Hepatitis B virus (HBV) causes acute and chronic infection ofthe liver leading to substantial morbidity and mortality. In the United States, since 1996, a total of 29 outbreaks of HBV infection in one or multiple long-term-care (LTC) facilities, including nursing homes and assisted-living facilities, were reported to CDC; ofthese, 25 involved adults with diabetes receiving assisted blood glucose monitoring (1; CDC, unpublished data, 2011). These outbreaks prompted the Hepatitis Vaccines Work Group o f the Advisory Committee on Immunization Practices (ACIP) to evaluate the risk for HBV infection among all adults with diagnosed diabetes. The Work Group reviewed HBV infection-related morbidity and mortality and the effectiveness o f implementing infection prevention and control measures. The strength o f scientific evi dence regarding protection was evaluated using the Grading o f Recommendations, Assessment, Development, and Evaluation (GRADE) methodology,- and safety, values, and cost-effectiveness were incorporated into a recommendation using the GRADE system. Based on the Work Group findings, on October 25, 2011, ACIP recommended that all previously unvaccinated adults aged 19 through 59 years with diabetes mellitus (type 1 and type 2) be vaccinated against hepatitis B as soon as possible after a diagnosis o f diabetes is made (recommendation category A). Data on the risk for hepatitis B among adults aged >60 years are less robust. Therefore, ACIP recommended that unvaccinated adults aged >60 years with diabetes may be vaccinated at the discretion ofthe treating clinician after assessing their risk and the likelihood ofan adequate immune response to vaccination (recommendation category B). This report summarizes these recommendations and provides the rationale used by ACIP to inform their decision making.# Risk for HBV Infection
An estimate o f the risk for HBV infection for adults with diabetes living in LTC facilities was not available; continuing outbreaks suggest that it might be substantial. T he population - Recommendation category A: a recommendation that applies to all persons in an age or risk-based group. Recommendation category B: a recommendation for individual clinical decision making. Evidence type 1: randomized controlled trials, or overwhelming evidence from observational studies. Evidence type 2: randomized controlled trials with important limitations, or exceptionally strong evidence from observational studies. Evidence type 3: observational studies, or randomized controlled trials with notable limitations.

# M orbidity and M ortality
The severity ofacute HBV infection among adults ranges from asymptomatic to fulminant hepatitis. National viral hepatitis surveillance data indicate that of the 3,371 acute HBV infec tions reported in 2009, 47% of the 2,126 infections for which information was available resulted in hospitalization, and 1% o f the 1,900 infections for which information was available were fatal (3). Data from EIP for the period 2009-2010 indicated a higher case-fatality rate among acute HBV-infected persons with diagnosed diabetes compared with those without diabetes, although the difference was not statistically significant (5% versus 2%, p=0.127) (2). Acute HBV infection progresses to chronic infection in approximately 5% of otherwise healthy adults (4), but is believed to be greater among older adults with diabetes (5). In the United States, an estimated 700,000 to 1.4 million persons are infected with HBV (3). Because chronic HBV infection can persist for decades, persons with chronic HBV infection are the reservoir for continuing HBV transmission. Chronic HBV infec tion is associated with high morbidity and mortality, leading to cirrhosis and liver cancer in >15% o f affected adults (5).
Diabetes is associated with nonalcoholic fatty liver disease, includ ing its most severe form, nonalcoholic steatohepatitis. A study o f veterans without HBV infection indicated that adults with diabetes have approximately twice the risk for chronic nonalcoholic liver disease and hepatocellular carcinoma as those without diabetes (6).

# Infection Control
HBV is highly infectious and environmentally stable (5); HBV can be transmitted by medical equipment that is contaminated with blood that is not visible to the unaided eye. Percutaneous exposures to HBV occur as a result o f assisted m onitoring o f blood glucose (7) and other procedures involving instruments or parenteral treatments shared between persons. Lapses in infection control during assisted blood glucose monitoring that have led to HBV transmission include multipatient use of finger stick devices designed for single-patient use and inadequate disinfection and cleaning o f blood glucose monitors between patients. Breaches have been documented in various settings, including LTC facilities, hospitals, community health centers, ambulatory surgical centers, private offices, homes, and health fairs (7; C D C , unpublished data, 2011). Initiatives are ongoing to encourage improvement in the design and labeling o f devices used in diabetes monitoring and care, and for greater oversight and training o f staff responsible for providing diabetes care.'f' Infection control guidelines for safe blood glucose monitoring have been available since 1990, and guidelines targeting LTC settings were published in 2005 (8). Since 1982, hepatitis B vaccination has been recommended for health-care personnel, including personnel exposed to blood in LTC settings, in con junction with meticulous attention to infection control practice (5,8). In addition, a recommendation for hepatitis B vaccination exists for persons beginning hemodialysis (5).

# Hepatitis B Vaccine
Two single-antigen recom binant hepatitis B vaccines, R ecom bivax H B (M erck & C o., Inc.) and Engerix-B (GlaxoSmithKline Biologicals), and one com bination hepa titis A and hepatitis B vaccine, Twinrix (GlaxoSmithKline Biologicals), are available in the United States. Hepatitis B vac cines have been used in the United States since 1982. Extensive data support their safety in all age groups (5).
Hepatitis B vaccination usually consists o f 3 doses o f vac cine administered intramuscularly at 0, 1, and 6 months; other schedules are available. At younger ages, the immune response to A dditional inform ation available at  ww.cdc.gov/injectionsafety/ meetings/stickingwsafety52010.html.
vaccine is similar among adults with and without diabetes. The proportion of adults who achieve seroprotection (>10 mIU/mL antibody to hepatitis B surface antigen ) after receipt o f the 3-dose vaccine series decreases with age, obesity, smoking, immunosuppression, and comorbid conditions including diabetes. W hen the antibody responses among older adults with and with out diabetes are compared, the response might be reduced among those with diabetes. A synthesis of available literature suggests a protective response is achieved after completion of the hepatitis B vaccine series in >90%, 80%, 65%, and 70 years, respectively (CDC, unpublished data, 2011). Revaccination with 1-3 additional doses ofhepatitis B vaccine safely increases the proportion ofadults who achieve a protective level o f anti-HBs (>10 mIU/mL) (5). The duration o f protection against symptomatic and chronic HBV infection lasts >22 years among healthy vaccine responders ( 9); duration o f immunity among persons with diabetes is unknown.

# Cost-Effectiveness
The Hepatitis Vaccines W ork Group developed economic models that yielded age-stratified calculations (base case) o f the incremental cost per quality-adjusted life-year (QALY) saved based on vaccinating adults with diabetes against hepatitis B.  The estimated cost per QALY saved was $75,100 for persons aged 20 through 59 years but increased substantially with increasing age. From a lifetime perspective, a one-time vaccination program consisting o f a 3-dose series of hepatitis B vaccine, covering 10% o f unvaccinated U.S. adults with diagnosed diabetes aged 20 through 59 years (or approximately 528,047 persons) would be expected to prevent 4271 HBV infections, 467 hospitalizations, 256 chronic cases, 33 cases o f hepatocellular carcinoma, 13 liver transplants, and 130 deaths. Postvaccination serologic testing and revaccination would add considerable cost, with limited increase in disease protection (CDC, unpublished data, 2011).

# ACIP Recommendations
O n the basis ofavailable information about HBV risk, morbid ity and mortality, available vaccines, age at diagnosis o f diabetes, and cost-effectiveness, ACIP recommends the following:  T he Charter of ACIP states that, when considering recommendations for use of a vaccine, ACIP members' deliberations should include consideration of vaccine efficacy as well as cost-benefit and risk-benefit analyses. N o predefined threshold for cost-effectiveness is considered. To ensure that economic data presented to the C om m ittee and its W orking G roups are uniform in presentation, understandable, and of the highest quality, lead economists and the Health Economics Research Group at C D C developed Guidance fo r Health Economics Studies Presented to the Advisory Committee on Immunization Practices (ACIP), available at . htm . T he guidance specifically mandates technical review of any economic study that is presented to ACIP
- Hepatitis B vaccination should be administered to unvaccinated adults with diabetes mellitus who are aged 19 through 59 years (recommendation category A; evidence type 2). - H epatitis B vaccination may be adm inistered at the discretion o f the treating clinician to unvaccinated adults w ith d ia b e te s m e llitu s w ho are aged >60 years (recommendation category B; evidence type 2).

# Remarks
Continued efforts are needed to increase adherence to rec omm ended infection control practice. Shared use o f bloodcontam inated equipm ent increases the risk for exposure to bloodborne pathogens, including hepatitis C virus, hum an immunodeficiency virus, and HBV, which is highly infectious.
A dm inistration o f the hepatitis B vaccine series should be completed as soon as feasible after diabetes is diagnosed. Available data do not confirm an advantage to any specific hepatitis B vaccine, dosage, or approved schedule for adults with diabetes. No serologic testing or additional hepatitis B vaccination is recommended for adults who received a com plete series o f hepatitis B vaccinations at any time in the past.
T he hepatitis B vaccination series can be given safely to persons o f any age, but current hepatitis B vaccines are less efficacious and less cost-effective among older adults. Evidence for the extent o f increased risk for acute HBV infection among persons with diabetes who are aged >60 years is less strong than for younger persons w ith diabetes. In 2008, the median age of diabetes diagnosis was 53 years; two thirds o f adult diabetes diagnoses were made before age 60 years.D ecisions to vaccinate adults with diabetes who are aged >60 years o f age should incorporate consideration o f the patient's likelihood o f acquiring HBV infection, including the risk posed by an increased need for assisted blood-glucose m onitoring in LTC facilities, the likelihood o f experiencing chronic sequelae if infected with HBV, and the declining immunologic responses to vaccines that are associated with frailty, a geriatric syndrome characterized by decreased physiologic reserve and increased vulnerability, leading to early m ortality in older adults (10).
Hepatitis B vaccine may be administered during health-care visits scheduled for other purposes as long as minimum intervals between doses are observed; there is no maximum interval between doses that makes the hepatitis B vaccination series ineffective.