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

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 worldwide^1,2. 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 countries^4,5, mainly in Pakistan, at 4.8%^6–8, 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 burden^11,12. 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 depth^6,7,9,10,15, 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 dependency^19,20. 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 level^{5,7,9,21–30}.

Materials and Methods

This study follows the methodology used in the previous systematic reviews of the MENA HCV Epidemiology Synthesis Project^{7,9,21–25,27}. The following subsections summarize this methodology while further details can be found in previous publications of this project^{7,9,21–25,27}.

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 27^th, 2016), the Scientific Information Database (SID) of Iran (up to June 29^th, 2016), the World Health Organization Index Medicus for the Eastern Mediterranean Region (IMEMR WHO) database (up to July 1^st, 2016), and the abstract archive of the International Aids Society (IAS) conferences (up to July 1^st, 2016). Additionally, the MENA HIV/AIDS Epidemiology Synthesis Project database was searched for further records in the form of country level reports and routine data^33,34. 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 identified^35,36.

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 reviews^{7,9,21–25,27}, 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.

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 reviews^{7,9,21–25,27}. 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 reviews^{7,9,21–25,27}. 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 reviews^{7,9,21–25,27}. 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 significant^38,39. The I² and its confidence intervals were calculated³⁸. The prediction intervals were also calculated to estimate the distribution of true effects around the estimated mean^38,40.

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 reviews^{7,9,21–25,27}, 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 database^33,34. 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%, respectively^45,46. 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%, respectively^47,48. 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 incarcerations^50–62, history and duration of intravenous drug use^{50,51,54,57,58,60–67}, history of sharing a needle or syringe^{55,57,62,68,69}, history of tattooing^{50–52,61,70,71}, history of sharing razors⁶⁷, multiple sex partners^{57,58,66,67,69,70,72}, being a man who have sex with men^54,62,68,73, history of surgery^70,73, history of blood transfusion^56,60,73, 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 2^nd 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 countries^{7,9,21–25,27} and globally^75–77. 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 PWID^16,79. 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 routes^21,80,81, 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 injection^17,82,83. 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 prisons^16,28, 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 prisons^{16,33,87–90}, 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 countries^{7,9,21–25,27}. 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)^91–93. 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 3^96,97. This shift may be due to the fact that injecting drug use is a major driver of HCV incidence^29,98 (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 countries^{7,9,21–25,27}, 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 Egypt^10,99–103 and Pakistan^6,15,104.

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 PWID^{16,87–90,105}, 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 syringes^106,107.

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.