Hepatitis B: Screening -- Nonpregnant Adolescents and Adults At High Risk


General

Grade: B The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. Offer or provide this service.

Specific Recommendations

The USPSTF recommends screening for hepatitis B virus (HBV) infection in persons at high risk for infection. 

Frequency of Service

Periodic screening may be useful in patients with ongoing risk for HBV transmission (for example, active injection drug users, men who have sex with men, and patients receiving hemodialysis) who do not receive vaccination. Clinical judgment should determine screening frequency, because the USPSTF found inadequate evidence to determine specific screening intervals.

Risk Factor Information

A major risk factor for HBV infection is country of origin. The risk for HBV infection varies substantially by country of origin in foreign-born persons in the United States. Persons born in countries with a prevalence of HBV infection of 2% or greater account for 47% to 95% of those with chronic HBV infection in the United States (Table 1). Another important risk factor for HBV infection is lack of vaccination in infancy in U.S.-born persons with parents from a country or region with high prevalence (≥8%), such as sub-Saharan Africa, central and southeast Asia, and China (Figure). Because HBV infection prevalence may gradually change over time, it is important to note that some countries and regions with prevalence rates between 5-7% are considered to be highly endemic areas. The CDC also recommends screening in persons receiving hemodialysis or cytotoxic or immunosuppressive therapy (for example, chemotherapy for malignant diseases and immunosuppression related to organ transplantation and for rheumatologic and gastroenterologic disorders). Some persons with combinations of risk factors who are not members of one of these risk factor groups may also be at increased risk for HBV infection. However, reliable information about combinations of risk factors is not available. Clinicians should exercise their judgment in deciding whether these persons are at sufficiently high risk to warrant screening. For example, screening is probably appropriate in settings that treat a large proportion of persons at increased risk, such as clinics for sexually transmitted infections; HIV testing and treatment centers; health care settings that provide services for injection drug users or men who have sex with men; correctional facilities; and institutions that serve populations from countries with a high prevalence of infection, including community health centers. The prevalence of HBV infection is low in the general U.S. population, and most infected persons do not develop complications. Therefore, screening is not recommended in those who are not at increased risk. The USPSTF notes that high rates of HBV infection have been found in cities and other areas with high numbers of immigrants or migrant persons from Asia or the Pacific Islands or their adult children. Providers should consider the population they serve when making screening decisions.


Clinical

Patient Population Under Consideration

This recommendation applies to asymptomatic, nonpregnant adolescents and adults at high risk for HBV infection (including those at high risk who were vaccinated before being screened for HBV infection).

Assessment of Risk

A major risk factor for HBV infection is country of origin. The risk for HBV infection varies substantially by country of origin in foreign-born persons in the United States. Persons born in countries with a prevalence of HBV infection of 2% or greater account for 47% to 95% of those with chronic HBV infection in the United States (Table 1). Another important risk factor for HBV infection is lack of vaccination in infancy in U.S.-born persons with parents from a country or region with high prevalence (≥8%), such as sub-Saharan Africa, central and southeast Asia, and China (Figure). Because HBV infection prevalence may gradually change over time, it is important to note that some countries and regions with prevalence rates between 5-7% are considered to be highly endemic areas.

Table 1. Geographic Regions With an HBsAg Prevalence ≥2%*

RegionCountries
Africa All
Asia§ All
Australia and South Pacific All except Australia and New Zealand
Middle East All except Cyprus and Israel
Eastern Europe All except Hungary
Western Europe Malta, Spain, and indigenous populations in Greenland
North America Alaska natives and indigenous populations in northern Canada
Mexico and Central America Guatemala and Honduras
South America Ecuador; Guyana; Suriname; Venezuela; and Amazonian areas of Bolivia, Brazil, Colombia, and Peru
Caribbean Antigua and Barbuda, Dominica, Grenada, Haiti, Jamaica, St. Kitts and Nevis, St. Lucia, and Turks and Caicos Islands

* Adapted from reference 2. Estimates of prevalence of HBsAg, a marker of chronic hepatitis B virus infection, are based on limited data and may not reflect current prevalence in countries that have implemented childhood hepatitis B virus vaccination. In addition, the prevalence of HBsAg may vary within countries by subpopulation and locality.
† The regions with the highest prevalence (>5%) are sub-Saharan Africa and central and southeast Asia. See Figure 2.
‡ A complete list of countries in each region is available at http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/hepatitis-b.
§ Asia includes 3 regions: southeast, east, and north Asia. Abbreviation: HBsAg = hepatitis B surface antigen. The Centers for Disease Control and Prevention (CDC) uses a prevalence threshold of 2% or greater to define countries with high risk for HBV infection. Because this threshold is substantially higher than the estimated prevalence of HBV infection in the general U.S. population (0.3% to 0.5%), it is a reasonable threshold for deciding to screen a patient population or risk group. Additional risk groups for HBV infection with a prevalence of 2% or greater that should be screened include HIV-positive persons, injection drug users, household contacts or sexual partners of persons with HBV infection, and men who have sex with men (Table 2).

Table 2. Prevalence of HBV Infection, by Risk Group

Risk GroupPersons with HBV Infection, %Reference
HIV-positive persons* 4.0–17.0 2, 6
Injection drug users 2.7–11.0 2, 7
Household contacts or sex partners of persons with HBV infection 3.0 to 20.0 2
Men who have sex with men 1.1 to 2.3 2

* Data from United States and western Europe.

Abbreviation: HBV = hepatitis B virus.

The CDC also recommends screening in persons receiving hemodialysis or cytotoxic or immunosuppressive therapy (for example, chemotherapy for malignant diseases and immunosuppression related to organ transplantation and for rheumatologic and gastroenterologic disorders).

Some persons with combinations of risk factors who are not members of one of these risk factor groups may also be at increased risk for HBV infection. However, reliable information about combinations of risk factors is not available. Clinicians should exercise their judgment in deciding whether these persons are at sufficiently high risk to warrant screening. For example, screening is probably appropriate in settings that treat a large proportion of persons at increased risk, such as clinics for sexually transmitted infections; HIV testing and treatment centers; health care settings that provide services for injection drug users or men who have sex with men; correctional facilities; and institutions that serve populations from countries with a high prevalence of infection, including community health centers.

The prevalence of HBV infection is low in the general U.S. population, and most infected persons do not develop complications. Therefore, screening is not recommended in those who are not at increased risk. The USPSTF notes that high rates of HBV infection have been found in cities and other areas with high numbers of immigrants or migrant persons from Asia or the Pacific Islands or their adult children. Providers should consider the population they serve when making screening decisions.

Screening Tests

The CDC recommends screening for HBsAg with tests approved by the U.S. Food and Drug Administration, followed by a licensed, neutralizing confirmatory test for initially reactive results. Immunoassays for detecting HBsAg have a reported sensitivity and specificity greater than 98%. A positive HBsAg result indicates acute or chronic infection.

Testing for antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc) is also done as part of a screening panel to help distinguish between infection and immunity. Acute HBV infection (acquired within 6 months after infection) is characterized by the appearance of HBsAg and followed by the appearance of IgM anti-HBc. The disappearance of HBsAg and the presence of anti-HBs and anti-HBc indicate the resolution of HBV infection and natural immunity. Anti-HBc, which persist for life, are present only after HBV infection and do not develop in persons whose immunity to HBV is due to vaccination.

Persons who have received HBV vaccination have only anti-HBs. Diagnosis of chronic HBV infection is characterized by persistence of HBsAg for at least 6 months. Levels of HBV DNA can fluctuate and are not a reliable marker of chronic infection.

Treatment

Antiviral Regimens

The goals of antiviral treatment are to achieve sustained suppression of HBV replication and remission of liver disease to prevent cirrhosis, hepatic failure, and hepatocellular carcinoma. Interferons or nucleoside or nucleotide analogues are used to treat HBV infection. The U.S. Food and Drug Administration has approved 7 antiviral drugs for treatment of chronic HBV infection: interferon-α2b, pegylated interferon-α2a, lamivudine, adefovir, entecavir, telbivudine, and tenofovir. Approved first-line treatments are pegylated interferon-α2a, entecavir, and tenofovir. Combination therapies have been evaluated but are not approved by the U.S. Food and Drug Administration and are generally not used as first-line treatment because tolerability, efficacy, and rates of resistance are low. 

Several factors affect the choice of antiviral drug, including patient characteristics, HBV DNA and serum aminotransferase levels, and HBeAg status. Biopsy is sometimes done to determine the extent of liver inflammation and fibrosis. Surrogate end points of antiviral treatment include loss of HBeAg and HBsAg, HBeAg seroconversion in HBeAg-positive patients, and suppression of HBV DNA to undetectable levels by polymerase chain reaction in patients who are HBeAg-negative and anti-HBe–positive. Duration of treatment varies depending on the time required to suppress HBV DNA levels and normalize alanine aminotransferase (ALT) levels; HBeAg status; the presence of cirrhosis; and the choice of drug.

Vaccination

The current U.S. strategy to eliminate HBV transmission includes universal vaccination of all infants at birth and vaccination of adolescents and high-risk adults, such as injection drug users and household contacts of patients with HBV infection. Three doses of HBV vaccine result in a protective antibody response of greater than 90% in adults and greater than 95% in adolescents. The CDC recommends that susceptible persons who are screened for HBV infection may, if indicated, receive the first dose of the HBV vaccine at the same medical visit.

Screening Interval

Periodic screening may be useful in patients with ongoing risk for HBV transmission (for example, active injection drug users, men who have sex with men, and patients receiving hemodialysis) who do not receive vaccination. Clinical judgment should determine screening frequency, because the USPSTF found inadequate evidence to determine specific screening intervals.

Other Considerations

Research Needs and Gaps

The development and validation of clinical decision support or other tools to help clinicians efficiently and accurately identify populations at high risk for HBV infection, including combinations of risk factors, are needed. Available clinical trials largely report intermediate or surrogate outcomes and are relatively short. Clinical trials of adequate duration and power to evaluate long-term health outcomes (for example, cirrhosis, end-stage liver disease, disease-specific mortality, quality of life, and all-cause mortality) are needed. In the absence of such randomized, controlled trials, registries to assess treatment efficacy are also needed.

Other Approaches to Prevention

For the USPSTF recommendation on screening for HBV infection in pregnancy, go to www.uspreventiveservicestaskforce.org/uspstf/uspshepbpg.htm. The USPSTF recommendation on screening for hepatitis C virus infection can be found at www.uspreventiveservicestaskforce.org/uspstf/uspshepc.htm.

Other Resources

The CDC provides information about HBV infection at www.cdc.gov/hepatitis/HBV/index.htm

For more information about adolescent vaccination, visit www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm?s_cid=rr5416a1_e.

For information on adult vaccination, visit www.cdc.gov/mmwr/preview/mmwrhtml/rr5516a1.htm?s_cid=rr5516a1_e.

Further resources for clinicians can be found at www.cdc.gov/hepatitis/HBV/ProfResourcesB.htm.

Rationale

No information available.


Others

The CDC and the American Association for the Study of Liver Diseases recommend screening for HBV infection in high-risk persons, including all foreign-born persons from regions with an HBsAg prevalence of 2% or greater regardless of vaccination history; U.S.-born persons not vaccinated as infants whose parents were born in regions with an HBsAg prevalence of 8% or greater; injection drug users; men who have sex with men; household contacts and sexual partners of HBsAg-positive persons; patients receiving hemodialysis; and immunosuppressed and HIV-positive persons. The CDC also recommends screening for HBV infection in blood, organ, or tissue donors; persons with occupational or other exposures to infectious blood or body fluids; and those who received HBV vaccination as adolescents or adults with high-risk behaviors. In addition, the American Association for the Study of Liver Diseases recommends that persons with multiple sexual partners or a history of sexually transmitted infections, inmates of correctional facilities, and persons with hepatitis C virus infection be screened.The Institute of Medicine endorses screening for HBV infection in high-risk groups similar to those recommended by the CDC. The American Academy of Family Physicians recommends screening for HBV infection in persons at high risk for infection and recommends against routinely screening the general asymptomatic population.


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