Screening for HBV Infections in Adolescents and Adults

In 2004, the United States Preventive Services Task Force (USPSTF) recommended against screening asymptomatic people for hepatitis B virus (HBV) infection on the basis of lack of evidence that screening would improve clinical outcomes, especially given the low prevalence of HBV infection in the general population. Screening for HBV infection, however, could identify chronically infected persons who might benefit from antiviral therapies, surveillance to diagnose hepatocellular carcinoma, or interventions to reduce behaviors associated with progression of liver disease.

A systematic review was recently conducted to update the USPSTF 2004 recommendation by evaluating the current evidence on screening for HBV infection [Ann Intern Med; 2014: DOI:10.7326/M13-2837]. Data for the review were collected via online searches through MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and PsycINFO.

A list of key questions was developed and analyzed for the studies reviewed (Please see Table below). The body of evidence for each key question was rated based on the number, quality, and size of studies; consistency of results; and directness of evidence. Additionally, meta-analyses were conducted to calculate relative risks using the DerSimonian-Laird random-effects model.

The research for this study was funded by the Agency for Healthcare Resource and Quality (AHRQ). Study investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions.

No study compared clinical outcomes or harms in persons screened for HBV infection versus those not screened. One systematic review found that HBV vaccination was associated with decreased risk for HBV infection in health care workers (4 trials; risk ratio [RR], 0.5; 95% confidence interval [CI], 0.4-0.7) on the basis of the presence of hepatitis B surface antigen (HBsAg) or antibodies to hepatitis B core antigen. No study evaluated the effects of HBV vaccination on long-term clinical outcomes.

A total of 22 placebo-controlled trials of antiviral therapy reported intermediate outcomes. Results showed antiviral therapy to be more effective than placebo or no treatment in achieving histologic improvement (7 trials; RR, 2.1; 95% CI, 1.8-2.6), HBsAg loss or seroconversion (10 trials; RR, 2.1; 95% CI, 1.6-2.9), virologic response (9 trials; RR, 7.2; 95% CI, 3.2-16), and HBsAg loss or seroconversion (12 trials; RR, 2.4; 95% CI, 1.2-4.9).

In the 11 trials of antiviral therapy versus placebo or no treatment that reported clinical outcomes, pooled estimates for incident of cirrhosis incident cirrhosis (3 trials; RR, 0.7; 95% CI, 0.33-1.46), hepatocellular carcinoma (5 trials; RR, 0.57; 95% CI, 0.32-1.04), and mortality (5 trials; RR, 0.55; 95% CI, 0.18-1.71) all favored antiviral therapy over placebo. Due to the small number of events, however, differences were not statistically significant and estimates were imprecise.

No difference was observed between antiviral therapy versus placebo or no treatment in risk for serious adverse events (12 trials; RR, 0.8; 95% CI, 0.6-1.1), or adverse event (7 trials; RR, 0.96; 95% CI, 0.9-1). However, an increased risk for withdrawal due to adverse events was observed (9 trials; RR, 4; 95% CI, 1.4-11).

Overall, the review found no direct evidence on the effects of screening for HBV infection versus not screening in terms of clinical outcomes. The beneficial effects of antiviral therapy versus placebo on intermediate histological, serological, and virological outcomes were supported by the review.

The researchers acknowledged a number of limitations of the study, such as excluding non-English language articles and articles only published as abstracts, not formally assessing publication bias due to the small number of studies, and including only studies performed in countries where the prevalence, characteristics, and natural history of HBV infection differ from the United States, potentially limiting applicability to screening.

The authors concluded that screening can identify persons with chronic HBV infections and antiviral treatment is associated with improved intermediate outcomes, however, more research is needed to better identify the effects of screening.