of anti-HBe (13); for HBeAg negative/anti-HBe-positive patients, relapse rates are 80%-90% if treatment is stopped in 1-2 years (13). Viral resistance to lamivudine occurs in up to 70% of persons during the first 5 years of treatment (32). Lower rates of resistance among treatment-naive patients have been observed with adefovir (30% in 5 years), entecavir (<1% at 4 years), and telbivudine (2.3%-5% in 1 year) (136) but more resistance might occur with longer usage or among patients who developed resistance previously to lamivudine. Although combination therapy has not demonstrated a higher rate of response than that using the most potent antiviral medication in the regimen, more studies are needed using combinations of different classes of different medications active against HBV to determine if com bination therapy will reduce the rate of the development of resistance.

# Development of Surveillance Registries of Persons with Chronic HBV Infection
Information systems, or registries, of persons with chronic HBV infection can facilitate the notification, counseling, and medical management of persons with chronic HBV infection. These registries can be used to distinguish newly reported cases of infection from previously identified cases, facilitate and track case follow-up, enable communication with case contacts and medical providers, and provide local, state, and national esti mates of the proportion of persons with chronic HBV infec tion who have been identified. Public health agencies use registries for patient case management as part of disease con trol programs for HIV and tuberculosis; for tracking cancers; and for identifying disease trends, treatment successes, and outcomes. Chronic HBV registries can similarly be used as a tool for public health program and clinical management. Widespread registry use for chronic HBV infection will be facilitated by the development of better algorithms for deduplication (i.e., methods to ensure that each infected per son is represented only once), routine electronic reporting of laboratory results, and improved communication with labo ratories.
A tiered approach to establishing a registry might allow pro grams to increase incrementally the number of data elements collected and the expected extent of follow-up as resources become available. The specific data elements to be included will depend upon the objectives of the registry and the feasi bility of collecting that information. At a minimum, suffi cient information should be collected to distinguish newly identified persons from those reported previously, including demographic characteristics and serologic test results. If an IgM anti-HBc result is not reported, information about the clinical characteristics of the patient (e.g., presence of symp toms consistent with acute viral hepatitis, date of symptom onset, and results of liver enzyme testing) and the reason for testing can help ensure that the registry includes only persons with chronic infection and excludes those with acute disease. Including data elements on ethnicity and/or country of birth can assist in targeting interventions, and information about contacts identified and managed and medical referrals made can be used to review program needs.
Collaboration between the registry and the perinatal hepa titis B prevention program is important to ensure that the registry captures data on women and infants with chronic infection identified through the perinatal hepatitis B preven tion program. Conversely, the perinatal hepatitis B preven tion program can use registry data to identify outcomes for infants born to infected women who might have been lost to follow-up. Periodic cross-matches with local cancer registry and death certificate data can allow a program to estimate the contribution of chronic HBV infection to cancer and death rates. Guidelines that clarify how and when data with or with out personal identifiers are transmitted and used should be developed to facilitate the protection of confidential data.

# Implementation of Testing Recommendations
Health departments provide clinical services in a variety of settings serving persons recommended for HBsAg testing, including many foreign-born persons, MSM, and IDUs. Ide ally, HBsAg testing should be available in venues such as home less shelters, jails, STD treatment clinics, and refugee clinics because of the increased representation of IDUs and former IDUs in homeless shelters (58% drug users ), substance abuse treatment programs (13%-50% IDUs ), and correctional facilities (25% IDUs ) and the overrepresentation of IDUs and MSM in STD clinics (6% IDUs and 10% MSM ), prevalence of chronic HBV infection is likely to be higher in these settings. However, few states have resources to implement HBsAg testing programs in these set tings and rely instead on limited community programs for needed public health and medical management.
In 2008, CDC supported adult viral hepatitis prevention coordinators (AVHPCs) in 49 states, the District of Colum bia, and five cities (Los Angeles, Chicago, New York City, Philadelphia, and Houston) who assist in integrating hepati tis A and hepatitis B vaccination, hepatitis B and hepatitis C testing, and prevention services among MSM, IDUs, and at-risk heterosexuals treated in STD clinics, HIV testing pro grams, substance abuse treatment centers, correctional facili ties, and other venues. AVHPCs can promote the implementation of hepatitis B screening for MSM and IDUs. Testing in refugee and immigrant health centers and other health-care venues is needed to reach U.S. residents born in regions with HBsAg prevalence of >2% (142); AVHPCs also can collaborate within these settings to ensure that persons from HBV-endemic regions are tested for HBsAg. CDC's perinatal hepatitis B prevention program provides case management for HBsAg-positive mothers and their infants, including educating mothers and providers about appropriate follow-up and medical management (143). This program currently identifies 12,000-13,000 HBsAg-positive pregnant women each year (CDC, unpublished data, 2007). Although perinatal prevention programs provide follow-up for infants born to HBV infected women, the majority of states and local perinatal prevention programs lack staff to offer care referrals for HBV infected pregnant women.
Multiple health-care providers play a role in identifying persons with chronic HBV infection and should seek ways to implement testing for chronic HBV in clinical settings: pri mary care, obstetrician, and other physician offices, refugee clinics, TB clinics, substance abuse treatment programs, dialysis clinics, employee health clinics, university health clin ics, and other venues. Medical compliance with testing rec ommendations already is high for certain populations, particularly among those who typically receive care in hospi tals or other health-care settings in which HBsAg testing is routine. For example, 99% of pregnant women deliver their infants in hospitals and 89%-96% of them are tested for HBV infection (144;CDC, unpublished data, 2007), and suscep tible dialysis patients are tested monthly for HBsAg (119). However, compliance with testing recommendations is lower in other settings. One study indicated that testing was per formed for 30%-50% of persons born in regions with high HBsAg prevalence who were seen in public primary care clin ics (145). Even in settings in which persons are tested rou tinely for HBsAg, more efforts are needed to educate, evaluate, and refer clients for appropriate medical follow-up. CDC sup ports education and training grants that help educate provid ers to screen patients at risk for chronic hepatitis B. Prevention research is needed to guide the delivery of hepatitis B screen ing in diverse clinical and community settings.
In addition, community outreach and education, conducted through developing partnerships between health departments and community organizations, is needed to encourage com munity members to seek HBsAg testing. These partnerships might be particularly important to overcome social and cul tural barriers to testing and care among members of racial and ethnic minority populations who are unfamiliar with the U.S. health-care system. Advisory groups of community rep resentatives, providers who treat patients for chronic hepatitis B, providers whose patient populations represent populations with high prevalence, and professional medical organizations can guide health departments in developing communications and prioritizing hepatitis B screening efforts.
The lack of sufficient resources for management of infected persons can be a barrier to implementation of screening pro grams. All persons with HBV infection, including those who lack insurance and resources, will need ongoing medical man agement and possibly therapy. This demand for care will increase as screening increases, and additional providers will be needed with expertise in the rapidly evolving field of hepa titis B monitoring and treatment.