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World J Gastroenterol. Oct 14, 2015; 21(38): 10790-10810
Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10790
Epidemiology of hepatitis C virus in Iran
Reza Taherkhani, Fatemeh Farshadpour
Reza Taherkhani, Fatemeh Farshadpour, Department of Microbiology and Parasitology, School of Medicine, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
Reza Taherkhani, Persian Gulf Biomedical Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
Fatemeh Farshadpour, Persian Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr 7514633341, Iran
Author contributions: Taherkhani R and Farshadpour F solely contributed to this paper.
Conflict-of-interest statement: The authors declare there are no conflicts of interest in the content of this review.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Fatemeh Farshadpour, PhD, Department of Microbiology and Parasitology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, PO Box 3631, Bushehr 7514633341, Iran.
Telephone: +98-9171712653 Fax: +98-7714550235
Received: March 27, 2015
Peer-review started: March 28, 2015
First decision: April 24, 2015
Revised: May 20, 2015
Accepted: August 31, 2015
Article in press: August 31, 2015
Published online: October 14, 2015


In Iran, the prevalence of hepatitis C virus (HCV) infection is relatively low according to the population-based epidemiological studies. However, the epidemiology of HCV is changing and the rate of HCV infection is increasing due to the growth in the number of injecting drug users in the society. In addition, a shift has occurred in the distribution pattern of HCV genotypes among HCV-infected patients in Iran. Genotype 1a is the most prevalent genotype in Iran, but in recent years, an increase in the frequency of 3a and a decrease in 1a and 1b have been reported. These variations in the epidemiology of HCV reflect differences in the routes of transmission, status of public health, lifestyles, and risk factors in different groups and geographic regions of Iran. Health policy makers should consider these differences to establish better strategies for control and prevention of HCV infection. Therefore, this review was conducted to present a clear view regarding the current epidemiology of HCV infection in Iran.

Key Words: Hepatitis C virus, Blood donors, Injecting drug users, Hemodialysis, Hemophilia, Thalassemia, Genotypes, Occult hepatitis C virus, Epidemiology, Iran

Core tip: The distribution patterns of hepatitis C virus (HCV) infection are related to different status of public health and the presence of risk factors in the society. In Iran, the predominance of risk factors for transmission of HCV has changed from blood transfusion to intravenous drug use; and due to the growth in the number of injecting drug users, the prevalence of HCV infection is rising in the country. Even the recent changes in the distribution pattern of HCV genotypes confirm this issue. Overall, the epidemiology of HCV is changing in Iran. Therefore, this review was conducted to present a clear view about current epidemiology of HCV in Iran.


Hepatitis C virus (HCV) is a small, enveloped positive-stranded RNA virus, belonging to the family Flaviviridae and the genus Hepacivirus[1,2]. Based on genomic heterogeneity, HCV has been classified into seven genotypes and over 70 different subtypes[3,4]. HCV is transmitted through exposure to infected blood and blood products. Blood transfusion, injecting drug use, sexual intercourse, surgery, and tattooing are some possible ways to spread HCV infection[5,6]. Among these, HCV transmission by sexual intercourse is less common and includes those that lead to mucosal exposure to infectious blood or blood-derived body fluids and is related to the presence of mucosal tears and genital ulcerative disease[7,8].

HCV is the major cause of chronic liver disease, and can lead to cirrhosis and hepatocellular carcinoma (HCC)[3,9]. Although the infection is preliminary acute with a wide spectrum of clinical manifestations from asymptomatic to mild or even severe clinical illness[10], about 75% to 85% of acute HCV infections slowly progress to chronic infection[11]. Approximately 10%-20% of those chronically infected are at risk of developing liver cirrhosis within 20 to 30 years, and of those with cirrhosis, 1%-5% per year will develop HCC[12].

HCV infection is defined as the presence of HCV-RNA and anti-HCV antibodies in serum or plasma. A positive HCV antibody test [enzyme linked immunosorbent assay (ELISA) and immunoblot assay] indicates exposure to HCV, however, it cannot distinguish between current or past infection. In general, anti-HCV antibody positive samples can be defined as current HCV infection if the HCV RNA test [reverse transcriptase polymerase chain reaction (RT-PCR)] is positive[8,13].

According to the World Health Organization reports, about 130-150 million of the world population have chronic HCV infection[14]. In addition, 3-4 million new cases of HCV infection emerge globally each year[15,16]. The chronic infection might result in cirrhosis, hepatic failure, or HCC, which are responsible for approximately 350000 to 500000 deaths per year[5,14,17,18]. Therefore, HCV is a life threatening global health problem, and its prevention is the main objective.

HCV has a high rate of genetic heterogeneity, therefore, no vaccine or immunoglobulin exist to prevent this infection[18]. Recent advances in HCV therapy have led to the development of new antiviral drugs for treatment of HCV infection, including the protease inhibitors telaprevir, simeprevir, boceprevir, and paritaprevir; NS5A inhibitors ledipasvir, daclatasvir, and ombitasvir; the nucleotide analog NS5B polymerase inhibitor sofosbuvir; and the non-nucleotide polymerase inhibitor dasabuvir[8,19,20]. These new therapies are well-tolerated and safer and much more effective than the previous therapies pegylated interferon (IFN)/ribavirin[20]. Despite these advantages, pegylated IFN-α in combination with ribavirin is recommended as the standard treatment for HCV infection in Iran[21-24]. The reasons for this are the high cost and restricted availability of the new medications in low- and middle-income countries[25].

Iran is a vast country with various ethnicities in different provinces. This country, with an area of about 1700000 km2, is located in the Middle East between Arab peninsula, Indian subcontinent, Europe, and Middle Asia[26,27]. There are variations in the prevalence and epidemiology of HCV in different groups and regions throughout the country. To achieve better strategies for the prevention and management of HCV infection, the current knowledge regarding the epidemiology of HCV infection merits reviewing. Therefore, we present here a clear review about the current epidemiology of HCV in Iran.


In Iran, the prevalence of HCV infection among blood donors in different studies varies considerably, depending on the study population, sample sizes, study periods, the geographic regions, risk factors, and the methods and type of kits used to determine HCV[15,28]. According to the results of a meta-analysis study, the prevalence of anti-HCV among 10739221 blood donors was 0.5% during 1996 to 2011[28]. In another study, the rate of anti-HCV seropositivity among 6499851 blood donors was 0.13% during 2004 to 2007[29]. The highest anti-HCV prevalence of 1.39% was declared in 2005, followed by a significant decreasing rate from 0.13% in 2007 to 0.03% in 2009[4,28]. The reasons for this decline were the implementation of more restrictive rules in physical examination prior to donation and the application of more sensitive HCV test kits for screening the blood by Iran Blood Transfusion Centers[27,28]. In addition, the public has become more aware of the routes of transmission of HCV infection in recent years[29].

Iran has the lowest anti-HCV prevalence among blood donors compared to corresponding figures in the Middle East countries, such as 0.6% in Lebanon, 0.8% in Kuwait, 0.9% in Oman, 2.7% in Yemen, and 5%-25% in Egypt[4,27,28,30,31]. Globally, however, the lowest HCV prevalence of 0.01%-0.1% has been reported in the United Kingdom and Scandinavia[5,18,32-34].

At present, the ELISA and confirmatory recombinant immunoblot assay (RIBA) are used routinely for screening of the blood donors by the Iranian blood bank transfusion centers. It seems screening of blood is an important factor in controlling and reducing the rate of HCV infection in the general population. However, the presence of asymptomatic or occult HCV infected donors with no detectable HCV Ab or low copy number of HCV genomes in their blood is a potential source of HCV transmission. Thus, the risk of HCV transmission through blood transfusion is considered an important public health concern[28,35] (Table 1[35-56]).

Table 1 Prevalence of hepatitis C virus among blood donors in Iran.
AuthorYear of studyCity or provinceLocationNo. of participantsNo. of positive samplesPrevalenceTestRef.
Taheri Azbarmi2003-2005Rasht, Gilan provinceNorth49820910.18%ELISA and RIBA[36]
Bani Aghil2006-2008GolestanNorth-East1281981610.12%ELISA and immunoblot[38]
Attarchi2003-2004TehranNorth-Center26645420.20%ELISA and RIBA[40]
Khedmat2005-2006TehranNorth-Center3180293230.09%ELISA, immunoblot and RT-PCR[35]
Bozorgi2002-2004QazvinWest-Center48116730.15%ELISA and RIBA[41]
350.17%HCV confirmatory tests (ND)
Karimi2004-2006Shahr-e KordCentral35124700.20%ELISA and immunoblot[46]
Masaeli2002-2003IsfahanCenter29458240.27%ELISA and RIBA[47]
Esmaieli2006-2007BushehrSouth20294420.20%ELISA and immunoblot[48]
Ghavanini1998ShirazSouth7897470.59%ELISA and immunoblot[49]
Emamghorashi2001-2003JahromSouth300090.30%ELISA and immunoblot[50]
Kasraian2007-2008ShirazSouth939872030.21%ELISA and RIBA[52]
Tajbakhsh2004Shahr-e kordWest11472690.60%ELISA[54]
Ghafouri2006-2009South KhorasanEast42652310.07%ELISA[56]

With an overall anti-HCV prevalence of less than 1% in the general population, Iran is considered a country with low frequency HCV infection[27]. However, it seems the prevalence of HCV is slightly rising in the country[57,58]. The prevalence of HCV infection in the general population varies considerably in different regions of Iran (Table 2[58-68]). These variations in the prevalence of HCV might be due to the differences in the quality of public health services, lifestyles, habits, and rates of high-risk behaviors in different geographic regions[15,28].

Table 2 Prevalence of hepatitis C virus among general population in Iran.
AuthorYear of studyCity or provinceLocationNo. of participantsNo. of positive samplesPrevalenceTestRef.
Zamani2008-2011Amol, MazandaranNorth6145120.20%ELISA[60]
Merat2006GolestanNorth-East1895181.00%ELISA and RIBA[58]
Merat2006TehranNorth-Center232680.30%ELISA and RIBA[58]
Merat2006HormozganSouth1463241.60%ELISA and RIBA[58]
Sistan and
Sayad2006KermanshahWest1721150.87%ELISA, immunoblot and RT-PCR[67]

In Iran, the prevalence of HCV infection in the general population is lower than those of the neighboring countries such as Afghanistan (1.1%), Turkey (1%-2.1%), Pakistan (4.7%), Iraq (7.1%), and Qatar (6.3%)[4,30]. Globally, the highest HCV prevalence of 17.5% (13%-22%) has been reported in Egypt[59].

The general population-based prevalence of HCV infection is used to describe and compare the local and global epidemiology of HCV infection[10,16]. The surveys on prevalence of HCV in the blood donor population fail to assess the true prevalence in an entire community. Since a large number of HCV positive cases are excluded from donating blood, the donor population is representative of a population at low risk of HCV infection. A recent study reported a HCV prevalence of 9.2% in the excluded individuals[27]. Therefore, the prevalence of HCV in the general population is higher than that in the donor population[27,28].

HCV in intravenous drug users

Presently, injecting drug use is the main route of HCV transmission[6,9,69]. Iran has one of the highest numbers of drug addicts in the world[9,70]. It has been reported that 2.8% of Iranian adults aged 15-64 years are drug abusers and about 180000 (12.2%) of this population are injecting drug users (IDUs)[9]. Estimates from Iran show a HCV prevalence of 50%-75% among IDUs[6]. However, the prevalence of anti-HCV among IDUs varies considerably in different regions of Iran (Table 3[70-90]). The outcomes revealed that Gilan, Hamedan, Tehran, and Hormozgan provinces have the highest rate of HCV infection, while Shahre Kord had the lowest rate of infection (Table 3). As a result, IDUs are the main source of HCV infection in Iran and account for the large proportion of current HCV transmission in the society[6,9,27]. In addition, the prevalence of HCV infection in prisons of Iran is extremely high, where 38% to 90% of imprisoned IDUs have been infected with HCV[9]. Interestingly, tattooing more effectively transmits HCV infection than injecting drug use among Iranian prisoners[6].

Table 3 Prevalence of hepatitis C virus among injecting drug users in Iran.
AuthorYear of studyCity or provincelocationNo. of participantsNo. of positive samplesPrevalenceTestRef.
Mohtasham Amiri2003GilanNorth817288.9%ELISA[72]
Zali1995TehranNorth-Center402 (Male imprisoned IDUs)18245.3%ELISA, RIBA[75]
Zamani2004TehranNorth-Center20210552.0%Particle Agglutination (PA) assay[76]
Fadaei Nobari2011IsfahanCenter174759534.0%ELISA[82]
Sofian2009Arak, MarkaziWest-Center153 (Male IDUs)9159.5%ELISA[83]
Ramezani2012ArakWest-Center100 (Male IDUs)5656.0%ELISA[84]
Honarvar2012-2013ShirazSouth569 (High risk groups)10919.1%ELISA and immunoblot[70]
233 (IDUs)9440.3%
336 (non-IDUs)154.4%
Davoodian2002Bandar Abbas, HormozganSouth24916364.8%ELISA[85]
Sarkari2009-2010Kohgiloyeh and BoyerahmadSouth-West1586742.4%ELISA[86]
Imani2004Shahr-e KordSout-West1331511.3%ELISA[87]
Mohammad Alizadeh2002HamadanWest149 (IDUs Prisoners)4731.5%ELISA, immunoblot[89]
Keramat2005-2007HamadanWest379 (High risk groups)13535.6%ELISA, immunoblot[90]
199 (IDUs)12663.3%

The global prevalence of HCV infection among IDUs varies considerably from 9.8% to 97.4%[71]. Approximately 10 million IDUs with a global midpoint prevalence of 67% are positive for anti-HCV. The highest rate of HCV infection among the IDUs has been reported in China (67%, 1.6 million), the United States (73.4%, 1.5 million), and Russia (72.5%, 1.3 million)[71].

HCV in hemodialysis patients

Distribution of HCV infection among hemodialysis patients has a vast geographic variation in different regions of Iran (Table 4[91-119]). According to a recent meta-analysis study in Iran, prevalence of HCV infection among this group of patients was reported to be 13.6%, 12.2%, and 7.6% by ELISA, RIBA, and PCR, respectively, which is lower than those of Saudi Arabia (50.5%), Kuwait (43.4%), Jordan (32.5%), and Pakistan (23.7%)[91-94] but higher than those of Australia (2.3%), United Kingdom (2.7%), Germany (3.9%), and Bahrain (7.4%)[95-97]. The risk of HCV infection is extremely high among hemodialysis patients[11]. Recent surveys show that the prevalence of HCV infection among hemodialysis patients is not related to history of blood transfusion. Considering the fact that the length of time on dialysis is significantly associated with HCV seropositivity, the nosocomial transmission is the main route of HCV transmission among Iranian hemodialysis patients[11,98].

Table 4 Prevalence of hepatitis C virus among hemodialysis in Iran.
AuthorYear of studyCity or provinceLocationNo. of participantsNo. of positive samplesPrevalenceTestRef.
Samimi-rad2005MarkaziWest-Center204115.4%ELISA, RIBA and RT-PCR[102]
Zamani1998–2005Amol, Tonekabon, Rasht and RamsarNorth3346720.0%ELISA, RT-PCR[107]
Mazandaran and Gilan provinces
Assarehzadegan2005-2006KhuzestanSouth-West214347.9%ELISA, RT-PCR[108]
Nemati1990-2006TehranCenter11265.3%ELISA, RT-PCR[109]
Jabbari2008GolestanNorth-East932324.7%ELISA, RIBA[116]
Hassanshahi2006-2007KermanSouth-East2036431.5%ELISA, RT-PCR[118]
HCV in hemophilia patients

Hemophilia patients may acquire HCV infection via contaminated blood products[98]. In Iran, the prevalence of HCV among hemophilia patients is very high, with an overall prevalence of 40.8%[98] and has a wide geographic variation (Table 5[120-134]). Most of the HCV infections among hemophilia patients are asymptomatic and may lead to liver failure. Therefore, routine screening for HCV infection in hemophilia patients is required to prevent the serious consequences of HCV infection[27].

Table 5 Prevalence of hepatitis C virus among hemophilia patients in Iran.
AuthorYear of studyCity or provinceLocationNo. of participantsNo. of positive samplesPrevalenceTestRef.
Torabi2004East AzarbaijanNorth-West1307256.00%ELISA, RIBA[121]
Valizadeh2010West AzarbaijanNorth-West3538.57%ELISA, RIBA and RT-PCR[122]
Mousavian2003-2005TehranNorth-Center109580272.30%ELISA and RT-PCR[123]
Javadzadeh Shahshahani2003YazdCenter743648.60%ELISA and RIBA[127]
Karimi1999-2000ShirazSouth2814415.65%ELISA and immunoblot[130]
Zahedi2002KermanSouth-East974344.30%ELISA and RIBA[132]
Sharifi-Mood2003-2006Zahedan, Sistan and BaluchistanSouth-East812429.60%ELISA and immunoblot[133]
HCV in thalassemia patients

HCV is a major cause of mortality in thalassemia patients due to post-transfusion HCV infection, which dramatically progresses to liver failure or even HCC[27,135]. Therefore, HCV infection is currently considered the main health problem in thalassemia patients, and much more attention to HCV screening in the blood transfusion process may improve survival of thalassemia patients[136]. Even though the current policies of blood banks have considerably decreased the incidence of HCV infection in thalassemia patients, blood transfusion remains the main risk factor for HCV infection among this group of patients because of transfusion of HCV-infected seronegative blood donated during the window period[27,136,137]. Therefore, the rate of HCV infection is high among thalassemia patients[137].

The geographical distribution of HCV infection among thalassemia patients varies widely in different regions of Iran (Table 6[86,118,119,127-129,137-151]), but a recent meta-analysis study reported the overall HCV prevalence is 18% among thalassemia patients in Iran[136]. Iran has the lowest rate of HCV infection among thalassemia patients in comparison with Eastern Mediterranean countries[136]. High prevalence of HCV infection has been reported among thalassemia in Egypt (69%), Saudi Arabia (63%), and Pakistan (45%)[136].

Table 6 Prevalence of hepatitis C virus among thalassemia patients in Iran.
AuthorYear of studyCity or provinceLocationNo. of participantsNo. of positive samplesPrevalenceTestRef.
Mirmomen2002TehranNorth-Center4108019.6%ELISA, RIBA[138]
Ghane2010-2011Gilan and MazandaranNorth2454618.8%ELISA[139]
AlaviNDTehranNorth-Center90 (pediatric patients)1213.3%ELISA, RT-PCR[141]
Alavian2002QazvinWest-Center962324.2%ELISA, RIBA[142]
Azarkeivan1996-2009TehranNorth-Center39510927.5%EIA, RIBA[144]
Javadzadeh Shahshahani2003YazdCenter8589.4%ELISA, RIBA[127]
Karimi1999-2000ShirazSouth466 (pediatric patients)7315.7%ELISA and immunoblot[147]
Kashef2006ShirazSouth1312418.3%ELISA and immunoblot[148]
Shahraki2005-2007ZahedanSouth-East560 (pediatric patients)305.3%ELISA[150]
Hassanshahi2006-2007KermanSouth-East1818144.7%ELISA, RT-PCR[118]
Ghafourian Boroujerdnia2005-2006AhvazSouth-West2065828.2%ELISA[151]
Sarkari2009-2010Kohgiloyeh and BoyerahmadSouth-West4936.1%ELISA[86]
HCV in health care workers

Health care workers are at the risk of acquiring HCV infection due to occupational exposures to blood and blood-derived body fluids[152]. There are few reports on the prevalence of HCV infection among health care workers in Iran. In Shoaei et al[153], HCV infection status was negative in 203 health care workers in Isfahan city in 2012. Similarly, all 191 health care workers were tested negative for HCV antibodies in Shahrud province in 2010[154]. Hadadi et al[155] reported a HCV prevalence of 6.6% (31/467) among health care workers in Tehran in 2004-2005, and Sarkari et al[86] reported a HCV seroprevalence of 4.2% among 212 health care workers in Kohgiloyeh and Boyerahmad province in 2009-2010.

The global prevalence of HCV infection among health care workers is 1%-6%[156]. After HBV, HCV is the most common blood-borne infection found among health care workers. Needle-stick or sharp injuries and mucosal exposure following blood splash are the most common risk factors for HCV infection among health care workers[152,153]. Therefore, prevention strategies and training programs are needed for health care workers to reduce the incidence of HCV infection in this group.

HCV in homeless people

Homeless people are one of the main high-risk groups for acquiring HCV infection because of high-risk behaviors, lifestyle, low levels of education, poverty, and poor hygiene[157,158]. There are over 100 million homeless people worldwide, and the prevalence of HCV infection among this group varies from 3.9% to 36.2% in different parts of the world[159]. Currently, there are no data on the number of homeless people in Iran, and only a few studies are available on the prevalence of HCV infection among homeless people in Tehran, the capital of Iran. Amiri et al[157] reported a HCV prevalence of 23.3% among 593 homeless individuals in Tehran in 2012. In another study by Vahdani et al[158], the prevalence of HCV infection was found to be 42.8% among 202 homeless men in Tehran city in 2007. According to the available data in Iran, the prevalence of HCV infection is considerably high among the older homeless population and homeless IDUs, especially those with a history of imprisonment[157,158]. The seroprevalence of HCV was reported to be 3.5% among the street children in Tehran city in 2008[160], while it was 1.0% in Isfahan city in 2005-2007[161].

The prevalence of HCV infection among homeless populations is higher than the other blood-borne infections, therefore, HCV infection is the main health problem among homeless population of Iran and implementation of HCV-controlling and educational programs are required to reduce HCV infection among this population[157,158,161].

HCV in human immunodeficiency virus-positive patients

Prevalence of HCV coinfection among human immunodeficiency virus (HIV) positive patients ranges from 11.5% to 94.0% in different regions of Iran[85,162] (Table 7[85,162-174]). This geographic variation in HCV/HIV coinfection reflects diversity of the risk factors, the types of exposure, and the epidemiology of these viruses in different regions of the country[163,164]. However, in all of these studies, intravenous drug use and a history of imprisonment were the most prevalent risk factors for HCV/HIV co-infection in Iran[164-169].

Table 7 Prevalence of hepatitis C virus among HIV-positive patients in Iran.
AuthorYear of studyCity or provinceLocationNo. of participantsNo. of positive samplesPrevalenceTestRef.
SeyedAlinaghi2004- 2005TehranNorth-Center20113567.2%ELISA[170]
Ataei1998-2007IsfahanCenter13010077.0%ELISA and RIBA[168]
Davoodian2002Bandar Abbas and RoodanSouth383594.0%ELISA[85]
Saleh2013Khorramabad, LorestanWest1032322.3%ELISA[174]

The prevalence of HCV coinfection is noticeably high among HIV-positive patients in Iran. The shared modes of transmission and the lack of an effective vaccine for HCV could explain this high prevalence[163-165,169,170]. In Iran, HCV and HIV are predominantly transmitted by injecting drug use[165,170,171]. Moreover, the rate of IDUs is increasing in Iran, which may boost the rate of HCV/HIV coinfection in the country[163].

HCV coinfection adversely affects HIV disease outcomes and leads to severe liver disorders, progression to cirrhosis and HCC, and subsequently lower survival of HIV infected patients[163-165]. HIV infection leads to higher rates of HCV persistence, increased risk of hepatotoxicity due to the extensive use of anti-retroviral drugs, and subsequently accelerated end stage liver disease[164,169-171]. Overall, one third of mortalities in HIV infected patients are related to liver diseases[163,164,170]. Therefore, HCV coinfection is considered a potential threat to HIV positive patients, and routine screening for HCV infection, as well as HCV treatment, seem to be necessary in all HIV-positive patients[164,165,169,172].

HCV in patients with mixed cryoglobulinemia

Mixed cryoglobulinemia is the most common immunological disorder reported in patients with chronic HCV infection[175-177]. The prevalence of HCV infection in patients with mixed cryoglobulinemia ranges from 40% to 90% worldwide[178]. Several studies have reported HCV infection as the etiological agent of mixed cryoglobulinemia[176,179,180]. Gharagozloo et al[181] reported an anti-HCV prevalence of 69% among patients with mixed cryoglobulinemia in Iran. In Owlia et al[182], 16% of patients (8/50) with HCV infection had cryoglobulins in central regions of Iran. However, this rate was relatively low in comparison with the high incidence of mixed cryoglobulinemia (19%-> 50%) among patients with chronic HCV infection.

HCV in patients with diabetes mellitus

Diabetes mellitus is one of the most prevalent metabolic disorders, and it affects 4.6%-10.0% of the Iranian population[183]. In 1994, a possible association between HCV infection and diabetes mellitus was first introduced[184]. Since then, many studies have demonstrated that HCV infection has a role in the activation of host innate immune responses and, via the TNF-α pathway, induces the destruction of insulin signaling pathways and subsequently the development of insulin resistance[185]. In addition, immune-mediated pathogenesis or direct cytotoxic effects of HCV on pancreatic islet cells results in dysfunction of β cells and declines the insulin production[183,185-188]. Although HCV infects the pancreas, autoimmunity is not involved in the occurrence of diabetes[186].

Several studies have shown that the prevalence of HCV among diabetic patients is significantly higher than that in non-diabetic patients[187,189,190]. Interestingly, male gender, age over 40 years, and abnormal liver enzymes are associated with high prevalence of HCV infection among patients with diabetes mellitus[191]. Although there are several reports on the prevalence of HCV infection among patients with diabetes mellitus in Iran, the results show great heterogeneity. Aghamohammadzadeh et al[192] reported HCV seropositivity in 2.5% (10/400) of Iranian patients with diabetes mellitus in Tabriz. In addition, Alavian et al[193] showed an increased risk of diabetes mellitus among Iranian patients with chronic HCV infection in Tehran. While, Janbakhsh et al[194] reported no association between HCV infection and the occurrence of diabetes in Kermanshah. Metanat et al[195] found no association between HCV and diabetes in Zahedan, and Bahar et al[196] reported similar findings in Tehran.

According to the epidemiological data, patients with chronic HCV infection are at an increased risk for developing diabetes[191,197,198]. HCV infection is a risk factor for occurrence of diabetes, and diabetes will enhance the risk of liver fibrosis, cirrhosis, and finally progression to HCC[187]. Therefore, screening of all HCV positive patients for diabetes mellitus is recommended to reduce the adverse effects associated with diabetes on HCV infection, which may progress to liver fibrosis, cirrhosis, or even HCC.

The incidence of diabetes mellitus among HCV positive patients ranges from 23% to 62% in different parts of the world[183]. This incidence is 18.3% among Iranian HCV-infected patients, which is higher than that in the general population of Iran[183]. Compared to other parts of the world, the prevalence of diabetes mellitus among Iranian patients with HCV infection is low. Overall, there are no adequate studies in this field in Iran. Therefore, more surveys are recommended to clearly identify the frequency of diabetes mellitus among HCV-infected patients in Iran.

HCV in patients with autoimmune thyroid disorders

Autoimmune thyroid disorders (ATD), including Hashimoto’s thyroiditis and Graves’ disease, are the most prevalent endocrine problems worldwide[199,200]. Many investigators have investigated the possible association between chronic HCV infection and autoimmune thyroiditis. However, the exact role of HCV infection in the development of autoimmune thyroiditis remains unclear[201]. Investigations have suggested several mechanisms, including the following: (1) Non-autoimmune-mediated pathogenesis through direct cytopathic effect of HCV on thyrocytes, which results in destruction of thyroid follicular cells[201]; (2) Autoimmune-mediated pathogenesis due to the presence of homologous amino acid sequences between viral proteins and thyroidal proteins or molecular mimicry and over activation of autoreactive T-cells and B-cells during HCV infection, which results in production of anti-thyroid antibodies[200-202]; and (3) The adverse effects of IFN-therapy on thyroid gland through immune stimulatory and direct effects of IFN on the thyrocytes, which ultimately results in destructive thyroiditis[199,201,203]. Therefore, monitoring thyroid function is recommended during IFN-therapy in patients with HCV infection[201,204].

There are limited reports on the significance of HCV infection in patients with ATD in Iran. Ziaee et al[204] reported thyroid dysfunction in 10.3% of patients with chronic HCV infection in Tehran in 2002-2003, while, Rahimi et al[205] found no relationship between chronic HCV infection and autoimmune thyroiditis in Kermanshah in 2010. Similarly, Jadali et al[206,207] reported no relationship between HCV infection and Hashimoto’s thyroiditis or Graves’ disease in Tehran in 2005. Still, more studies are recommended to generate a clear epidemiological pattern of HCV infection among patients with thyroid disorders in Iran.

HCV in patients with lichen planus

Lichen planus (LP) is a chronic inflammatory disease of the skin and mucous membranes with unknown etiology[199,208,209]. Chronic HCV infection appears to have a role in the pathogenesis of LP through induction of host immune responses and immune dysregulation in susceptible patients[200,210,211]. This mechanism was confirmed by the presence of HCV-RNA and HCV-specific T lymphocytes in the skin and mucous membrane specimens of patients with LP[200,209]. Another possibility is the effect of IFN-therapy in the development of LP in patients with HCV infection[209]. However, HCV replicates in skin and mucous lesions of patients with LP, but no direct cytotoxic effect of HCV on skin and mucosa cells could be proposed in the development of LP[209]. The majority of patients with LP have not been infected with HCV[212]. In addition, the incidence of LP among patients with chronic HCV infection was estimated about 5% (1%-6%)[199,209]. Therefore, it seems that HCV contributes to the development of LP, with some unknown underlying factors also involved in this process[210].

According to the epidemiological data, the prevalence of HCV among LP patients varies considerably from 4% to 62% in different parts of the world, where this prevalence is higher in HCV endemic countries[209,210]. There are limited reports on the prevalence of HCV among patients with LP in Iran. Rabiei et al[213] reported high prevalence of oral lichen planus (OLP) in HCV-infected patients (4.7%) compared to the general population (0.5%-2.0%) and suggested an association between HCV infection and OLP in Gilan in 2002. Similary, Khatibi et al[214] reported a higher prevalence of OLP in HCV-infected patients (4%) than the general population in Tehran. In contrast, Rahnama et al[215] reported no association between LP and HCV in Kerman in 2005. Similarly, Taghavi Zenouz et al[216] found no relationship between LP and HCV in Tabriz in 2009, and Ansar et al[208] reported a similar result in Hamedan province in 2011. Overall, Petti et al[212] reported a weak association between HCV and OLP in Iranian population. Further investigations are needed to clearly identify the association between HCV and LP in Iran.

HCV in patients with B-cell non-Hodgkin’s lymphoma

HCV is not only primarily hepatotropic, but it can also affect lymphatic systems and lead to B cell lymphoproliferative disorders such as non-Hodgkin’s lymphoma (NHL)[217]. Few studies have evaluated the relationship between HCV seropositivity and the incidence of NHL in Iran. Aledavood et al[218] reported low prevalence of HCV infection among patients with NHL (0.7%) compared to the general population (0.5%-1%) and found no relationship between HCV infection and NHL in Northeast of Iran in 2014. In contrast, Rezaeian et al[219] reported high prevalence of HCV in patients with NHL (15.7%) compared to the control group (0%) and suggested an association between HCV infection and NHL. Similarly, Rastin et al[217] found a HCV prevalence of 7.4% among patients with NHL in Mashhad city. NHL is prevalent worldwide and is the eighth and 11th most common cancer in males and females, respectively[220]. Although the exact risk factor for NHL has not yet been determined, it seems that HCV infection has a role in the pathogenesis of this lymphoproliferative disorder[178].

According to the results of a meta-analysis study, the global prevalence of HCV infection in NHL patients is approximately 15%, which is higher than the prevalence of HCV in general population (1.5%), suggesting a possible role of HCV infection in the development of NHL[221]. Although the role of other factors, such as genetic and environmental factors, should also be considered in the pathogenesis of NHL malignancy[217,221].

HCV in patients with HCC

HCC is the fifth most common malignancy and the second most fatal cancer, with approximately 600000 deaths annually worldwide[222]. HBV and HCV infections account for 50% and 25% of global HCC cases, respectively. However, HCV infection is the most predominant cause of HCC in Japan and the United States[222]. Iran is considered a low endemic area for HCC, with less than five cases per 100000 persons annually[26,223]. Kerman province, located in Southeast of Iran, has a higher incidence of HCC compared to other provinces. This may be due to higher frequency of HBV and HCV infections in this part of the country[224].

In Hajiani et al[225]’s study, the seroprevalence of HBV and HCV infections among patients with HCC in southern Iran were 52.1% and 8.5%, respectively. They pointed out that the prevalence of HCV infection among HCC patients may be underestimated due to the potential contribution of occult HCV infection in the development of HCC. Therefore, the prevalence of occult HCV infection among patients with HCC should be investigated in future surveys. Ansari et al[135] found a very low incidence of HCC (0.6%) among thalassemia patients with HCV infection due to the anti-HCV treatment in this group of patients. In Iran, HCV is the second most common cause of HCC after HBV infection[26,223]. However, it is predicted that chronic HCV infection will replace HBV infection as the main cause of HCC in the future[26].


HCV genotypes differ in their nucleotide sequence and biological properties, such as pathogenicity, infectivity, antigenicity, response to antiviral therapy, mode of transmission, as well as geographical distribution and age-distribution[226,227]. Distribution of HCV genotypes is variable in different regions of Iran (Table 8[101,102,128,131,228-251]). Subtypes 1a is more prevalent in southern and northern Iran, 3a is more prevalent in northern and central Iran, 1b is more prevalent in southern and western Iran, and genotype 2 is more prevalent in western regions of Iran[4,226,228]. Overall, the most frequent genotype in Iran is 1a, followed by 3a and 1b[4].

Table 8 Distribution of hepatitis C virus genotypes among hepatitis C virus -infected patients in Iran n (%).
Study groupCity or provinceLocationYear of studySample sizeGenotype 1Genotype 2Genotype 3Genotypes 4 and 5Mixed genotypeNon typableMethodAuthorRef.
Blood donorsAhvazSouth-West2007-2008451a: 24 (53.3)3a: 21 (46.7)RFLPFarshadpour[233]
Blood donorsTehranNorth-Center2006-20081031a: 53 (51.5)3a: 39 (37.9)7 (6.8)Type-specific primersSharifi[234]
1b: 4 (3.9)
General populationIranIran2000-20051161a: 71 (61.2)3a: 29 (25.0)RFLPAmini[235]
1b: 16 (13.8)
General populationIranIran2004-20072061a: 53 (25.73)2: 4 (1.95)3a: 96 (46.60)11 (5.34)6 (2.91)PCR kitHajia[236]
1b: 36 (17.47)
General populationIsfahanCenter2007-2009971a: 29 (29.5)2: 2 (2.0)3a: 59 (61.2)2 (2.0)PCR based genotyping kitZarkesh-Esfahani[237]
1b: 5 (5.1)
General populationZanjanWest2007-2013ND1a: 22.05%2: 5.14%3a: 38.26%4: 4.41%4.41%LiPAEsmaeilzadeh[238]
1b: 25.73%
General populationYazdCenter2010-20131911a: 74 (38.7)2: 3 (1.6)3: 96 (50.3)5 (2.6)PCR based genotyping kitHadinedoushan[239]
1b: 13 (6.8)
General populationMashhadNorth-East2009-20103821a: 147 (39.2)2a: 9 (2.4)3a: 150 (40.0)5: 13(3.4)Genotype specific primersVossughinia[240]
1b: 41(10.9)
General populationTehranNorth-Center200722311a: 886 (39.7)3a: 613 (27.5)33 (1.6)401 (18.0)Genotype specific primersKeyvani[241]
1b: 271 (12.1)
General populationGolestanNorth2010771a: 15 (19.5)2a: 2 (2.6)3a: 12 (15.6)4: 6 (7.8)8 (6.5)Genotype specific primersMoradi[242]
1b: 15(19.5)3b: 19 (24.7)
General populationAhvazSouth-West2009801a: 43 (53.8)3a: 37 (46.2)RFLPHamidi-Fard[243]
ThalassemiaMazandaranNorth2009-2011341a: 13 (38.24)3a: 15 (44.12)4 (11.76)1 (2.94)Type-specific primerRafiei[244]
1b: 1 (2.94)
ThalassemiaMazandaran and GuilanNorth2010281a: 9 (32.1)3a: 18 (64.3)RFLPGhane[245]
1b: 1 (3.6)
ThalassemiaFarsSouth2009-2012381: 17 (44.7)3: 6 (15.8)15 (39.5)Real-time PCRJamalidoust[231]
HaemophiliaMazandaranNorth2009-2011331a: 7 (21.21)3a: 25 (75.76)1 (3.03)Type-specific primerRafiei[244]
HaemophiliaFarsSouth2009-201281: 5 (62.5)3: 1 (12.5)2 (25.0)Real-time PCRJamalidoust[231]
HaemophiliaAhvazSouth-West2008-2009421a: 26 (61.9)3a: 5 (11.9)Genotype specific primersAssarehzadegan[131]
1b: 11 (26.1)
HaemophiliaMarkaziWest-Center2004221: 6 (27.3)2: 1 (4.54)3a: 4 (18.2)6 (27.3)LiPASamimi-Rad[128]
1a: 3 (13.6)
1b: 2 (9.1)
IDUsMazandaranNorth2009-2011371a: 11 (29.73)3a: 5 (13.51)11 (29.73)Type-specific primerRafiei[244]
1b: 10 (27.03)
IDUsTehranNorth-Center2008-2009361a: 9 (25)3a: 21 (58.3 )Type-specific primersRanjbar Kermani[246]
1b: 6 (16.7)
IDUsFarsSouth2009-20125501: 283 (51.5)3: 192 (34.9)8 (12.2)67 (12.2)Real-time PCRJamalidoust[231]
IDUsTehranNorth-Center2008-2009831a: 35 (42)3a: 48 (58.0)SequencingSamimi-Rad[247]
HaemodialysisMazandaranNorth2009-2011311a: 6 (19.36)3a: 24 (77.42)1 (3.22)Type-specific primerRafiei[244]
HaemodialysisMarkaziWest-Center200581a: 4 (50)3a: 1 (12.5)4: 2 (25)LiPASamimi-Rad[102]
1b: 1 (12.5)
HaemodialysisFarsSouth2009-201261: 4 (66.7)4: 1(16.7)1 (16.7)Real-time PCRJamalidoust[231]
HaemodialysisEast AzerbaijanNorth-West2006551a: 42 (76.4)3a: 3 (5.5)1 (1.8)4 (10.9)Type-specific primersomi[248]
1b: 3 (5.5)
HaemodialysisGilanNorth2008321a: 19 (59.4)3a: 13 (40.6)Genotype-specific primersJoukar[101]
HaemodialysisTehranNorth-Center2004661a: 19 (28.8)3a: 20 (30.3)4:11(16.7)2 (3.0)RFLPHosseini-Moghaddam[249]
1b: 12 (18.2)3b: 2 (3.0)
HIV/HCV co-infectionShirazSouth2004-2005501a: 20 (40)3a: 17 (34.0)RFLPDavarpanah[250]
1b: 13 (26)
Occult HCV infected patientsTehranNorth-Center2007-201071a: 2 (29)3a: 2 (29.0)RFLPBokharaei-Salim[251]
1b: 3 (43)

Distribution of HCV genotypes in Iran is different from other Middle Eastern countries with predominant genotype 4, but it is similar to the pattern seen in North America, with predominant genotypes 1, 2, and 3[4]. Genotype 2 is generally uncommon in Iran, therefore, the genotypic pattern differs from the United States, Europe, and Asia but is similar to Pakistan and India, where genotype 2 is very rare[226,229]. Genotype 4 is uncommon in Iran and only seen in special patient groups[226]. A similar pattern regarding genotype 4 is seen in Europe, the United States, and India. However, due to changes in immigration patterns, the prevalence of genotype 4 is increasing in western countries in recent years (Table 9)[4,229,230]. Overall, the worldwide distribution of HCV genotypes shows that the genotypes 1, 2, and 3 have a global prevalence, while genotypes 4, 5, and 6 have a restricted prevalence[4,226,229,231].

Table 9 Global distribution of hepatitis C virus genotypes[4,229,230].
Region/countryPredominant genotype/subtypeUncommon genotype/subtype
Latin America
Chile and Colombia1b2, 1a
Brazil1b, 1a, 34, 2
Argentina1b, 2, 1a4
North America
United States1a, 1b, 24, 3
Canada1a, 3, 1b4
Central Europe
Albania1b, 2, 41a, 3
Bosnia and Herzegovina, Czech Republic and Croatia1b, 34, 2, 1a
Hungary1b, 1a2, 4
Romania1b3, 4
Western Europe
Switzerland, Belgium, Germany, Spain and France1b, 3, 1a5, 2, 4
Italy1b, 25, 3, 4
United Kingdom and Denmark3, 1a2
Eastern Europe
Russia, Latvia, Lithuania and Estonia1b, 31a, 2
Central Africa42
South Africa52
West Africa
Guinea-Bissau, Ghana and Burkina Faso21
East Africa
Ethiopia4, 21
North Africa
Tunisia, Morocco, Algeria1b, 24
Middle East
Saudi Arabia, Bahrain, Yemen, Kuwait, Qatar, Iraq and Egypt41, 3, 2
Jordan1a, 1b, 4-
Iran1a, 3a, 1b4, 2
Turkey1b4, 2, 3, 1a
Asia Pacific
Japan and Korea1b, 21a
Asia, Central
Uzbekistan, Tajikistan, Turkmenistan and Georgia1b1a
East Asia
China, Taiwan1b, 21a, 3, 6
South East Asia
Philippines1a, 26, 4
South Asia
Pakistan and India31b, 2, 4
Australia and New Zealand3, 1a, 1b4, 2

Different HCV genotypes may be associated with particular patient groups. Therefore, the genotypic patterns can be used to trace the routes of transmission[4]. Genotype 1 is more prevalent among thalassemia, hemophilia, hemodialysis, and solid organ recipient patients[231]. Subtype 1b is prevalent in individuals with a history of hospitalization, surgery, blood transfusion, and alcohol consumption[226]. Subtype 1a is frequently found in infection by blood and blood products[228]. High frequency of genotypes 3a and 1a are seen among IDUs in Iran[228], which is similar to the genotypic pattern among IDUs in Europe and the United States[226]. Genotype 4 is found in patients undergoing hemodialysis and piercing[226,228]. This might be due to communication by dialysis during the Hajj ceremony in Saudi Arabia[4]. The mixed infection with two or more genotypes is more common in patients with hemophilia and thalassemia and may lead to chronic infection, more severe disease, re-infection, and poor response to therapy[2,4].

There has been a shift in the distribution pattern of HCV genotypes over time[4,6,232]. Genotype 1a is the most prevalent genotype in Iran, but in recent years, an increase in the frequency of 3a and a decrease in 1a and 1b have been reported among HCV-infected patients in Iran. Genotype 1 with subtypes 1a and 1b are more prevalent in older patients and genotype 3a in younger patients and IDUs[4,228,232]. Therefore, it seems that injection drug use has contributed to the majority of new HCV infections in Iran[4,232].

Distribution of HCV genotypes is variable in different groups and geographic regions of Iran. This genotypic variability reflects differences in the routes of transmission, population and socioeconomic factors, and the presence of risk factors in the society. Thus, some genotypes are more frequent in certain regions or groups of patients[4,232]. Studies on the molecular epidemiology of HCV in Iran are needed to reveal the current genotypic pattern of HCV infection in the country[228], which can predict the dose, duration, and type of treatment as well as clinical outcome of the infection[2,228-231].


Occult HCV infection is described by the absence of detectable HCV-RNA and anti-HCV antibodies in serum or plasma with elevated liver enzymes or by the presence of anti-HCV antibodies but undetectable levels of HCV-RNA in serum or plasma with normal levels of liver enzymes[252-254]. In both cases, HCV-RNA is detectable in 100% of liver biopsy, up to 70% of peripheral blood mononuclear cells (PBMCs) specimens, and in nearly 60% of ultracentrifugated serum samples of infected patients[255]. Occult HCV can persist and replicate in hepatocytes and lymphoid cells for a long time even after an apparently spontaneous eradication or therapy-induced resolution of HCV infection[256]. In this condition, low copy numbers of HCV RNA are present in serum while it cannot be detected by conventional RT-PCR assays but remains potentially infectious[253,254].

Distribution of occult HCV infection has been reported all around the world, and it seems that all genotypes are involved in this infection[253]. A few studies are available regarding the prevalence of occult HCV in Iran. Bokharaei-Salim et al[251] found occult HCV in 10% (7/69) of patients with cryptogenic liver disease in Iran, while 43%, 29%, and 29% of these patients had genotypes 1b, 1a and 3a, respectively. Keyvani et al[257] described 8.9% occult HCV infection with genotypes 3a (50%) and 1b (50%) in patients with cryptogenic cirrhosis in Iran. Farahani et al[258] found 1.9% occult HCV infection with genotype 1a in patients with lymphoproliferative disorders in Iran. Makvandi et al[259] reported 32% occult HCV infection in patients with abnormal levels of alanine aminotransferase in Ahvaz city. Rezaee Zavareh et al[260] reported the absence of HCV-RNA in PBMC samples of 53 patients with autoimmune hepatitis in Iran. Ramezani et al[261], reported the absence of occult HCV infection in 30 hemodialysis patients in Tehran.

Occult HCV infection has also been found in apparently healthy populations[253,255]. The possible presence of occult HCV infection in the general population or blood donors poses a real concern about undetectable transmission of HCV[255,262]. In a recent study in Italy, the prevalence of occult HCV infection was higher than the frequency of anti-HCV seropositivity in the general population[262]. Therefore, the prevalence of HCV infection may be underestimated in the society[253,255], and the risk of HCV transmission through blood donation may be higher than predicted. Although screening of blood reduces the risk of HCV transmission by blood transfusion, transmission of occult HCV cannot be prevented in this way[253,255].

Currently, the prevalence of occult HCV infection in the general population of Iran and even blood donors is unknown. Therefore, further studies on the prevalence and significance of occult HCV in different cities are needed to identify the real burden of this infection in the country and subsequently in healthy subjects, especially among blood donors, to prevent the most of unknown transmission of HCV.


HCV infects large proportion of the high-risk populations in almost all regions of Iran and has a role in occurrence of different immunological disorders and even malignancies. The distribution patterns of HCV infection are related to different status of public health and the presence of risk factors in the society. Available estimates emphasize that injecting drug use is the most important risk factor for HCV infection in Iran and due to the growth in the number of injecting drug users, the prevalence of HCV infection is growing in the country. In addition, it seems that injection drug use has contributed to the occurrence of the majority of new HCV infections in Iran. Even the recent changes in the distribution pattern of HCV genotypes in Iranian patients confirm this issue. In fact, the predominance of risk factors for transmission of HCV has changed over time, from blood transfusion to intravenous drug use. The possible presence of occult HCV infection among the apparently healthy general population or blood donors proposes a real concern about undetectable transmission of HCV. Therefore, it seems that the prevalence of HCV infection will increase in near future not only among high-risk groups but even in the general population and blood donors of Iran. However, by breaking the cycle of infection among drug users, the rate of HCV infection will decrease. To approach this goal, efforts to screen, prevent, and treat HCV infection as well as reduce the high-risk behaviors are required.


We would like to express our sincere thanks to Manoochehr Makvandi, PhD, professor, Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, for editing the manuscript.


P- Reviewer: Hu ZJ, Lo SY, Stahmeyer JT S- Editor: Yu J L- Editor: Filipodia E- Editor: Ma S

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