Need to take special care of non-responders to hepatitis B vaccination among health-care workers, students and chronic patients

ABSTRACT

Both our research and that published by Sticchi et al. on immunological memory against hepatitis B virus (HBV) in health-care workers (HCWs) vaccinated as infants or adolescents confirm that in those testing negative after the primary course, one additional (fourth) booster dose is able to elicit an anti-HBs response in >85% subjects. The fifth and the sixth doses further contribute substantially to a high overall response rate. The rate of subjects showing an anamnestic response after the booster dose was almost six-fold higher in HCWs compared to chronic patients. Since universal vaccination in Italy resulted in a significant decrease in HBV infections, special attention and testing should be addressed to those affected by chronic diseases.

KEYWORDS:

• Hepatitis B
• vaccination
• healthcare workers
• chronic patients
• non-responders
• additional doses
• anti-HBs testing

Dear Editor,

We are responding to the Letter to the Editor by Sticchi et al.¹ The majority of points raised in their Letter were mentioned in our study,² and we take the opportunity to highlight the importance of these findings. Sticchi et al. cited our study on the assessment of the effectiveness of booster vaccine doses in eliciting the immunological response in seronegative (<10 mIU/mL) HCWs and students of health-care courses.²

We are pleased to note that Sticchi et al. observed a similar response to a booster dose of Hepatitis B vaccine in subjects at occupational risk of HBV infection. Firstly, they found no differences in the response rate among groups stratified by age at the time of the first HBV vaccination course. One of the implications of this result is that subjects receiving the HepB primary course of immunization in the first year of life have the same response to a booster dose of subjects immunized during adolescence.

Secondly, as in our study, Sticchi et al. evaluated the possible role of gender in the immune response to HBV. In both studies, being female was found to be associated with a higher percentage of subjects with anti-HBs titers >10 mIU/ml.

Many other factors can be related to HBV vaccination non-response, including age older than 40 years, genetic factors, chronic liver/kidney diseases, obesity, and smoking.^3–7

Another interesting point raised by Sticchi et al. is the comparison between the immune response rate observed in occupational risk groups and the response rate to a booster dose in adults with underlying diseases. Their results provide further knowledge to the understanding of the effect of potential factors such as clinical conditions on the response rate to HBV re-vaccination.

These interesting findings show the importance of offering a second HBV vaccination course to subjects at risk for health conditions. The evidence further supports what is recommended by the Italian National Immunization Plan (NIP 2017–19) and the Vaccination Calendar for Life recommended by the Italian Scientific Societies.^8–10

Unlike their study, we did not have access to the information on other health conditions because our Occupational Medicine Service database did not routinely collect those risk factors, which can potentially influence the immunogenicity of the vaccine.^1,11

Furthermore, we positively noted that subjects with underlying diseases, who are less immunologically responsive, are more likely to adhere to a proposed revaccination course. These results by Sticchi et al. confirm that those subjects, when appropriately informed, show a high compliance to active immunization. In particular, they observed a different rate of compliance to revaccination, 65% and 45% among subjects at risk for medical conditions and for occupational exposure, respectively. Patients with underlying diseases are more likely to accept all three additional doses proposed by the protocol. This is an important outcome that underlines the need for tailored counseling to overcome any hesitancy about vaccine effectiveness and safety.¹² The involvement of HCWs in promoting vaccination of at-risk subjects is crucial. Not only General Practitioners but also Specialists in Infectious Diseases, Diabetologists, Hematologists, and Oncologists are essential partners in this effort. Finally, additional communication strategies and the use of social network and educational interventions should aim at improving the awareness among HCWs and high-risk groups, and at overcoming the barriers to Hepatitis B vaccination uptake.¹³

The role of communication is crucial even in case of compliance with serological testing for anti-HBs antibodies. Monitoring the serological profile of high-risk groups, especially in fragile or immunocompromised patients as suggested by Sticchi et al., should be encouraged to quickly identify potentially unprotected subjects. Previous non-responders to the primary vaccination course, when re-vaccinated, became seronegative more rapidly than those who responded to the first three doses; those patients could derive the highest benefit from serological follow-up. From a Public Health perspective, it could be asked to assess the cost-effectiveness of such a strategy. In this regard, there is a concern regarding the costs related to this practice: who should sustain the cost of serological analyses? We feel that this is an important point to address, but decision-makers should bear in mind that economic savings generated by almost 30 years of universal HepB vaccination in Italy in addition to the reduction of the burden of HBV-related diseases also should be reinvested for the benefit of those particularly at risk.^14,15

Prior to the availability of recombinant Hepatitis B vaccines in Italy, HepB vaccination was recommended only to HCWs and high-risk groups. Starting from 1991, Hepatitis B vaccination became mandatory in Italy for all newborns and 12-year-old adolescents, a double-cohort approach active until 2003. That strategy led to the protection of all subjects aged 0–24 years within 12 years, and to the virtual elimination of circulating HBV in the younger age cohorts (presently up to 40 years) in three decades. In 2003, HepB vaccination in adolescence was discontinued after the merging of birth and adolescent cohorts. The incidence of acute HBV disease has clearly declined, with a reduction of >95% since universal vaccination implementation.^16–19

In conclusion, all current and effective prevention activities against HBV should be maintained for the general population and for specific risk groups. In the future, all public health efforts should be addressed to monitor subjects exposed to professional risk of HBV infection and to identify non-responders, offering serological tests after the primary course, and revaccination to further reduce the risk of HBV infection.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.