Genotype distribution of hepatitis C virus in Khorasan Razavi Province, Iran

656
http://journals.tubitak.gov.tr/medical/
Turkish Journal of Medical Sciences Turk J Med Sci
(2014) 44: 656-660
© TÜBİTAK
doi:10.3906/sag-1305-64
Genotype distribution of hepatitis C virus in Khorasan Razavi Province, Iran
Reza AFSHARI1, Hosein NOMANI2, Fatemeh RIYAHI ZANIANI2, Maryam Sadat NABAVINIA3,
Zohreh MIRBAGHERI2, Mojtaba MESHKAT4, Sina GERAYLI5, Sina ROSTAMI5, Zahra MESHKAT2,*
1
Addiction Research Center, Department of Clinical Toxicology, Mashhad University of Medical Sciences, Mashhad, Iran
2
Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3
Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
4
Islamic Azad University, Mashhad Branch, Mashhad, Iran
5
Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
* Correspondence: meshkatz@mums.ac.ir
1. Introduction
The infection caused by the hepatitis C virus (HCV) is
one of the most serious health problems in the world (1).
In many countries, this infection is the most common
cause of malignant and severe liver diseases. About 3% of
the world’s population suffers from HCV infection (1,2),
among which 80% exhibit a chronic form of hepatitis.
Twenty percent of patients with chronic hepatitis C are
likely to progress to cirrhosis and 1.5%–4% may develop
hepatocellular carcinoma (3,4).
Several studies highlight the importance of clinical and
laboratory diagnostic tests in determining HCV genotypes.
Epidemiology (5), pathogenesis (6,7), response to antiviral
treatments (7,8), and duration of standard HCV treatment
with PEG interferon and ribavirin for reaching a sustained
virological response are in part dependent on the HCV
genotype (9,10). Genotype 1 is considered to be the most
antiviral-resistant genotype of HCV. In addition, patients
suffering from chronic infection with HCV subtype 1b,
when compared with other HCV subtypes, are more likely
to develop severe liver diseases (11,12).
In the past, blood transfusions and blood products were
the main culprits for HCV transmission. Recently, however,
intravenous drug usage has become the most common
form of transmission (13). According to our previous study,
the prevalence of HCV infection is low (≤1%) among the
general population of Mashhad, Iran (14). However, due to
common needle injection, the frequency of this infection is
high among intravenous drug users (IDUs).
This study was performed to determine the frequency
of HCV genotypes among HCV-positive subjects in
Mashhad, Iran.
2. Materials and methods
This cross-sectional study was performed between October
2009 and October 2011 on 103 patients with HCV infection
Background/aim: Several types of the hepatitis C virus (HCV), with variations in different parts of the genome, have been isolated from
different regions of the world. Based on heterogenic sequences in the isolated genome, HCV is classified into different genotypes and
subtypes. Data on distribution of HCV genotypes in a certain region could be important to patient management. Therefore, this study
was conducted to determine the distribution of HCV in Mashhad, Northeast Iran.
Materials and methods: This cross-sectional study was conducted on 103 patients with HCV infections in Mashhad. Among the
participants, at least 22 (21.4%) were intravenous drug users. HCV seropositivity was determined by an enzyme-linked immunosorbent
assay and was confirmed by reverse transcriptase polymerase chain reaction. HCV-positive samples were selected for HCV genotyping
using genotype specific primers.
Results: Of 103 subjects, 43 (41.7%) and 34 (33.0%) had genotypes 1a and 3a, respectively. Other genotypes including 1b, 2a, 2b, 3b, and
5a were found in 4 (3.9%), 1 (1.0%), 3 (2.9%), 4 (3.9%), and 1 (1.0%), respectively. Coinfections with 2 genotypes were also observed in
11 (10.7%) patients. Genotyping for 2 (1.9%) of 103 samples did not produce any results.
Conclusion: Genotypes 1a and 3a were found to be the most prevalent HCV genotypes in Mashhad, Iran.
Key words: Hepatitis C virus, genotype, Khorasan Razavi Province, Iran
Received: 14.05.2013 Accepted: 23.09.2013 Published Online: 27.05.2014 Printed: 26.06.2014
Research Article
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AFSHARI et al. / Turk J Med Sci
[serum-positive patients confirmed by reverse transcriptase
polymerase chain reaction (RT-PCR)] in Khorasan Razavi
Province. Included in this study were patients referred
to the clinical diagnostic laboratory of Qaem Hospital
and other clinical diagnostic laboratories, as well as IDUs
referred to the Addiction Research Center of Imam Reza
Hospital. This sample included at least 22 (21.4%) IDUs.
After informed consent was obtained from participants, a
10-mL blood sample was taken from each patient. Samples
that were positive by enzyme-linked immunosorbent
assay (ELISA) and confirmed by RT-PCR were considered
HCV infections. HCV antibody was determined by ELISA
(Delaware Biotech, USA) and HCV RNA was investigated
by RT-PCR. In brief, HCV antibody positive sera were
selected for viral RNA extraction using a commercial
Viral RNA Extraction Kit (QIAGEN, USA). Next, reverse
transcription (using random hexamers) and PCR were
performed with an ASTEC pc818 Thermal Cycler using
an HCV detection kit (STRP Hepatitis C Virus Detection
Kit, CinnaGen, Iran) following the manufacturer’s
recommended procedures. Using the method of Ohno et
al., HCV isolates of all positive samples were genotyped (13)
and 2 rounds of PCR were performed on cDNA samples
to determine HCV genotypes. Core specific primers Sc2
(5’-GGGAGGTCTCGTAGACCGTGCACCATG-’3)
and Ac2 (5’-GAG(AC)GG(GT)AT(AG)
TACCCCATGAG(AG)TCGGC-’3) were used for the first
round of PCR and 2 mixtures of primers were used for the
second round of PCR. Mix 1 primers were used for the
detection of HCV genotypes 1b, 2a, 2b, and 3b while mix
2 primers were used for the detection of HCV genotypes
1a, 3a, 4, 5a, and 6a. The PCR product was visualized on a
2% agarose gel by Green-Viewer staining (Pars Tous, Iran)
and UV photography.
3. Results
Of 103 HCV RNA-positive patients, 86 (83.5%) were male
and 17 (16.5%) were female. Patient age ranged from 18 to
65 years and the mean was 39.6 ± 11.1 years.
The authors were not able to perform genotyping for
2 (1.9%) of the 103 samples. HCV genotypes 1a with 43
(41.7%) and 3a with 34 (33.0%) had the highest frequencies.
Genotypes 1b, 2b, and 3b were reported from 4 (3.9%), 3
(2.9%), and 4 (3.9%) patients, respectively. One (1.0%)
patient was found positive for both genotypes 2a and 5a.
Eleven (10.7%) were reported to have coinfections with 2
different genotypes. Coinfections with genotypes 1a–1b,
1a–3b, and 1b–3a were observed in 3, 2, and 2 individuals,
respectively. However, only 1 patient each was found with
other coinfections, including 2b–3a, 5a–3a, 2a–1a, and
1b–1a (Table). This sample of 103 patients included at least
22 (21.4%) IDUs. Other patients may have had a history of
drug usage but did not report it. Five cases (45.5% of 11
cases of coinfection) were observed among patients with
addiction.
4. Discussion
Various virus genotypes and subtypes with different
frequencies have been reported from different countries
(15). In the current study, the Ohno et al. method was
used for HCV genotyping. The results obtained based
on this method are in conformity with the gold standard
method of HCV genotyping (sequencing). A PCR of the
core region of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a,
and 6a with specific primers is the basis of the Ohno et al.
method. Ohno et al. also suggested that due to a rather
limited number of samples available for genotypes 3 to 6
in their study, their method requires further confirmation
for these genotypes (16).
In many European studies, genotype 1 and subtype
1b seem dominant, and in Germany, subtype 3a had the
highest frequency (46%) in patients with drug addiction.
However, in considering all the subjects, subtype 1b was
the most prevalent one (17). Among 236 patients with
HCV infection in Belarus, 127 (53.8%) and 58 (28.8%)
were found with genotypes 1b and 3a, respectively (18).
A study among French hemodialyzed patients reported a
rate of 77% for genotype 1b (19). Subtype 1b (54%) had
the highest frequency in Vienna, Austria, and surrounding
areas (20). A retrospective study conducted on 373 Italian
children with HCV noted the dominance of genotype 1b
(41%), followed by 1a (20%) (21).
Two studies in Brazil in the states of Rondônia (22)
and Alagoas (23) noted a higher prevalence of genotype
1b, followed by 1a. However, unlike Europe and South
America, in the United States, genotype 1a is considered
to be dominant. In Appalachia (USA), genotype 1a (66%)
was by far the most prevalent genotype (24). Another
study in the United States performed in Galveston, Texas,
also reported the dominance of 1a (62.8%) over other
genotypes (25).
It has been suggested that 2 trends exist in the Middle
East. Genotypes 4 and 1 are generally considered to
have the highest prevalence in Arab countries (apart
Table. Percentage of different genotypes among the 103 participants.
1a 3a Coinfections 1b 3b 2b Not
determined 2a 5a
43 (41.7%) 34 (33.0%) 11 (10.7%) 4 (3.9%) 4 (3.9%) 3 (2.9%) 2 (1.9%) 1 (1.0%) 1 (1.0%)
658
AFSHARI et al. / Turk J Med Sci
from Jordan) and non-Arab countries (Iran, Turkey,
and Israel), respectively (26). In Iran, genotypes 1a and
3a predominate. A study by Amini et al., which was
performed on 116 samples representing the whole country,
showed that genotypes 1a (61.2%) and 3a (25.0%) were the
most prevalent ones (27). The authors observed that the
frequency of genotypes 1a and 3a were 41.7% and 33.0%,
respectively, in the city of Mashhad. Several studies were
conducted among HCV-positive patients and also among
different disease groups in Tehran. Kabir et al. reported
the frequency of 37.8% and 28.9% for genotypes 1a and
3a, respectively, in Tehran (28). Another study in Tehran
reported similar results (39.7% for 1a and 27.5% for 3a)
(29). This finding was also confirmed by 2 other studies
in this city (30,31). In Isfahan (Central Iran), however,
genotype 3a (61.2%) was more prevalent than 1a (29.5%)
(32). The frequency observed in Shiraz was 44.1% for 1a
and 42.0% for 3a (33). For Golestan Province, in the north
of Iran, 3b (24.7%), followed by 1b (19.5%) and 1a (19.5%),
was predominant (34). In Shahrekord, in West Iran, the
prevalence rates of 54.26% and 27.66% were reported for
1a and 3a, respectively (35). Among hemodialytic patients
in Guilan Province, in the north of Iran, 1a (59.38%) and
3a (40.62%) were the most prevalent genotypes (36).
Although Turkey and Pakistan border Iran, their
genotype distribution differs from that of Iran. Turkey
seems to follow the distribution pattern of other European
countries with a high prevalence of genotype 1b. In a
study in Turkey of 365 patients with chronic HCV, 306
(84%) were of genotype 1b (37). It is noteworthy that in
a study conducted in Northwest Iran, a rate of 71.4% was
found for 1a, followed by 14.2% for 1b (38). This finding
contrasts with those in many other cities in Iran in which
only 1a and 3a were the prevailing genotypes. Therefore,
it could be concluded that in the mentioned geographical
area (which is near Turkey), genotype 1b is more or less
dominant. Pakistan is Iran’s neighbor to the east. In the
Khyber Pakhtunkhwa area of Pakistan, a rather different
trend was observed with 2a (39%) and 3a (31%) being
the most prevalent genotypes (39), while in another study
performed on 1000 samples from remote cities in Pakistan,
3a, followed by 3b, was reported to be dominant (40).
Regarding other regions of Asia, a study on 138 patients
with HCV infection in Korea suggested that 1b (71%) was
the most prevalent genotype, similar to many European
studies (41).
Several molecular epidemiological studies suggested a
clear relationship between intravenous drug usage and the
prevalence of infection with genotype 3 (42,43). A study
by Samimi-Rad et al. in 2012 among IDUs in Iran reported
the prevalence rate of 58.0% for genotype 3a and 42.0%
for genotype 1a (44). The authors observed that among
the studied group, genotype 1a had the highest frequency,
both among patients known to be IDUs and others. Among
our patients, coinfection with 2 different genotypes of
HCV was more common among IDUs. Previous studies
proposed several reasons for the existence of 2 or 3
genotypes in 1 patient. One reason included an unspecific
band resulting from the interaction of the specific primers
of a genotype with the sequences of another genotype
and/or exposure to 2 different HCV genotypes (45,46). In
our study, common needle injections among patients with
addiction might have had a role in infection with different
HCV genotypes.
In the current study, the participants’ extensive medical
histories were not available. Further studies with larger
sample sizes that include complete patient records during
a certain period are encouraged for the city of Mashhad.
Our results from Mashhad (a major city of the
Khorasan Razavi region) confirmed that genotypes 1a
and 3a are prevailing, which is similar to the study of
Vossughinia et al. (47). However, contrary to that study,
which reported almost the same proportion of 40% for 1a
and 3a, we observed that genotype 1a was more common
than 3a (41.7% vs. 33.0%). The slight difference observed
may have been due to the nature of the sample or the
fact that the sample sizes of both studies were not large
enough.
Acknowledgment
This study was supported by Mashhad University of
Medical Sciences, Mashhad, Iran (Grant No. 87581).
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