Immune Profiles of Hepatitis A in Patients with Chronic Liver Disease across Three Major Hospitals in Sri Lanka

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Among the various types, hepatitis A, B, and D are preventable through effective vaccination. Patients with chronic liver disease (CLD) are particularly vulnerable to severe complications if they contract hepatitis A. Therefore, protecting this high-risk group through immunization is crucial. However, in Sri Lanka, there is limited information available on how many CLD patients are already immune to hepatitis A and how many have been vaccinated. This study was conducted to assess both the immunity levels and vaccination status of CLD patients attending three major government hospitals in Sri Lanka. Methods: A descriptive cross-sectional study was carried out from February to June 2022 among 151 newly registered patients with CLD attending gastroenterology clinics at three tertiary care hospitals. Information on age, gender, and hepatitis A vaccination history was collected through interviewer-administered questionnaires. Blood samples were tested for the presence of hepatitis A-specific IgG antibodies using a commercial Chemiluminescence Immunoassay to determine immunity status. Results: The ages of the study participants ranged from 10 to 81 years, with an average age of 59.5 years (Standard Deviation: 10.66 years). The majority of patients (54.9%) were over the age of 61, and 58.9% were male. Hepatitis A immunity was detected in 79.4% of participants, suggesting past natural infection or previous vaccination. However, only one participant (0.66%) reported receiving the hepatitis A vaccine, indicating extremely low vaccination coverage among this group. Conclusion: The findings show that a significant proportion (79.4%) of CLD patients in the study were already immune to hepatitis A, likely due to past natural infection. Vaccination rates, however, were remarkably low. These results suggest that instead of offering the hepatitis A vaccine to all CLD patients, it may be more practical and cost-effective to first screen for immunity and then selectively vaccinate only those who are not already protected. This targeted approach could help optimize resource use and provide better protection for vulnerable patients in Sri Lanka. Chronic liver disease Hepatitis A Hepatitis A vaccine Figures Figure 1 Figure 2 1. Introduction Chronic Liver Disease is a progressive condition marked by the gradual decline of liver function for over six months due to chronic liver injury, leading to inflammation and, eventually, irreversible fibrosis. If untreated, it develops into cirrhosis, the disease's end stage[ 1 ]. Globally, about 1.5 billion people were affected by CLD in 2017, with non-alcoholic fatty liver disease (60%) as the leading cause, followed by viral hepatitis B (29%) and C (9%)[ 2 ]. The clinical presentation varies with disease progression. Early stages have nonspecific symptoms, while advanced stages manifest severe complications such as ascites, variceal bleeding, jaundice, and hepatic encephalopathy. Diagnosis is challenging, with liver biopsy as the gold standard, though non-invasive methods like serum biomarkers (AST, ALT, hyaluronic acid) and imaging techniques (ultrasound, MRI) are commonly used for their greater sensitivity and specificity[ 3 ]. Management requires a multidisciplinary approach addressing the underlying cause and complications. This includes antiviral therapy for viral hepatitis, nutritional support, avoiding hepatotoxic substances, and vaccinating against hepatitis A and B[ 4 ]. Patients with CLD are at high risk of experiencing severe outcomes if they contract viral hepatitis, potentially leading to acute-on-chronic liver failure (ACLF), a severe form of hepatic decompensation. Preventing viral hepatitis is therefore critical in managing CLD patients, and vaccination plays a significant role in this, particularly for hepatitis A and B, which are preventable through immunization[ 5 ]. Despite the importance of vaccination, studies highlight inadequate vaccine coverage among CLD patients. In the United States, from 2013 to 2014, only 40% of adults with CLD had received the hepatitis A vaccine[ 6 ]. A Sri Lankan study during the same period reported no hepatitis A vaccination coverage among adults with CLD[ 7 ]. These findings underline the need for improving hepatitis A vaccination rates in CLD populations globally. Viral hepatitis has emerged as a major public health problem across the globe. It causes considerable morbidity and mortality in the human population. Hepatitis A, B, C, D and E viruses are the major hepatitis viruses that cause viral hepatitis[ 8 ]. Among them, only hepatitis A, hepatitis B and hepatitis D viral infections can be prevented by effective vaccination[ 8 ]. Hepatitis A virus is a non-enveloped RNA virus from the picornavirus family, primarily transmitted through the fecal-oral route[ 9 ]. It does not cause chronic disease but can lead to severe, and rarely fulminant, hepatitis. HAV infection is particularly common in regions with inadequate sanitation, where most children contract it early in life, usually without symptoms. Globally, regions such as South Asia and Sub-Saharan Africa are considered hyperendemic for hepatitis A, while countries like Western Europe and the United States report lower infection rates due to improved sanitation and widespread vaccination efforts[ 10 ]. The Centre for Disease Control and Prevention (CDC) reports that hepatitis A accounted for 7,134 deaths globally in 2016, approximately 0.5% of all viral hepatitis-related deaths[ 11 ]. Sri Lanka is classified as an intermediate endemic country for hepatitis A, with an estimated incidence of 15 cases per 100,000 population. While hepatitis A occurs sporadically in Sri Lanka, there have been significant outbreaks, including the largest in 2009 among the armed forces, which resulted in 13,477 cases[ 12 ]. Limited studies on hepatitis A seroprevalence in Sri Lanka have provided valuable insights into the current situation. A study conducted in the Gampaha District, in western Sri Lanka in 2015–2016 reported an overall seroprevalence of 80.7% across all age groups[ 13 ]. Similarly, a retrospective analysis at the Department of Virology, National Hospital Kandy, revealed an 88.8% seroprevalence in the central region during 2019–2021[ 14 ]. These findings suggest that while many individuals have acquired immunity, there remains a need for ongoing vaccination efforts, particularly among vulnerable populations such as individuals with chronic liver disease. Hepatitis A infection symptoms typically appear 14 to 28 days after exposure and range from mild to severe. They include fever, malaise, abdominal discomfort, diarrhea, and jaundice. Adults tend to experience more severe symptoms than children, with the risk of complications increasing with age. HAV infection is diagnosed through the detection of HAV-specific IgM antibodies in blood, while PCR testing can be used to detect HAV RNA if needed[ 9 ]. The presence of HAV-specific IgG antibodies indicates serological evidence of immunity against the virus, either due to previous exposure or vaccination[ 11 ]. Although HAV infection is generally self-limiting and there is no specific antiviral treatment, supportive care is used to manage symptoms. Preventive strategies for hepatitis A include improving sanitation, ensuring a safe food supply, and vaccination[ 11 ]. In Sri Lanka, where hepatitis A is endemic, a substantial portion of the population gains immunity early in life, reducing the need for widespread vaccination[ 12 ], [ 13 ], [ 15 ]. However, with improvements in sanitation, the seroprevalence of HAV IgG antibodies has declined, and the population is now more susceptible to infection. This highlights the ongoing importance of vaccination efforts, especially among vulnerable groups like those with CLD[ 16 ], [ 17 ], [ 18 ]. This study aimed to assess the seroprevalence of hepatitis A virus immunity and evaluate hepatitis A vaccination coverage among patients with chronic liver disease attending three tertiary care government hospitals in Sri Lanka. By determining the proportion of naturally immune versus non-immune individuals, the study sought to inform targeted immunization strategies, specifically, whether a selective vaccination approach for non-immune CLD patients may be more appropriate and cost-effective than implementing universal vaccination in this high-risk population. 2. Methodology This study was a cross-sectional descriptive design and was conducted over a four-month period from February to June 2022. The focus was on patients diagnosed with chronic liver disease who were newly registered at gastroenterology clinics in three major government hospitals in three districts: National Hospital Kandy, Teaching Hospital Kurunegala, and General Hospital Kegalle in Sri Lanka. These hospitals serve as the main centers for the follow-up of CLD patients within their respective districts. Specimen processing and laboratory testing were carried out at the Department of Virology, National Hospital Kandy. The sample size for this study was calculated using statistical formulas based on hepatitis A sero-prevalence rates. According to a prior study by Ariyarathna and Abeysena (2019), the sero-prevalence rate of hepatitis A was 89.7% among individuals aged 20 to over 80 years[ 19 ]. Consequently, the final sample size for this study was determined to be 151 participants. Patients were eligible for inclusion in the study if they had a confirmed diagnosis of CLD made by a medical specialist in gastroenterology, based on clinical presentation and relevant investigations, including biochemical tests, imaging studies, or histopathological findings. Only patients who were newly registered at the gastroenterology clinics of the National Hospital Kandy, Teaching Hospital Kurunegala, or General Hospital Kegalle during the study period from February to June 2022 were considered. Additionally, patients were required to be willing and able to provide written informed consent after receiving a clear explanation of the study’s objectives and procedures. Patients were excluded from the study if they did not meet the diagnostic criteria for CLD, as determined by the attending gastroenterologist, or if they were unwilling or unable to provide informed consent due to factors such as cognitive impairment or communication difficulties. Furthermore, any patients who had already been enrolled in the study or were identified as duplicate entries based on clinic and medical records were also excluded. Recruitment of patients was carried out by the principal investigator during clinic registrations. Patients were identified through clinic records and other relevant medical records, with measures taken to avoid duplicate entries. Once identified, patients were informed about the study and given consent forms. Data collection involved the use of a questionnaire and the collection of venous blood samples. Demographic data such as age, gender, and area of residence were collected through patient interviews, while clinical data including duration of illness and vaccination status against hepatitis A and B were gathered from clinical records. Blood samples were tested for hepatitis A immunity using chemiluminescence immunoassays on the LIAISON® XL Analyzer (Diasorin S.p.A, Italy). HAV-specific IgG antibodies were measured to assess immune status, ensuring high sensitivity and specificity. All procedures followed the manufacturer’s instructions and adhered to strict quality control measures. Strict biosafety protocols were followed while handling potentially infectious clinical materials, and all biological waste was disposed of according to institutional protocols. Data collected was entered into an Excel spreadsheet, cleaned, and analyzed using SPSS Version 25.0. Descriptive statistics such as frequencies and percentages were used for categorical variables, while mean and standard deviation were used for continuous variables. 3. Results Study participants were represented from three study settings. Both genders were included in the study sample. The sample size was 151 with a 100% response rate. The sociodemographic profile of the study participants was described at the initial stage and then the descriptive evaluation of anti-HAV IgG antibody detection was conducted. 3.1 Participants’ characteristics The age of the study participants ranged from 10 years to 81 years (Mean = 59.5yrs: SD = 10.66 yrs). The majority of the participants were above 61 years of age (N = 83:54.9%). Male predominance was observed among study participants (N = 89:58.9%). Table 1 Age and Sex distribution of the study participants Category Frequency(N) Percentage (%) Age Groups 70 yrs 15 9.9 Gender Male 89 58.9 Female 62 41.1 Total 151 100.0 The majority of the participants have been suffering the liver disease less than one year duration. There was only 2% of study participants had liver disease more than 10 years duration. 3.2 Sero-prevalence of hepatitis A, and its associations The majority of the participants tested positive for Hepatitis A IgG antibodies (n = 120:79.4%). Table 2 Association of HAV IgG with age of the study participants Positive Negative Total Age Category 71 12(80.0) 3(20.0) 15 Total 120 31 151 The highest percentage of HAV antibodies was detected among the age group of 61 years to 70 years (N = 64:94.1%). HAV antibody detection is significantly associated with age of the study participants(X 2 = 34.6: p < 0.001). The majority of the study participants below the age of 40 years were detected as negative for HAV antibodies (N = 8: 88.9%). Table 3 Association of hepatitis A immune status with gender of the study participants Positive N (%) Negative N (%) Total HAV IgG Male 67(75.2) 22(24.8) 89 Female 53(85.4) 9(14.5) 62 Total 120 31 151 The association of hepatitis A immune status and gender of the study participants were illustrated in Table 3 . Females were presented more with HAV antibodies compared to males. The association between HAV antibody detection and gender was not statistically significant (OR = 1.93:95%CI = 0.82–4.54). Table 4 Distribution of vaccination status and association of hepatitis A immune status with vaccination status Vaccination status Total Yes (%) No (%) Hepatitis A 1(0.7) 150(99.3) 151 HAV IgG Positive 1 Negative - 119 31 120 31 The prevalence of hepatitis A vaccination status (0.7%) is relatively low Only one person was identified as vaccinated against hepatitis A among study participants. The vaccinated person was positive for HAV antibodies. 4. Discussion In Sri Lanka, CLD is increasingly driven by non-alcoholic fatty liver disease (NAFLD), which has emerged as a significant global and national concern[ 20 ]. NAFLD is a major cause of both CLD and hepatocellular carcinoma (HCC) in the country. Ultrasound evidence indicates that more than half of middle-aged and elderly individuals in urban Sri Lanka are affected by NAFLD, with prevalence also observed in rural populations and children. Consequently, Sri Lankans face a heightened risk of CLD, with non-alcoholic steatohepatitis (NASH) cirrhosis, a severe form of NAFLD, becoming the most common reason for liver transplant referrals[ 21 ]. Traditionally, CLD in South Asia has been predominantly associated with viral hepatitis, particularly hepatitis B and C, along with contributions from hepatitis A. However, Sri Lanka stands out in the region for maintaining a notably low burden of chronic viral hepatitis. This positive trend is attributed to several public health measures, including national childhood immunization with the hepatitis B vaccine, centrally managed state-regulated blood banks, safe handling of sharps, strengthened infection prevention and control practices in healthcare settings, low prevalence of intravenous drug use, and the limited use of intramuscular injections in clinical practice[ 20 ]. Despite this low burden, hepatitis A infection remains a significant concern in patients with CLD, as it can exacerbate disease progression, leading to severe complications. These include an increased risk of cirrhosis and hepatocellular carcinoma, particularly in cases of co-infection with hepatitis B or C[ 11 ]. Vaccination against hepatitis A is strongly recommended for all CLD patients to mitigate these risks[ 22 ]. The hepatitis A vaccine is both safe and effective; however, its efficacy diminishes in advanced liver disease, underscoring the importance of early vaccination to ensure optimal immune response[ 23 ]. 4.1 Comparison of Study Findings with Previous Studies The current study found a seroprevalence rate of 79.4% for HAV IgG antibodies among patients with CLD. This result aligns with the seroprevalence reported by Ariyarathna and Abeysinghe (2015–2016), who found a 78.6–82.7% rate in the general population within the Gampaha district in western Sri Lanka[ 13 ]. However, our findings differ significantly from those of Niriella et al. (2017), who reported a lower HAV seroprevalence of 42% in adult cirrhotic patients registered at the gastroenterology clinic at Colombo North Teaching Hospital, Ragama, in same geographical area[ 7 ]. This disparity could reflect regional or demographic differences in exposure to HAV, as well as the impact of socioeconomic and environmental factors affecting HAV transmission. Our study and the work by Ariyarathna & Abeysena (2019) both highlight higher HAV seroprevalence rates in middle-aged adults compared to younger adults. This pattern may indicate cumulative immunity through natural exposure over time, resulting in higher immunity rates in older adults. Findings from De Silva et al. (2005), who documented a low prevalence (10.8%) of HAV IgG in children at Lady Ridgeway Hospital, Colombo, further support the trend of increasing seroprevalence with age[ 24 ]. The sustained antibody response post-infection also suggests that HAV immunity is long-lasting, which could reduce the need for universal vaccination in areas with high natural immunity. A gender-based difference in HAV immunity was observed in our study, with females showing a higher seroprevalence (85.4%) than males (75.2%). This finding is consistent with the results of Ariyarathna & Abeysena (2019), who also noted a higher HAV seroprevalence in females, though the reasons for this disparity warrant further investigation[ 13 ]. It may be influenced by cultural or occupational factors leading to differing exposure risks between genders in this population. 4.2 Implications of Study Findings The study findings underscore a high level of natural immunity to HAV among CLD patients, which could suggest a limited necessity for universal vaccination. Although the ACIP and CDC recommend HAV vaccination for all CLD patients to prevent complications, this may not be cost-effective in regions with high natural immunity[ 25 ]. A targeted vaccination strategy, where only non-immune patients are vaccinated, could provide a more economical and effective approach in Sri Lanka. Currently, the HAV vaccine is not available in the Sri Lankan government healthcare sector free of charge, and patients must seek vaccination through private providers at a high cost. Also, the HAV and HBV combined vaccine is often the only available option. Given the relatively high cost of the HAV IgG test and the vaccine, a tailored approach involving immunity assessment prior to vaccination would reduce unnecessary vaccinations and avoid additional expenses. Based on cost analysis, screening and selectively vaccinating the 31 non-immune patients in the study group could save substantial resources compared to universal vaccination. This approach not only conserves resources but also minimizes patient exposure to unnecessary interventions. Furthermore, high HAV IgG seroprevalence among CLD patients may reflect broader issues related to food and water safety. Since HAV is primarily transmitted through contaminated food and water, these findings suggest areas for public health interventions focused on improving sanitation and hygiene in the community. Such improvements could reduce HAV transmission and the associated risk of exacerbated illness in CLD patients. Future research involving a larger population and extended duration is recommended to further validate these observations and guide vaccination strategies more broadly. 4.3Conclusion This study found that nearly 80% of patients with chronic liver disease in the Kurunegala, Kegalle, and Kandy districts of Sri Lanka already had protection against hepatitis A, as shown by the presence of IgG antibodies in their blood. This means that most of them had been exposed to the virus in the past and developed natural immunity. Because of this high level of natural protection, it may not be necessary or cost-effective to give the hepatitis A vaccine to every CLD patient. Instead, it would be more practical to test each patient first to see if they are already immune. Then, only those who are not immune can be given the vaccine. This targeted approach could save money and resources while still helping to protect those most at risk from serious complications of hepatitis A infection. 5. Limitations This study has several limitations that should be acknowledged. Firstly, the analysis did not include an in-depth assessment of the underlying causes of CLD among the participants, nor did it evaluate the statistical significance of different CLD etiologies in relation to HAV immunity status. Understanding the etiology-specific risk profiles could have added further depth to the interpretation of immunity patterns and vaccination needs. Also, including a smaller sample size and the use of a convenient sample from three locations was a limitation. Although this approach provides reliable data, the findings may have limited generalizability across all CLD patients in Furthermore, the cost analysis was conducted using current private-sector rates for HAV IgG testing and vaccination in Sri Lanka, while government sector options, though limited, may affect the overall cost assessment. The low vaccine coverage in the study group may also reflect timing constraints, as patients were recruited at their initial clinic visits without sufficient opportunity to pursue vaccination. Since this was not a comparative study designed to assess HAV immunity in individuals without CLD or in the general population. As such, the findings are specific to the CLD patient group and cannot be directly generalized to broader populations. Abbreviations ACLF – Acute on Chronic Liver Failure ALT – Alanine Aminotransferase AST – Aspartate Aminotransferase CLD – Chronic Liver Disease HCC – Hepatocellular Carcinoma IgG – Immunoglobulin G IgM – Immunoglobulin M MRI – Magnetic Resonance Imaging NAFLD – Non-Alcoholic Fatty Liver Disease NASH – Non-Alcoholic Steatohepatitis PCR – Polymerase Chain Reaction RNA – Ribonucleic Acid SPSS – Statistical Package for the Social Sciences Ultrasound – Ultrasonography Declarations Ethical approval The ethical approval was obtained from the Ethics Review Committee of National Hospital, Kandy, Sri Lanka (Reference No: NHK/ERC/87/2021; Date: 11/02/2022). before the commencement of the study. Data disclosure was subjected to confidentiality requirements. Consent to Participate Written informed consent was obtained from all participants prior to their inclusion in the study. Funding Information This study did not receive any specific grant or funding from public, commercial, or not-for-profit agencies. Acknowledgements The authors acknowledge the staff at the Regional Virology Laboratory, National Hospital, Kandy, Sri Lanka Author contributions The study was carried out and the data was analyzed by H.A.R.K Ranaweera under the supervision of M.A.R.V.Muthugala. The manuscript was drafted by T.T.Pattiyakumbura and it was edited and revised by all authors. Conflicts of interest The authors declare that there are no conflicts of interest. Data summary section The data generated throughout this study, along with the supporting data, form the basis for the conclusions presented. These data were essential for replicating the described procedures and validating the findings. Detailed methodologies, results, and supplementary data have been provided to ensure that the research is transparent and reproducible. 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Niriella et al. , “Incidence and risk factors for non-alcoholic fatty liver disease: A 7-year follow-up study among urban, adult Sri Lankans,” Liver Int. , vol. 37, no. 11, pp. 1715–1722, 2017, doi: 10.1111/liv.13478 . “Acute hepatitis A and B in patients with chronic liver disease: prevention through vaccination,” Am. J. Med. , vol. 118, no. 10, pp. 21–27, Oct. 2005, doi: 10.1016/j.amjmed.2005.07.013 . “Hepatitis A: the green book, Chap. 17 - GOV.UK.” Accessed: Nov. 16, 2024. [Online]. Available: https://assets.publishing.service.gov.uk/media/65a1743269fbd3000d25c075/Greenbook-chapter–17-hepatitis-A–12January24.pdf/preview K. De Silva, D. Weerasuriya, M. Peelawattage, and S. Fernando, “Seroprevalence of hepatitis A antibodies in relation to social factors - a preliminary study,” Ceylon Med. J. , vol. 50, no. 2, p. 54, Feb. 2010, doi: 10.4038/cmj.v50i2.1569 . CDC, “Hepatitis A Vaccine Administration,” Hepatitis A. Accessed: Nov. 16, 2024. [Online]. Available: https://www.cdc.gov/hepatitis-a/hcp/vaccine-administration/index.html Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5632760","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":445829833,"identity":"2a701f99-0bf7-4c34-a4c6-6d21c560c56f","order_by":0,"name":"Ruwanthi Ranaweera","email":"","orcid":"","institution":"Postgraduate Institute of Medicine, University of Colombo, Sri Lanka 00700","correspondingAuthor":false,"prefix":"","firstName":"Ruwanthi","middleName":"","lastName":"Ranaweera","suffix":""},{"id":445829836,"identity":"22f8194d-a194-4b59-bdbd-0f9eb0f47789","order_by":1,"name":"Thulani Pattiyakumbura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABNUlEQVRIiWNgGAWjYDACCQbGAyASBICMBCi7goHBAIcOHgmwSiDJxoys5QxBLQxgLQxwLYxtuLXYS/cYHPi5wyKPf37/wcM8NWmJa2f3mH34Oe+wvDl78wGGHxXbMGyROWNwsPeMRLHEMWaGwzzHchK33TljPLN322HDnT3HEhh7ztzGdFiOwQHeNonEBrAWtorEbTdyjBl4tx1m3HAjx4CZsQ2rloN/gVrmg7X8g2hh/DvnsD0+LYdBtmwAaeFtywFrYeZtOJyIU8uNtILDsm0SxYbHkg0Ozu1LM95251gxs8yx9OQNZ44lHMTiF/YZyRsfvm2ry5M7fPDxhzffkmW33W7ezPimxtp2w/Hmgw9+VGBogYEEEMHEgxBoBpMHcKmHaWH8gRCow6N4FIyCUTAKRhgAAE/rf2aJXWbSAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Virology, National Hospital, Kandy, Sri Lanka, 20000","correspondingAuthor":true,"prefix":"","firstName":"Thulani","middleName":"","lastName":"Pattiyakumbura","suffix":""},{"id":445829840,"identity":"12a760da-b66f-4aa6-bc94-889b82e964a6","order_by":2,"name":"Rohitha Muthugala","email":"","orcid":"","institution":"Department of Virology, National Hospital, Kandy, Sri Lanka, 20000","correspondingAuthor":false,"prefix":"","firstName":"Rohitha","middleName":"","lastName":"Muthugala","suffix":""}],"badges":[],"createdAt":"2024-12-12 15:23:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5632760/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5632760/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81508593,"identity":"47c7bb90-a028-4577-95e9-09dcfcda9e91","added_by":"auto","created_at":"2025-04-28 05:39:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":94556,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGeographical Locations of Study Sites in Sri Lanka\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5632760/v1/1f1ae4b3817b3df61c77aab6.png"},{"id":81508581,"identity":"cd5e951a-5513-41d0-8df2-94c54a7bebe7","added_by":"auto","created_at":"2025-04-28 05:39:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5730,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of HAV IgG among study participants\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5632760/v1/ff4e45a1d718dfaf46b804ab.png"},{"id":83753587,"identity":"6f717a0d-100e-42b9-ad5f-c4b3c65cd0e8","added_by":"auto","created_at":"2025-06-02 07:39:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":754925,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5632760/v1/54cdf67e-8390-4d29-97ae-024e7149541a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immune Profiles of Hepatitis A in Patients with Chronic Liver Disease across Three Major Hospitals in Sri Lanka","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eChronic Liver Disease is a progressive condition marked by the gradual decline of liver function for over six months due to chronic liver injury, leading to inflammation and, eventually, irreversible fibrosis. If untreated, it develops into cirrhosis, the disease's end stage[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Globally, about 1.5\u0026nbsp;billion people were affected by CLD in 2017, with non-alcoholic fatty liver disease (60%) as the leading cause, followed by viral hepatitis B (29%) and C (9%)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The clinical presentation varies with disease progression. Early stages have nonspecific symptoms, while advanced stages manifest severe complications such as ascites, variceal bleeding, jaundice, and hepatic encephalopathy. Diagnosis is challenging, with liver biopsy as the gold standard, though non-invasive methods like serum biomarkers (AST, ALT, hyaluronic acid) and imaging techniques (ultrasound, MRI) are commonly used for their greater sensitivity and specificity[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Management requires a multidisciplinary approach addressing the underlying cause and complications. This includes antiviral therapy for viral hepatitis, nutritional support, avoiding hepatotoxic substances, and vaccinating against hepatitis A and B[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Patients with CLD are at high risk of experiencing severe outcomes if they contract viral hepatitis, potentially leading to acute-on-chronic liver failure (ACLF), a severe form of hepatic decompensation. Preventing viral hepatitis is therefore critical in managing CLD patients, and vaccination plays a significant role in this, particularly for hepatitis A and B, which are preventable through immunization[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite the importance of vaccination, studies highlight inadequate vaccine coverage among CLD patients. In the United States, from 2013 to 2014, only 40% of adults with CLD had received the hepatitis A vaccine[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A Sri Lankan study during the same period reported no hepatitis A vaccination coverage among adults with CLD[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These findings underline the need for improving hepatitis A vaccination rates in CLD populations globally.\u003c/p\u003e\u003cp\u003eViral hepatitis has emerged as a major public health problem across the globe. It causes considerable morbidity and mortality in the human population. Hepatitis A, B, C, D and E viruses are the major hepatitis viruses that cause viral hepatitis[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Among them, only hepatitis A, hepatitis B and hepatitis D viral infections can be prevented by effective vaccination[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHepatitis A virus is a non-enveloped RNA virus from the picornavirus family, primarily transmitted through the fecal-oral route[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. It does not cause chronic disease but can lead to severe, and rarely fulminant, hepatitis. HAV infection is particularly common in regions with inadequate sanitation, where most children contract it early in life, usually without symptoms. Globally, regions such as South Asia and Sub-Saharan Africa are considered hyperendemic for hepatitis A, while countries like Western Europe and the United States report lower infection rates due to improved sanitation and widespread vaccination efforts[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The Centre for Disease Control and Prevention (CDC) reports that hepatitis A accounted for 7,134 deaths globally in 2016, approximately 0.5% of all viral hepatitis-related deaths[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Sri Lanka is classified as an intermediate endemic country for hepatitis A, with an estimated incidence of 15 cases per 100,000 population. While hepatitis A occurs sporadically in Sri Lanka, there have been significant outbreaks, including the largest in 2009 among the armed forces, which resulted in 13,477 cases[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Limited studies on hepatitis A seroprevalence in Sri Lanka have provided valuable insights into the current situation. A study conducted in the Gampaha District, in western Sri Lanka in 2015\u0026ndash;2016 reported an overall seroprevalence of 80.7% across all age groups[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Similarly, a retrospective analysis at the Department of Virology, National Hospital Kandy, revealed an 88.8% seroprevalence in the central region during 2019\u0026ndash;2021[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. These findings suggest that while many individuals have acquired immunity, there remains a need for ongoing vaccination efforts, particularly among vulnerable populations such as individuals with chronic liver disease.\u003c/p\u003e\u003cp\u003eHepatitis A infection symptoms typically appear 14 to 28 days after exposure and range from mild to severe. They include fever, malaise, abdominal discomfort, diarrhea, and jaundice. Adults tend to experience more severe symptoms than children, with the risk of complications increasing with age. HAV infection is diagnosed through the detection of HAV-specific IgM antibodies in blood, while PCR testing can be used to detect HAV RNA if needed[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The presence of HAV-specific IgG antibodies indicates serological evidence of immunity against the virus, either due to previous exposure or vaccination[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough HAV infection is generally self-limiting and there is no specific antiviral treatment, supportive care is used to manage symptoms. Preventive strategies for hepatitis A include improving sanitation, ensuring a safe food supply, and vaccination[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In Sri Lanka, where hepatitis A is endemic, a substantial portion of the population gains immunity early in life, reducing the need for widespread vaccination[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, with improvements in sanitation, the seroprevalence of HAV IgG antibodies has declined, and the population is now more susceptible to infection. This highlights the ongoing importance of vaccination efforts, especially among vulnerable groups like those with CLD[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study aimed to assess the seroprevalence of hepatitis A virus immunity and evaluate hepatitis A vaccination coverage among patients with chronic liver disease attending three tertiary care government hospitals in Sri Lanka. By determining the proportion of naturally immune versus non-immune individuals, the study sought to inform targeted immunization strategies, specifically, whether a selective vaccination approach for non-immune CLD patients may be more appropriate and cost-effective than implementing universal vaccination in this high-risk population.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"2. Methodology","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThis study was a cross-sectional descriptive design and was conducted over a four-month period from February to June 2022. The focus was on patients diagnosed with chronic liver disease who were newly registered at gastroenterology clinics in three major government hospitals in three districts: National Hospital Kandy, Teaching Hospital Kurunegala, and General Hospital Kegalle in Sri Lanka. These hospitals serve as the main centers for the follow-up of CLD patients within their respective districts. Specimen processing and laboratory testing were carried out at the Department of Virology, National Hospital Kandy.\u003c/p\u003e\u003cp\u003eThe sample size for this study was calculated using statistical formulas based on hepatitis A sero-prevalence rates. According to a prior study by Ariyarathna and Abeysena (2019), the sero-prevalence rate of hepatitis A was 89.7% among individuals aged 20 to over 80 years[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Consequently, the final sample size for this study was determined to be 151 participants. Patients were eligible for inclusion in the study if they had a confirmed diagnosis of CLD made by a medical specialist in gastroenterology, based on clinical presentation and relevant investigations, including biochemical tests, imaging studies, or histopathological findings. Only patients who were newly registered at the gastroenterology clinics of the National Hospital Kandy, Teaching Hospital Kurunegala, or General Hospital Kegalle during the study period from February to June 2022 were considered. Additionally, patients were required to be willing and able to provide written informed consent after receiving a clear explanation of the study\u0026rsquo;s objectives and procedures.\u003c/p\u003e\u003cp\u003ePatients were excluded from the study if they did not meet the diagnostic criteria for CLD, as determined by the attending gastroenterologist, or if they were unwilling or unable to provide informed consent due to factors such as cognitive impairment or communication difficulties. Furthermore, any patients who had already been enrolled in the study or were identified as duplicate entries based on clinic and medical records were also excluded.\u003c/p\u003e\u003cp\u003eRecruitment of patients was carried out by the principal investigator during clinic registrations. Patients were identified through clinic records and other relevant medical records, with measures taken to avoid duplicate entries. Once identified, patients were informed about the study and given consent forms. Data collection involved the use of a questionnaire and the collection of venous blood samples. Demographic data such as age, gender, and area of residence were collected through patient interviews, while clinical data including duration of illness and vaccination status against hepatitis A and B were gathered from clinical records.\u003c/p\u003e\u003cp\u003eBlood samples were tested for hepatitis A immunity using chemiluminescence immunoassays on the LIAISON\u0026reg; XL Analyzer (Diasorin S.p.A, Italy). HAV-specific IgG antibodies were measured to assess immune status, ensuring high sensitivity and specificity. All procedures followed the manufacturer\u0026rsquo;s instructions and adhered to strict quality control measures.\u003c/p\u003e\u003cp\u003eStrict biosafety protocols were followed while handling potentially infectious clinical materials, and all biological waste was disposed of according to institutional protocols. Data collected was entered into an Excel spreadsheet, cleaned, and analyzed using SPSS Version 25.0. Descriptive statistics such as frequencies and percentages were used for categorical variables, while mean and standard deviation were used for continuous variables.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"3. Results","content":"\u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eStudy participants were represented from three study settings. Both genders were included in the study sample. The sample size was 151 with a 100% response rate. The sociodemographic profile of the study participants was described at the initial stage and then the descriptive evaluation of anti-HAV IgG antibody detection was conducted.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1 Participants\u0026rsquo; characteristics\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe age of the study participants ranged from 10 years to 81 years (Mean\u0026thinsp;=\u0026thinsp;59.5yrs: SD\u0026thinsp;=\u0026thinsp;10.66 yrs). The majority of the participants were above 61 years of age (N\u0026thinsp;=\u0026thinsp;83:54.9%). Male predominance was observed among study participants (N\u0026thinsp;=\u0026thinsp;89:58.9%).\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAge and Sex distribution of the study participants\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCategory\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFrequency(N)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge Groups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;40 yrs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u0026ndash;50 yrs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u0026ndash;60 yrs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u0026ndash;70 yrs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;70 yrs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e151\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e100.0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eThe majority of the participants have been suffering the liver disease less than one year duration. There was only 2% of study participants had liver disease more than 10 years duration.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 Sero-prevalence of hepatitis A, and its associations\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe majority of the participants tested positive for Hepatitis A IgG antibodies (n\u0026thinsp;=\u0026thinsp;120:79.4%). \u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAssociation of HAV IgG with age of the study participants\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge Category\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u0026ndash;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(66.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(33.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u0026ndash;60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35(74.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u0026ndash;70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64(94.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e120\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e151\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe highest percentage of HAV antibodies was detected among the age group of 61 years to 70 years (N\u0026thinsp;=\u0026thinsp;64:94.1%). HAV antibody detection is significantly associated with age of the study participants(X\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;34.6: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The majority of the study participants below the age of 40 years were detected as negative for HAV antibodies (N\u0026thinsp;=\u0026thinsp;8: 88.9%).\u003cbr\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAssociation of hepatitis A immune status with gender of the study participants\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHAV IgG\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67(75.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(24.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53(85.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e120\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e31\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e151\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe association of hepatitis A immune status and gender of the study participants were illustrated in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. Females were presented more with HAV antibodies compared to males. The association between HAV antibody detection and gender was not statistically significant (OR\u0026thinsp;=\u0026thinsp;1.93:95%CI\u0026thinsp;=\u0026thinsp;0.82\u0026ndash;4.54).\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDistribution of vaccination status and association of hepatitis A immune status with vaccination status\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eVaccination status\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHepatitis A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1(0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e150(99.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHAV IgG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive 1\u003c/p\u003e\n \u003cp\u003eNegative -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe prevalence of hepatitis A vaccination status (0.7%) is relatively low Only one person was identified as vaccinated against hepatitis A among study participants. The vaccinated person was positive for HAV antibodies.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn Sri Lanka, CLD is increasingly driven by non-alcoholic fatty liver disease (NAFLD), which has emerged as a significant global and national concern[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. NAFLD is a major cause of both CLD and hepatocellular carcinoma (HCC) in the country. Ultrasound evidence indicates that more than half of middle-aged and elderly individuals in urban Sri Lanka are affected by NAFLD, with prevalence also observed in rural populations and children. Consequently, Sri Lankans face a heightened risk of CLD, with non-alcoholic steatohepatitis (NASH) cirrhosis, a severe form of NAFLD, becoming the most common reason for liver transplant referrals[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Traditionally, CLD in South Asia has been predominantly associated with viral hepatitis, particularly hepatitis B and C, along with contributions from hepatitis A. However, Sri Lanka stands out in the region for maintaining a notably low burden of chronic viral hepatitis. This positive trend is attributed to several public health measures, including national childhood immunization with the hepatitis B vaccine, centrally managed state-regulated blood banks, safe handling of sharps, strengthened infection prevention and control practices in healthcare settings, low prevalence of intravenous drug use, and the limited use of intramuscular injections in clinical practice[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Despite this low burden, hepatitis A infection remains a significant concern in patients with CLD, as it can exacerbate disease progression, leading to severe complications. These include an increased risk of cirrhosis and hepatocellular carcinoma, particularly in cases of co-infection with hepatitis B or C[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Vaccination against hepatitis A is strongly recommended for all CLD patients to mitigate these risks[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The hepatitis A vaccine is both safe and effective; however, its efficacy diminishes in advanced liver disease, underscoring the importance of early vaccination to ensure optimal immune response[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Comparison of Study Findings with Previous Studies\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe current study found a seroprevalence rate of 79.4% for HAV IgG antibodies among patients with CLD. This result aligns with the seroprevalence reported by Ariyarathna and Abeysinghe (2015\u0026ndash;2016), who found a 78.6\u0026ndash;82.7% rate in the general population within the Gampaha district in western Sri Lanka[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, our findings differ significantly from those of Niriella et al. (2017), who reported a lower HAV seroprevalence of 42% in adult cirrhotic patients registered at the gastroenterology clinic at Colombo North Teaching Hospital, Ragama, in same geographical area[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This disparity could reflect regional or demographic differences in exposure to HAV, as well as the impact of socioeconomic and environmental factors affecting HAV transmission.\u003c/p\u003e \u003cp\u003eOur study and the work by Ariyarathna \u0026amp; Abeysena (2019) both highlight higher HAV seroprevalence rates in middle-aged adults compared to younger adults. This pattern may indicate cumulative immunity through natural exposure over time, resulting in higher immunity rates in older adults. Findings from De Silva et al. (2005), who documented a low prevalence (10.8%) of HAV IgG in children at Lady Ridgeway Hospital, Colombo, further support the trend of increasing seroprevalence with age[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The sustained antibody response post-infection also suggests that HAV immunity is long-lasting, which could reduce the need for universal vaccination in areas with high natural immunity.\u003c/p\u003e \u003cp\u003eA gender-based difference in HAV immunity was observed in our study, with females showing a higher seroprevalence (85.4%) than males (75.2%). This finding is consistent with the results of Ariyarathna \u0026amp; Abeysena (2019), who also noted a higher HAV seroprevalence in females, though the reasons for this disparity warrant further investigation[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. It may be influenced by cultural or occupational factors leading to differing exposure risks between genders in this population.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Implications of Study Findings\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe study findings underscore a high level of natural immunity to HAV among CLD patients, which could suggest a limited necessity for universal vaccination. Although the ACIP and CDC recommend HAV vaccination for all CLD patients to prevent complications, this may not be cost-effective in regions with high natural immunity[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. A targeted vaccination strategy, where only non-immune patients are vaccinated, could provide a more economical and effective approach in Sri Lanka.\u003c/p\u003e \u003cp\u003eCurrently, the HAV vaccine is not available in the Sri Lankan government healthcare sector free of charge, and patients must seek vaccination through private providers at a high cost. Also, the HAV and HBV combined vaccine is often the only available option. Given the relatively high cost of the HAV IgG test and the vaccine, a tailored approach involving immunity assessment prior to vaccination would reduce unnecessary vaccinations and avoid additional expenses. Based on cost analysis, screening and selectively vaccinating the 31 non-immune patients in the study group could save substantial resources compared to universal vaccination. This approach not only conserves resources but also minimizes patient exposure to unnecessary interventions.\u003c/p\u003e \u003cp\u003eFurthermore, high HAV IgG seroprevalence among CLD patients may reflect broader issues related to food and water safety. Since HAV is primarily transmitted through contaminated food and water, these findings suggest areas for public health interventions focused on improving sanitation and hygiene in the community. Such improvements could reduce HAV transmission and the associated risk of exacerbated illness in CLD patients.\u003c/p\u003e \u003cp\u003eFuture research involving a larger population and extended duration is recommended to further validate these observations and guide vaccination strategies more broadly.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e4.3Conclusion\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThis study found that nearly 80% of patients with chronic liver disease in the Kurunegala, Kegalle, and Kandy districts of Sri Lanka already had protection against hepatitis A, as shown by the presence of IgG antibodies in their blood. This means that most of them had been exposed to the virus in the past and developed natural immunity. Because of this high level of natural protection, it may not be necessary or cost-effective to give the hepatitis A vaccine to every CLD patient. Instead, it would be more practical to test each patient first to see if they are already immune. Then, only those who are not immune can be given the vaccine. This targeted approach could save money and resources while still helping to protect those most at risk from serious complications of hepatitis A infection.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"5. Limitations","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThis study has several limitations that should be acknowledged. Firstly, the analysis did not include an in-depth assessment of the underlying causes of CLD among the participants, nor did it evaluate the statistical significance of different CLD etiologies in relation to HAV immunity status. Understanding the etiology-specific risk profiles could have added further depth to the interpretation of immunity patterns and vaccination needs. Also, including a smaller sample size and the use of a convenient sample from three locations was a limitation. Although this approach provides reliable data, the findings may have limited generalizability across all CLD patients in\u003c/p\u003e \u003cp\u003eFurthermore, the cost analysis was conducted using current private-sector rates for HAV IgG testing and vaccination in Sri Lanka, while government sector options, though limited, may affect the overall cost assessment. The low vaccine coverage in the study group may also reflect timing constraints, as patients were recruited at their initial clinic visits without sufficient opportunity to pursue vaccination.\u003c/p\u003e \u003cp\u003eSince this was not a comparative study designed to assess HAV immunity in individuals without CLD or in the general population. As such, the findings are specific to the CLD patient group and cannot be directly generalized to broader populations.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACLF – Acute on Chronic Liver Failure\u003c/p\u003e\n\u003cp\u003eALT – Alanine Aminotransferase\u003c/p\u003e\n\u003cp\u003eAST – Aspartate Aminotransferase\u003c/p\u003e\n\u003cp\u003eCLD – Chronic Liver Disease\u003c/p\u003e\n\u003cp\u003eHCC – Hepatocellular Carcinoma\u003c/p\u003e\n\u003cp\u003eIgG – Immunoglobulin G\u003c/p\u003e\n\u003cp\u003eIgM – Immunoglobulin M\u003c/p\u003e\n\u003cp\u003eMRI – Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003eNAFLD – Non-Alcoholic Fatty Liver Disease\u003c/p\u003e\n\u003cp\u003eNASH – Non-Alcoholic Steatohepatitis\u003c/p\u003e\n\u003cp\u003ePCR – Polymerase Chain Reaction\u003c/p\u003e\n\u003cp\u003eRNA – Ribonucleic Acid\u003c/p\u003e\n\u003cp\u003eSPSS – Statistical Package for the Social Sciences\u003c/p\u003e\n\u003cp\u003eUltrasound – Ultrasonography\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ethical approval was obtained from the Ethics Review Committee of National Hospital, Kandy, Sri Lanka (Reference No: NHK/ERC/87/2021; Date: 11/02/2022). before the commencement of the study. Data disclosure was subjected to confidentiality requirements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all participants prior to their inclusion in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any specific grant or funding from public, commercial, or not-for-profit agencies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the staff at the Regional Virology Laboratory, National Hospital, Kandy, Sri Lanka\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was carried out and the data was analyzed by H.A.R.K Ranaweera under the supervision of M.A.R.V.Muthugala. The manuscript was drafted by T.T.Pattiyakumbura and it was edited and revised by all authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData summary section\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data generated throughout this study, along with the supporting data, form the basis for the conclusions presented. These data were essential for replicating the described procedures and validating the findings. Detailed methodologies, results, and supplementary data have been provided to ensure that the research is transparent and reproducible. This data will enable other researchers to accurately follow the protocol and verify the outcomes described in this article\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eA. Sharma and S. 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Niriella \u003cem\u003eet al.\u003c/em\u003e, \u0026ldquo;Incidence and risk factors for non-alcoholic fatty liver disease: A 7-year follow-up study among urban, adult Sri Lankans,\u0026rdquo; \u003cem\u003eLiver Int.\u003c/em\u003e, vol. 37, no. 11, pp. 1715\u0026ndash;1722, 2017, doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/liv.13478\u003c/span\u003e\u003cspan address=\"10.1111/liv.13478\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026ldquo;Acute hepatitis A and B in patients with chronic liver disease: prevention through vaccination,\u0026rdquo; \u003cem\u003eAm. J. Med.\u003c/em\u003e, vol. 118, no. 10, pp. 21\u0026ndash;27, Oct. 2005, doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.amjmed.2005.07.013\u003c/span\u003e\u003cspan address=\"10.1016/j.amjmed.2005.07.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026ldquo;Hepatitis A: the green book, Chap. 17 - GOV.UK.\u0026rdquo; Accessed: Nov. 16, 2024. [Online]. Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://assets.publishing.service.gov.uk/media/65a1743269fbd3000d25c075/Greenbook-chapter\u0026ndash;17-hepatitis-A\u0026ndash;12January24.pdf/preview\u003c/span\u003e\u003cspan address=\"https://assets.publishing.service.gov.uk/media/65a1743269fbd3000d25c075/Greenbook-chapter\u0026ndash;17-hepatitis-A\u0026ndash;12January24.pdf/preview\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eK. De Silva, D. Weerasuriya, M. Peelawattage, and S. Fernando, \u0026ldquo;Seroprevalence of hepatitis A antibodies in relation to social factors - a preliminary study,\u0026rdquo; \u003cem\u003eCeylon Med. J.\u003c/em\u003e, vol. 50, no. 2, p. 54, Feb. 2010, doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4038/cmj.v50i2.1569\u003c/span\u003e\u003cspan address=\"10.4038/cmj.v50i2.1569\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCDC, \u0026ldquo;Hepatitis A Vaccine Administration,\u0026rdquo; Hepatitis A. Accessed: Nov. 16, 2024. [Online]. Available: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/hepatitis-a/hcp/vaccine-administration/index.html\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/hepatitis-a/hcp/vaccine-administration/index.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chronic liver disease, Hepatitis A, Hepatitis A vaccine","lastPublishedDoi":"10.21203/rs.3.rs-5632760/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5632760/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction:\u003c/p\u003e\n\u003cp\u003eViral hepatitis remains a major global public health concern. Among the various types, hepatitis A, B, and D are preventable through effective vaccination. Patients with chronic liver disease (CLD) are particularly vulnerable to severe complications if they contract hepatitis A. Therefore, protecting this high-risk group through immunization is crucial. However, in Sri Lanka, there is limited information available on how many CLD patients are already immune to hepatitis A and how many have been vaccinated. This study was conducted to assess both the immunity levels and vaccination status of CLD patients attending three major government hospitals in Sri Lanka.\u003c/p\u003e\n\u003cp\u003eMethods:\u003c/p\u003e\n\u003cp\u003eA descriptive cross-sectional study was carried out from February to June 2022 among 151 newly registered patients with CLD attending gastroenterology clinics at three tertiary care hospitals. Information on age, gender, and hepatitis A vaccination history was collected through interviewer-administered questionnaires. Blood samples were tested for the presence of hepatitis A-specific IgG antibodies using a commercial Chemiluminescence Immunoassay to determine immunity status.\u003c/p\u003e\n\u003cp\u003eResults:\u003c/p\u003e\n\u003cp\u003eThe ages of the study participants ranged from 10 to 81 years, with an average age of 59.5 years (Standard Deviation: 10.66 years). The majority of patients (54.9%) were over the age of 61, and 58.9% were male. Hepatitis A immunity was detected in 79.4% of participants, suggesting past natural infection or previous vaccination. However, only one participant (0.66%) reported receiving the hepatitis A vaccine, indicating extremely low vaccination coverage among this group.\u003c/p\u003e\n\u003cp\u003eConclusion:\u003c/p\u003e\n\u003cp\u003eThe findings show that a significant proportion (79.4%) of CLD patients in the study were already immune to hepatitis A, likely due to past natural infection. Vaccination rates, however, were remarkably low. These results suggest that instead of offering the hepatitis A vaccine to all CLD patients, it may be more practical and cost-effective to first screen for immunity and then selectively vaccinate only those who are not already protected. This targeted approach could help optimize resource use and provide better protection for\u003c/p\u003e\n\u003cp\u003evulnerable patients in Sri Lanka.\u003c/p\u003e","manuscriptTitle":"Immune Profiles of Hepatitis A in Patients with Chronic Liver Disease across Three Major Hospitals in Sri Lanka","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-28 05:39:01","doi":"10.21203/rs.3.rs-5632760/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2eec8636-59de-41dc-86b8-fb5b41c87981","owner":[],"postedDate":"April 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-02T07:39:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-28 05:39:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5632760","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5632760","identity":"rs-5632760","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}