European Journal of Cardiovascular Medicine

Hepatitis B is a blood borne viral infection and commonly produces an acute self-limiting hepatitis which may be subclinical or symptomatic; it is also capable of causing a range of hepatic complications including chronic hepatitis, fulminant hepatitis, cirrhosis of liver and liver cancer. World Health Organization (WHO) estimates that 254 million people were living with chronic Hepatitis B infection worldwide in 2022, with 1.2 million new infections each year, leading to an estimated 1.1 million deaths, mostly from cirrhosis and hepatocellular carcinoma. 1

Hepatitis B infection is one of the most common occupational hazards among health care workers (HCWs). It is contagious and gets transmitted by exposure to infected blood or body fluids and by injuries with contaminated sharp objects like needles. Due to frequent handling of blood and body fluids of patients, HCWs are four times more at risk of contracting Hepatitis B infection compared to general population. The risk of acquiring this infection among non-vaccinated individual ranges within 6-30% following single exposure. According to WHO, 5.9% of HCWs are exposed annually to blood-borne HBV infections.2

Currently, vaccination is the effective measure of preventing HBV infection. It confers long term protection against both clinical illness and its sequel. Centres for Disease Control and Prevention (CDC) has recommended that all HCWs should receive a complete course of Hepatitis B vaccination at 0,1 and 6 months which is administered intramuscularly.3

Occupational Safety and Health Act recommends HBV vaccine followed by confirmation of vaccine response in all HCWs. Testing for evidence of protective immunity to HBsAg vaccination is required as some individuals do not develop sufficient levels of antibodies against HBsAg (anti HBs). An anti-HBs titre less than 10 mIU/ml (even after 2 complete vaccination series) is regarded as non-response and more than 100 mIU/ml is considered as high level of immunity. Levels more than 10 mIU/ml at any time after vaccination is considered as a marker of sustained immunity which provides protection against infection.4 Poor sero-protection rates to Hepatitis B vaccine are documented in subjects of older age group, Body Mass Index (BMI) ≥ 25, smokers, poor nutritional status and reduced immunity.5 This makes it necessary to identify the individuals who are hyporesponsive to vaccination to necessitate further action.

Even though infection control practices have been advocated and administration of hepatitis B immunoglobulin following suspected exposure reduces the risk of HBV transmission, none have been as effective as active immunization with Hepatitis B vaccine. Health care providers need special consideration for HBV vaccination and there is a need to check post-vaccination antibody titres as a matter of hospital policy to ensure seroconversion has occurred and they have attained protective antibody levels. This study aims to estimate proportion of health care workers having protective antibody titres following Hepatitis B vaccination and to determine factors affecting immune response like age, gender, body mass index, smoking, alcoholism and diabetes mellitus

A cross sectional analytical study was conducted in the Department of Microbiology, Government Medical College, Kollam for a period of 3 months (January 2022 - March 2022) after getting clearance from the Institutional Ethics Committee (IEC No. 4/EC-1/2022/GMCKLM dated 04/01/2022). The study population included health care workers such as doctors, nurses, medical students, technicians and housekeeping staff who had taken all 3 doses of Hepatitis B vaccination (0,1 and 6 months) and completed atleast 2 months post-vaccination to upto 10 years. Exclusion criteria included individuals who failed to give consent for the study, unvaccinated and partially vaccinated individuals, individuals with past history of Hepatitis B infection and individuals on prolonged steroid therapy. Operational Definitions Health care worker - A health care worker is one who delivers care and services to the sick and ailing either directly as doctors and nurses or indirectly as aides, helpers, laboratory technicians or even medical waste handlers. Sero-protected (anti- HBs positive) - Anti HBs titre value ≥ 10 mIU/ml Non Sero-protected (anti- HBs negative) - Anti HBs titre value < 10 mIU/ml A semi-structured questionnaire consisting of socio-demographic details like designation, name, age, gender, height, weight, vaccination status, history of smoking, diabetes and alcoholism was given to all eligible participants after obtaining informed consent. BMI was calculated from the data collected using the formula BMI= Weight (kg)/ Height (m)2. 2-5 ml blood was collected by direct venepuncture, and sera was separated and stored at -20°C until the test was performed. Antibody to hepatitis B surface antigen (anti-HBs) was determined quantitatively using commercially available anti-HBs enzyme imunoassay kit (DIA.PRO, Italy) as per manufacturer’s instructions. The data collected was coded and entered in Microsoft Excel. Statistical analysis was done using SPSS software version 28. Qualitative variables were expressed as numbers and percentages. Chi square test and Fisher’s exact test was used to find the association between the variables. A p value of less than 0.05 was considered statistically significant for evaluating the strength of these associations.

The evaluation of immune response to Hepatitis B vaccination among 202 health care workers revealed an overall seroprotection rate of 84.7% (171/202) with 15.3% (31/202) failing to achieve protective anti-HBs antibody levels. [Table 1]

Seroprotection rates varied across occupational categories. Medical students (89.5%) and nurses (88.6%) demonstrated the highest levels of seroprotection whereas housekeeping staff had the lowest (73.5%) [Table 2].

Health care workers aged <40 years demonstrated a significantly higher seroprotection rate (89.9%) compared to those aged ≥ 40 years (70.4%). Age was significantly associated with immune response to Hepatitis B vaccination (p - 0.001). Although, seroprotection was slightly higher among females (85.3%) compared to males (82.6%), the difference was not statistically significant (p-0.65) [Table 3].

Health care workers with BMI ≥25 had a significantly lower seroprotection rate (72.6%) compared to those with BMI <25 (91.5%). Higher BMI was significantly associated with reduced immune response to Hepatitis B vaccination (p-0.001). None of the HCWs with diabetes mellitus achieved seroprotection, whereas (85.9%) of non-diabetic participants were seroprotected. Diabetes mellitus was significantly associated with poor immune response (p-0.003).

Seroprotection was lower among smokers (60%) and alcohol consuming health care workers (75%) compared to nonsmokers (85.3%) and non-alcoholics (85.1%), but this difference was not statistically significant.

The present study evaluated the immune response to Hepatitis B vaccination among 202 health care workers and examined factors influencing seoconversion like age, gender, body mass index, smoking, alcoholism and diabetes mellitus. Understanding the determinants of vaccine response in HCWs is crucial, as these individuals are at high risk of exposure to blood-borne pathogens particularly Hepatitis B virus, which remains a significant occupational hazard despite the availability of effective vaccination.

The study findings indicate that 84.7% of HCWs achieved serporotective anti-HBs levels (≥ 10mIU/ml) after completing a standard three-dose Hepatitis B vaccination series. The overall seroprotection rate is consistent with previous studies from similar populations which generally report rates ranging from 70% to 95% after standard vaccination.6-12 The fact that nearly 15% of HCWs remain non-seroprotected underscores the need for routine post vaccination testing. Non-seroprotected individuals may remain susceptible to HBV infection which could have serious occupational health consequences. This highlights the importance of institutional vaccination policies that include both administration of full vaccine series and mandatory post-vaccination serological assessment after 1-2 months.13

The analysis identified age ≥ 40 years, higher body mass index (BMI ≥25 kg/m2) and diabetes mellitus as significant predictors of poor serological response. Older age was associated with reduced seroprotection (70.4% vs 89.9% in <40 years). This aligns with evidence from previous studies that immunogenicity to Hepatitis B vaccination declines with advancing age,5,14,15 likely due to immunosenescence that impairs both humoral and cellular responses. A recent meta-analysis demonstrated significantly lower vaccine response among adults ≥ 40 years, supporting the need for early vaccination and vigilant post-vaccination monitoring in older HCWs.16

HCWs with BMI ≥25 kg/m2 had lower seroprotection (72.6%) compared to those with BMI< 25 kg/m2 (91.5%). Overweight and obesity has been recognized as a factor that impairs immune function, possibly through vaccine distribution in fat tissue, chronic low grade inflammation, altered lymphocyte function and decreased vaccine-specific antibody function.16,17 The findings in this study is in alignment with previous studies showing a higher risk of non-response in adults with higher BMI.5,14,18,19,20 All diabetics in this study were non -seroprotected indicating a particularly high risk group which aligns with findings from studies by Nasha et al and Bouter et al.15,21 Hyperglycemia and immune dysregulation associated with diabetes mellitus make these individuals more susceptibe to hypo-responsiveness.16

Female participants had a slightly higher seroprotection rate (85.3%) compared to males (82.6%), but this difference was not statistically significant (p- 0.65). This suggests that gender may not be a major determinant of immune response, although some studies have reported marginally better vaccine responsiveness in females.17 Other factors like smoking status and alcohol consumption were not significantly associated with seroprotection. These factors had limited representation in this study, which may have affected statistical power. Nevertheless, lifestyle factors should not be disregarded, as other studies have suggested they may influence immune response in larger populations.17

The findings from this study emphasize the importance of post- vaccination serological testing, especially for high risk groups such as older HCWs with higher BMI or chronic conditions like diabetes. Those who fail to attain protective antibody titres after first series of vaccination should be subjected to second series of vaccination (3 doses at 0, 1, 6 months) to ensure adequate protection against Hepatitis B infection.

Limitations

The less number of participants in certain subgroups (eg smokers, alcohol consumers, diabetics) limits power to detect statistically significant differences. Also, the study population included HCWs who had completed standard dose vaccination atleast 2 months prior to upto 10 years. This could influence seroprotection rates, as antibody titres naturally wane over time.

In summary the study reveals that although most HCWs achieve seroprotective titres following Hepatitis B vaccination, a substantial minority do not, with older age, elevated BMI and diabetes being key predictors of poor immune response. These findings are corroborated by recent research emphasizing similar risk factors and reinforcing the need for enhanced occupational health strategies that encompass serological monitoring and tailored re-vaccination efforts. Financial Support and Sponsorship This study was funded by State Board of Medical Research, Government of Kerala. Conflicts of Interest None

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