CDC Recommendation for Hepatitis B Vaccination among Adults with Diabetes: Grading of Scientific Evidence in Support of Key Recommendations

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Evidence of benefits, harms, values and preferences, and cost effectiveness were reviewed in accordance with GRADE methods to determine the recommendation category (Ahmed F, Temte JL, Campos-Outcalt D, Schünemann HJ; for the ACIP Evidence Based Recommendations Work Group (EBRWG). Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of the U.S. Centers for Disease Control and Prevention (CDC). Vaccine 29(49):9171-6, 2011). Pooled data from 6 placebo-controlled randomized trials (5798 subjects) indicated a relative risk for hepatitis B infection events of 0.37 (95% CI 0.29, 0.48) among vaccinated subjects, although evidence type was downgraded for indirectness as trials did not focus on subjects with diabetes. Pooled data from 5 observational studies (285 subjects with diabetes) indicated 91.6% of subjects with diabetes achieved seroprotection, although evidence type was downgraded for imprecision due to small numbers. No serious vaccine-related adverse events were reported in any study. The Institute of Medicine found evidence supporting a causal relationship between hepatitis B vaccination and anaphylaxis in yeast-sensitive individuals; the risk of anaphylaxis following hepatitis B vaccine is estimated at 1.1 per million doses. [IOM (Institute of Medicine). 2011. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: The National Academies Press; Bohlke K, Davis RL, Marcy SM, Braun MM, DeStefano F, Black SB, Mullooly JP, Thompson RS; Vaccine Safety Datalink Team. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003;112:815-20]

GRADE Tables: Hepatitis B Vaccination Among Persons with Diabetes

Table 1. Benefits and Harms of Hepatitis B Vaccination Among Persons with Diabetes^a

Table 1 Footnotes
^aSome studies include persons with and without diabetes
^bFollow-up ranged from 12-29 months; figures do not account for person-time of follow-up for all studies; relative risk and 95% CI calculated from RevMan software version 5.1
^cCalculated from GRADEprofiler software version 3.6 assuming fixed effects
^dNumber needed to treat (number needed to vaccinate) calculated from modeling analysis of adults with diabetes ages ≥20 years (lifetime perspective)
^eNo serious events reported. Study sizes not sufficient to detect rare serious adverse events

Table 2. Type of Evidence for Hepatitis B Vaccination Benefits and Harms among Persons with Diabetes^a

Table 2 Footnotes
^aSome studies include persons with and without diabetes
^bSubjects with diabetes not focus of RCT studies; one RCT used 3 mcg dose on 0,1,2 month schedule; one study used 5 mcg dose on 0,1,2 month schedule with subcutaneous administration
^cTotal number of events <300, 95% CI 0.88, 0.94
^dStudy sizes not sufficient to detect rare adverse events:  rate of anaphylaxis estimated 1.1 per million doses (95% CI 0.1, 3.9 per million doses); (Bohlke K. et al. Pediatrics 2003;112:815-20). Widespread vaccine use for 30 years has not revealed other serious adverse events (IOM (Institute of Medicine). 2011. Adverse Effects of Vaccines:  Evidence and Causality.  Washington, DC: The National Academies Press)

Table 3. Summary of Evidence for Benefits and Harms of Hepatitis B Vaccination among Adults with Diabetes^a

Table 3 Footnotes
^aSome studies include persons with and without diabetes
^bStudy sizes not sufficient to detect rare adverse events

Table 4. Considerations for Formulating Recommendations: Hepatitis B Vaccine for Adults with Diabetes

Summary: Benefits are greater than potential harms; overall evidence is type 2. High values were placed on prevention of the morbidity and mortality of hepatitis B virus infection among adults with diabetes.

Study References

1. Arslanoglu I, Cetin B, Isguven P, Karavus M. Anti-HBs response to standard hepatitis B vaccination in children and adolescents with diabetes mellitus. J Pediatric End & Metabolism 2002;15(4):389-95.
2. Bouter KP, Diepersloot RJ, Wismans PJ, et al. Humoral immune response to a yeast-derived hepatitis B vaccine in patients with type 1 diabetes mellitus. Diabet Med 1992 Jan-Feb;9(1):66-9.
3. Douvin C, Simon D, Charles MA, et al. Hepatitis B vaccination in diabetic patients. Randomized trial comparing recombinant vaccines containing and not containing pre-S2 antigen. Diabetes Care 1997 Feb;20(2):148-51.
4. Li Volti S, Caruso-Nicoletti M, Biazzo F, et al. Hyporesponsiveness to intradermal administration of hepatitis B vaccine in insulin dependent diabetes mellitus. Arch Dis in Childhood 1998;78(1):54-7.
5. Marseglia GL, Scaramuzza A, dAnnunzio G, Comolli G, Gatti M, Lorini R. Successful immune response to a recombinant hepatitis B vaccine in young patients with insulin-dependent diabetes mellitus. Diabetic Medicine 1996;13(7):630-3.
6. Dienstag JL, Werner BG, Polk BF, et al. Hepatitis B vaccine in health care personnel: safety, immunogenicity, and indicators of efficacy. Ann Intern Med 1984 Jul;101(1):34-40.
7. Szmuness W, Stevens CE, Harley EJ, et al. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med 1980 Oct 9;303(15):833-41.
8. Francis DP, Hadler SC, Thompson SE, et al. The prevention of hepatitis B with vaccine. Report of the centers for disease control multi-center efficacy trial among homosexual men. Ann Intern Med 1982 Sep;97(3):362-6.
9. Szmuness W, Stevens CE, Harley EJ, et al. Hepatitis B vaccine in medical staff of hemodialysis units: efficacy and subtype cross-protection. N Engl J Med 1982 Dec 9;307(24):1481-6.
10. Crosnier J, Jungers P, Courouce AM, et al. Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in French haemodialysis units: I, Medical staff. Lancet 1981 Feb 28;1(8218):455-9.
11. Coutinho RA, Lelie N, Albrecht-Van Lent P, et al. Efficacy of a heat inactivated hepatitis B vaccine in male homosexuals: outcome of a placebo controlled double blind trial. Br Med J (Clin Res Ed) 1983 Apr 23;286(6374):1305-8.