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 Dec 15;324(23):2423-2436. doi: 10.1001/jama.2020.19750.


Importance: A 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited.

Objective: To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF.

Data sources: Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020.

Study selection: Randomized clinical trials (RCTs) on screening and antiviral therapy; cohort studies on screening, antiviral therapy clinical outcomes, and the association between achieving intermediate outcomes after antiviral therapy and clinical outcomes.

Data extraction and synthesis: One investigator abstracted data; a second investigator checked accuracy. Two investigators independently assessed study quality. Random-effects profile likelihood meta-analysis was performed.

Results: Thirty trials and 20 cohort studies, with a total of 94 168 participants, were included. No study directly evaluated the effects of screening for HBV infection vs no screening on clinical outcomes such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high-prevalence countries and demographic and behavioral risk factors would identify nearly all HBV infection cases. In 1 study (n = 21 008), only screening immigrants from high-prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (n = 2972), antiviral therapy compared with placebo or no treatment was associated with greater likelihood of achieving intermediate outcomes, such as virologic suppression and hepatitis B e-antigen (HBeAg) or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virologic suppression to 17 for HBeAg seroconversion. Based on 12 trials (n = 4127), first-line antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (n = 4809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (n = 3893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes but were heterogeneous (hazard ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events vs placebo or no antiviral therapy.

Conclusions and relevance: There was no direct evidence for the clinical benefits and harms of HBV screening vs no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Antiviral Agents / therapeutic use
  • Emigrants and Immigrants
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus* / immunology
  • Hepatitis B, Chronic / diagnosis*
  • Hepatitis B, Chronic / drug therapy
  • Humans
  • Mass Screening / adverse effects
  • Mass Screening / standards*
  • Practice Guidelines as Topic
  • Risk Factors


  • Antiviral Agents
  • Hepatitis B Surface Antigens