Screening for Hepatitis B Virus Infection in Adolescents and Adults: Recommendation Statement

Am Fam Physician. 2021;103(8):495-501

Related Putting Prevention into Practice: Screening for Hepatitis B Virus Infection in Adolescents and Adults

As published by the USPSTF.

Summary of Recommendation

The USPSTF recommends screening for hepatitis B virus (HBV) infection in adolescents and adults at increased risk for infection (Table 1). B recommendation.

See the Practice Considerations section for a description of adolescents and adults at increased risk for infection.

Importance

An estimated 862,000 persons in the United States are living with chronic infection with HBV.¹ Persons born in regions with a prevalence of HBV infection of 2% or greater, such as countries in Africa and Asia, the Pacific Islands, and parts of South America, often become infected at birth and account for up to 95% of newly reported chronic infections in the United States. Other high-prevalence populations include persons who inject drugs; men who have sex with men; persons with HIV infection; and sex partners, needle-sharing contacts, and household contacts of persons with chronic HBV infection.²

According to the Centers for Disease Control and Prevention (CDC), an estimated 68% of people with chronic hepatitis B are unaware of their infection,³ and many remain asymptomatic until onset of cirrhosis or end-stage liver disease.^4,5 This contributes to delays in medical evaluation and treatment and ongoing transmission to sex partners and persons who share objects contaminated with blood or other bodily fluids that contain HBV.^3,6 From 15% to 40% of persons with chronic infection develop cirrhosis, hepatocellular carcinoma, or liver failure, which lead to substantial morbidity and mortality.⁴

USPSTF Assessment of Magnitude of Net Benefit

The USPSTF concludes with moderate certainty that screening for HBV infection in adolescents and adults at increased risk for infection has moderate net benefit.

See Table 2 for more information on the USPSTF recommendation rationale and assessment.

Rationale	Nonpregnant adolescents and adults at increased risk
Detection	Adequate evidence that the identification of HBV infection is accurate based on laboratory-based immunoassays for detecting hepatitis B surface antigen, with reported sensitivity and specificity exceeding 98%.
Benefits of early detection and treatment	Inadequate direct evidence on benefits of screening on health outcomes due to lack of studies. Convincing evidence that antiviral treatment of patients with chronic HBV infection is effective at improving intermediate outcomes, including HBeAg loss and virologic suppression. Adequate evidence from clinical trials and cohort studies that antiviral treatment of patients with chronic HBV infection improves health outcomes, such as reduced risk of mortality or hepatocellular carcinoma. Adequate evidence that improvements in intermediate outcomes of chronic HBV infection related to antiviral treatment (such as HBeAg clearance and virologic suppression) are associated with reduced risk of adverse health outcomes (such as cirrhosis and hepatocellular carcinoma).
Harms of early detection and treatment	Inadequate direct evidence on the harms of screening for HBV infection due to lack of studies. Adequate evidence to bound the harms of screening as small to none based on the nature of the intervention and the low likelihood of serious harms. (When direct evidence is limited, absent, or restricted to select populations or clinical scenarios, the USPSTF may place conceptual upper or lower bounds on the magnitude of benefit or harms.) Adequate evidence that the magnitude of harms of treatment is small, based on several trials showing that risks of adverse events, nausea, and diarrhea are not significantly greater in persons receiving treatment than in persons receiving placebo or no treatment, and that some adverse events resolve after discontinuing therapy.
USPSTF assessment	Moderate certainty that screening for HBV infection in nonpregnant adolescents and adults at increased risk for infection has a moderate net benefit, given the accuracy of screening tests and the effectiveness of antiviral treatment.

For more details on the methods the USPSTF uses to determine the net benefit, see the USPSTF Procedure Manual.⁷

Practice Considerations

PATIENT POPULATION UNDER CONSIDERATION

This recommendation applies to asymptomatic, nonpregnant adolescents and adults at increased risk for HBV infection, including those who were vaccinated before being screened for HBV infection. The USPSTF has made a separate recommendation on screening in pregnant women.⁸

ASSESSMENT OF RISK

The risk for HBV infection varies substantially by country of origin in non–U.S.-born persons living in the United States. Persons born in countries with a prevalence of hepatitis B surface antigen (HBsAg) of 2% or greater (Table 3,^2,9 Figure¹⁰ at https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/hepatitis-b-virus-infection-screening#fig) account for the majority of cases of new chronic HBV infection in the United States; most persons in these countries acquired HBV infection from perinatal transmission.² Persons born in the United States with parents from regions with higher prevalence are also at increased risk of HBV infection during birth or early childhood, particularly if they do not receive appropriate passive and active immunoprophylaxis (and antiviral therapy for pregnant women with a high viral load) (Figure¹⁰ at https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/hepatitis-b-virus-infection-screening#fig).^11–13 The CDC classifies HBV endemicity levels by prevalence of positive HBsAg (high [8%], moderate [2%–7%], or low [<2%]) (Figure 10 at https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/hepatitis-b-virus-infection-screening#fig). The estimated prevalence of HBV infection in the general U.S. population is 0.3% to 0.5%,^{8,9,11,12,14,15} which makes it reasonable to screen adolescents and adults born in countries or regions with an HBsAg prevalence of 2% or greater (regardless of vaccination history in their country of origin) and adolescents and adults born in the United States who did not receive the HBV vaccine as infants and whose parents were born in regions with an HBsAg prevalence of 8% or greater (regardless of their biological mother's HBsAg status).

Continent/region	Prevalence				No data

	High (≥ 8.0%)	High moderate (5.0%–7.9%)	Low moderate (2.0%–4.9%)	Low (≤ 1.9%)
Africa	Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Congo, Côte d'Ivoire, Djibouti, Equatorial Guinea, Gabon, Gambia, Ghana, Guinea, Liberia, Malawi, Mali, Mauritania, Mozambique, Namibia, Niger, Nigeria, Senegal, Sierra Leone, Somalia, South Sudan, Sudan, Swaziland, Togo, Uganda, Zimbabwe	Cape Verde, Democratic Republic of the Congo, Ethiopia, Kenya, Rwanda, South Africa, Tanzania, Tunisia, Zambia	Algeria, Eritrea, Libya, Madagascar	Egypt, Morocco, Seychelles	Botswana, Chad, Comoros, Guinea-Bissau, Lesotho, Mauritius, Príncipe, São Tomé
Caribbean	Haiti		Dominican Republic, Jamaica	Barbados, Cuba	Antigua and Barbuda, The Bahamas, Dominica, Grenada, Saint Kitts and Nevis, Saint Lucia, Saint Vincent and the Grenadines, Tobago, Trinidad
Oceania	Kiribati, Nauru, Niue, Papua New Guinea, Solomon Islands, Tonga, Vanuatu	Marshall Islands, Samoa, Tuvalu	Federated States of Micronesia, Fiji, New Zealand, Palau, Tahiti	Australia	Cook Islands
Central Asia	Kyrgyzstan	Bhutan, Kazakhstan, Tajikistan, Uzbekistan	Azerbaijan		Armenia, Turkmenistan
South Asia			Pakistan, Sri Lanka	Afghanistan, India, Nepal	Maldives
Southeast Asia	Laos, Vietnam	Thailand	Bangladesh, Brunei Darussalam, Bulgaria, Cambodia, Myanmar, Philippines, Singapore	Indonesia, Malaysia	Timor-Leste
East Asia	Mongolia	China	South Korea	Japan	North Korea
Middle East	Yemen	Oman	Cyprus, Saudi Arabia, Syria, Turkey	Bahrain, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Palestine, Qatar, United Arab Emirates
Eastern Europe		Albania, Moldova, Romania	Belarus, Georgia, Kosovo, Russia	Bosnia and Herzegovina, Croatia, Czech Republic, Hungary, Lithuania, Poland, Serbia, Slovakia, Slovenia, Ukraine	Latvia, Lithuania, Macedonia, Montenegro
Western Europe			Italy	Austria, Belgium, Denmark, France, Germany, Greece, Iceland, Ireland, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, United Kingdom	Andorra, Finland, Luxembourg, Malta, Monaco, San Marino
North (Central) America			Belize	Canada, Costa Rica, Guatemala, Nicaragua, Mexico, Panama, U.S.	El Salvador, Honduras
South America			Colombia, Ecuador, Peru, Suriname	Argentina, Bolivia, Brazil, Chile, Venezuela	Guyana, Paraguay, Uruguay

HBV screening should also be offered to other risk groups defined by clinical and behavioral characteristics in which prevalence of positive HBsAg is 2% or greater. Persons from such risk groups include persons who have injected drugs in the past or currently; men who have sex with men; persons with HIV; and sex partners, needle-sharing contacts, and household contacts of persons known to be HBsAg positive^{2,3,9,12–14,16,17} (Table 4^{2,9,11,12,15–19}). Some persons with combinations of risk factors who are not members of risk factor groups listed previously may also be at increased risk for HBV infection. Clinicians should therefore consider the populations they serve when making screening decisions.

Risk group	Proportion with HBV infection, %	Sources
HIV-positive persons*	3.3–17.0	Chou, et al.¹¹
		Schweitzer, et al.⁹
		Nelson, et al.¹⁶
		Thio¹⁷
		Abara and Schillie¹⁸
		Chou, et al.¹⁹
Persons who inject drugs	2.7–19.7	Chou, et al.¹¹
		Kim, et al.¹²
		Schweitzer, et al.⁹
		Le, et al.¹⁵
		Chou, et al.¹⁹
Household contacts or sex partners of persons with HBV infection	3.0–20.0	Schillie, et al.²
	3.0–20.0	Schweitzer, et al.⁹
Men who have sex with men	1.1–2.3	Schweitzer, et al.⁹

SCREENING TESTS

Screening for hepatitis B should be performed with HBsAg tests approved by the U.S. Food and Drug Administration, followed by a confirmatory test for initially reactive results.^2,18

A positive HBsAg result indicates chronic or acute infection. Serologic panels performed concurrently with or after HBsAg screening allow for diagnosis and to determine further management. (See the Additional Tools and Resources section for serologic test interpretation.)

SCREENING INTERVALS

For patients with negative HBsAg results who have not received the HBV vaccine series, periodic screening may be useful for those who report continued risk for acquiring HBV transmission, such as persons who continue to inject drugs and men who have sex with men. Clinical judgment should be used to determine screening frequency. The USPSTF found no evidence to determine optimal screening intervals.

TREATMENT

Persons with testing results indicative of acute or chronic HBV infection generally receive education about reducing the risk of transmission (e.g., during childbirth or with sex partners, needle-sharing partners, and household contacts).²⁰ Between 20% and 40% of patients with chronic HBV infection require treatment⁴ (see Additional Tools and Resources section for information on treatment). Several antiviral medications are approved by the U.S. Food and Drug Administration for treatment of chronic HBV infection.²¹

IMPLEMENTATION

Many persons at risk for HBV infection are not screened or vaccinated.⁴ For example, approximately 11% to 67% of non–U.S.-born persons and 28% to 52% of men who have sex with men have undergone HBV screening.⁴ Low uptake of screening may be related to several barriers, including language, lack of awareness about HBV, limited access to health care, inability to access affordable treatment, stigmatization, concerns about suspension from jobs and other communal activities, and patients' concerns about reporting and follow-up of screening results by public health authorities that may involve notification of close contacts.^4,14,22–24 When offering screening, clinicians should understand the positive and negative implications of reporting (as required by most U.S. jurisdictions²⁵), case investigations, and contact notification.^24,26

ADDITIONAL TOOLS AND RESOURCES

Several tools may help clinicians implement this screening recommendation. The CDC provides the following tools.

Resources on hepatitis B for professionals (https://www.cdc.gov/hepatitis/hbv/profresourcesb.htm)
A fact sheet on interpretation of hepatitis B serologic tests (https://www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf)
Information about HBV prevention, vaccination, transmission, screening, counseling, and treatment (https://www.cdc.gov/hepatitis/HBV/index.htm and https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm)
Information on adolescent and adult HBV vaccination (https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm?s_cid=rr5416a1_e)

OTHER RELATED USPSTF RECOMMENDATIONS

Other related USPSTF recommendations are available at https://www.uspreventiveservicestaskforce.org/uspstf/. These include screening for HBV infection during pregnancy⁸; screening for hepatitis C virus infection in adults aged 18 to 79 years²⁷; screening for HIV in adolescents and adults aged 15 to 65 years²⁸; and behavioral counseling to prevent sexually transmitted infections.²⁹

This recommendation statement was first published in JAMA. 2020;324(23):2415–2422.

The “Update of Previous USPSTF Recommendation,” “Supporting Evidence,” “Research Needs and Gaps,” and “Recommendations of Others” sections of this recommendation statement are available at https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/hepatitis-b-virus-infection-screening#fullrecommendationstart.

The USPSTF recommendations are independent of the U.S. government. They do not represent the views of the Agency for Healthcare Research and Quality, the U.S. Department of Health and Human Services, or the U.S. Public Health Service.

This summary is one in a series excerpted from the Recommendation Statements released by the USPSTF. These statements address preventive health services for use in primary care clinical settings, including screening tests, counseling, and preventive medications.

The complete version of this statement, including supporting scientific evidence, evidence tables, grading system, members of the USPSTF at the time this recommendation was finalized, and references, is available on the USPSTF website at https://www.uspreventiveservicestaskforce.org/.

Patel EU, Thio CL, Boon D, et al. Prevalence of hepatitis B and hepatitis D virus infections in the United States, 2011–2016. Clin Infect Dis. 2019;69(4):709-712.

Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67(1):1-31.

U.S. Department of Health and Human Services. Hepatitis B basic information. Updated August 31, 2020. Accessed November 18, 2020. https://www.hhs.gov/hepatitis/learn-about-viral-hepatitis/hepatitis-b-basics/index.html

Abara WE, Qaseem A, Schillie S, et al.; High Value Care Task Force of the American College of Physicians and the Centers for Disease Control and Prevention. Hepatitis B vaccination, screening, and linkage to care: best practice advice from the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2017;167(11):794-804.

McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology. 2009;49(5 suppl):S45-S55.

Lin SY, Chang ET, So SK. Why we should routinely screen Asian American adults for hepatitis B: a cross-sectional study of Asians in California. Hepatology. 2007;46(4):1034-1040.

U.S. Preventive Services Task Force. Procedure manual; 2015. Accessed October 22, 2020. https://www.uspreventiveservicestaskforce.org/uspstf/procedure-manual

US Preventive Services Task Force. Screening for hepatitis B virus infection in pregnant women: US Preventive Services Task Force reaffirmation recommendation statement [published correction appears in JAMA. 2019;322(11):1108]. JAMA. 2019;322(4):349-354.

Schweitzer A, Horn J, Mikolajczyk RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386(10003):1546-1555.

Harris AM; Centers for Disease Control and Prevention. Chapter 4: travel-related infectious diseases. In: CDC Yellow Book 2020: Health Information for International Travel. 2020. Accessed October 22, 2020. https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/hepatitis-b#5182

Chou R, Blazina I, Bougatsos C, et al. Screening for hepatitis B virus infection in nonpregnant adolescents and adults: a systematic review for the U.S. Preventive Services Task Force recommendation. Evidence synthesis no. 194. AHRQ publication 20-05262-EF-1. Agency for Healthcare Research and Quality; 2020.

Kim HS, Rotundo L, Yang JD, et al. Racial/ethnic disparities in the prevalence and awareness of hepatitis B virus infection and immunity in the United States. J Viral Hepat. 2017;24(11):1052-1066.

Weinbaum CM, Williams I, Mast EE, et al.; Centers for Disease Control and Prevention. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(RR-8):1-20.

Shing JZ, Ly KN, Xing J, et al. Prevalence of hepatitis B virus infection among US adults aged 20–59 years with a history of injection drug use: National Health and Nutrition Examination Survey, 2001–2016. Clin Infect Dis. 2020;70(12):2619-2627.

Le MH, Yeo YH, Cheung R, et al. Chronic hepatitis B prevalence among foreign-born and U.S.-born adults in the United States, 1999–2016. Hepatology. 2020;71(2):431-443.

Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378(9791):571-583.

Thio CL. Hepatitis B and human immunodeficiency virus coinfection. Hepatology. 2009;49(5 Suppl):S138-S145.

Abara WE, Schillie SF; Centers for Disease Control and Prevention. Chapter 4: hepatitis B. In: Manual for the Surveillance of Vaccine-Preventable Diseases. May 31, 2018. Accessed October 22, 2020. https://www.cdc.gov/vaccines/pubs/surv-manual/chpt04-hepb.html

Chou R, Blazina I, Bougatsos C, et al. Screening for hepatitis B virus infection in nonpregnant adolescents and adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2020;324(23):2423-2436.

Workowski KA, Bolan GA Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015 [published correction appears in MMWR Recomm Rep. 2015;64(33):924]. MMWR Recomm Rep. 2015;64(RR-03):1-137.

Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560-1599.

Hepatitis B Foundation. Know your rights. 2020. Accessed October 22, 2020. https://www.hepb.org/resources-and-support/know-your-rights/

Centers for Disease Control and Prevention. Guidelines for viral hepatitis surveillance and case management. Updated May 31, 2005. Accessed October 22, 2020. https://www.cdc.gov/hepatitis/statistics/surveillanceguidelines.htm

World Health Organization. Guidelines on hepatitis B and C testing. February 2017. Accessed October 22, 2020. https://www.who.int/hepatitis/publications/guidelines-hepatitis-c-b-testing/en/

Centers for Disease Control and Prevention. Viral hepatitis surveillance—United States. Hepatitis B tables and figures (Table 3.3). Updated November 14, 2019. Accessed October 22, 2020. https://www.cdc.gov/hepatitis/statistics/2017surveillance/TablesFigures-HepB.htm#tabs-1-3

Spradling PR, Xing J, Rupp LB, et al.; Chronic Hepatitis Cohort Study (CHeCS) Investigators. (CHeCS) Investigators. Infrequent clinical assessment of chronic hepatitis B patients in United States general healthcare settings. Clin Infect Dis. 2016;63(9):1205-1208.

US Preventive Services Task Force. Screening for hepatitis C virus infection in adolescents and adults: US Preventive Services Task Force recommendation statement. JAMA. 2020;323(10):970-975.

US Preventive Services Task Force. Screening for HIV infection: US Preventive Services Task Force recommendation statement. JAMA. 2019;321(23):2326-2336.

U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161(12):894-901.

What does the USPSTF recommend?	For adolescents and adults: Screen adolescents and adults at increased risk for HBV infection. Grade B
To whom does this recommendation apply?	All asymptomatic, nonpregnant adolescents and adults at increased risk for HBV infection, including those who were vaccinated before being screened for HBV infection.
What's new?	This recommendation is consistent with the 2014 USPSTF recommendation. It is strengthened by new evidence that treatment of HBV infection consistently leads to better health outcomes.
How to implement this recommendation?	Screen adolescents and adults at increased risk using hepatitis B surface antigen tests followed by a confirmatory test for initially reactive results. Important risk groups for HBV infection with a prevalence of ≥ 2% who should be screened include: Persons born in countries and regions with a high prevalence of HBV infection (≥ 2%), such as Asia, Africa, the Pacific Islands, and parts of South America U.S.-born persons not vaccinated as infants whose parents were born in regions with a very high prevalence of HBV infection (≥ 8%) HIV-positive persons Persons with injection drug use Men who have sex with men Household contacts or sex partners of persons with HBV infection For more information on countries and regions with a high prevalence of HBV infection, visit: https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/hepatitis-b#5182
How often?	Periodically screen persons with continued risk for HBV infection (e.g., persons with current injection drug use, men who have sex with men).
What are other relevant USPSTF recommendations?	The USPSTF has made recommendations on screening for HBV infection in pregnant persons, hepatitis C virus infection in adolescents and adults, and HIV infection. These recommendations are available at https://www.uspreventiveservicestaskforce.org.
Where to read the full recommendation statement?	Visit the USPSTF website to read the full recommendation statement. This includes more details on the rationale of the recommendation, including benefits and harms; supporting evidence; and recommendations of others.