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. 2018 Jan 9;8:150. doi: 10.1038/s41598-017-18296-9

The epidemiology of hepatitis C virus in Iran: Systematic review and meta-analyses

Sarwat Mahmud 1, Vajiheh Akbarzadeh 1,2, Laith J Abu-Raddad 1,2,
PMCID: PMC5760657  PMID: 29317673

Abstract

The aim of this study was to characterize hepatitis C virus (HCV) epidemiology in Iran and estimate the pooled mean HCV antibody prevalence in different risk populations. We systematically reviewed and synthesized reports of HCV incidence and/or prevalence, as informed by the Cochrane Collaboration Handbook, and reported our findings following the PRISMA guidelines. DerSimonian-Laird random effects meta-analyses were implemented to estimate HCV prevalence in various risk populations. We identified five HCV incidence and 472 HCV prevalence measures. Our meta-analyses estimated HCV prevalence at 0.3% among the general population, 6.2% among intermediate risk populations, 32.1% among high risk populations, and 4.6% among special clinical populations. Our meta-analyses for subpopulations estimated HCV prevalence at 52.2% among people who inject drugs (PWID), 20.0% among populations at high risk of healthcare-related exposures, and 7.5% among populations with liver-related conditions. Genotype 1 was the most frequent circulating strain at 58.2%, followed by genotype 3 at 39.0%. HCV prevalence in the general population was lower than that found in other Middle East and North Africa countries and globally. However, HCV prevalence was high in PWID and populations at high risk of healthcare-related exposures. Ongoing transmission appears to be driven by drug injection and specific healthcare procedures.

Introduction

Hepatitis C virus (HCV) related morbidity and mortality places a substantial burden on healthcare systems worldwide1,2. While viral hepatitis is the seventh leading cause of death globally, it is the fifth leading cause of death in the Middle East and North Arica (MENA), predominantly due to HCV3. High HCV antibody prevalence levels are found in few MENA countries4,5, mainly in Pakistan, at 4.8%68, and Egypt, at 14.7%9,10. Recent major breakthroughs in HCV treatment, in the form of Direct Acting Antivirals (DAA), have provided promising prospects for reducing HCV transmission and disease burden11,12. Elimination of HCV as a public health problem by 2030 has recently been set as a global target by the World Health Organization (WHO)13,14.

While HCV epidemiology in MENA countries, such as Egypt and Pakistan, has been studied in depth6,7,9,10,15, HCV epidemiology in Iran remains not well-characterized. Iran is estimated to have the highest population proportion of people who inject drugs (PWID) in MENA16, a key population at high risk of HCV infection. Iran shares a border with Afghanistan, the world’s largest opiates producer17, and therefore has become a major transit country for drug trafficking18. Nearly half of opium, heroine, and morphine seizures globally occur in Iran alone18. Increased availability and lower prices of injectable drugs have led to increased injecting drug use and dependency19,20. Understanding HCV epidemiology in Iran is critical for developing and targeting cost-effective and cost-saving prevention and treatment interventions against HCV.

The aim of this study was to characterize HCV epidemiology in Iran by (1) systematically reviewing and synthesizing records, published and unpublished, of HCV incidence and prevalence among the different population groups, (2) systematically reviewing and synthesizing evidence on HCV genotypes, and (3) estimating pooled mean HCV prevalence among the general population and other key risk populations by pooling available HCV prevalence measures. This study is conducted as part of the MENA HCV Epidemiology Synthesis Project, an on-going effort to characterize HCV epidemiology in MENA, providing empirical evidence to inform key public health research, policy, and programming priorities at the national and regional level5,7,9,2130.

Materials and Methods

This study follows the methodology used in the previous systematic reviews of the MENA HCV Epidemiology Synthesis Project7,9,2125,27. The following subsections summarize this methodology while further details can be found in previous publications of this project7,9,2125,27.

Data sources and search strategy

We systematically reviewed all HCV incidence and prevalence data in Iran as informed by the Cochrane Collaboration Handbook31. We reported our results using the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines (Table S1)32. Our main data sources included PubMed and Embase databases (up to June 27th, 2016), the Scientific Information Database (SID) of Iran (up to June 29th, 2016), the World Health Organization Index Medicus for the Eastern Mediterranean Region (IMEMR WHO) database (up to July 1st, 2016), and the abstract archive of the International Aids Society (IAS) conferences (up to July 1st, 2016). Additionally, the MENA HIV/AIDS Epidemiology Synthesis Project database was searched for further records in the form of country level reports and routine data33,34. A broad search criteria was used (Fig. S1) with no language restrictions. Articles were restricted to those published after 1989, the year in which HCV was first identified35,36.

Study selection

All records identified through our search were imported into a reference manager, Endnote, where duplicate publications were identified and excluded (Fig. 1). Similar to our previous systematic reviews7,9,2125,27, the remaining unique reports underwent two stages of screening, performed by SM and VA. The titles and abstracts were first screened, and those deemed relevant or potentially relevant underwent further screening, in which the full-texts were retrieved and assessed for eligibility, based on our inclusion and exclusion criteria. Eligible reports were included in this study, while the remaining ineligible reports were excluded for reasons indicated in Fig. 1. The references of all full-text articles and literature reviews were also screened for further potentially relevant reports.

Figure 1.

Figure 1

Flow chart of article selection for the systematic review of hepatitis C virus (HCV) incidence and prevalence in Iran, adapted from the PRISMA 2009 guidelines32.

Inclusion and exclusion criteria

The inclusion and exclusion criteria used were developed based also on our previous systematic reviews7,9,2125,27. Briefly, any document, of any language, reporting HCV antibody incidence and/or antibody prevalence in Iran, based on biological assays and on primary data, qualified for inclusion in this review. Our exclusion criteria included case reports, case series, editorials, letters to editors, commentaries, literature reviews, and studies reporting HCV prevalence based on self-reporting and/or on Iranian nationals outside of Iran. Studies performed before 1989, and studies referring to HCV as non-A non-B hepatitis, were also excluded. A secondary independent screening was also performed for articles reporting HCV genotype information, regardless of whether information on HCV incidence and/or prevalence was included.

In the subsequent sections, any document including outcome measures of interest will be referred to as a ‘report’, while details of a specific outcome measure will be referred to as a ‘study’. Accordingly, one report may contribute multiple studies, and multiple reports of the same study (outcome measure) were identified as duplicates and considered as one study.

Data extraction and data synthesis

Data from relevant reports were extracted by SM and VA. To check for consistency in extractions, 37% of reports were double extracted. Nature of extracted data followed our previous HCV systematic reviews7,9,2125,27. HCV prevalence measures were rounded to one decimal place, with the exception of those below 1%, which were rounded to two decimal places. Risk factors for HCV infection (at the individual level), which were found to be statistically significant through multivariable regression analyses, were extracted from all articles, when available.

Risk factors for HCV infection were extracted when identified as significant after controlling for confounders through multivariable regression analyses. Data on HCV ribonucleic acid (RNA) prevalence were extracted whenever available in reports including an HCV prevalence measure(s). HCV genotype studies identified through the independent secondary screening were extracted to a separate data file. Extracted data were stratified by study populations’ risk of acquiring HCV infection as follows:

  1. General populations (that is populations at low risk): these consisted of blood donors, pregnant women, children, healthy adults, and army recruits, among other general population groups.

  2. Populations at intermediate risk: these consisted of healthcare workers, household contacts of HCV infected patients, female sex workers, prisoners, homeless people, and drug users (only where the route of drug use was not specified or excluded drug injection), among others. Drug users were classified into the intermediate risk category as we could not assess, with the available information, the extent to which drug injection is common in any such specific population—it is possible that the majority of these drug users were not injecting drugs at the time of the study.

  3. Populations at high risk: these consisted of HIV patients, PWID, and of populations at high risk of healthcare-related exposures, such as hemodialysis patients, hemophilia patients, thalassemia, patients, and patients with bleeding disorders.

  4. Special clinical populations: these consisted of populations with liver-related conditions, such as chronic liver disease, acute viral hepatitis, hepatocellular carcinoma, and liver cirrhosis. This also consisted of other special clinical populations for which the level of HCV risk of exposure could not be ascertained a priori, such as lichen planus patients.

Quantitative assessment

The quantitative analyses were conducted following an analysis plan similar to that in our previous HCV systematic reviews7,9,2125,27. HCV prevalence data in reports comprising at least 50 participants were stratified by risk and summarized using reported prevalence measures. Meta-analyses of HCV prevalence measures were conducted by risk category for studies consisting of a minimum of 25 participants. Stratified measures were used in place of HCV prevalence for the total sample only if the sample size requirement was met for each stratum.

A pre-defined sequential order was followed when considering stratifications. Nationality was prioritized, followed by sex, year, region, and age. One stratification was included per study to avoid double-counting.

The variance of the prevalence measures was stabilized using the Freeman-Tukey type arcsine square-root transformation of the corresponding proportions37. Estimates for HCV prevalence were weighted using the inverse variance method and then pooled using a DerSimonian-Laird random effects model. This model accounts for sampling variation and expected heterogeneity in effect size across studies38. Heterogeneity was assessed using several measures. The forest plots were visually inspected and Cochran’s Q test was conducted, where a p-value < 0.10 was considered significant38,39. The I² and its confidence intervals were calculated38. The prediction intervals were also calculated to estimate the distribution of true effects around the estimated mean38,40.

Univariable and multivariable random-effects meta-regressions, based on established methodology31, were conducted to determine population-level associations with HCV prevalence and sources of between-study heterogeneity. Variables entered into the univariable model included risk population, sample size (<100 or ≥100), study site, sampling methodology (probability-based or nonprobability-based), publication year, and median year of data collection. Variables were included into the final multivariable model if the p-value was <0.10. Variables with a p-value < 0.05 in the final multivariable meta-regression were considered significant.

The majority of HCV prevalence measures in the general population were among blood donors, a population that mainly includes healthy adults. Therefore, we performed a sensitivity analysis to ascertain the impact of excluding blood donors on our pooled mean estimate for HCV prevalence among the general population (Fig. S5).

Descriptive analyses of HCV genotypes and subtypes were also performed. Individuals with mixed HCV genotypes contributed to the quantification of each identified genotype separately. Meta-analyses of genotype proportions were also performed to estimate the pooled mean proportions for each genotype. The diversity of HCV genotypes was assessed using the Shannon Diversity Index41.

Meta-analyses were performed on R version 3.1.242, using the package meta 43. Meta-regressions were performed on STATA 13, using the metan command44.

Qualitative analysis

Similar to our previous HCV systematic reviews7,9,2125,27, the quality of each incidence or prevalence measure was determined by assessing sources of bias that may affect the reported measure. The Cochrane approach was used to infer the risk of bias (ROB)31, and the precision of the reported measures was also evaluated. Studies were categorized into low or high ROB based on three quality domains: type of HCV ascertainment (biological assay or otherwise), rigor of sampling methodology (probability-based or nonprobability-based), and response rate (≥80% of the target sample size was reached or otherwise).

Studies with missing information for any of the three domains were categorized as unclear ROB for that specific domain. Studies where HCV measures were obtained from individuals presenting voluntarily to facilities where routine blood screening is conducted, or retrieved from patients’ medical records, were considered as having low ROB on the response rate domain. HCV prevalence measures obtained from country-level routine reporting, with limited description of the methodology used to be able to conduct ROB assessment, were categorized as of unknown quality.

Studies where HCV measures were obtained from a sample size of at least 100 individuals were considered as having high precision. For an HCV prevalence of 1% and a sample size of 100, the 95% confidence interval (CI) is 0–5%; a reasonable CI for an HCV prevalence estimate.

Results

Search results

Figure 1 describes the selection process by which studies were included in this systematic review, adapted from the PRISMA flow diagram32. We identified a total of 3,696 citations: 443 from PubMed, 772 from Embase, 1,885 from SID, 242 from IMEMR WHO, and 354 from the abstract archive of the IAS. After exclusion of duplicates and screening of titles and abstracts, 844 unique reports remained, for which the full-texts were retrieved for full-text screening. After full-text screening, 515 reports were excluded for reasons specified in Fig. 1. An additional 10 records were identified through screening references of full-text articles and reviews. One country-level report was retrieved and included from the MENA HIV/AIDS Epidemiology Synthesis Project database33,34. In total, 340 eligible reports were included in this systematic review. This yielded five HCV incidence measures and 472 HCV prevalence measures.

All 3,696 citations underwent an independent secondary screening for HCV genotype studies (Fig. S2). After title and abstract screening and exclusion of duplicates, the full-texts of 144 reports were screened. In total, 44 reports were found eligible for inclusion in this secondary systematic review, yielding 66 HCV genotype measures.

HCV incidence overview

We identified five incidence measures through our search (Table 1), three of which were conducted in Tehran. The highest sero-conversion risks were observed in thalassemia patients and hemodialysis patients, of 6.8% and 4.3%, respectively45,46. In special clinical populations, HCV incidence was measured in renal transplant patients and impaired glucose tolerance patients. The HCV sero-conversion risks were 2.1% and 0.71%, respectively47,48. In female drug users on methadone treatment (where the route of drug use was not specified) the sero-conversion risk was 2.5%49. No studies reported incidence rate, nor provided sufficient information for incidence rate to be calculated.

Table 1.

Studies reporting hepatitis C virus (HCV) incidence in Iran.

Author, year (citation) Year of data collection Study site Population’s classification based on risk of HCV exposure Population Sample size at recruitment Lost to follow-up HCV sero-conversion risk (relative to total sample size) Duration of follow-up
Pourmand, 200747 2002–04 Hospital Special clinical population Renal transplant patients 141 0 2.1% 24 months
Jabbari, 200846 2005–06 Hospital High risk population Hemodialysis patients 70 0 4.3% 18 months
Azarkeivan, 201245 1996–09 Blood transfusion center High risk population Thalassemia patients 307 0 6.8% 168 months
Dolan, 201249 2007–08 Rehab center Intermediate risk population Female drug users on methadone treatment 78 38 2.5% 7 months
Bahar, 200748 1998–01 Hospital Special clinical population Impaired glucose tolerance patients 560 0 0.71% 36 months

HCV prevalence overview

General population

A total of 122 HCV prevalence measures were identified in the general population (Table 2), ranging from 0.0% to 3.1%, with a median of 0.3%. Most measures were obtained from blood donors (n = 72) where HCV prevalence ranged from 0.0% to 3.1%, with a median of 0.3%. In pregnant women (n = 6), HCV prevalence ranged from 0.0% to 0.8%, with a median of 0.3%. In other general populations (n = 44), HCV prevalence ranged from 0.0% to 2.4%, with a median of 0.5%.

Table 2.

Studies reporting hepatitis C virus (HCV) prevalence among the general population (populations at low risk) in Iran.

Author, year (citation) Year(s) of data collection City or country of survey Study site Study design Study sampling procedure Population Sample size HCV prevalence (%)
Afzali, 2003108 1996 Kashan Blood transfusion center CS NS Blood donors 6,669 0.37
Afzali, 2003108 1997 Kashan Blood transfusion center CS NS Blood donors 6,750 0.64
Afzali, 2003108 1998 Kashan Blood transfusion center CS NS Blood donors 6,922 0.59
Afzali, 2003108 1999 Kashan Blood transfusion center CS NS Blood donors 6,986 1.6
Afzali, 2003108 2001 Kashan Blood transfusion center CS NS Blood donors 7,721 1.7
Afzali, 2003108 2000 Kashan Blood transfusion center CS NS Blood donors 8,683 1.5
Aghanjanipoor, 2006109 2002 Babol Blood transfusion center CS Conv Blood donors 16,576 0.48
Alavi, 2012110 NS Tehran NS CC Conv Healthy children 90 0.00
Alavian, 2002111 1996–1998 Tehran Blood transfusion center CC Conv Blood donors 319,375 0.09
Alavian, 2015112 2012 Isfahan Clinical: hospital & health care centers CC Conv Healthy adults 275 0
Amini, 2005113 NS Tehran Blood transfusion center CS Conv Blood donors 100 0.00
Ansar, 2002114 1997–1998 Rasht Blood transfusion center CS SRS Blood donors 5,976 0.03
Ansari-Moghaddam, 2012115 2008–2009 Zahedan Primary health care centers (community) CS Cluster sampling Residents (male) 1,207 0.66
Ansari-Moghaddam, 2012115 2008–2009 Zahedan Primary health care centers (community) CS Cluster sampling Residents (female) 1,380 0.36
Ardebili, 2012116 2007–2011 Kavar Community CS Conv General population 6,095 0.24
Arfaee, 2002117 NS Tehran Clinical: hospital & health care centers CS Conv Veterans 307 0.97
Assarehzadegan, 2008118 2005 Khuzestan Blood bank CS Conv Blood donors 400 0.00
Babak, 2008119 2006 Kermanshah Community CS Cluster sampling Residents 1,721 0.87
Barhaghtalab, 2008120 2002–2007 Fasa Blood transfusion center CS Conv Blood donors 25,491 0.55
Bozorgi, 2012121 2009 Ghazvin Blood bank CS Conv Blood donors 20,591 0.17
Chamani, 2007122 2004 Tehran Fertility clinic/IVF NS NS Infertile individuals (female) 533 0.40
Chamani, 2007122 2004 Tehran Fertility clinic/IVF CS NS Infertile individuals (male) 716 0.00
Delavari, 2004123 2003 Kerman Blood transfusion center CS NS Blood donors (female) 2,921 0.10
Delavari, 2004123 2003 Kerman Blood transfusion center CS NS Blood donors (male) 12,331 0.46
Doosti, 2009124 2003–2004 Shahre-Kord Regional blood transfusion center CS Conv Blood donors 11,200 0.59
Emam, 2006125 2001–2003 Jahrom Blood bank CS Conv Blood donors 3,000 0.30
EMRO, 2011126 2011 National National CS Conv Blood donors 1,986,992 0.06
Esfandiarpour, 2005127 2002–2003 Kerman NS CC NS General population 149 1.3
Esmaeili, 2004128 2004 Babol Clinical: hospital & health care centers CC NS Children not receiving blood 100 0.00
Esmaeili, 2004128 2004 Babol Clinical: hospital & health care centers CC NS Children receiving blood 100 2.0
Esmaeili, 2009129 2006–2007 Bushehr NS CS Conv Blood donors 20,294 0.21
Farajzadeh, 2005130 2001–2002 Kerman Blood transfusion center CC Conv Blood donors 96 3.1
Farshadpour, 2010131 2007–2007 Ahvaz Regional blood transfusion center CS Conv Blood donors 2,376 2.3
Farshadpour, 2016132 2004–2014 Bushehr Blood transfusion center CS Conv Blood donors 293,454 0.10
Gachkar, 2015133 2004 Tabriz Blood transfusion center CS Conv Blood donors (male) 399 0.00
Gerayli, 2015134 2012 Mashhad Medical Laboratory CC Conv Healthy adults 134 0
Ghaderi, 2007135 2004–2006 Birjand NS CC Conv Blood donors 150 0.67
Ghadir, 2006136 NS Golestan Community NS NS General population (male) 736 0.18
Ghadir, 2006136 NS Golestan Community NS NS General population (female) 1,387 0.85
Ghafouri, 2011137 2006–2009 South Khorasan NS CS Conv Blood donors 95,538 0.01
Ghavanini, 2000138 1998 Shiraz Regional blood transfusion center CS Conv Blood donors 7,879 0.59
Ghezeldasht, 2015139 2009–2010 Khorasan Razavi Community CS Cluster sampling General population 1,227 0.57
Habibzadeh, 2005140 2003 Ardabil Blood transfusion center CS Conv Blood donors 441 0.23
Hajiani, 2006141 2003–2004 Tehran Blood transfusion center CC NS Blood donors 500 1.2
Hajiani, 2006142 1998–2003 Ahvaz NS CC Conv Healthy adults 360 1.0
Heydarabad, 2012143 2010–2012 Malekan NS NS NS Pregnant women 420 0.48
Hosseien, 2009144 2003–2005 Tehran Regional blood transfusion center CS Conv Blood donors 1,004,889 2.1
Hosseini, 2007145 2005 Boushehr NS NS NS Blood donors 19,627 0.23
Jadali, 2005146 NS Tehran NS CC NS Healthy individuals 50 0.00
Jadali, 2005147 NS NS NS CC Conv Healthy individuals 50 0.00
Jamali, 2008148 2006 Golestan Community CS Cluster sampling General population 2,049 1.0
Kafi-abad, 2009149 2004–2007 National Blood transfusion center CS Conv Blood donors 6,499,851 0.13
Karim, 2008150 2003–2005 Ahvaz Blood transfusion center CC Conv Blood donors 125 2.4
Karimi, 2008151 2004–2006 Shahre-Kord Blood transfusion center CS Conv Blood donors 35,124 0.20
Kasraian, 2008152 2007–2008 Shiraz Blood transfusion center CC Conv Blood donors 93,987 0.21
Kasraian, 2010153 2003 Shiraz Blood transfusion center Pre-post Conv Blood donors (post-earthquake) 239 0.84
Kasraian, 2010153 2003 Shiraz Blood transfusion center Pre-post Conv Blood donors (pre-earthquake) 1,694 0.47
Kasraian, 2015154 2002 Shiraz Regional blood transfusion center CS Conv Blood donors NS 0.19
Kasraian, 2015154 2003 Shiraz Regional blood transfusion center CS Conv Blood donors NS 0.13
Kasraian, 2015154 2004 Shiraz Regional blood transfusion center CS Conv Blood donors NS 0.09
Kasraian, 2015154 2005 Shiraz Regional blood transfusion center CS Conv Blood donors NS 0.16
Kavoosi, 2008155 2004–2005 Kermanshah NS CC Conv Healthy adults 57 1.7
Kazeminejad, 2005156 2003 Gorgan Blood transfusion center CS Conv Blood donors 38,920 0.19
Keshvari, 2015157 2008 Tehran Blood transfusion center CS Conv Blood donors 296,567 0.14
Keshvari, 2015157 2013 Tehran Blood transfusion center CS Conv Blood donors 282,010 0.07
Khedmat, 2007158 2005–2006 Tehran Blood transfusion center CS SRS Blood donors 1,014 2.1
Khodabandehloo, 2013159 2008–2011 Semnan NS CS Conv Blood donors 124,704 0.03
Kordi, 2011160 NS Tehran Community CC Cluster sampling Volleyball and soccer players 410 0.00
Kordi, 2011160 NS Tehran Community CC Cluster sampling Wrestlers (male) 420 0.48
Mahmoudian, 2006161 2003–2004 Mixed (28 provinces unspecified) Blood transfusion center CS Conv Blood donors 1,489,935 0.07
Maneshi, 2010162 2004–2008 Bushehr Blood transfusion center CS Conv Blood donors 51,884 0.33
Mansour-Ghanaei, 2007163 1998–2003 Guilan Blood transfusion center CS Conv Blood donors 221,508 0.32
Masaeli, 2006164 2002–2003 Isfahan Blood transfusion center CS Conv Blood donors 29,458 0.24
Merat, 201054 2006 Mixed (Golestan, Tehran, Hormozgan) Community CS Cluster sampling General population 5,684 0.88
Metanet, 2006165 2004 Zahedan NS CC Conv Blood donors 1,399 0.07
Moezzi, 2015166 NS Chaharmahal and Bakhtiari Community CS Single stage cluster sampling Adults 3,000 1.4
Mogaddam, 2010167 NS Ardabil Blood bank CC NS Blood donors 60 0.00
Mohammadali, 2014168 2005–2011 Tehran Blood transfusion center CS Conv Blood donors 2,031,451 0.39
Mohebbi, 2011169 2007–2008 Lorestan Primary health care centers (community) CS Conv Pregnant women 827 0.24
Moniri, 2004170 2001–2002 Kashan Blood bank CS Conv Blood donors 600 0.50
Monsour-Ghanaei, 200773 2003 Guilan Community CS Conv Residents of nursing home 383 2.3
Moradi, 2007171 2001–2002 Saravan city, Sistan and Baluchistan Community CS Cluster sampling Women in childbearing ages 356 0.84
Motlagh, 2001172 1999–2000 Ahvaz NS CS Conv Pregnant women 80 0.00
Mousavi, 2010173 2008 Khuzestan Clinical setting (hospital) CS Conv Renal transplant donors 79 0.00
Mousavi, 2011174 2009–2010 Ahvaz Clinical setting (hospital) CS Conv Renal transplant donors 52 0.00
Pourshams, 2005175 2001 Tehran Blood bank CS SRS Blood donors 1,959 0.46
Poustchi, 201156 NS Golestan Community CS Cluster sampling General population 49,338 0.50
Rahbar, 2004176 2001–2002 Mashhad Blood transfusion center CS NS Blood donors 60,892 0.10
Rahnama, 2005177 2000–2001 Kerman Regional blood transfusion center CC SRS Blood donors 140 2.1
Razjou, 2012178 2009 National Blood bank CS Conv Blood donors 1,494,282 0.13
Rezaie, 2016179 2011–2015 Semnan Blood transfusion center CS Conv Blood donors 42,253 0.06
Rezazadeh, 2006180 2004–2005 Hamadan Blood transfusion center CS Conv Blood donors 18,306 0.43
Roshan, 2012181 2007–2008 Ahvaz Fertility clinic/IVF CS Conv Infertile couples (male) 712 0.84
Roshan, 2012181 2007–2008 Ahvaz Fertility clinic/IVF CS Conv Infertile couple (female) 712 0.42
Salehi, 2011182 2002–2006 Isfahan Clinical: hospital & health care centers CS Conv Blood donors 4,808 0.27
Samadi, 2014183 2012 Ahvaz Blood transfusion center CS Conv Blood donors 2,108 0.00
Seyed-Askari, 2015184 2009–2013 Kerman Blood transfusion center CS Conv Blood donors 360,722 0.08
Shaheli, 2015185 2012 Shiraz Community CC Conv Healthy adults 100 0
Shahshahani, 2013186 2004–2010 Yazd Blood transfusion center CS Conv Blood donors 346,471 0.07
Shakeri, 2013187 2010–2011 Mashhad Community CS Cluster sampling General population 3,870 0.13
Shamsdin, 2012188 2010–2011 Shiraz Community CS Conv General population 2,080 0.72
Sofian, 2010189 2008 Arak Regional blood transfusion center CS SRS Blood donors 531 0.19
Sohrabpour, 2010190 NS Mixed (Hormozgan, Tehran, Golestan) Community CS Cluster sampling General population 5,589 0.88
Tahereh, 2005191 2000–2002 Ghazvin Blood transfusion center CS SRS Blood donors 39,598 0.25
Taheri, 2008192 2003–2005 Rasht Blood transfusion center CS Conv Blood donors 49,820 0.18
Tajbakhsh, 2007193 2004 Shahrekord Blood transfusion center CS Conv Blood donors 11,472 0.60
Tanomand, 2007194 2005 Malekan city Clinical setting (hospital) CS SRS General population 346 0.29
Vahidi, 2000195 1996 Kerman Clinical setting (hospital) CC Conv Healthy children 107 0.00
Yazdani, 2006196 1998–2000 Kermanshah Clinical setting (hospital) CS Conv Pregnant women 2,000 0.60
Zamani, 2013197 2008–2011 Mazandaran Primary health care centers (community) CS Cluster sampling General population 6,145 0.08
Zanjani, 2013198 2005–2006 Zanjan Blood transfusion center CS Conv Blood donors 29716 0.11

aAbbreviations: CC, case-control; Conv, convenience; CS, cross-sectional; EMRO, Eastern Mediterranean Regional Office (WHO); IVF, in vitro fertilization; NS, not specified, SRS; simple random sampling.

bThe decimal places of the prevalence figures are as reported in the original reports, but prevalence figures with more than one decimal places were rounded to one decimal place, with the exception of those below 1%.

Populations at high risk

A total of 208 HCV prevalence measures were identified in populations at high risk (Table 3), ranging from 0.0% to 90.0%, with a median of 26.3%. The majority were conducted on high risk clinical populations (n = 127). In hemophilia patients (n = 25), HCV prevalence ranged from 6.0% to 90.0%, with a median of 54.0%. In thalassemia patients (n = 58), HCV prevalence ranged from 0.0% to 68.9%, with a median of 16.6%. In hemodialysis patients (n = 41), HCV prevalence ranged from 0.0% to 31.4%, with a median of 8.3%. In HIV positive patients (n = 25), HCV prevalence ranged from 3.9% to 89.3%, with a median of 67.7%. Among PWID (n = 56), HCV prevalence ranged from 11.3% to 88.9%, with a median of 51.4%.

Table 3.

Studies reporting hepatitis C virus (HCV) prevalence among populations at high risk in Iran.

Author, year (citation) Year(s) of data collection City or country of survey Study site Study design Study sampling procedure Population Sample size HCV prevalence (%)
Abdollahi, 2008199 2003 NS Hemophilia units CS Conv Hemophilia patients 174 83.3
Aghakhani, 2009200 NS Tehran NS CS Conv HIV patients 106 67.0
Aghakhani, 2009200 NS Tehran NS CS Conv Hemodialysis patients 289 3.1
Akbari, 2011201 2003–2004 Shiraz Thalassemia center CC SRS Thalassemia patients 200 25.0
Alavi, 2005202 2002 Tehran Clinical: hospital & health care centers CS Conv Thalassemia patients 110 11.8
Alavi, 2007203 2001–2003 Ahvaz Clinical: hospital & health care centers CS Conv PWID with HIV 104 74.0
Alavi, 2009204 2001–2006 Ahvaz Clinical: hospital & health care centers CS Conv PWID 142 52.1
Alavi, 2012110 NS Tehran Clinical: hospital & health care centers CC Conv Thalassemia patients (<18) 90 13.3
Alavia, 2003205 NS Ghazvin Clinical: hospital & health care centers NS NS Thalassemia patients 95 24.2
Alavian, 2003206 2000–2001 NS Hemophilia units CS Conv Hemophilia patients 176 60.2
Alavian, 200894 1999 National NS NS NS Hemodialysis patients NS 14.4
Alavian, 200894 2000 National NS NS NS Hemodialysis patients NS 11.2
Alavian, 200894 2001 National NS NS NS Hemodialysis patients NS 8.8
Alavian, 200894 2002 National NS NS NS Hemodialysis patients NS 8.2
Alavian, 200894 2003 National NS NS NS Hemodialysis patients NS 6.7
Alavian, 200894 2004 National NS NS NS Hemodialysis patients NS 5.6
Alavian, 200894 2005 National NS NS NS Hemodialysis patients NS 4.8
Alavian, 200894 2006 National NS NS NS Hemodialysis patients NS 4.5
Alavian, 2015112 2012 Isfahan Hemodialysis units CC Conv Hemodialysis units 274 0
Alipour, 201361 2003–2011 Shiraz Counseling centers CS Conv HIV patients (male) 215 17.7
Alipour, 201361 2003–2011 Shiraz Counseling centers CS Conv HIV patients (female) 1,230 89.1
Alipour, 2013207 NS Mixed (Shiraz, Tehran, Mashhad) Drop in centers and rehab centers CS Conv PWID (male) 226 38.6
Alipour, 201367 2011 Shiraz Counseling centers CS SRS HIV patients 168 87.5
Alizadeh, 2005208 2002 Hamedan Prison CS SRS PWID 149 31.5
Alizadeh, 2006209 NS Hamadan Clinical: hospital & health care centers CS NS Hemophilia patients 66 59.1
Ameli, 2008210 2006 Mazandaran Clinical: hospital & health care centers CS Conv Thalassemia patients 65 16.9
Amin-Esmaeili, 201257 2006–2007 Tehran Drop in centers and rehab centers CS Conv PWID 895 34.5
Amiri, 2005211 2001 Guilan Hemodialysis units CS Conv Hemodialysis patients 298 24.8
Ansar, 2002114 1997–1998 Rasht Clinical: hospital & health care centers CS SRS Thalassemia patients (female) 50 62.0
Ansar, 2002114 1997–1998 Rasht Clinical: hospital & health care centers CS SRS Thalassemia patients (male) 55 65.0
Ansar, 2002114 1997–1998 Rasht Clinical: hospital & health care centers CS SRS Hemophilia patients 93 55.9
Ansari, 2007212 2005–2006 Shiraz Clinical: hospital & health care centers CS Conv Thalassemia patients (female) 400 16.0
Ansari, 2007212 2005–2006 Shiraz Clinical: hospital & health care centers CS Conv Thalassemia patients (male) 406 12.8
Asl, 2013213 2003–2005 Alborz Prisons Coh Conv PWID 150 69.3
Assarehzadegan, 2012214 2008–2009 Ahvaz Clinical: hospital & health care centers CS Conv Hemophilia patients 87 54.0
Ataei, 2010215 2008–2009 Isfahan Drop in centers and rehab centers CS Conv PWID 3,284 38.0
Ataei, 201053 1998–2007 Isfahan Clinical: hospital & health care centers CS Conv HIV patients 130 77.0
Ataei, 2011216 NS Isfahan Prison, drop in centers and rehab centers CS Conv PWID 1,485 43.4
Ataei, 2011217 NS Isfahan Drop in centers and rehab centers CS Conv PWID 136 19.8
Ataei, 2012218 1996–2011 Isfahan Clinical: hospital & health care centers CS Conv Thalassemia patients 463 8.0
Azarkeivan, 2010219 1996–2005 Tehran Thalassemia center CS Conv Thalassemia patients 395 27.5
Azarkeivan, 2011220 2008 Tehran Thalassemia center CS Conv Thalassemia patients 695 24.5
Azarkeivan, 201245 1996–2009 Tehran Clinical: hospital & health care centers Coh Conv Thalassemia patients 395 7.6
Babamahmoodi, 2012221 2008–2010 Mazandaran Clinical: hospital & health care centers CS Conv HIV patients 80 58.8
Basiratnia, 2010222 1999 Shahrekord Clinical: hospital & health care centers NS NS Thalassemia patients (female) 50 22.0
Basiratnia, 2010222 1999 Shahrekord Clinical: hospital & health care centers NS NS Thalassemia patients (male) 63 23.8
Boroujerdnia, 2009223 2006–2007 Khuzestan Clinical: hospital & health care centers CS Conv Thalassemia patients 206 28.1
Bozorghi, 2006224 2004 Ghazvin Clinical: hospital & health care centers CS Conv Hemodialysis patients 89 6.7
Bozorgi, 2008225 2005 Ghazvin Clinical: hospital & health care centers CS Conv Thalassemia patients 207 24.2
Broumand, 2002226 NS Tehran Hemodialysis units CS Conv Hemodialysis patients 548 19.6
Company, 2007227 2005–2006 Ahvaz Clinical: hospital & health care centers CS Conv Thalassemia patients 195 20.5
Dadgaran, 2005228 NS Guilan Hemodialysis units NS NS Hemodialysis patients 393 17.8
Dadmanesh, 2015229 2012–2013 Tehran Clinical: hospital & health care centers CS Conv Hemodialysis patients 138 0
Davarpanah, 2013230 2006–2007 Shiraz Counseling centers CS Conv HIV patients 226 86.7
Davoodian, 2009231 2002 Tehran Prisons CS SRS PWID 249 64.8
Eghbalian, 2000232 NS Hamedan Clinical: hospital & health care centers CS NS Thalassemia patients (<15) 53 34.0
Esfahani, 2014233 2012 Hamedan Hemophilia units CS Conv Hemophilia patients 89 49.4
Eskandarieh, 2013234 NS Tehran Drop in centers and rehab centers CS Conv PWID 258 65.9
Eslamifar, 2007235 2006 Tehran Hemodialysis units CS Conv Hemodialysis patients 77 6.5
Etminani-Esfahani, 2012236 NS Tehran Clinical: hospital & health care centers CS Conv HIV patients 98 55.1
Faramarzi, 2013237 2010 Shiraz Voluntary counseling center CS Conv HIV patients (male) 222 64.0
Faranoush, 2006238 2002 Mixed (Semnan, Damaghan, Garmsar) Clinical: hospital & health care centers CS Conv Thalassemia patients 630 39.7
Farhoudi, 2016239 2013–2014 Tehran Prison CS Conv HIV patients 56 89.3
Ghaderi, 1996240 NS Fars Blood transfusion center CS Conv Thalassemia patients 90 68.5
Ghadir, 2009241 2008 Qom Hemodialysis units CS Conv Hemodialysis patients 90 21.1
Ghafoorian-Broujerdnia, 2006242 1999–2004 Ahvaz Clinical: hospital & health care centers CS Conv Thalassemia patients 122 26.2
Ghane, 2012243 2010 Mixed (Mazandaran and Guilan) Clinical: hospital & health care centers CS Conv Thalassemia patients 245 14.7
Haghazali, 2011244 2007 Ghazvin Clinical: hospital & health care centers CS Conv Hemodialysis patients (males) 76 7.5
Hamissi, 2011245 2009 Ghazvin Clinical: hospital & health care centers CS Conv Hemodialysis patients 195 6.7
Hariri, 2006246 2004 Isfahan Clinical: hospital & health care centers CS Conv Hemophilia patients 120 64.0
Hariri, 2006246 2004 Isfahan Clinical: hospital & health care centers CS Conv Thalassemia patients 616 10.9
Honarvar, 2013247 2012–2013 Shiraz Drop in centers and rehab centers CS Conv PWID 233 40.3
Hosseini, 201063 2006 Tehran Prison CS Conv PWID 417 80.0
Imani, 2008248 2004 Shahr-e-Kord Drop in centers and rehab centers CS Conv PWID 133 11.3
Ismail, 2005249 NS Tehran Clinical: hospital & health care centers CS Conv PWID 65 17.0
Jabbari, 200846 2005–2006 Golestan Clinical: hospital & health care centers CS Conv Hemodialysis patients 93 24.7
Joukar, 2011250 2009 Guilan Hemodialysis units CS Conv Hemodialysis patients 514 11.9
Kaffashian, 2011251 NS Isfahan Prison CS Conv PWID 951 42.0
Kalantari, 2011252 2008–2010 Isfahan Clinical: hospital & health care centers CS Conv Thalassemia patients 545 9.1
Kalantari, 2011252 2008–2010 Isfahan Clinical: hospital & health care centers CS Conv Hemophilia patients 615 80.5
Kalantari, 2014253 2010–2011 Isfahan Hemodialysis units CS Cluster sampling Hemodialysis patients 499 5.2
Karimi, 2001254 1999–2001 Shiraz Thalassemia center CS Conv Thalassemia patients 466 15.7
Karimi, 2001255 1999–2001 Shiraz Hemophilia unit CS Conv Hemophilia patients 281 15.7
Karimi, 2002256 2002 Shiraz Clinical: hospital & health care centers CS Conv Coagulation disorder patients 367 13.1
Kashef, 2008257 NS Tabriz Clinical: hospital & health care centers CS Conv Thalassemia patients 131 18.3
Kassaian, 2011258 2009 Isfahan Thalassemia center CS Conv Thalassemia patients 570 10.5
Kassaian, 2011258 2009 Isfahan Hemodialysis unit CS Conv Hemodialysis patients 800 2.1
Kassaian, 201258 2009 Isfahan Prison CS Conv PWID 943 41.6
Keramat, 2011259 2005–2007 Hamadan Counseling center CS Conv PWID 199 63.3
Keshvari, 2014260 2008–2010 Tehran Thalassemia center CS Conv Thalassemia patients 257 40.1
Khani, 2003261 2001 Zanjan Prison CS Conv PWID 346 50.9
Kheirandish, 200952 2006 Tehran Prison CS Conv PWID 454 80.0
Khorvash, 2008262 2005 Isfahan Clinical: hospital & health care centers CS Conv PWID 92 74.3
Khosravi, 2010263 NS Shiraz Counseling center CS Conv HIV patients 101 86.1
Kiakalayeh, 2013264 2002–2011 Rasht Clinical: hospital & health care centers CS Conv Thalassemia patients 1,113 10.5
Lak, 2000265 NS Tehran Hemophilia units CS Conv Hemophilia patients 100 90.0
Lak, 2000265 NS Tehran Clinical: hospital & health care centers CS Conv VWD patient 385 55.1
Langarodi, 2011266 2009–2010 Karaj Clinical: hospital & health care centers CS Conv Thalassemia patients 206 14.1
Mahdaviani, 2008267 2004 Markazi Clinical: hospital & health care centers CS Conv Hemophilia patients 68 36.7
Mahdaviani, 2008267 2004 Markazi Clinical: hospital & health care centers CS Conv Thalassemia patients 97 7.2
Mahdavimazdeh, 2009268 2005 Tehran Hemodialysis units CS Conv Hemodialysis patients 2,403 9.5
Mak, 2001269 NS Isfahan Hemodialysis units CS Conv Hemodialysis patients 86 31.1
Makhlough, 2008270 2006 Sari and Ghaemshahr, Mazandaran Hemodialysis units CS Conv Hemodialysis patients 186 11.3
Mansour-Ghanaei,2002271 1999 Guilan Hemophilia units CS Conv Hemophilia patients 101 71.3
Mansour-Ghanaei,2009272 2007 Rasht Clinical: hospital & health care centers CS Conv Hemodialysis patients 163 10.4
Mansour-Ghanaei,2009273 NS Guilan Thalassemia center CS Conv Thalassemia patients 370 50.4
Mashayekhi, 2011274 2008–2009 Tabriz Thalassemia center CS Conv Thalassemia patients 100 3.0
Mehrjerdi, 201468 2011 Tehran Drop in centers and rehab centers CS Conv PWID 209 26.8
Meidani, 2009275 2007–2008 Isfahan Clinical: hospital & health care centers CS Conv PWID 150 26.0
Mirahmadizadeh, 2004276 NS Shiraz NS CS NS PWID 186 80.1
Mirahmadizadeh, 2009277 NS National Drop in centers and rehab centers CS SRS PWID 1,531 43.4
Mirmomen, 2006278 2002 Mixed (Tehran, Kerman, Ghazvin, Semnan, Zanjan) Blood transfusion centers CS Conv Thalassemia patients 732 19.6
Mir-Nasseri, 200562 2001–2002 Tehran Drop in centers and rehab centers CS NS PWID 467 66.0
Mir-Nasseri, 201155 2001–2002 Tehran Prison, drop in centers and rehab centers CS Conv PWID 518 69.3
Mobini, 2010279 2006 Yazd Clinical: hospital & health care centers CS Conv Hemophilia patients 77 49.4
Mohammadi, 2009280 2007–2008 Lorestan NS CS Conv HIV patients 391 72.1
Momen-Heravi, 2012281 NS Kashan Drop in centers and rehab centers CS Cluster sampling PWID 300 47.3
Mousavi, 2002282 NS NS NS NS NS Thalassemia patients 81 27.2
Mousavian, 2011283 2003–2005 Tehran Hemophilia units CS Conv Hemophilia patients 1,095 72.3
Naini, 2007284 1993–2006 Isfahan Hemophilia units CS Conv Hemophilia patients 553 22.6
Najafi, 2001285 1998 Qaemshahr Thalassemia centers CS Conv Thalassemia patients 100 18.0
Rahbar, 2004176 2001 Mashhad Prison CC Conv PWID 101 59.4
Rahimi-Movaghar, 2010286 2006–2007 Tehran Drop in centers and rehab centers CS Snowball sampling PWID 899 34.5
Ramezani, 2008287 2005–2006 Tehran Counseling center CS Conv HIV patients 171 52.6
Ramezani, 2009288 NS Tehran Clinical: hospital & health care centers CS Conv HIV patients 91 68.5
Ramzani, 2014289 2012 Arak Drop in centers and rehab centers CS Conv PWID 100 56.0
Rostami, 2013290 2010–2011 Mixed Hemodialysis units CS Conv Hemodialysis patients 3963 1.3
Rostami-Jalilian, 2006291 2002–2004 Isfahan Clinical: hospital & health care centers CS Conv PWID with thrombosis 72 45.8
Rostami-Jalilian, 2006291 2002–2004 Isfahan Clinical: hospital & health care centers CS Conv PWID without thrombosis 76 34.2
Sabour, 2003292 1999–2000 Kermanshah Clinical: hospital & health care centers CS Conv Hemodialysis patients 140 26.4
Saleh, 2011293 2007–2008 Hamedan Clinical: hospital & health care centers CC Conv PWID (corpses) 94 60.6
Salehi, 201569 2006–2011 Shiraz Drop in centers and rehab centers CS Conv PWID 1,327 13.5
Sali, 2013294 2010–2012 Tehran Clinical: hospital & health care centers CS Conv HIV patients 200 71.0
Samak, 2012295 2007 Qom Clinical: hospital & health care centers CS Conv Thalassemia patients 142 13.4
Samarbaf-Zadeh, 2015296 NS Khuzestan Clinical: hospital & health care centers CS Conv Hemodialysis patients 430 9.1
Samimi-Rad, 2007297 2004 Markazi Clinical: hospital & health care centers CS Conv Thalassemia patients (male) 50 4.0
Samimi-Rad, 2007297 2004 Markazi Clinical: hospital & health care centers CS Conv Patients with Inherited bleeding disorder 76 43.4
Samimi-Rad, 2007298 2005 Isfahan Clinical: hospital & health care centers CS Conv Hemophilia patients 50 100.0
Samimi-Rad, 2007298 2005 Isfahan Clinical: hospital & health care centers CS Conv Thalassemia patients 53 100.0
Samimi-Rad, 2008299 2005 Markazi Hemodialysis units CS Conv Hemodialysis patients 204 4.9
Sanei, 2004300 2002 Zahedan Clinical: hospital & health care centers CS Conv Thalassemia patients 364 13.5
Sani, 2012301 2007–2009 Mashhad Clinical: hospital & health care centers CS Conv PWID 62 71.0
Sarkari, 201259 2009–2010 Mixed (Kohgiloyeh and Boyerahmad) NS CS Conv PWID 158 42.2
SeyedAlinaghi, 2011302 2004–2005 Tehran Clinical: hospital & health care centers CS Conv HIV patients 201 67.2
Seyrafian, 2006303 2005 Isfahan Hemodialysis units CS Conv Hemodialysis patients 556 2.9
Shahshahani, 2006304 NS Yazd NS CS NS Hemophilia patients 74 48.6
Shahshahani, 2006304 NS Yazd NS CS NS Thalassemia patients 85 9.4
Sharif, 2009305 2001–2006 Kashan Clinical: hospital & health care centers CS Conv PWID 200 12.0
Sharifi-Mood, 2006306 1986–2005 Zahedan Hemophilia units CS Conv Hemophilia patients 74 31.1
Sharifi-Mood, 2007307 2003–2006 Zahedan Hemophilia units CS Conv Hemophilia patients 81 29.6
Siavash, 2008308 2007 Kermanshah Clinical: hospital & health care centers CS Conv HIV patients 888 3.9
Sofian, 2012309 2009 Markazi Prison CS Conv PWID 153 59.5
Somi, 2007310 2006 Tabriz Hemodialysis units CS Conv Hemodialysis patients 462 14.9
Somi, 2014311 2012 Tabriz Hemodialysis units CS Conv Hemodialysis patients 455 8.1
Taremi, 2005312 2004 Tabriz Hemodialysis units CS Conv Hemodialysis patients 324 20.4
Tayeri, 2008313 2000–2007 Isfahan Clinical: hospital & health care centers CS Conv PWID with HIV 106 75.5
Taziki, 2008314 2001 Mazandaran Hemodialysis units CS Conv Hemodialysis patients 348 18.0
Taziki, 2008314 2006 Mazandaran Hemodialysis units CS Conv Hemodialysis patients 497 12.0
Toosi, 2007315 NS Tehran Clinical: hospital & health care centers CS Conv Hemodialysis patients 130 8.5
Torabi, 2005316 2003 Azerbaijan Clinical: hospital & health care centers CS Conv Thalassemia patients (<18) 84 7.1
Torabi, 2006317 2003 Azerbaijan Clinical: hospital & health care centers CS Conv Hemophilia patients 130 55.4
Vahidi, 2000195 1996 Kerman Clinical: hospital & health care centers CC Conv Thalassemia patients 107 22.4
Valizadeh, 2013318 2010 Urmia Hemophilia units CS Conv Hemophilia patients 50 6.0
Yazdani, 2012319 1996–2010 Isfahan Hemophilia units CS Conv Hemophilia patients 350 66.0
Zadeh, 2007320 2007 Tehran NS CS Conv PWID (males) 70 36.0
Zahedi, 2004321 2002 Kerman Clinical: hospital & health care centers CS Conv Hemophilia patients 97 44.3
Zahedi, 2012322 2010 Kerman Hemodialysis centers CS Conv Hemodialysis patients 228 3.0
Zali, 2001323 1995 Tehran Prison CS SRS PWID (male) 402 45.0
Zamani, 200751 2004 Tehran Community, drop in centers and rehab centers CS Conv PWID 202 52.0
Zamani, 201064 2008 Foulad-Shahr City Drop in centers and rehab centers CS Snowball sampling PWID 117 60.7
Ziaee, 2005324 2000 Khorasan Drop in centers and rehab centers CS Conv Hemophilia patients 80 55.0
Ziaee, 2007325 NS South Khorassan Hemophilia units CS Conv Hemophilia patients 80 26.3
Ziaee, 2015326 2010–2012 Birjand Hemophilia units CS Conv Hemophilia patients 108 20.4

aAbbreviations: CC, case-control; Coh, cohort; Conv, convenience; CS, cross-sectional; NS, not specified; PWID, people who inject drugs; SRS, simple random sampling; VWD, von Willebrand disease.

bThe decimal places of the prevalence figures are as reported in the original reports, but prevalence figures with more than one decimal places were rounded to one decimal place, with the exception of those below 1%.

Populations at intermediate risk

A total of 70 HCV prevalence measures were identified in intermediate risk populations (Table S2), ranging from 0.0% to 48.0%, with a median of 3.3%. In prisoners (n = 15), HCV prevalence ranged from 0.7% to 37.9%, with a median of 4.1%. In homeless people (n = 10), HCV prevalence ranged from 0.0% to 48.0%, with a median of 3.0%. Half of these studies were conducted on homeless children, among which HCV prevalence ranged from 0.0% to 3.5%, with a median of 1.0%. In household contacts of HCV index patients (n = 5), HCV prevalence ranged from 0.0% to 3.3%, with a median of 2.2%. In healthcare workers (n = 11), HCV prevalence ranged from 0.0% to 37.0%, with a median of 0.0%. In drug users (where the route of drug use was not specified (n = 13), HCV prevalence ranged from 3.4% to 36.1%, with a median of 14.5%.

Special clinical populations

A total of 72 HCV prevalence measures were identified in special clinical populations (Table S3), ranging from 0.0% to 69.1%, with a median of 3.2%. In hepatitis B virus patients, prevalence ranged from 0.0% to 18.0%, with a median of 10.3%. In viral hepatitis patients (n = 9), HCV prevalence ranged from 0.0% to 34.9%, with a median of 6.1%. In patients with liver cirrhosis (n = 5), HCV prevalence ranged from 1.7% to 14.9%, with a median of 7.3%.

Pooled mean HCV prevalence estimates

Table 4 shows the results of our meta-analyses for HCV prevalence. The estimated national population-level HCV prevalence, based on the pooled HCV prevalence in the general population, was 0.3% (95% CI: 0.2–0.4%). There was significant evidence of heterogeneity (p < 0.0001). I2 was estimated at 99.8% (95% CI: 99.8–99.8%), indicating that almost all observed variation is attributed to true variation in HCV prevalence rather than sampling error. The prediction interval was 0.0–1.5%.

Table 4.

Results of the meta-analyses for hepatitis C virus (HCV) prevalence measures in Iran stratified by populations’ risk of exposure.

Population at risk Studies Samples HCV prevalence Heterogeneity measures
Total N Total n Range (%) Mean (%) 95% CI Q (p-value)ª I² (confidence limits)c Prediction interval (%)d
General population (populations at low risk) 122 16,073,479 0.0–3.1 0.3 0.2–0.4 56269.6 (p < 0.0001) 99.8% (99.8–99.8%) 0.0–1.5
Populations at high risk 208 55,257 0.0–90.0 32.1 28.1–36.2 217272.1 (p < 0.0001) 99.0% (99.0–99.1%) 0.0–88.5
    PWID 56 17,999 11.3–88.9 52.2 46.9–57.5 2615 (p < 0.0001) 97.9% (97.6–98.1%) 15.8–87.3
    Populations at high risk of healthcare-related exposures 127 32,517 0.0–90.0 20.0 16.4–23.9 8786.2 (p < 0.0001) 98.6% (98.5–98.8%) 0.0–69.7
Populations at intermediate risk 70 36,879 0.0–48.0 6.2 3.4–9.6 9,128 (p < 0.0001) 99.2% (99.2–99.3%) 0.0–49.9
Special clinical populations 72 55,187 0.0–69.1 4.6 3.2–6.1 2293.6 (p < 0.0001) 96.9% (96.5–97.3%) 0.0–21.6
 Populations with liver-related conditions 28 6,338 0.0–34.9 7.5 4.3–11.4 639.5 (p < 0.0001) 95.8% (94.8–96.6%) 0.0–35.2
    Other special clinical populations 44 48,849 0.0–69.1 2.7 1.8–3.6 520.6 (p < 0.0001) 91.7% (89.8–93.3%) 0.0–9.6

aAbbreviations: CI, confidence interval.

bQ: Cochran Q statistic assessing the existence of heterogeneity in HCV prevalence estimates.

cI²: a measure assessing the magnitude of between-study variation that is due to difference in HCV prevalence estimates across studies rather than chance.

dPrediction interval: a measure estimating the 95% interval in which the true HCV prevalence in a new HCV study will lie.

The pooled mean HCV prevalence for populations at high risk was 32.1% (96% CI: 28.1–36.2%). There was significant evidence of heterogeneity (p < 0.0001), with an I2 of 99.0% (95% CI: 99.0–99.1%). The prediction interval was 0.0–88.5%. For the subpopulations of PWID and populations at high risk of healthcare-related exposures, the pooled means were 52.2% and 20.0%, respectively.

The pooled mean HCV prevalence for populations at intermediate risk was 6.2% (95% CI: 3.4–9.6%). There was significant evidence of heterogeneity (p < 0.0001), with an I2 of 99.2% (95% CI: 99.2–99.3%). The prediction interval was 0.0–49.9%.

The pooled mean HCV prevalence for special clinical populations was 4.6% (95% CI: 3.2–6.1%). There was significant evidence of heterogeneity (p < 0.0001), with an I2 of 96.9% (95% CI: 96.5–97.3%). The prediction interval was 0.0–21.6%. For the subpopulations of populations with liver-related conditions and other special clinical populations, the pooled means were 7.5% and 2.7%, respectively.

The forest plots for the HCV prevalence meta-analyses can be found in Figs S3 and S4.

Sensitivity analysis

After excluding blood donor data, the national population-level HCV prevalence was estimated at 0.3% (95% CI: 0.2–0.5%). There was significant evidence of heterogeneity (p < 0.0001), with an I2 of 76.3% (95% CI: 67.5–81.7%). The prediction interval was 0.0–1.3%. The forest plot for this sensitivity analysis can be found in Fig. S5.

HCV RNA prevalence

Our search identified a total of 55 HCV RNA measures. The details of each of these measures can be found in Table S4. These were reported either among HCV antibody positive individuals, or as a proportion of the entire sample. HCV RNA prevalence among HCV antibody positive individuals ranged from 0% to 89.3%, with a median of 61.9%. HCV RNA prevalence as a proportion of the entire sample ranged from 0% to 60.0%, with a median of 8.6%. HCV RNA prevalence as a proportion of the entire sample was high in several populations at high risk of healthcare-related exposures.

Risk factors for HCV infection

A number of studies assessed risk factors for HCV exposure using multivariable regression analyses. Risk factors most commonly reported included history and duration of incarceration and multiple incarcerations5062, history and duration of intravenous drug use50,51,54,57,58,6067, history of sharing a needle or syringe55,57,62,68,69, history of tattooing5052,61,70,71, history of sharing razors67, multiple sex partners57,58,66,67,69,70,72, being a man who have sex with men54,62,68,73, history of surgery70,73, history of blood transfusion56,60,73, and history of hemodialysis74.

HCV genotypes

HCV genotype data was identified in 66 studies including a total of 24,029 HCV RNA positive individuals. Of these, 895 individuals had an undetermined genotype and were therefore excluded from further analysis. The vast majority of individuals were infected by a single genotype, with only 2.9% being infected by multiple genotypes. The proportion of infections for each HCV genotype was highest in genotype 1 (58.2%), followed by genotype 3 (39.0%), genotypes 2 (1.7%), and genotype 4 (1.0%).

The pooled mean proportion for genotype 1 was 56.3% (95% CI: 52.9–59.6%), genotype 3 was 38.8% (95% CI: 35.7–41.9%), genotype 2 was 0.4% (95% CI: 0.0–1.0%), and genotype 4 was 0.0% (95% CI: 0.0–0.1%).

Genotype 1 was more common among populations at high risk of healthcare-related exposures than genotype 3. Meanwhile, genotype 3 was more common among PWID than genotype 1. Within genotype 1, subtype 1a and subtype 1b were isolated (where subtype information was available) from 79.5% and 20.5% of individuals, respectively.

Quality assessment

The results of the quality assessment are summarized in Table 5. The majority of HCV incidence measures (60%) were based on samples with >100 participants, and therefore were classified as having high precision. Incidence studies were based on convenience sampling from clinical facilities, and 60% had a response rate >80%. All incidence measures were based on biological assays.

Table 5.

Summary of precision and risk of bias (ROB) assessment for the hepatitis C virus (HCV) incidence and prevalence measures extracted from eligible reports.

Quality assessment HCV incidence HCV prevalence
n % n %
Precision of estimates
High precision 3 60.0 312 77.4
Low precision 2 40.0 79 19.6
Uncleara 12 3.0
Risk of bias quality domains
 HCV ascertainment
Low risk of bias 5 100 402 100
High risk of bias 0 0 0 0
Sampling methodology
Low risk of bias 0 0 48 11.9
High risk of bias 5 100 350 87.1
Unclear 0 0 4 1.0
Response rate
Low risk of bias 3 60.0 370 92.0
High risk of bias 2 40.0 10 2.5
Uncleara 0 0 22 5.5
Total studies where risk of bias assessment was possible 5 100 402 99.8
Unknown b 0 0 0.2
Total studies 5 100 403 100
Summary of risk of bias assessment for HCV prevalence measures n %
Low risk of bias
In at least one quality domain 402 100
In at least two quality domains 371 92.3
In all three quality domains 47 11.7
High risk of bias
In at least one quality domain 350 87.1
In at least two quality domains 10 2.5
In all three quality domains 0 0
Total studies where risk of bias assessment was possible 402 99.8
Total studies 403 100

aStudies with missing information for any of the domains were classified as having unclear risk of bias for that specific domain.

bStudies extracted through country-level routine reporting with limited description of the sample (not permitting the conduct of risk of bias assessment) were classified as being of unknown quality.

The majority of HCV prevalence measures (77.4%) were based on samples with >100 participants, and therefore were classified as having high precision. Of the 403 prevalence measures, ROB assessment was possible for 402 measures.

All HCV prevalence measures were based on biological assays. In 25.0% of measures, information on the exact biological assay was missing. Approximately one third of the samples underwent secondary confirmatory testing, with the majority using the more sensitive and specific recombinant immunoblot assay (RIBA). Among studies where information was available on assay generation, the majority (71.2%) used the more recent, sensitive, and specific 3rd generation Enzyme-linked immunosorbent assay (ELISA) tests, and 26.9% used 2nd generation ELISA. The majority of samples (82.6%) were drawn using non-probability based sampling. Response rate was high in 92.0% of studies.

In summary, HCV prevalence measures were of reasonable quality. All studies had a low ROB in at least one quality domain, 92.3% had a low ROB in at least two of the three quality domains, and 11.7% had a low ROB in all three quality domains. Only 2.5% of studies had a high ROB in two of the three quality domains, and no study had a high ROB in all three quality domains.

Meta-regressions and sources of heterogeneity

The results of our meta-regression models can be found in Table 6. The univariable meta-regression analyses identified population, study site, sample size, and year of data collection as significant predictors (with p < 0.1), and therefore eligible for inclusion in the final multivariable meta-regression model. Sampling methodology used (probability-based or nonprobability-based) was not associated with HCV prevalence (p > 0.1). In the final multivariable meta-regression analysis, all variables remained statistically significant (p < 0.05) with the exception of healthcare setting and unspecified study site. The final multivariable model explained 71.7% of the variability in HCV prevalence. Of note, the model indicated a statistically significant declining trend in HCV prevalence in Iran—year of data collection had an AOR of 0.93 (95% CI: 0.91–0.96).

Table 6.

Univariable and multivariable meta-regression models for the mean HCV prevalence among populations in Iran.

Number of studies Univariable analysis Multivariable analysisa
OR (95% CI) p-value AOR (95% CI) p-value
Population classification General population (low risk) 122 1 1
PWID 56 269.41 (175.01–414.72) 0.000 88.80 (52.30–150.75) 0.000
HIV patients 25 273.98 (152.38–492.64) 0.000 135.48 (72.30–253.87) 0.000
Populations at high risk of healthcare-related exposures 127 48.08 (34.26–67.46) 0.000 39.33 (25.69–60.20) 0.000
Populations at intermediate risk 70 10.10 (6.76–15.10) 0.000 4.36 (2.74–6.94) 0.000
Populations with liver-related conditions 28 16.34 (9.34–28.61) 0.000 10.24 (5.65–18.55) 0.000
Other special clinical populations 44 7.22 (4.51–11.55) 0.000 6.01 (3.61–10.02) 0.000
Study site Community 42 1 1
Blood bank 73 0.31 (0.15–0.64) 0.002 0.45 (0.7–0.77) 0.003
Prison 44 28.12 (12.6–62.71) 0.000 3.66 (2.05–6.52) 0.000
Rehab/Drop-in-center 35 48.49 (20.71–113.56) 0.000 2.26 (1.19–4.33) 0.013
Healthcare setting 256 5.72 (3.08–10.62) 0.000 0.64 (0.40–1.02) 0.063
Unspecified 22 3.74 (1.41–9.96) 0.008 1.11 (0.56–2.18) 0.766
Sampling methodology Probability-based 52 1 1
Nonprobability-based 390 1.7 (0.88–3.46) 0.114
Unspecified 30 1.81 (0.62–5.26) 0.274
Sampling size <100 144 1 1
≥100 328 0.28 (0.18–0.44) 0.000 0.70 (0.53–0.92) 0.010
Year of data collection 472 0.95 (0.90–1.00) 0.032 0.93 (0.91–0.96) 0.000
Year of publication 472 1.00 (0.91–1.02) 0.150

aThe adjusted R-square for the full model was 71.74%. Abbreviations: OR= Odds ratio; AOR= Adjusted odds ratio; CI = Confidence interval; PWID = People who inject drugs.

Discussion

We presented a comprehensive systematic review and synthesis of HCV epidemiology in Iran. The pooled mean HCV prevalence in the general population was estimated at only 0.3%, on the lower side of the levels observed in other MENA countries7,9,2125,27 and globally7577. Despite this low prevalence in the general population, high prevalence was found among PWID and populations at high risk of healthcare-related exposures. These findings suggest that most ongoing HCV transmission in Iran is driven by injecting drug use and specific healthcare-related exposures. Genotypes 1 and 3 were the most frequently circulating strains. Of note, HCV prevalence in Iran is on a declining trend (Table 6).

Our estimate for the general population is slightly lower than an estimate provided for the whole adult population as part of a global estimation using a different methodology—0.3% in our study versus 0.5% in Gower et al.78. The difference may be explained by the fact that our estimate is strictly for the general (normally healthy) population. Moreover, our estimate is a pooled estimate of 122 studies as opposed to Gower’s et al. estimate which was based on five studies78. Inclusion of blood donor studies in our estimation did not explain the difference—our sensitivity analysis showed that estimated HCV prevalence in the general population was invariable with exclusion of blood donors (Fig. S5).

Iran has one of the highest population proportion of current PWID in the adult population (0.43%) in MENA, with an estimate of 185,000 current PWID16,79. Our synthesis indicated that injecting drug use was one of the most commonly reported risk factors for HCV infection, and that the pooled mean HCV prevalence among PWID was 52.2% (Table 4). These results suggest that injecting drug use is a main driver, if not the main driver, of HCV incidence in this country (Table 6). The regional context of Iran and the drug trafficking routes21,80,81, support an environment of active injection and a major role for PWID in HCV transmission. In this regard, HCV epidemiology in Iran appears to resemble that in developed countries, such as in the United States of America (USA), where most HCV incidence is attributed to drug injection17,82,83. Of note, we identified high HCV prevalence even among drug users where the route of drug use was not specified or excluded drug injection. This may suggest under-reporting of drug injection among those who report just drug use, or past drug injection among them before shifting to other forms of drug use.

Having said so, the estimated low HCV prevalence in the general population of only 0.3% apparently contradicts with a large PWID population in Iran. In the USA, it is estimated that the population proportion of current PWID is 0.3%84, and that of lifetime PWID is 2.6%84, compared to 0.43% for current PWID in Iran16. HCV prevalence among PWID in the USA is just over 50%85, therefore comparable with the pooled estimate of 52.2% for PWID in Iran (Table 4). HCV prevalence in the wider adult population in the USA is estimated at 1.0%86, much higher than the pooled estimate for HCV prevalence in the general population in Iran (0.3%). This discrepancy may be explained by an over-estimated current PWID population in Iran, very recent trend of drug injection with relatively small lifetime PWID population, or that the estimated HCV prevalence in the general population considerably underestimates the actual HCV prevalence in the whole adult population in Iran.

Our synthesis suggests that prisons have been a major setting for HCV transmission in Iran (Table 6). With nearly 60% of prisoners being incarcerated for drug-related offences81, high reported injecting risk behaviors in prisons16,28, and the high HCV prevalence among prisoners (Tables 3 and S2), prisons should be a main focus of HCV prevention and treatment efforts. Iran has made major and internationally-recognized strides in establishing harm reduction services for PWID including in prisons16,33,8790, but further scale-up of these services in all prisons is warranted.

High HCV prevalence was found in populations at high risk of healthcare-related exposures such as hemodialysis, hemophilia, and thalassemia patients, though with geographical variation (Tables 3 and 6). This finding, along with the higher HCV prevalence generally among clinical populations (Table S3), suggests that healthcare is also a main driver of HCV transmission, though less so than in most other MENA countries7,9,2125,27. The quality of healthcare and application of stringent protocols for infection control appear also to vary by setting within Iran. Overall, however, Iran seems to have made major progress in reducing HCV exposures through healthcare, which may explain the declining trend in HCV prevalence (Table 6)9193. For example, HCV prevalence among hemodialysis patients was reported in one study to have declined from 14.4% in 1999 to 4.5% in 200694.

HCV genotype 1 was the dominant circulating strain in Iran (56% of infections), followed by genotype 3 (39% of infections). This shows similarity to the pattern observed in multiple countries globally95. Nevertheless, this genotype distribution differs substantially from that found in most other MENA countries29. Several recent studies have also indicated an increasing presence of genotype 396,97. This shift may be due to the fact that injecting drug use is a major driver of HCV incidence29,98 (Table 6), or the fact that this is a sub-regional pattern—genotype 3 is the main circulating strain in neighboring Pakistan29.

Our meta-analyses confirmed high heterogeneity in estimated effect sizes (Table 4). This was expected, due to differences between studies in variables such as risk population, study site, sampling methodology, sample size, and year of data collection, among others. Our meta-regressions identified several sources of heterogeneity in HCV prevalence studies in Iran. As expected, large differences in HCV prevalence by risk population were observed (Table 6). A small-study effect was also observed, with small studies reporting higher HCV prevalence. Importantly, a time trend was also observed with a declining HCV prevalence with time.

Our study is limited by the quality of available studies, as well as their representativeness of the different risk populations. High heterogeneity in prevalence measures were identified in all meta-analyses for all risk populations (Table 4). Meta-regression analyses were performed to identify the sources of heterogeneity, and while the final multivariable regression model accounted for 71.7% of observed heterogeneity, there are variables that we are unable to assess, such as “hidden” selection bias in recruitment.

Another limitation is the absence of reporting of the specific used biological assay in 25.0% of studies. The majority of included studies were based on convenience sampling. Although this is presumed a limitation, the meta-regression analyses did not identify sampling methodology as a statistically significant source of heterogeneity in HCV prevalence (p = 0.114; Table 6).

Despite these limitations, the main strength of our study is that we identified a very large number of studies, in fact the largest of all MENA countries7,9,2125,27, that covered all risk populations and that allowed us to have such a comprehensive synthesis of HCV epidemiology.

Conclusions

HCV prevalence in the wider population in Iran appears to be considerably below 1%—on the lower range compared to HCV prevalence in other MENA countries and globally. However, high HCV prevalence was found among PWID and populations at high risk of healthcare-related exposures. Most ongoing HCV transmission appears to be driven by injecting drug use and specific healthcare-related exposures. Genotypes 1 and 3 were the most frequently circulating strains.

There are still gaps in our understanding of HCV epidemiology in this country. Conduct of a nationally-representative population-based survey is strongly recommended to provide a better estimate of HCV prevalence in the whole population, delineate the spatial variability in prevalence, identify specific modes of exposure, and assess HCV knowledge and attitudes, as has been recently conducted in Egypt10,99103 and Pakistan6,15,104.

Our study informs planning of health service provision, development of policy guidelines, and implementation of HCV prevention and treatment programming to reduce HCV transmission and decrease the burden of its associated diseases. Our findings suggest the need of a targeted approach to HCV control based on settings of exposure. Iran has established internationally-celebrated harm reduction services for PWID16,8790,105, but these services need to be accessible to all PWID across the country, as well as in relevant settings, such as prisons. Further focus on infection control in healthcare facilities is also warranted, such as the adoption of the new WHO guidelines for the use of safety-engineered syringes106,107.

Electronic supplementary material

Supplementary material (4.2MB, pdf)

Acknowledgements

The authors would like to thank Dr. Karima Chaabna for providing methodological expertise for the conduct of this study. This publication was made possible by NPRP grant number 9–040–3–008 from the Qatar National Research Fund (a member of Qatar Foundation). The findings achieved herein are solely the responsibility of the authors. The authors are also grateful for support provided by the Biostatistics, Epidemiology, and Biomathematics Research Core at Weill Cornell Medicine-Qatar.

Author Contributions

S.M. conducted the systematic review of the literature, data retrieval, extraction, analysis, and wrote the first draft of the paper. V.A. contributed to the systematic review of the literature, data retrieval, and extraction. L.J.A. conceived and led the design of the study, analyses, and drafting of the article. All authors have read and approved the final manuscript.

Competing Interests

The authors declare that they have no competing interests.

Footnotes

Electronic supplementary material

Supplementary information accompanies this paper at 10.1038/s41598-017-18296-9.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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