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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2008  |  Volume : 19  |  Issue : 3  |  Page : 461-465
Hepatitis C virus Genotypes in Patients with End-Stage Renal Disease in East Azerbaijan, Iran

1 Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Virology, Iran University of Medical Sciences, Tehran, Iran

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Information about the genotypes and associated risk factors in hepatitis C virus (HCV) infected patients in Iran is limited. The aim of this study was to identify the HCV genotypes and associated risk factors in a group of HCV infected patients on dialysis therapy in Iran. The sera of 753 patients with chronic renal failure from fifteen dialysis units in East Azerbaijan Province were screened for anti-HCV antibodies as well as HCV RNA; viral RNA was extracted for the genotype specific primer approach. Patients were questioned concerning documented risk factors. Genotyping analysis was performed in 55 patients with positive anti-HCV and HCV-RNA. Genotypes 1 and 3 were found in 46 (83.7%) and three (5.5%) patients, respectively. The most frequent HCV subtype was 1a (76.4%), followed by 3a and 1b and 1b (5.5% each) while one patient was infected with both 1a and 1b. There was no statistically significant difference between the risk factors analyzed and the acqui­sition of HCV infection. This study gives added evidence of the predominant HCV genotypes in Iran, which is different than reports from other Arab countries and similar with the pattern of genotype in both Europe and United States.

Keywords: Hepatitis C genotype, Chronic renal failure, Dialysis, East Azerbaijan

How to cite this article:
Somi MH, Keivani H, Ardalan MR, Farhang S, Pouri AA. Hepatitis C virus Genotypes in Patients with End-Stage Renal Disease in East Azerbaijan, Iran. Saudi J Kidney Dis Transpl 2008;19:461-5

How to cite this URL:
Somi MH, Keivani H, Ardalan MR, Farhang S, Pouri AA. Hepatitis C virus Genotypes in Patients with End-Stage Renal Disease in East Azerbaijan, Iran. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2022 Sep 26];19:461-5. Available from: https://www.sjkdt.org/text.asp?2008/19/3/461/40515

   Introduction Top

Infection with the hepatitis C virus (HCV) is the most frequent cause of chronic hepa­titis. It is estimated that 170 million persons are chronically infected with HCV. About 80% of newly infected patients progress to develop chronic infection, which may result in cirrhosis and hepatocellular carcinoma, carrying a high morbidity and mortality.

The HCV is a blood-borne pathogen and the modes of transmission of the disease are parenteral and, to a lesser extent, sexual. It is a major cause of chronic liver disease among patients with chronic renal failure (CRF) undergoing maintenance hemodialysis (HD). [1] Epidemiological studies about HCV infection among HD patients in Iran have reported a prevalence of 5.5 to 55.9% in different cities [2],[3],[4] while the reported prevalence in the general population in Iran is less than 1%. [5] The mortality rate as a result of liver disease has been reported to be significantly higher in anti-HCV positive patients than their nega­tive counterparts. [6]

HCV genotypes have been of considerable epidemiological concern and their prevalence varies in different parts of the world. The nucleotide sequence of HCV may vary con­siderably from one isolate to another and according to the most accepted classification, HCV falls into six major genotypes and more than 100 subtypes. [7] The clinical significance and natural history of the disease in relation to genotype and subtype is controversial. There is evidence to suggest that patients with HCV subtype 1b have a poorer response to treatment with interferon alpha. [8],[9]

Previous studies from Iran show a diffe­rence between the dominant genotypes of HCV in Iran compared to other countries in the Middle East. The aim of this study was to reveal the distribution of different HCV genotypes in East Azerbaijan located in North East Iran, where consistent data is seriously lacking.

   Patients and Methods Top

Study population

This survey was carried out in fifteen dia­lysis units in East Azerbaijan (over 3,500,000 inhabitants). Between January and March 2006, 753 patients including 674 on HD and 61 on continuous ambulatory peritoneal dia­lysis (CAPD), were asked to take part in this study, and informed consent was obtained from all.

A standardized form was used to collect socio-demographic data such as number of previous blood transfusions, length of time on dialysis, kidney transplantation, war injury, tattooing, intravenous drug use, surgical interventions, multiple sex partners, and possi­ble household contact with hepatitis. The du­ration on HD treatment was grouped into 12, 12-48 and more than 48 months.

The studied population ranged in age from 7 to 91 years (mean 52.1 ± 16.9 years) and included 409 males (54.3%) and 344 females (45.7%). The etiology of CRF was diabetic nephropathy (n=166), hypertension (n=184), chronic glomerulonephritis (n=73), polycystic kidney disease (n=67), nephrolithiasis (n=31), pyelonephritis (n=13), renal diseases of un­known etiology (n=171), and others (systemic lupus erythematosus, Alport's syndrome, drug induced) (n = 47).

The diagnosis of chronic hepatitis C was made on the basis of the presence of anti­HCV antibodies in sera detected by third generation enzyme-linked immunosorbent assay (ELISA) kits (Abbott Laboratories, Chicago, US) and for HCV-RNA as tested by PT-PCR amplification of 5'-UTR with nested primers. HCV genotyping was per­formed in accordance with the procedure described by Ohno et al. [10]

Statistical analysis

Prevalence and 95% confidence intervals (CI) were calculated. Chi-square test or Fisher's exact test were performed to evaluate the distribution of characteristics associated with HCV infection. Statistical significance was assessed at the 0.05 probability level in all analyses. Statistical evaluations were performed using SPSS package (ver 13).

   Results Top

A predominant prevalence of genotype 1a (42 patients, 76.4%) was found in fifty-five HCV-RNA positive patients with CRF. Three patients (5.5%) were infected with genotype 1b, three others (5.5%) with genotype 3a, one (1.8%) had mixed infection with 1a and 1b and only four (10.9%) had non-typeable genotype.

[Table - 1] compares the distribution of sub­types of HCV genotypes in relation to age, sex, and possible source of infection. Neither the presence of anti-HBsAb nor the etiology of CRF had significant bearing on the subtypes of HCV genotypes.

The prevalence of HCV-RNA in patients undergoing HD was related to the duration of treatment (p< 0.005). None of the patients who were receiving HD for less than one year were infected while 3.8% and 14.9% of patients under treatment for one to three years and more than three years respec­tively, were infected with HCV.

Patients with history of blood transfu­sion(s) seemed to be at significantly higher risk for acquiring infection with HCV (p= 0.001). Anti-HCV was positive in 0%, 4.2%, 11.7% and 100% of patients who had re­ceived one, two, three and more than three units of blood transfusion, respectively (p= 0.004).

Distribution of infection with HCV and its genotypes in the dialysis centers studied was not significantly different. Logistic regression model for risk factors for acquiring HCV showed that the duration (p< 0.005) and fre­quency (p= 0.002) of HD therapy, intrave­nous drug use (p< 0.005) and history of transplantation (p< 0.005) were good predic­tive factors; however, there were no pre­dictors of the genotype. The HD center, etiology of CRF, war injury, tattooing, surgical interventions, multiple sex partners, and possible house-hold contact with hepatitis were not good predictors (p= NS).

   Discussion Top

This is the first study to report on the sero­prevalence and genotyping of HCV in HD patients in east Azerbaijan. A predominant prevalence of genotype 1 was found among our study patients. This is in accordance with the predominance of genotype 1 observed in most countries worldwide. With respect to the zero frequency of genotype 4, our data differ from those published for patients in the United States, Europe, and even Asia, which showed a different prevalence of genotype 4.

The first study on the prevalence of specific genotypes of HCV from Iranian population was conducted by Zali and his group [11] in Tehran, who showed Type I/1, Type II/1b and Type V/3a in seven, three and four pa­tients respectively. A recently published article by Samimi-Rad et al [12] in Iranian patients who were anti-HCV Ab positive, from Tehran and five cities from different locations of Iran, showed that genotype 1a was predo-minant (47%), and 3a, 1b, and 4 were seen in 36%, 8%, and 7% of the patients, respectively.

The pattern of our genotypes are similar to those reported from England, [13] but it is different from other Middle East countries such as Republic of Yemen, Kuwait, Iraq, and Saudi Arabia, where genotype 4 is the most prevalent. [14] HCV genotype 4 was de­tected in 50% and genotype 1b was found in nearly 40% of Saudi patients. [15],[16]

In another large study, the predominance of HCV genotype 4 was reported in the Arab world, Lebanon and most other coun­tries in the Middle East. [17] However, sub-type 1b is prevalent in Turkey [18],[19] and the western border of Iran and subtype 3a is prevalent in Pakistan and the eastern border of Iran. [20] HCV 1b was found to be the pre­dominant virus type both among blood donors and chronic hepatitis patients. [21]

Although genotype 4 is reported almost entirely from the Middle East and western countries, [22] this genotype is uncommon in our country. [23] Similar observation has been reported from other provinces of Iran as well.

Genotypes 3a and 1a are more prevalent in intravenous drug abusers (IVDA) in Europe and USA. [23],[24],[25] In the present study, one patient (2.4%) with IVDA had genotype 1a. It seems that there is a high similarity bet­ween the pattern of genotype in IVDA in Europe and United States when compared with Iran. In the present study, most of the patients seem to have several routes of con­tamination, which limits the conclusion on association between genotype and route of contamination. There was no difference in genotypes in terms of age and sex of the patients. This pattern is different when compared to reports from developed countries, where the molecular epidemiology of HCV seems to be influenced by lifestyles among young adults as reported from the USA and Southeast Asia in their young drug addicts. [26]

This study involved all of the CRF patients on dialysis in the province and the sero­positivity to HCV increased significantly with increase in the duration and frequency of HD and history of transplantation, suggesting possible nosocomial transmission between patients.

   References Top

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2.Rais-Jalali G, Khajehdehi P. Anti-HCV seropositivity among hemodialysis patients of Iranian origin. Nephrol Dial Transplant 1999;14(8):2055-6.  Back to cited text no. 2    
3.Ansar MM, Kooloobandi A. Prevalence of hepatitis Cvirus infection in thalassemia and emodialysis patients in North Iran, Rasht. J Viral Hepat 2002;9(5):390-2.  Back to cited text no. 3    
4.Alavian SM, Einollahi B, Hajarizadeh B, Bakhtiari S, Nafar M, Ahrabi S. Prevalence of hepatitis C virusinfection and related risk factors among patients on hemodialysis. Nephrology 2003;8(5):256-60.  Back to cited text no. 4    
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7.Davidson F, Simmonds P, Fergusen JC. Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from 5' noncoding region. J Gen Virol 1995;76(5):1197-204.  Back to cited text no. 7    
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9.Takada N, Takase S, Enomoto N, Takada A, Date T. Clinical backgrounds of the patients having different types of hepatitis C virus genomes. J Hepatol 1992;14(1):35-40.  Back to cited text no. 9    
10.Ohno O, Mizokami M, Wu RR, et al. New hepatitis C virus (HCV) geno-typing system that allows for identification of HCV geno­types 1a,1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol 1997;35(1):201-7.  Back to cited text no. 10    
11.Zali MR, Mayumi M, Raoufi M, Nowroozi A. Hepatitis C virus genotypes in the Islamic Republic of Iran: A preliminary study. East Mediterr Health J 2000;6(2-3):372-7.  Back to cited text no. 11    
12.Samimi-Rad K, Nategh R, Malekzadeh R, Norder H, Magnius L. Molecular epidemio­logy of hepatitis C virus in Iran as reflected by phylogenetic analysis of the NS5B region. J Med Virol 2004;74(4):246-52.  Back to cited text no. 12    
13.Harris A, Gilbam C, Mortimor PP, Teo CG. The most prevalent hepatitis C virus genotypes in England and Wales are 3a and 1a. J Med Virol 1999;58(2):127-31.  Back to cited text no. 13    
14.Ohno T, Mizokami M, Saleh MG, et al. Usefulness and limitation of phylogenetic analysis for hepatitis C virus core region: Application to isolates from Egyptian and Yemeni patients. Arch Virol 1996;141(6): 1101-13.  Back to cited text no. 14    
15.Al-Knawy B, Okamoto H, Ahmed El-Mekki A, et al. Distribution of hepatitis C genotype and coinfection rate with hepatitis G in Saudi Arabia. Hepatol Res 2002;24 (2):95.  Back to cited text no. 15    
16.Osoba AO. Hepatitis C virus genotypes in Saudi Arabia. Saudi Med J 2002;23(1):7-12.  Back to cited text no. 16    
17.Matar GM, Sharara HM, Abdelnour GE, Abdelnour AM. Genotyping of hepatitis C virus isolates from lebanese hemodialysis patients by reverse transcription-PCR and restriction length polymorphism analysis of 59 noncoding region. J Clin Microbiol 1996; 34(10):2623-4.  Back to cited text no. 17    
18.Abacioglu YH, Davidson F, Tuncer S, et al. The distribution of hepatitis C virus geno­ypes in Turkish patients. J Viral Hepatol 1995;2(6):297-301 .  Back to cited text no. 18    
19.Turkoglu S, Bozaci M, Bozfakioglu S, Kaymakoglu S, Badur S. Molecular epide­miology of hepatitis C virus in Istanbul, Turkey. J Microbiol Met 1996;27(1):98.  Back to cited text no. 19    
20.Shah HA, Jafri W, Malik I, Prescott L, Simmonds P. Hepatitis C virus (HCV) genotypes and chronic liver disease in Pakistan. J Gastroenterol Hepatol 1997;12 (11):758-61.  Back to cited text no. 20    
21.Viazov S, Kuzin S, Paladi N, et al. Hepa­titis C virus genotypes in different regions of the former Soviet Union (Russia, Belarus, Moldova, and Uzbekistan). J Med Virol 1997;53(1):36-40.  Back to cited text no. 21    
22.Mellor J, Holmes EC, Jarvis LM, Yap PL, Simmonds P. Investigation of the pattern of hepatitis C virus sequence diversity in different geographical regions: Implications for virus classification. J Gen Virol 1995;76 (10):2493-507.  Back to cited text no. 22    
23.Kabir A, Alavian SM, Keyvani H. Distri­bution of hepatitis C virus genotypes in patients infected by different sources and its correlation with clinical and virological parameters: A preliminary study. Comp Hepatol 2006;5:4.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.McOmish F, Chan SW, Dow BC, et al. Detection of three types of hepatitis C virus in blood donors: Investigation of type­specific differences in serologic reactivity and rate of alanine aminotransferase abnor­malities. Transfusion 1993;33(1):7-13.  Back to cited text no. 24    
25.Pistello M, Maggi F, Vatteroni L, et al. Prevalence of hepatitis C virus genotypes in Italy. J Clin Microbiol 1994;32(1):232-4.  Back to cited text no. 25    
26.Dal Molin G, Ansaldi F, Biagi C, et al. Changing molecular epidemiology of heap­titis C virus infection in Northeast Italy. J Med Virol 2002;68(3):352-6.  Back to cited text no. 26    

Correspondence Address:
Sara Farhang
Liver and Gastrointestinal Diseases Research Center, Imam Hospital, Tabriz, East Azerbaijan
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