PREVALENCE OF HEPATITIS A VIRUS, HEPATITIS B VIRUS, AND HEPATITIS C VIRUS, AMONG PATIENTS WITH HEPATIC JAUNDICE IN SANA’A CITY, YEMEN: A HOSPITAL BASED STUDY

Huda Zaid Al-Shami1image, Zaid Ali Mohammed Al-Mutawakal1image, Abdulwahab Ismail Mohamed Al-Kholani2image, Muhamed Ahmed Al-Haimi3image, Ahmed Mohammed  Al-Haddad4image,  

Redhwan A. Ahmed1,5image,  Ali Abdullah Al-Somainy1,6 image, Hassan Abdulwahab Al-Shamahy1,7image  

1Medical Microbiology and Clinical Immunology Department, Faculty of Medicine and Health Sciences, Sana’a University. 

2Department of conservative dentistry, Faculty of Dentistry, Sana’a University, Republic of Yemen.

3Departement of Medicine, Faculty of Medicine and Health Sciences, Sana’a University, Republic of Yemen. 

4Department of Medical Laboratories, College of Medicine and Health Sciences, Hadhramout University, Al-Mukalla, Yemen. 

5Laboratory Department, University of Science and Technology Hospital, Sana'a, Yemen.

6The National Center for Public Health Laboratories in Sana'a, The Ministry of Health and Population, Sana’a, Yemen.

7Medical Microbiology department, Faculty of Medicine, Genius University for Sciences &  Technology, Dhamar city, Republic of Yemen. 

ABSTRACT 

Background: Hepatic jaundice results from abnormal metabolism of bilirubin in the liver. The main hepatic jaundice causes are severe damage to hepatocytes due to autoimmune diseases, infectious diseases, drugs/ medication induced, or, less commonly, hereditary genetic diseases. 

Aim: The aim of this study is to determine the prevalence of hepatitis B Virus (HBV), hepatitis A virus (HAV), and hepatitis C virus (HCV), in patients with hepatic jaundice as causes of acute viral hepatitis (AVH) in Sana'a city, Yemen. 

Subjects and Methods: Data of patients with hepatic jaundice tested for hepatitis B surface antigen, total anti-HCV antibody, and anti-HAV immunoglobulin M (IgM) by enzyme-linked immunosorbent assay were collected from Class I Viral Diagnostic Laboratories in Sana'a for 3 years. Then the statistical analysis of the data was used where the descriptive analysis was calculated: frequency and percentage, as well as the association of infection with sex and age group by means of detection odds ratio, 95% CI and X2 more than 3.9 and p<0.05 were considered statistically significant. 

Results: The study included 644 males (43.8%) and 826 females (56.2%), while most patients were less than 21 years old. The rate of Hepatitis viruses positive was 27.6% positive. Hepatitis A virus infection was the most common virus diagnosed accounting for 259 cases (17.6% of the total), while HBV was less common with 104 (7.1%) and HCV only 42 cases (2.9%). The highest incidence of hepatitis B was in 11-20 years patients (18.2%), with an associated OR 9.3 (p<0.0001). The highest incidence of hepatitis C was in 31-40 years patients (7.3%), with an associated OR 3.3 (p<0.0001). 

Conclusion:  Alarmingly changing the epidemiology and dynamics of hepatitis A-C viruses in Yemen, a detailed study is required to understand the definite disease problem caused by these viruses. It is noticeable in this study the high prevalence of hepatitis A virus and hepatitis B virus in the Yemeni population with hepatic jaundice. Also, to our knowledge, this study is the first to report epidemiological transformation of hepatitis A virus in Sana'a, Yemen.

 Keywords: Hepatic jaundice, Hepatitis A virus,  Hepatitis B virus, Hepatitis C virus,  prevalence, Sana’a, viral hepatitis, Yemen.

 

INTRODUCTION

 

Hepatic jaundice results from abnormal metabolism of bilirubin in the liver. The main causes of hepatic jaundice are severe damage to the liver cells due to infectious agents such as viral hepatitis and leptospirosis, drug/drug-induced hepatitis, autoimmune etiologies or, less commonly, due to hereditary genetic diseases such as Gilbert's syndrome, Crigler-Najjar syndrome, type I and Crigler-Najjar syndrome type II1,2. Liver disease caused by hepatitis virus is a major global public health problem influence millions of people worldwide3,4. A distinctive group of hepatitis B (HBV), hepatitis C (HCV), hepatitis A (HAV), hepatitis E (HEV), hepatitis D virus (HDV), and newly classified hepatitis viruses such as hepatitis G (HGV) are responsible for liver disease. The whole of these viruses are connected with considerable mortality and  morbidity in developed and developing countries5,6. In 2015, the World Health Organization expected 1.34 million deaths from viral hepatitis with hepatitis B, and HCV being a leading cause of death7. Clinical findings of viral hepatitis can range from subclinical to life-threatening infection6,8,9. HAV and HEV are spread by intake of contaminated food or water by human feces10; While Hepatitis B virus and HCV are transmitted mainly by perinatal route, including saliva exchange; by sexual contact, from mother to offspring  by vertical transmission, and exposure to infected blood products11. HAV and HEV typically have an effect on children and young adults correspondingly, and are endemic in numerous developing countries in Africa  and Asia12; While HBV and HCV are mostly reported from adults and are found intermittently in North America, Western Europe, and other developed countries13 HAV and HEV most cases are undetectable clinically or self-healing; while 70-80% of acutely infected with hepatitis B and HCV develop chronic hepatitis14,15. Only recently, there were few reliable commercial assays (sensitive and specific) for the detection of hepatitis viruses (HAV, HEV, HCV, and HBV) antigens and antibodies that could be used for routine diagnosis. Even though newly new assays have been developed that demonstrate high sensitivity and specificity, make available for more perfect detection/diagnosis of hospital cases. On the other hand, the high charge of these assays has limited evaluation in third world developing countries such as Yemen.    The prevalence of hepatitis viruses in Yemen has been estimated to be high, but detailed information concerning the current status of infection due to hepatitis viruses in Yemen is still insufficient to understand the burden of hepatitis disease due to the limitation of these studies in which only HBV, HCV and HGV were studies while there are no studies discusses the endemicity of HAV and HEV in Yemen16-26. The aim of this study is to clarify the prevalence of hepatitis B Virus (HBV), hepatitis A virus (HAV) and hepatitis C virus (HCV), in patients with hepatic jaundice as causes of acute viral hepatitis (AVH) in Sana'a city, Yemen.

 

SUBJECTS AND METHODS 

 

Data collection

Data of patients with hepatic jaundice tested for hepatitis B surface antigen, total anti-HCV antibody, and anti-HAV immunoglobulin M (IgM) by enzyme-linked immunosorbent assay were collected from Class I Viral Diagnostic Laboratories in Sana'a ( Department of Laboratories, University of Science and Technology Hospital, Al-Olagi Private Laboratory, and the viral department in the National Center for Public Health Laboratories in Sana’a, Ministry of Health and Population) for the last 3 years in which the information provided was complete and clear. Then the statistical analysis of the data was used where the descriptive analysis was calculated: frequency and percentage, as well as the association of infection with sex and age group by means of detection odds ratio, 95% CI and X2 more than 3.9 and p<0.05 were considered statistically significant.

Ethical approval 

Before inclusion in the study, approval was obtained on the condition that the names of the participants be confidential. From the Medical Research and Ethics Committee of the College of Medicine and Health Sciences, Sana’a University by document with reference number (223) dated 10 January 2021 the ethical approval was obtained to conduct the research.

 

ESULTS

 

Table 1 presents the demographic data of jaundice patients screened for hepatitis A, B and C viruses in the main laboratories in Sana'a city for a period of 3 years. It included 644 males (43.8%) and 826 females (56.2%), while most patients were less than 21 years old (2-10 years old 33.7% and 11-20 years old 29.9%), while patients over 40 years old only 5.4% of total patients. Hepatitis viruses (HAV+HBV+HCV) were 405 (27.6%) positive, while 1065 (72.4%) patients with jaundice were negative for HAV, HBV and HCV. When considering sex, the positive rates of the three viruses were approximately equal in males (27.8%) and females (27.4%).  Table 2 shows the distribution of different hepatitis viruses among male and female jaundice patients. Hepatitis A virus infection was the most common virus diagnosed among patients with jaundice accounting for 259 cases (17.6% of the total), while HBV was less common with 104 (7.1%) and HCV only 42 cases (2.9%). Table 3 shows the distribution of the age groups of patients infected with hepatitis A virus. The highest incidence of hepatitis A at 2-10 years jaundice patients was 220 cases (44.4%), with an associated OR 19.3, with a 95% CI equal to 13.3-77.6 and this correlation was highly significant with X2 being 364, p<0.0001. While the rates of hepatitis A virus infection in the older age groups were very low and ranged between 0 and 6.8%.

Table 4 shows the distribution of the age groups of patients infected with hepatitis B virus. The highest incidence of hepatitis B at 11-20 years jaundice patients was 89 cases (18.2%), with an associated OR 9.3, with a 95% CI equal to 5.8-14.9 and this correlation was highly significant with X2 being 118, p<0.0001. While the rates of hepatitis B virus infection in younger age group (2-10 years) was 0.2%, and in other older age groups were ranged from 2.5%  to 6.7%.  

Table 5 shows the distribution of the age groups of patients infected with hepatitis C virus. The highest incidence of hepatitis C at 31-40 years jaundice patients was 7.3%, with an associated OR 3.3, with a 95% CI equal to 1.6-6.6 and this correlation was highly significant with X2 being 13, p<0.0001. While the rates of hepatitis c virus infection in younger age group (2-10 years) was 0%, and in other age groups were ranged from 3.8% to 6.3%.

 

DISCUSSION

 

The causes of hepatitis can be divided into the following main categories: metabolic, ischemic, infectious, genetic, autoimmune, and others more. Metabolic causes include prescription drugs, toxins (especially alcohol), and nonalcoholic fatty liver disease. Autoimmune and genetic causes of hepatitis include a genetic predisposition and tend to affect distinct populations. In the current study, hepatitis viruses (HAV+HBV+HCV) were positive in 405 (27.6%) patients with hepatitis (hepatic jaundice) while the remaining 1065 (72.4%) jaundiced patients were negative for HAV and HBV and HCV (Table 1). This result indicated that the majority of cases in the current study may be infected with other infectious agents including viruses, bacteria, and parasites or suffer from other previously mentioned causes of hepatitis27,28. Viral hepatitis is the most common type of hepatitis worldwide29, and this fact differs from the current study in that 72.4% of patients with hepatitis may have other causes. These results can be explained by the fact that other viral hepatitis was not investigated in the current study and only 3 viruses were examined. Viral hepatitis is caused by five different viruses (hepatitis A, B, C, D, and E)30.

Hepatitis A virus infection was the most common virus diagnosed among patients with jaundice accounting for 259 cases (17.6% of the total) (Table 2). Therefore, hepatitis A, which is transmitted through fecal-oral, is more widespread in third world developing countries, and with its high prevalence, it is a self-limiting disease that does not lead to chronic hepatitis and its complications as liver cancer30. There are a number of hospital-based reports, sporadic cases and outbreaks of HAV in Yemen; but limited scholarly publication is presented on the Internet31. Only one published report detected hepatitis A virus antibodies indicating that 86% of the tested population had total IgG antibodies indicating previous exposure and immunity31. While the results of the current study showed 17.6% of the tested patients had active infection (IgM positive) among children and adults. In the current study the highest incidence of hepatitis A was in children (2-10 years)  (44.4%), with an associated OR 19.3, with a 95% CI equal to 13.3-77.6 (p<0.0001) (Table 3).   The current finding is similar to that in developing countries where they have higher circulating levels of HAV and most cases are reported in children while most adolescents and adults in developing countries have already contracted the disease and are thus immune32.  On the other hand, we found that active infection with hepatitis A virus is present in adults in the current study, therefore, it is necessary to examine the immune status of adults and children in Yemen and to vaccinate non-immune children and people at risk of infection with the virus, as well as people suffering from other liver diseases in which active Hepatitis A infection might lead to liver failure33,34.  Hepatitis A virus (HAV) infection is mostly associated with poor hygiene and spreads through the oral and fecal route. Although the HAV vaccine is available in the immunization programs of many countries of the world; however, this vaccine is not available at all in Yemen.

The rate of HBV among patients with hepatic jaundice in the current study was 7.1%, and the highest rate was in 11-20 years of patients (18.2%). The prevalence of hepatitis B virus in previous studies in Yemen ranged from 1% among the general population to 20% among high-risk groups such as health care workers, dialysis patients etc16-23. Hepatitis B cases are still reported from different hospitals in Yemen, though the hepatitis B vaccine has been obtainable for about 22 years in the country, there are still many people in Yemen who do not benefit from the protection available for this successful vaccine. This is due to its high cost and its low priority for the decision-maker at the governmental level, in addition to the ongoing war in Yemen over the past seven years. The rate of HCV among patients with hepatic jaundice in the current study was 2.9%, and the highest incidence of hepatitis C was in the 31-40 year old patients with jaundice (7.3%), with an associated odds ratio of 3.3 (p<0.0001). While the infection rates of hepatitis C virus in the younger age group (2-10 years) were 0% (Table 5). The prevalence of hepatitis C virus in previous studies in Yemen ranged from 0.1% among the general population and blood donors to 19% among high-risk groups such as public health center cleaners, health care workers and dialysis patients16,17,23,24. Although the exact reasons for the spread of HCV in this population remain unclear; Blood transfusion without proper screening and the use of non-sterile syringes may be one of the factors for the spread of hepatitis C virus in Yemen. A detailed study should be done in the future because hepatitis C is one of the main causes of cirrhosis and hepatocellular carcinoma in chronic patients16,17. 

Even though the hospital-based data obtainable in this study will not characterize the entire country, the burden of disease from this viral infection appears to be alarming these days and relevant authorities should prioritize overcoming viral hepatitis in the country.

 

CONCLUSION AND RECOMMENDATION

 

Alteration the epidemiology and dynamics of hepatitis A-C viruses in Yemen is alarming and comprehensive study must be conducted to understand the real disease problem produced by these viruses. This study, which was conducted on hospitals, noted the high prevalence of hepatitis A virus and hepatitis B virus in the Yemeni population with hepatic jaundice and elevated liver enzymes. The study found HAV is a major causative agent for hepatic Jaundice followed by HBV and  HCV, indicating that group of hepatitis virus to produce a critical health problem in Yemen with a large population (about 30 millions). More accurate data on the on the whole prevalence of these viral infections may done by comprehensive studies, comprising well-designed systematic surveillance with random selection of people.  We believe that an urgent standard public health approach should be followed in implementation such as provision of clean water, appropriate disposal of wastewater and improved hygiene of persons through health education and application of the HAV vaccine that may help control HAV infection in the future. Also, mass vaccination of hepatitis B virus should be started which should reach all rural and urban areas in Yemen to prevent future infection with hepatitis B virus because vaccination against hepatitis B virus has not been achieved by the Yemeni government as expected. This may be unaware of this vaccine or the financial district due to the high cost of the vaccine. As well, standard quality control of the kit utilized in the blood bank will improve prevent transfusion of hepatitis B and HCV-infected blood to the recipient. Since the hepatitis C vaccine is not available, raising awareness of the handling of blood and its derivatives may help reduce the spread of hepatitis C infection in Yemen

 

ACKNOWLEDGMENTS

 

The authors extend their thanks and appreciation to the Laboratory Department of the University of Science and Technology Hospital, the Al-Olagi Private Laboratory, the National Center for Public Health Laboratories in Sana'a, and the Ministry of Health and Population who provided us with the data for the study.

 

CONFLICT OF INTEREST 

 

No conflict of interest associated with this work. 

 

AUTHOR’S CONTRIBUTIONS

 

All authors co-wrote the articles and reviewed the results. 

 

REFERENCES

 

  1. Torre DM, Lamb GC, Ruiswyk JV, Schapira RM.Kochar's Clinical Medicine for Students. Lippincott Williams & Wilkins 2009; 101. ISBN 9780781766999.
  2. Alastot E, Al-Shamahy H. Prevalence of leptospirosis amongst slaughterhouse workers and butchers in Sana’a city-Yemen. Universal J Pharm Res 2018; 3(2):17-20. https://doi.org/10.22270/ujpr.v3i2.133
  1. Gupta BP, Adhikari A, Chaudhary S. Hepatitis viruses in Kathmandu, Nepal: hospital-based study. BMC Res Notes. 2018; 11(1):627. https://doi.org/10.1186/s13104-018-3739-1
  1. Popping S, El-Sayed M, Feld J, et al. Report from the international viral hepatitis elimination meeting (IVHEM), 17–18 November 2017, Amsterdam, the Netherlands: gaps and challenges in the WHO 2030 hepatitis C elimination framework 2018.
  2. Al-Dabis EM, Al-Shamahy HA, Al-Hadad AM, and Al-Shamahi EY. Prevalence of hepatitis G virus among patients with chronic liver disease and healthy individuals, Sana’a city-Yemen. Universal J Pharm Res 2019; 3 (6):1-6. https://doi.org/10.22270/ujpr.v3i6.216
  3. Lemon SM, Walker CM. Hepatitis A virus and hepatitis E virus: emerging and re-emerging enterically transmitted hepatitis viruses. Cold Spring Harb Perspect Med 2018. https://doi.org/10.1101/cshperspect.a031823
  1. World Health Organization. Global hepatitis report 2017. Geneva: World Health Organization; 2017.
  2. Wu VCC, Chen TH, Wu M, et al. Comparison of cardiovascular outcomes and all-cause mortality in patients with chronic hepatitis B and C: a 13-year nationwide population-based study in Asia. Atherosclerosis 2018; 269:178–84. https://doi.org/10.1016/j.atherosclerosis.2019.05.025
  1. Obiri-Yeboah D, Awuku YA, Adu J, Pappoe F, et al. Sero-prevalence and risk factors for hepatitis E virus infection among pregnant women in the Cape Coast Metropolis, Ghana. PLoS ONE 2018; 13(1):e0191685. https://doi.org/10.1371/journal.pone.0191685
  1. Hofmeister MG, Foster MA, Teshale EH. Epidemiology and transmission of hepatitis A virus and hepatitis E virus infections in the United States. Cold Spring Harb Perspect Med 2018. https://doi.org/10.1101/cshperspect.a033431
  2. Demsiss W, Seid A, Fiseha T. Hepatitis B and C: seroprevalence, knowledge, practice and associated factors among medicine and health science students in Northeast Ethiopia. PLoS ONE 2018;13(5):e0196539. https://doi.org/10.1371/journal.pone.0196539
  1. Gupta BP, Lama TK, Adhikari A, et al. First report of hepatitis E virus viremia in healthy blood donors from Nepal. Virus Disease 2016; 27(3):324–6. https://doi.org/10.1007/s13337-016-0331-y
  1. Maucort-Boulch D, de Martel C, Franceschi S, Plummer M. Fraction and incidence of liver cancer attributable to hepatitis B and C viruses worldwide. Int J Cancer 2018; 142(12):2471–7. https://doi.org/10.1002/ijc.31280
  2. Jung G, Olivas P, Díaz A, Lens S. Hepatitis E-induced acute-on-chronic liver failure and VI nerve paralysis. Liver Int 2018. https://doi.org/10.1111/ liv.13897
  3. Moore MS, Bocour A, Tran OC, et al. Effect of hepatocellular carcinoma on mortality among individuals with hepatitis B or hepatitis C infection in New York City, 2001–2012. Open Forum Infect Dis 2018. https://doi.org/10.1093/ofid/ofy14 4
  1. Al-kadassy AM, Al-Ashiry AFS, and Al-Shamahy HA. Sero-epidemiological study of hepatitis B, C, HIV and treponema pallidum among blood donors in Hodeida city- Yemen. Universal J Pharm Res 2019; 4(2): 1-8. https://doi.org/10.22270/ujpr.v4i2.256
  1. AL-Marrani WHM and Al-Shamahy HA. Prevalence of HBV and HCV; and their associated risk factors among public health center cleaners at selected public health centers in Sana’a city-Yemen. Universal J Pharm Res 2018:3 (5):1-8. https://doi.org/10.22270/ujpr.v3i5.204
  2. AL-Shamahy HA. Prevalence of Hepatitis B surface antigen and Risk factors of HBV infection in a sample of healthy mothers and their infants in Sana’a, Yemen. Ann Saudi Medicine 2000; 20: 464-467. https://doi.org/10.5144/0256-4947.2000.464 
  1. Al-Shamahy HA, Rabbad IA, Al-Hababy A. Hepatitis B virus serum markers among pregnant women in Sana'a, Yemen. Ann Saudi Med 2003; 23:87-89. https://doi.org/10.5144/0256-4947.2003.87
  1. Al-Shamahy HA, Hanash SH, Rabbad IA, Al-Madhaji NM, Naser SM. Hepatitis B Vaccine Coverage and the Immune Response in Children under ten years old in Sana'a, Yemen. Sultan Qaboos Univ Med J 2011 Feb;11(1):77-82. PMID: 21509212
  2. Al-Shamahy HA, Ajrah MAA, Al-Madhaji AG, et al. Prevalence and potential risk factors of hepatitis b virus in a sample of children in two selected areas in Yemen. Universal J Pharm Res 2019; 4(3):1-6. https://doi.org/10.22270/ujpr.v4i3.269
  1. Al-Shawkany EM, AlShawkany ARM, Al-Shamahy HA, et al. Prevalence of different hepatitis b virus genotypes and risk factors associated among selected Yemeni patients with chronic hepatitis B infection. Universal J Pharm Res 2021; 6 (3):1-8.https://doi.org/10.22270/ujpr.v6i3.603
  1. Amran OAA, Al-Shamahy HA, Al Hadad AM, and Jaadan BM. Explosion of hepatitis B and C viruses among hemodialysis patients as a result of hemodialysis crisis in Yemen. Universal J Pharm Res 2019; 4(5):1-8.https://doi.org/10.22270/ujpr.v4i5.311
  1. Hanash SH, Al-Shamahy HA, Bamshmous MHS. Prevalence and genotyping of hepatitis C virus in hemodialysis patients and evaluation of HCV-core antigen test in screening patients for dialysis in Sana’a city, Yemen. Universal J Pharm Res 2019; 4(2): 14-18.https://doi.org/10.22270/ujpr.v4i2.251
  1. Al-Shamahy HA, Abdu SSA‏. Genotyping of Hepatitis C Virus (HCV) in infected patients from Yemen‏. Eur J Basic Med Sci 2014; 3(4):78-82‏.
  2. Rabbad IA, Al-Somainy AAM, Al-Shamahy HA, Nasser SM. Prevalence of hepatitis G virus infection among chronic hepatitis B, chronic hepatitis C and HIV patients in Sana'a, Yemen.‏ J Chinese Clin Med 2014; 5 (11), 654-658‏.
  3. Hepatitis. NIAID. Archivedfrom the original on 4 November 2016. Retrieved 2 November 2016.
  4. Bernal W, Wendon J. Acute Liver Failure. New England J Med 2013; 369 (26): 2525–2534. https://doi.org/10.1056/nejmra1208937
  1. World Health Organization. Hepatitis. World Health Organization. Archivedfrom the original on 2 December 2013. Retrieved 25 November 2013.
  2. Dienstag JL. Chapter 360: Acute Viral Hepatitis". In Kasper, D; Fauci, A; Hauser, S; Longo, D; Jameson, J; Loscalzo, J (eds.). Harrison's Principles of Internal Medicine 2015; 19e. New York, NY: McGraw-Hill. ISBN978-0-07-180215-4.
  3. D-Bawazir AA, Anthony Hart C, Sallam TA, et al. Seroepidemiology of hepatitis A and hepatitis E viruses in Aden, Yemen. Transactions Royal Soc Trop Med Hygiene 2010; 104(12):801-5.https://doi.org/10.1016/j.trstmh.2010.08.007
  1. Jacobsen KH, Wiersma ST. Hepatitis A virus sero-prevalence by age and world region, 1990 and 2005. Vaccine 2010; 28 (41): 6653–7.https://doi.org/10.1016/j. vaccine. 2010.08.037
  1. Guidelines for viral hepatitis surveillance and case management. Retrieved 2021-08-12.
  2. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Manual of Medicine 2013; 18e, Chapter 164: Chronic Hepatitis. New York, NY: McGraw-Hill.