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Final Research Plan

Final Research Plan for Hepatitis B Virus Infection: Screening, 2014

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.


The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report forms the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from October 9 until November 6, 2012 at 5:00 p.m., ET.

I. Analytic Framework

Select Text Description below for details.

D Select for Text Description.

II. Key Questions to be Systematically Reviewed

  1. What are the benefits of screening for hepatitis B virus (HBV) versus no screening in asymptomatic, nonpregnant adolescents and adults on morbidity, mortality, and disease transmission?
  2. What are the harms of screening for HBV infection (e.g., labeling, anxiety, and harms of confirmatory tests, including biopsy)?
  3. How well do different screening strategies identify individuals with HBV infection (e.g., strategies that target persons from high prevalence countries, men who have sex with men, injection drug users, immunization history, or other risk factors)?
  4. In nonpregnant adolescents and adults with no evidence of HBV immunity at screening, how effective is HBV vaccination in improving clinical outcomes?
  5. In nonpregnant adolescents and adults with chronic HBV infection, how effective is antiviral treatment in improving intermediate outcomes (e.g., virologic or histologic improvement or clearance of hepatitis B e antigen [HbeAg])?
  6. In nonpregnant adolescents and adults with chronic HBV infection, how effective is antiviral treatment in improving health outcomes?
  7. In nonpregnant adolescents and adults with chronic HBV infection, how effective is education or behavioral change counseling in reducing transmission and improving health outcomes?
  8. What are the harms associated with antiviral treatment for HBV infection?
  9. Do improvements in intermediate outcomes improve final health outcomes?

III. Research Approach

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the evidence report. Criteria are overarching as well as specific to each of the key questions (KQs).

  Include Exclude
Disease Chronic HBV infection: detectable hepatitis B surface antigen in serum for >6 months Acute HBV infection
KQs 1–3 Nonpregnant adults (ages ≥18 years) and adolescents (ages 13 to <18 years) who are asymptomatic for HBV infection Symptomatic patients, children and pregnant women, HIV(+) or hepatitis C virus(+) persons or other special populations, such as hemodialysis and transplant patients
KQ 4 Persons without evidence of HBV immunity or disease upon screening  
KQs 5–9 Nonpregnant adults and adolescents with chronic HBV infection  
KQs 1, 2 Screening  
KQ 3 Screening strategies Laboratory test results
KQs 4, 9 Vaccination  
KQs 5–8 Education or behavior change counseling

Antiviral treatments for treatment-naive patients (Note: Food and Drug Administration [FDA]-approved treatments include interferon alpha, lamivudine, adefovir, entecavir, telbivudine, tenofovir)

NonFDA-approved antiviral treatments, combination therapy
KQs 1, 2 No screening  
KQs 4, 9 No vaccination  
KQs 5–7 No treatment  
KQ 3 Gold standard diagnostic test  
KQ 8 No treatment  
KQs 2 Labeling, anxiety; harms from liver biopsy; side effects  
KQ 3 Measures of predictive validity  
KQ 4 Disease prevention  
KQ 5 Intermediate outcomes: virologic improvement, histologic improvement, HBeAg clearance  <3 months followup data; drug resistance; development of mutations or antibodies to drugs
KQs 1, 6, 7, 9 Final outcomes: mortality, cirrhosis, hepatocellular cancer, quality of life, disease transmission  
KQ 8 Harms from antiviral medications  
Setting Primary care and primary care referable settings, such as correctional and community care settings serving injection drug users, men who have sex with men, or sexually transmitted disease populations; United States and countries with similar HBV prevalence, except for antiviral therapies (all countries)  
Study Designs
All KQs Good-quality systematic reviews  
KQ 1 Randomized, controlled trials and controlled observational studies Uncontrolled studies
KQs 2, 8 Randomized, controlled trials and controlled observational studies; large, uncontrolled observational studies with long-term followup Very small uncontrolled studies; case studies
KQ 3 Studies assessing predictive validity of screening strategies  
KQs 4–7 Randomized, placebo-controlled trials  
KQ 9 Cohort studies examining the association between intermediate and clinical outcomes after antiviral treatment  


IV. Response to Public Comment

The draft Research Plan was posted for public comment on the U.S. Preventive Services Task Force (USPSTF) Web site from October 9 to November 6, 2012. The USPSTF received several comments requesting clarification on the inclusion and exclusion criteria, analytic framework, and key questions related to populations, risk factors, settings, interventions, and outcomes. The Research Plan was revised in response to these comments. Several commenters identified “stigma” as an important potential outcome of screening, and it was added to the inclusion criteria.

Current as of: March 2013

Internet Citation: Final Research Plan: Hepatitis B Virus Infection: Screening, 2014. U.S. Preventive Services Task Force. October 2014.

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