The frequency, related cause of disease, and treatment of hepatitis B virus infection: A systematic review and meta-analysis in Iran
Gholamreza Kalvandi1, Ghobad Abangah2, Yousef Veisani3, Hassan Nourmohammadi4, Mohamad Golitaleb5, Hamed Tavan6
1 Associate Professor of Pediatrics Gastroenterology Department of Pediatrics, School of Medicine, Besat Hospital, Hamadan University of Medical Sciences, Hamadan, Iran
2 Associate Professor of Gastroenterology and Hepatology, School of Medicine, Shahid Mostafa Khomaeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
3 Research Assistant Professor of Epidemiology Department of Epidemiology, School of Health Psychosocial Injuries Research Center Ilam University of Medical sciences, Ilam, Iran
4 Assistant Professor of Hematology and Oncology, Department of Internal Medicine, School of Medicine,Shahid Mostafa Khomaeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
5 Instructor of Critical Care Nursing Department of Nursing, School of Nursing Arak University of Medical Sciences, Arak, Iran
6 MSs of nursing Medical-Surgical, Clinical Research Development Unit, Shahid Mostafa Khomeini Hospital, Ilam University of Medical Sciences, Ilam, Iran
|Date of Submission||07-Mar-2019|
|Date of Decision||22-Oct-2019|
|Date of Acceptance||08-Sep-2021|
|Date of Web Publication||18-Feb-2022|
Dr. Hamed Tavan
Clinical Research Development Unit, Shahid Mostafa Khomeini Hospital, Ilam University of Medical Sciences, Ilam
Source of Support: None, Conflict of Interest: None
Background: Hepatitis B virus (HBV) is one of the most dreadful viruses causing high mortality rates and serious damages to hepatocytes. The aim of this study was to assess the frequency, related causes/risk factors, and treatments of HBV infection in Iran by systematic review and meta-analysis. Materials and Methods: The data were obtained by a literature search in the PubMed, Scopus, SID, and Web of Sciences databases. Keywords included prevalence, risk factors, causes, treatment, and HBV. The Persian equivalents of these keywords were also searched. The time span included 2004 to2021. The Q and I2 statistics were used to check heterogeneity among studies. The data were analyzed using Stata (version 14). Results: The frequencies of HBV infection and its pharmaceutical therapy were P = 6% (95% confidence interval [CI]: 4–9, I2 = 95.2%, P < 0.001) and 19% (95% CI: 18%–30%, I2 = 98.9%, P < 0.001), respectively. The most common risk factors/causes of HBV were narcotic consumption, blood-related factors, and transmission from infected individuals with the respective frequencies of 27% (95% CI: 16%–38%, I2 = 88.7%, P < 0.001), 32% (95% CI: 11%–53%, I2 = 99.8%, P < 0.001), 25% (95% CI: 10%–41%, I2 = 99.3%, P < 0.001), and 15% (95% CI: 7%–22%, I2 = 98.4%, P < 0.001), respectively. Conclusion: The most important causes of HBV infection were transmission from infected people, narcotic consumption, and blood-related factors. The main therapeutic intervention for HBV was pharmaceutical therapy.
Keywords: Hepatitis B virus, frequency, treatment, meta-analysis
|How to cite this article:|
Kalvandi G, Abangah G, Veisani Y, Nourmohammadi H, Golitaleb M, Tavan H. The frequency, related cause of disease, and treatment of hepatitis B virus infection: A systematic review and meta-analysis in Iran. J Res Med Sci 2022;27:15
|How to cite this URL:|
Kalvandi G, Abangah G, Veisani Y, Nourmohammadi H, Golitaleb M, Tavan H. The frequency, related cause of disease, and treatment of hepatitis B virus infection: A systematic review and meta-analysis in Iran. J Res Med Sci [serial online] 2022 [cited 2022 May 18];27:15. Available from: https://www.jmsjournal.net/text.asp?2022/27/1/15/337899
| Introduction|| |
Hepatitis B virus (HBV) is responsible for a human viral infectious disease inflicting major damages to the patient's hepatic tissue., HBV can cause both acute and chronic infections. In most infected individuals, there are no signs of the disease at initial phases. In others; however, the disease may acutely present with nausea, icter, fatigue, black urine, and abdominal pain. Nevertheless, the window period may last 30–180 days. In the individuals affected with HBV at birth, more than 90% of the cases progress toward a chronic disease. This is while chronic HBV is observed in <10% of the patients infected after 5 years of age. The majority of patients with chronic HBV do not show any sign of the disease; nevertheless, the disease still can progress to hepatic cirrhosis and cancer (hepatocellular carcinoma). This phenomenon (concomitant HBV infection and cirrhosis) increases the mortality rate (as high as 15%–25%) in these patients.
HBV is transmitted by being exposed to contaminated blood or other biological products. In endemic regions with a high penetrance of HBV, transmission at birth and being infected via blood products at childhood are the most common ways of the spread of the virus. In regions with a low prevalence, HBV is most commonly transmitted by sharing contaminated syringes for infusing intravenous narcotics among addicts, as well as via unprotected sexual intercourse.
The clinical symptoms of HBV include abdominal pain, black urine, fever, joint and muscle pain, nausea and vomiting, yellowish discoloration of skin and the white of the eye, as well as fatigue and weakness. The common ways of HBV transmission include unsafe sexual intercourse, using contaminated syringes, mother-to-child transmission, and transfusion of contaminated blood products. The most frequent used HBV therapeutics are nucleoside/nucleotide analogs (NAs). However, these therapeutics only halt the virus proliferation and rarely eradicate it, which limits the cure rate of HBV infection. HBV vaccination is the most effective preventive measure against this infection. By triple vaccination (including 3–4 infusions on multiple occasions), it is possible to prevent as high as 95% of HBV infections.
One of the advantages of meta-analysis studies is the pooling of the results of valid studies conducted on a certain issue. Therefore, the results of meta-analyses can be regarded among the most credible scientific data., Furthermore, meta-analyses are necessary to validate the results obtained by various studies and to provide a precise and reliable scale for both researchers and policymakers. The present study aimed to assess the frequency, causes, risk factors, and therapeutic modalities of the HBV infection in Iran by systematic review and meta-analysis.
| Materials and Methods|| |
The data were obtained by searching the studies conducted in Iran in the PubMed, Scopus, Web of Sciences, and SID databases. Keywords included hepatitis B virus, treatment, prevalence, and causes, as well as their Persian equivalents. The articles published within 2004–2021 were included.
Study selection and data extraction
Initially, all the Iranian studies related to HBV were collected. After the primary search, a checklist was prepared for recording the specifications of each study. All the articles with the phrases of “HBV treatment in Iran” and “the etiology and complications of HBV in Iran” entered into the primary checklist. The studies assessing surgical therapies, coping and preventive measures, as well as HBV risk factors were omitted at this stage.
A second checklist was prepared for obtaining required information from the primary screened studies (i.e., the first author's name, title, year of study publication, location, sample size, number of women and men, HBV total prevalence, HBV prevalence in men and women, age groups, therapeutic interventions and their subgroups, as well as a specific code for the location of the study). After scrutinizing the final checklist, the articles related to the study's aims were selected for meta-analysis.
Selection and qualification of studies
The STROBE checklist, was used to evaluate the articles. Two of the authors independently gave each part of the checklist a score between 0 and 2. Based on the scores obtained from the checklist, the qualities of the articles were designated as weak, moderate, and good with the scores of 1–15, 16–30, and 31–44, respectively. The articles that received at least 16 scores were included in the meta-analysis phase.
In the primary literature search, 100 studies were obtained using the keywords. Out of these, 12 articles entered the checklist prepared for study qualification. At this stage, the studies were assessed for extracting required information (1 – sample size, 2 – year of publication, 3 – HBV treatment subgroups including medical therapeutics, and 4 – causes of the disease).
The studies evaluating HBV treatment in Iran were finally approved. Accordingly, 12 studies entered the meta-analysis phase after studying their full texts in detail [Figure 1].
The variance of each study was calculated using normal and bi-nominal distributions. Weighted mean was applied for synthesizing the HBV prevalence reported in different studies. Each study was assigned with a weight inversely correlated with its variance. Considering the wide spectrum of HBV prevalence reported in different studies (i.e., heterogeneous studies) and a statistically significant heterogeneity index (I2), the random-effects model was used for meta-analysis. The heterogeneity rate was 92.1%, rendering a high heterogeneity. The I2 index is a numerical value for estimating the variance ratio between studies and is utilized as a surrogate for the probability index. The I2 values of ≤25%, 26%–50%, 51%–75%, and 76%–100% indicate low, moderate, significant, and high heterogeneity, respectively.,
Meta-regression was utilized to determine hepatitis B treatment in separate years and to evaluate the reasons of heterogeneity among the studies. The cure rate of HBV in Iran was calculated based on different risk factors and age groups by subgroup analysis. The data were analyzed by Stata (version 14) software.
| Results|| |
The finally included studies had been published from 2004 to 2021. The total sample size was 10815 (i.e., 901 subjects per study). The data extracted from the qualified studies included hepatic functional tests, the causes of the HBV infection, and HBV treatments.
The highest and lowest HBV frequencies were reported by Azad et al. (11.25%) in Qom in 2020 and Navaifar et al. (1.57%) in Sari in 2020, respectively. The features of the studies reporting HBV treatments are shown in [Table 1]. HBV risk factors, hepatic functional tests (aspartate transaminase [AST], alanine transaminase [ALT], and alkaline phosphatase [ALP]), and HBV treatments are demonstrated in [Table 2]. Other parameters related to the HBV infection are also presented in [Table 3].
|Table 2: Treatments, risk factors, and liver functional tests for the hepatitis B infection reported in the included studies|
Click here to view
|Table 3: The pooled prevalence of the treatments and causes of the hepatitis B infection|
Click here to view
The forest plot of HBV frequency is presented for each study in [Figure 2], and [Figure 3]a shows the meta-regression of the HBV infection in separate years. [Figure 3]b shows HBV meta-regression based on the sample size, revealing a lower HBV prevalence in the studies with larger sample sizes. Publication bias is presented in [Figure 4].
|Figure 2: The forest plot of hepatitis B virus prevalence with 95% confidence interval. The frequency of hepatitis B virus in individual studies. The overall prevalence of hepatitis B virus was P = 6% (95% confidence interval: 4–9, I2 = 95.2%, P < 0.001). The lines represent the confidence intervals of hepatitis B virus prevalence in each study. The middle point on each line shows the estimated hepatitis B virus prevalence in each study, and the diamond-shaped figure demonstrates the overall confidence interval of hepatitis B virus prevalence|
Click here to view
|Figure 3: (a) The meta-regression of hepatitis B prevalence in separate years. Hepatitis B prevalence meta-regression in each year. The annual prevalence of hepatitis B virus has increased since 2005 toward 2021. (b) The meta-regression of studies based on the sample size. The meta-regression of hepatitis B prevalence based on the sample size. The prevalence of hepatitis B virus was lower in the studies with larger sample sizes|
Click here to view
|Figure 4: The publication bias regarding hepatitis B prevalence and its pharmaceutical therapies|
Click here to view
As shown in [Figure 4], the symmetrical appearance of the funnel plot indicated no publication bias in the assessed studies. The circles “sizes exhibit the studies” weights (i.e., bigger circles reflect larger sample sizes).
| Discussion|| |
HBV is responsible for one of the most dreadful viral hepatic infections. Hepatitis (i.e., liver inflammation) is caused by a variety of viruses that induce hepatic inflammation and liver injury.,, In the present study, we assessed HBV prevalence in various geographical regions of Iran. The overall prevalence of HBV was obtained as 0.7%. In a review study in Iran, the overall prevalence of chronic HBV infection was reported to be 1.7%. Furthermore, chronic HBV infection has been reported in 3.2% and 1.5% of intravenous drug users and β-thalassemia major patients, respectively. This shows an overall combined prevalence of 6% in these groups, which is in line with the results of the present study.
According to our results, and based on the data obtained in various studies conducted in different regions of Iran, the overall rate of pharmaceutical treatment for HBV-infected patients was obtained 12%. Antiviral therapies are considered the most effective treatments for HBV infection.,, In the present study, liver functional tests showed the mean levels of 47, 78, and 10.36 IU/L for AST, ALT, and ALP liver enzymes, respectively. As the HBV infection is a blood-borne disease affecting hepatocytes, an elevation in the liver enzymes can be the primary sign of severe liver damage.,,
Educating vulnerable and at-risk people can reduce the incidence of HBV infection. In addition, since HBV infection is a blood-borne disease, it is advisable for vulnerable people, including hospital staff and those who are in direct contact with the blood, to be vaccinated against the virus to upgrade their safety levels.,
According to our findings, the main risk factors of HBV infection included the use of narcotics, suffering from underlying diseases, blood-related factors, and disease transmission from an infected person with the frequencies of 41%, 30%, 27%, and 18%, respectively. In addition, other studies have mentioned that lifestyle can be an important risk factor for the disease. Blood-related risk factors are the most important ways of HBV transmission among the addicts sharing syringes for injecting intravenous drugs, as well as among health-care providers who are in direct contact with the blood and blood products., Overall, it is presumable that environmental and occupational parameters are critical players that increase the risk of HBV infection. Therefore, these factors should be controlled to effectively confine the spread of the disease. This is a prerequisite for treating and supporting HBV-infected patients.
HBV meta-regression based on the year of study conduction showed a rise in HBV prevalence from 2005 to 2021. This observation demonstrated the inability of scientific achievements to effectively manage the disease, which may be partly due to the higher rates of unprotected sexual contacts, donation of infected blood products, and seeking health care from unapproved facilities (such as dentistry or tattoo centers)., This shows that the disease has not yet been taken seriously by the community. Therefore, boosting awareness about the disease may significantly reduce its prevalence and help save its costs and reduce its complications and hospitalization rate.
A limited number of disease-related variables had been mentioned in some of the assessed studies. Some of the studies reported etiologies, risk factors, symptoms, and treatments in separate categories, with no overall estimations. Furthermore, there were no comparisons between different age groups in some of the studies, and the following-up duration had not been reported in some others. Finally, some studies did not describe therapeutic interventions other than pharmaceutical therapies, curbing to determine the best therapeutic strategy in these patients.
Based on our findings, contact with infected individuals, suffering from underlying comorbidities, using narcotics, and finally, blood-related factors constituted the most prominent HBV risk factors. It is important to implement screening tests to identify at-risk individuals and therefore manage the disease spread. Timely diagnosis of underlying conditions (i.e., cancer) may be effective to prevent liver cirrhosis. It is also amenable to boost social knowledge about narcotics and their associated diseases by producing educational contents and movies. This can decrease the incidence of HBV infection. It is advisable for people to seek health-care services from safe facilities to prevent HBV transmission via infected blood products.
| Conclusion|| |
The major risk factors of HBV infection were disease transmission via infected individuals, suffering from underlying conditions, using narcotics, and blood-related factors. Pharmaceutical treatments included the most important therapeutic strategy in HBV-infected patients.
The authors express their thanks to the Deputy of Research and Technology of Ilam University of Medical Sciences for financially supporting the project. This was a research project approved by the Ilam University of Medical Sciences (IR.MEDILAM.REC.1399.192).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mitchison D, Davies G. The chemotherapy of tuberculosis: Past, present and future. Int J Tuberc Lung Dis 2012;16:724-32.
Babalık A, Arda H, Bakırcı N, Ağca S, Oruç K, Kızıltaş S, et al.
Management of and risk factors related to hepatotoxicity during tuberculosis treatment. Tuberk Toraks 2012;60:136-44.
Aljarbou AN. The emergent concern of hepatitis B globally with special attention to Kingdom of Saudi Arabia. Int J Health Sci (Qassim) 2013;7:333-40.
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al.
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the global burden of disease study 2010. Lancet 2012;380:2095-128.
Hsu YC, Wu CY, Lin JT. Hepatitis C virus infection, antiviral therapy, and risk of hepatocellular carcinoma. Semin Oncol 2015;42:329-38.
Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg sero prevalence and endemic city. Vaccine 2012;30:2212-9.
Hashiani AA, Sadeghi F, Ayubi E, Rezaeian S, Moradi Y, Mansori K, et al.
Prevalence of HIV, Hepatitis B and C Virus Co-infections among Iranian high-risk groups: A systematic review and meta-analysis. Malays J Med Sci 2019;26:37-48.
Kupek E, Petry A. Changes in the prevalence, incidence and residual risk for HIV and hepatitis C virus in Southern Brazilian blood donors since the implementation of NAT screening. Rev Soc Bras Med Trop 2014;47:418-25.
Namululi BA, Guerrieri C, Dramaix MW. Prevalence and incidence of HIV and hepatitis B among blood donors and estimated residual risk of transmission of HIV and HBV virus by blood transfusion. A study at the Provincial General Referee Hospital Bukavu, Democratic Republic of the Congo. Rev Epidemiol Sante Publique 2013;61:139-44.
Marwaha N, Sachdev S. Current testing strategies for hepatitis C virus infection in blood donors and the way forward. World J Gastroenterol 2014;20:2948-54.
Apata IW, Averhoff F, Pitman J, Bjork A, Yu J, Amin NA, et al
. Progress toward prevention of transfusion-transmitted hepatitis B and hepatitis C infection-sub-Saharan Africa, 2000-2011. MMWR Morb Mortal Wkly Rep 2014;63:613-9.
Salehi M, Alavian SM, Tabatabaei SV, Izadi SH, Sanei Moghaddam E, Amini Kafi-Abad S, et al.
Seroepidemiology of HBV infection in South-East of Iran; A population based study. Iran Red Crescent Med J 2012;14:283-8.
Azami M, Hafezi Ahmadi MR, Sayehmiri K. Hepatitis B vaccination efficacy in Iranian healthcare workers: A meta-analysis study. Hepat Mon 2017;17:e37781.
Parizad Nasirkandy M, Badfar G, Shohani M, Rahmati S, YektaKooshali MH, Abbasalizadeh S, et al.
The relation of maternal hypothyroidism and hypothyroxinemia during pregnancy on preterm birth: An updated systematic review and meta-analysis. Int J Reprod Biomed 2017;15:543-52.
Azami M, Sayehmiri K. Prevalence of diabetes mellitus in Iranian patients with thalassemia major: A systematic review and meta-analysis. J Mazandaran Univ Med Sci 2016;26:192-204.
Moradzadeh R, Golmohammadi P, Ashraf H, Nadrian H, Fakoorziba MR. Effectiveness of paromomycin on cutaneous leishmaniasis in Iran: A systematic review and meta-analysis. Iran J Med Sci 2019;44:185-95.
Hatefi M, Abdi A, Tarjoman A, Borji M. Prevalence of depression and pain among patients with spinal cord injury in Iran: A systematic review and meta-analysis. Trauma Mon 2019;24:1-8.
Teymoorzadeh Baboli M, Yousefi Abdolmaleki E, Shirzad M, Abedi Samakoosh M, Ghasemian R. Prevalence of drug-induced hepatitis and its risk factors in the treatment of tuberculosis in TB infected patients attending Razi Hospital, 2006-2011. Mazandaran Univ Med Sci 2014;23:235-9.
Pourshams A, Nasiri J, Mohammadkhani A, Nasrollahzadeh D. Hepatitis B in Gonbad-Kavoos: Prevalence, risk factors and interfamilial spreading. Govaresh 2004;9:222-5.
Ebrahim Zadeh A, Madarshahian F, Sharif Zadeh GR, Kamal Zadeh A. Investigating the relationship of virologic and epidemiologic markers with treatment outcomes in patients with chronic hepatitis B. SJIMU 2015;22:7-13.
Bakhshizadeh F, Hekmat S, Keshvari M, Alavian SM, Mostafavi E, Keivani H, et al.
Efficacy of tenofovir disoproxil fumarate therapy in nucleoside-analogous naive Iranian patients treated for chronic hepatitis B. Hepat Mon 2015;15:e25749.
Mohammadzadeh M, Fattahi B, Ghari T. The burden economic estimation of hepatitis B virus infection in Iran. Hepat Mon 2017;17:e40541.
Mokhtarifar A, Rezvani HR, Esmaielzadeh A, Ghaffarzadegan K, Goshayeshi L. The prevalence of HIV and transmission risk factors among hepatitis B and C patients referred to Emam Reza Hospital, Mashhad, Iran from 2005-2008. Govaresh 2014;19:14-9.
Alavian SM, Assari S, Manzoori-Joybari H, Moghani Lankarani M, Doroudi T, Haji-Beigi B, et al
. Frequency and risk factors of hepatitis D virus in hepatitis B patients. Govaresh 2005;10:21-6.
Somi MH, Khayatzadeh S, Nalbandy M, Naghashi S. and Nikniaz Z. (2020) Estimating the Incidence Rate of Hepatitis B and C in East Azerbaijan, Islamic Republic of Iran. Eastern Mediterranean Health Journal, 26, 803-9. https://doi.org/10.26719/emhj.19.077
Mokhtari A, Moghadami M, Seif M, Mirahmadizadeh A. Association of routine hepatitis B vaccination and other effective factors with hepatitis B virus infection: 25 years since the introduction of national hepatitis B vaccination in Iran. Iran J Med Sci 2021;46:93-102.
Gholamzadeh Khoei S, Sadeghi H, Bakht M, Rahimi S, Mirshahabi H, Gheibi N. Serosurvey of hepatitis-B surface antigen in afghan refugees; the first report from Qazvin, Iran. RABMS 2020;6:194-8.
Navaifar MR, Rahimzadeh G, Fahimzad AR, Safar MJ, Shamshiri AR, Rezai S, et al
. Seroepidemiology of hepatitis B in pregnant women in Sari, Iran 2018-2020. J Mazandaran Univ Med Sci 2021;30:121-6.
Azad AR, Zargar M, Zolfaghari MR, Mohammadbeigi A. The prevalence of hepatitis B and D viruses and evaluating YMDD mutation in HBV-suspected patients in Qom Province, Iran. Jundishapur J Microbiol 2020;13:e100038.
Poorolajal J, Majdzadeh R. Prevalence of chronic hepatitis B infection in Iran: A review article. J Res Med Sci 2009;14:249-58.
Sayehmiri K, Azami M, Nikpey S, Borji M, Sayehmiri F. Hepatitis B vaccination coverage in health personnel of Iran: A systematic review and meta-analysis study. IRJE 2015;11:1-10.
A'zami M, Nikpey S, Pakzad I, Sayehmiri K. Effects of immunization to hepatitis B vaccine in Iranian health staff: A systematic review and meta-analysis study. Koomesh 2016;17:789-95.
Azami M, Hafezi Ahmadi M R, Sayehmiri K. Hepatitis B Vaccination Efficacy in Iranian Healthcare Workers: A Meta-Analysis Study, Hepat Mon. 2017; 17(1):e37781. doi: 10.5812/hepatmon.37781.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]