Submitted:
16 July 2026
Posted:
17 July 2026
You are already at the latest version
Abstract
Keywords:
1. Introduction
2. Materials and Methods
3. Results
3.1. Occupational Exposure Risk in Healthcare Students
3.2. Vaccine-Induced Immunity: Mechanisms and Expected Trajectory
3.3. Seroprotection and Waning Immunity in Healthcare Students
3.4. Management of Low or Absent Anti-HBs Titres
3.5. Challenges in Multicultural and International Student Populations
3.6. Fitness for Duty Assessment: The Italian Framework and Its International Relevance
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| ACIP | Advisory Committee on Immunization Practices |
| anti-HBc | Antibody to hepatitis B core antigen |
| anti-HBs | Hepatitis B surface antibodies |
| CDC | Centers for Disease Control and Prevention (United States) |
| CI | Confidence interval |
| D.Lgs. | Decreto Legislativo (Italian Legislative Decree) |
| EU | European Union |
| HBIG | Hepatitis B immunoglobulin |
| HBsAg | Hepatitis B surface antigen |
| HBV | Hepatitis B virus |
| HCW | Healthcare worker |
| HBeAg | Hepatitis B e-antigen |
| mIU/mL | Milli-international units per millilitre |
| NR | Not reported |
| NSI | Needlestick and sharps injury |
| PEP | Post-exposure prophylaxis |
| PY | Person-years |
| QALY | Quality-adjusted life year |
| RR | Relative risk |
| WHO | World Health Organization |
References
- Jeng, W.J.; Papatheodoridis, G.V.; Lok, A.S.F. Hepatitis B. Lancet 2023, 401(10381), 1039–1052. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Global hepatitis report 2024: Action for access in low- and middle-income countries; WHO: Geneva, 2024. [Google Scholar]
- Stella, L.; Santopaolo, F.; Gasbarrini, A.; Pompili, M.; Ponziani, F.R. Viral hepatitis and hepatocellular carcinoma: from molecular pathways to the role of clinical surveillance and antiviral treatment. World J. Gastroenterol. 2022, 28(21), 2251–81. [Google Scholar] [CrossRef] [PubMed]
- Gerlich, W.H. Medical virology of hepatitis B: how it began and where we are now. Virol. J. 2013, 10, 239. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Global health sector strategies on HIV, viral hepatitis and sexually transmitted infections for the period 2022–2030; WHO: Geneva, 2022. [Google Scholar]
- Shen, F.; Li, B.; Lv, H.; Li, Z.; Li, D.; Yang, H.; Cai, W.; Hu, Y.; Zhang, Y.; Zhao, Y.; Chen, H.; Liu, Y.; Deng, Y. Global, regional, and national burden of chronic hepatitis B, 1990–2021, and projections to 2030: An urgent call for action to achieve hepatitis B elimination goals by 2030. Hum. Vaccin Immunother. 2026, 22(1), 2641857. [Google Scholar] [CrossRef] [PubMed]
- Yue, T.; Zhang, Q.; Cai, T.; Xu, M.; Zhu, H.; Pourkarim, M.R.; De Clercq, E.; Li, G. Trends in the disease burden of HBV and HCV infection in China from 1990–2019. Int. J. Infect. Dis. 2022, 122, 476–85. [Google Scholar] [CrossRef] [PubMed]
- Tavoschi, L.; Mason, L.; Petriti, U.; Bunge, E.; Veldhuijzen, I.; Duffell, E. Hepatitis B and C among healthcare workers and patient groups at increased risk of iatrogenic transmission in the European Union/European Economic Area. J. Hosp. Infect. 2019, 102(4), 359–68. [Google Scholar] [CrossRef] [PubMed]
- Pappas, S.C. Hepatitis B and health care workers. Clin. Liver Dis. 2021, 25(4), 859–74. [Google Scholar] [CrossRef] [PubMed]
- Coppeta, L.; Pompei, A.; Balbi, O.; De Zordo, L.M.; Mormone, F.; Policardo, S.; Lieto, P.; Pietroiusti, A.; Magrini, A. Persistence of immunity for hepatitis B virus among healthcare workers and Italian medical students 20 years after vaccination. Int. J. Env. Res. Public Health 2019, 16(9), 1515. [Google Scholar] [CrossRef] [PubMed]
- Rahmani, A.; Montecucco, A.; Kusznir Vitturi, B.; Debarbieri, N.; Dini, G.; Durando, P. Long-term effectiveness of hepatitis B vaccination in the protection of healthcare students in highly developed countries: a systematic review and meta-analysis. Vaccines 2022, 10(11), 1841. [Google Scholar] [CrossRef] [PubMed]
- Ippoliti, L.; Pizzo, A.; Paolino, A.; Coppeta, L.; Bizzarro, G.; Ferrari, C.; Mazza, A.; Salvi, C.; Buonomo, E.; Cenko, F.; Magrini, A.; Pietroiusti, A. Evaluation of anti-HB levels in a multi-ethnic cohort of health profession students. Vaccines 2025, 13(7), 771. [Google Scholar] [CrossRef] [PubMed]
- Kasteler, S.D.; Reid, M.; Lee, P.C.; Sparer-Fine, E.; Laramie, A.K. Sharps Injuries Among Medical Trainees and Attending Physicians. Acad. Med. 2023, 98(7), 805–812. [Google Scholar] [CrossRef] [PubMed]
- Ouyang, B.; Li, L.D.; Mount, J.; Jamal, A.J.; Berry, L.; Simone, C.; Law, M.; Tai, R.M. Incidence and characteristics of needlestick injuries among medical trainees at a community teaching hospital: A cross-sectional study. J. Occup. Health 2017, 59(1), 63–73. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Hajjaji Darouiche, M.; Chaabouni, T.; Jmal Hammami, K.; Messadi Akrout, F.; Abdennadher, M.; Hammami, A.; Karray, H.; Masmoudi, M.L. Occupational blood exposure among health care personnel and hospital trainees. Int. J. Occup. Env. Med. 2014, 5(1), 57–61. [Google Scholar] [PubMed] [PubMed Central]
- Chen, L.; Liu, W.; Dong, C.; Yang, J.; Gan, Y.; Zhong, Y.; Liang, D. Assessment of Occupational Exposure to Blood and Other Body Fluids Among Healthcare Workers in a South-Western Chinese Tertiary Hospital From 2018 to 2023: A Descriptive Cross-Sectional Study. Nurs. Open. 2026, 13(1), e70432. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Smith, D.R.; Leggat, P.A. Needlestick and sharps injuries among nursing students. J. Adv. Nurs. 2005, 51(5), 449–55. [Google Scholar] [CrossRef] [PubMed]
- Massaro, T.; Cavone, D.; Orlando, G.; Rubino, M.; Ciciriello, M.; Musti, E.M. Infortuni da dispositivi taglienti tra gli studenti di infermieristica: un rischio lavorativo emergente [Needlestick and sharps injuries among nursing students: an emerging occupational risk]. G. Ital. Med. Lav. Ergon. 2007, 29((3) Suppl, 631–2. [Google Scholar] [PubMed]
- Cheung, K.; Ho, S.C.; Ching, S.S.; Chang, K.K. Analysis of needlestick injuries among nursing students in Hong Kong. Accid. Anal. Prev. 2010, 42(6), 1744–50. [Google Scholar] [CrossRef] [PubMed]
- Hasak, J.M.; Novak, C.B.; Patterson, J.M.M.; Mackinnon, S.E. Prevalence of Needlestick Injuries, Attitude Changes, and Prevention Practices Over 12 Years in an Urban Academic Hospital Surgery Department. Ann. Surg. 2018, 267(2), 291–296. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Hepatitis B vaccines: WHO position paper, July 2017. Wkly. Epidemiol. Rec. 2017, 92(27), 369–92. [Google Scholar] [PubMed]
- Poovorawan, Y.; Chongsrisawat, V.; Theamboonlers, A.; Leroux-Roels, G.; Crasta, P.D.; Hardt, K. Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers. Hum. Vaccin Immunother. 2012, 8(7), 896–904. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Bruce, M.G.; Bruden, D.; Hurlburt, D.; Zanis, C.; Thompson, G.; Rea, L.; Toomey, M.; Townshend-Bulson, L.; Rudolph, K.; Bulkow, L.; Spradling, P.; McMahon, B.J. Antibody levels and protection after hepatitis B vaccine: results of a 30-year follow-up study and response to a booster dose. J. Infect. Dis. 2016, 214(1), 16–22. [Google Scholar] [CrossRef] [PubMed]
- Bruce, M.G.; Bruden, D.; Hurlburt, D.; Morris, J.; Bressler, S.; Thompson, G.; Lecy, D.; Rudolph, K.; Bulkow, L.; Hennessy, T.; Simons, B.C.; Weng, M.K.; Nelson, N.; McMahon, B.J. Protection and antibody levels 35 years after primary series with hepatitis B vaccine and response to a booster dose. Hepatology 2022, 76(4), 1180–9. [Google Scholar] [CrossRef] [PubMed]
- Phattraprayoon, N.; Kakheaw, J.; Soonklang, K.; Cheirsilpa, K.; Ungtrakul, T.; Auewarakul, C.; Mahanonda, N. Duration of Hepatitis B Vaccine-Induced Protection among Medical Students and Healthcare Workers following Primary Vaccination in Infancy and Rate of Immunity Decline. Vaccines 2022, 10(2), 267. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Di Giampaolo, L.; Coppeta, L.; Borrelli, P.; Astolfi, P.; Resta, A.; Loffredo, L.; Di Menno Di Bucchianico, F.; Mangifesta, R.; Ippoliti, L.; Ferrari, C. Persistence of anti-HB antibodies in healthcare trainees: the impact of childhood versus adolescent vaccination. Vaccines 2025, 13(6), 562. [Google Scholar] [CrossRef] [PubMed]
- Makan, N.; Song, E.; Kinge, C.W.; Kramvis, A. Hepatitis B virus immunity prior to and after administration of a 'booster' dose of vaccine among health-care students at a South African university. Vaccine X 2023, 14, 100284. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Bianchi, F.P.; Stefanizzi, P.; Migliore, G.; Martinelli, A.; Vimercati, L.; Germinario, C.A.; Tafuri, S. Prevalence of healthcare workers fully vaccinated against hepatitis B without circulating antibodies in Italy and role of age at baseline cycle vaccination: a systematic review and meta-analysis. Expert Rev. Vaccines 2023, 22(1), 139–147. [Google Scholar] [CrossRef] [PubMed]
- Cocchio, S.; Baldo, V.; Volpin, A.; Fonzo, M.; Floreani, A.; Furlan, P.; Mason, P.; Trevisan, A.; Scapellato, M.L. Persistence of anti-HBs after up to 30 years in health care workers vaccinated against hepatitis B virus. Vaccines 2021, 9(4), 323. [Google Scholar] [CrossRef] [PubMed]
- Meireles, L.C.; Marinho, R.T.; Van Damme, P. Three decades of hepatitis B control with vaccination. World J. Hepatol. 2015, 7(18), 2127–32. [Google Scholar] [CrossRef] [PubMed]
- Schillie, S.; Murphy, T.V.; Sawyer, M.; Ly, K.; Hughes, E.; Jiles, R.; de Perio, M.A.; Reilly, M.; Byrd, K.; Ward, J.W. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm. Rep. 2013, 62(RR-10), 1–19. [Google Scholar] [PubMed]
- Sato, H.; Nozawa, Y.; Tajiri, M.; Yutani, M.; Takeshi, K. Effectiveness of stepwise hepatitis B revaccination according to vaccination history in healthcare students: a retrospective observational study. J. Infect. Chemother. 2026, 32(7), 102988. [Google Scholar] [CrossRef] [PubMed]
- Gerlich, W.H. Prophylactic vaccination against hepatitis B: achievements, challenges and perspectives. Med. Microbiol. Immunol. 2015, 204(1), 39–55. [Google Scholar] [CrossRef] [PubMed]
- Senoo-Dogbey, V.E.; Ohene, L.A.; Wuaku, D.A. Occupational exposure to Hepatitis B virus, disease burden and pathways for postexposure prophylaxis management: recommendations for healthcare workers in highly endemic settings. Infect. Prev. Pract. 2024, 6(2), 100354. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- US Public Health Service. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm. Rep. 2001, 50(RR-11), 1–52. [Google Scholar] [PubMed]
- Auerbach, J.D.; Malone, S.; Forsyth, A.D. Occupational post-exposure prophylaxis among healthcare workers: a scoping review of factors affecting optimal utilization. J. Int. AIDS Soc. 2024, 27(8), e26341. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Chang, H.H.; Lee, W.K.; Moon, C.; Choi, W.S.; Yoon, H.J.; Kim, J.; Ryu, S.Y.; Kim, H.A.; Jo, Y.M.; Kwon, K.T.; Kim, H.I.; Sohn, J.W.; Yoon, Y.K.; Jung, S.I.; Park, K.H.; Kwon, H.H.; Lee, M.S.; Kim, Y.K.; Kim, Y.S.; Hur, J.; Kim, S.W. The acceptable duration between occupational exposure to hepatitis B virus and hepatitis B immunoglobulin injection: Results from a Korean nationwide, multicenter study. Am. J. Infect. Control. 2016, 44(2), 189–93. [Google Scholar] [CrossRef] [PubMed]
- Paccoud, O.; Surgers, L.; Lacombe, K. Hepatitis B virus infection: natural history, clinical manifestations and therapeutic approach. Rev. Med. Interne 2019, 40(9), 590–8. [Google Scholar] [CrossRef] [PubMed]
- European Centre for Disease Prevention Control Systematic review on hepatitis, B.; Cprevalence in the, E.U./.E.E.A; ECDC: Stockholm, 2016.
- Prüss-Üstün, A.; Rapiti, E.; Hutin, Y. Estimation of the global burden of disease attributable to contaminated sharps injuries among health-care workers. Am. J. Ind. Med. 2005, 48, 482–490. [Google Scholar] [CrossRef] [PubMed]
- Al-Busafi, S.A.; Alwassief, A. Global perspectives on the hepatitis B vaccination: challenges, achievements, and the road to elimination by 2030. Vaccines 2024, 12(3), 288. [Google Scholar] [CrossRef] [PubMed]
- Razwiedani, L.L.; Mogale, N.M.; Mawela, M.P.B. Hepatitis B vaccination coverage amongst healthcare workers in a tertiary academic hospital in Gauteng province, South Africa. S Afr. J. Infect. Dis. 2022, 37(1), 393. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Italian Legislative Decree No. 81/2008, Article 279. Italian Legislative Decree No. 81/2008, Article 279.
- Katsevman, G.A.; Sedney, C.L.; Braca, J.A., Iii; Hatchett, L. Interdisciplinary differences in needlestick injuries among healthcare professionals in training: Improving situational awareness to prevent high-risk injuries. Work 2020, 65(3), 635–645. [Google Scholar] [CrossRef] [PubMed]
- Ghanei Gheshlagh, R.; Ebrahimi, H.; Masih, S.; Asmat, K.; Sharafi, S. Prevalence of needlestick injuries among nurses and nursing students in Pakistan: a meta-analysis of observational studies. BMC Nurs. 2025, 24(1), 1147. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Wicker, S.; Stirn, A.V.; Rabenau, H.F.; von Gierke, L.; Wutzler, S.; Stephan, C. Needlestick injuries: causes, preventability and psychological impact. Infection 2014, 42(3), 549–52. [Google Scholar] [CrossRef] [PubMed]
- Cheetham, S.; Ngo, H.T.; Liira, J.; Liira, H. Education and training for preventing sharps injuries and splash exposures in healthcare workers. Cochrane Database Syst. Rev. 2021, 4(4), CD012060. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Datar, U.V.; Kamat, M.; Khairnar, M.; Wadgave, U.; Desai, K.M. Needlestick and sharps' injury in healthcare students: Prevalence, knowledge, attitude and practice. J. Fam. Med. Prim. Care 2022, 11(10), 6327–6333. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Hoerger, T.J.; Bradley, C.; Schillie, S.F.; Reilly, M.; Murphy, T.V. Cost-effectiveness of ensuring hepatitis B protection for previously vaccinated healthcare personnel. Infect. Control Hosp. Epidemiol. 2014, 35(7), 845–54. [Google Scholar] [CrossRef] [PubMed]
| Step | Action/Decision | Note |
|---|---|---|
| Step 1 | Obtain vaccination history and measure anti-HBs, HBsAg, and anti-HBc in all incoming healthcare students | Perform at clinical training entry, regardless of self-reported vaccination history. Include anti-HBc to identify natural immunity or chronic infection |
| Step 2a | Anti-HBs ≥10 mIU/mL: document seroprotection; no further intervention required | No further vaccination required. Document result in occupational health record |
| Step 2b | Anti-HBs <10 mIU/mL, with documented complete primary series: administer a single booster dose; retest anti-HBs after 4–8 weeks | Applicable to students with documented complete primary series only. If vaccination history is unknown or incomplete, proceed directly to full primary series |
| Step 3a | Post-booster anti-HBs ≥10 mIU/mL: confirm immunological memory; document seroprotection | Confirms persistence of immunological memory. Seroprotection expected to be durable; no routine booster required thereafter |
| Step 3b | Post-booster anti-HBs <10 mIU/mL: complete a second full three-dose vaccination series | Administer standard 3-dose series (0, 1, 6 months). Retest anti-HBs 4–8 weeks after final dose |
| Step 4a | After second series, anti-HBs ≥10 mIU/mL: document seroprotection | Document seroprotection. Consider periodic monitoring in high-exposure settings |
| Step 4b | After second series, anti-HBs <10 mIU/mL: classify as a non-responder; consider a preS1/preS2-containing vaccine; provide specific post-exposure prophylaxis counselling | PreS1/PreS2-containing vaccines (third-generation) may achieve seroprotection in a proportion of non-responders. Restrict high-risk clinical activities according to institutional policy |
| Special case | Anti-HBc positive, HBsAg negative: natural immunity is documented. Anti-HBc positive, HBsAg positive: refer to hepatology for chronic HBV management | Anti-HBc+/HBsAg– students do not require vaccination. Anti-HBc+/HBsAg+ students should be referred to hepatology before commencing clinical activities |
| Exposed student's HBV immune status | Source HBsAg positive | Source HBsAg negative | Source HBsAg unknown |
|---|---|---|---|
| Documented seroprotection (anti-HBs ≥10 mIU/mL) | No PEP required | No PEP required | No PEP required |
| Vaccinated; anti-HBs unknown or not previously tested | Test anti-HBs; if <10 mIU/mL, administer HBIG and revaccinate | Test anti-HBs; manage according to result | Test anti-HBs; manage according to result |
| Vaccinated, documented non-responder (anti-HBs <10 mIU/mL after two complete vaccine series) | HBIG ×2 (1 month apart) | No PEP required | Assess exposure risk; manage according to institutional protocol |
| Unvaccinated or incompletely vaccinated | HBIG + initiate HBV vaccination | Initiate HBV vaccination | Initiate HBV vaccination |
| Natural immunity (anti-HBc positive, HBsAg negative) | No PEP required | No PEP required | No PEP required |
| Chronic HBV infection (HBsAg positive) | No PEP required* | No PEP required* | No PEP required* |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.