ACIP Grading of Recommendations Assessment, Development and Evaluation (GRADE) for Hepatitis B (HepB) Vaccine in Adults

Introduction

Since hepatitis B (HepB) vaccine introduction in 1982, there have been substantial declines in reported hepatitis B cases. However, despite reductions in hepatitis B incidence achieved through incremental HepB vaccine policy over the past four decades, from a high of 26,654 reported cases (287,000 estimated) in 1985 to a low of 2,791 reported cases (19,200 estimated) in 2014, progress has stalled in further reducing hepatitis B incidence (1). In 2018, the reported HepB vaccination coverage (≥3 doses) was overall 30.0% for adults ≥19 years old, demonstrating small increases in coverage throughout the past four decades (2), including low coverage among persons in risk groups recommended for vaccination (e.g., 33% coverage among persons with chronic liver disease).

As part of ACIP's process, a systematic review and Grading of Recommendations Assessment, Development and Evaluation (GRADE) of the evidence of benefits and harms was conducted and presented to ACIP. The GRADE approach for evaluating evidence, which indicates the certainty of estimates from the available body of evidence, was adopted by ACIP in 2010 (3).

Methods

During September 2019–October 2021, the ACIP Hepatitis Work Group held monthly conference calls to review and discuss scientific evidence relevant to the use of HepB vaccines in a universal adult vaccination recommendation. The Work Group identified critical and important outcomes for inclusion in the GRADE tables, conducted a systematic review of the evidence, and subsequently reviewed and discussed findings and evidence quality (GRADE Evidence Tables – Recommendations in MMWR | Advisory Committee on Immunization Practices (ACIP) | CDC) (Evidence to Recommendations Frameworks | Advisory Committee on Immunization Practices (ACIP) | CDC) (3) (Table 1). In the GRADE approach, evidence certainty can range from type 1 (high certainty) to type 4 (very low certainty). Evidence was found to be available only for the cardiovascular and serious adverse events outcomes. Ultimately, no studies were available comparing the two strategies of universal and risk-based adult HepB vaccination. Thus, only the outcomes of serious adverse events and cardiovascular events associated with Heplisav-B were assessed, as noted below.

1. 2019 Viral Hepatitis Surveillance Report. 2021, Centers for Disease Control and Prevention.
2. Lu, P.J., et al., Surveillance of Vaccination Coverage Among Adult Populations -United States, 2018. MMWR Surveill Summ, 2021. 70(3): p. 1-26.
3. CDC. New Framework (GRADE) for Development of Evidence-Based Recommendations by the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2012;61:327.

Table 1: Policy Question and PICO

^*This outcome is solely aimed at assessing the 2-dose Heplisav-B vaccine (approved in 2017). The 3-dose HepB vaccines have already been evaluated for their adverse events profiles and recommended by ACIP based on their safety records.

Table 2: Outcomes and Rankings

Table 3a. Summary of studies reporting seroprotection (SPR)*

Table 3b. Summary of Studies Reporting Serious Adverse Events

Table 4. Grade Summary of Findings Table

CI: Confidence interval; RR: Risk ratio; HR: Hazard Ratio
a. Heterogeneity of estimates across studies. I² = 43%
b. Few events suggest fragility of the estimate. 95% CI cannot exclude the possibility of meaningful harm.

Appendix 1: Evidence retrieval strategies used for systematic review*

^*Exclusion criteria: articles dated earlier than year 2006, articles discussing vaccines not licensed in United States, articles not addressing the population of interest, and articles where data could not be abstracted.