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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2011  |  Volume : 22  |  Issue : 4  |  Page : 712-716
Prevalence of mixed hepatitis C virus (HCV) genotypes among recently diagnosed dialysis patients with HCV infection


Department of Pathology and Laboratory Medicine, King Saud Bin Abdulaziz University for Health Sciences, College of Medicine, King Abdullah International Medical Research Center, Molecular Biology, King Abdulaziz Medical City, Riyadh, Saudi Arabia

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Date of Web Publication9-Jul-2011
 

   Abstract 

Hepatitis C virus (HCV) infection is considered a major health problem recognized globally. HCV is a major cause of chronic liver disease that may lead to cirrhosis and hepatocellular carcinoma. The aim of this study was to investigate the prevalence of multiple (mixed) HCV genotypes in Saudi patients recently diagnosed with HCV infection and their association with various clinical risk factors. We examined a total of 1,292 newly diagnosed HCV-positive cases between January 2006 and July 2009 at the Molecular Pathology Laboratory, King Abdulaziz Medical City, Riyadh. The clinical and laboratory data of the study patients were collected. The HCV-RNA viral load and its genotyping were carried out with RT-PCR technology to assist in the follow-up and management of HCV-infected patients undergoing antiviral therapy. Twenty-two patients (1.7%) were found to have mixed HCV genotypes; of them, mixed genotypes associated with genotype-4 were seen in 19 patients (86%), mixed genotypes associated with genotype-1 were found in 68.4%, with genotype-3 in 26.3% and with genotype-2 in 5.3%. Additionally, mixed genotypes associated with genotype-1 were seen in three cases (13.6%); they were associated with genotype-2 in two (66.7%) and with genotype-5 in one patient (33.3%). In conclusion, the prevalence rate of mixed HCV genotypes in the cohort of the newly infected Saudi patients was 1.7%, with genotype-4 being the most frequent genotype encountered.

How to cite this article:
Al Balwi MA. Prevalence of mixed hepatitis C virus (HCV) genotypes among recently diagnosed dialysis patients with HCV infection. Saudi J Kidney Dis Transpl 2011;22:712-6

How to cite this URL:
Al Balwi MA. Prevalence of mixed hepatitis C virus (HCV) genotypes among recently diagnosed dialysis patients with HCV infection. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Oct 17];22:712-6. Available from: http://www.sjkdt.org/text.asp?2011/22/4/712/82648

   Introduction Top


Hepatitis C virus (HCV) infection is considered a major health problem recognized globally. [1] Worldwide, it is estimated that around 200 million people are infected with HCV, with an overall prevalence of 3.3% of the world's population. [2] Individuals infected with HCV are at risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). [3]

The prevalence of HCV infection varies among blood donors worldwide, and is estimated to be between 1 and 5%. [2],[4] HCV has six major genotypes according to its viral genome, numbered one to six. These viral types and sub-types differ in their geographical distribution and anti-genicity. [4] According to the World Health Organization (WHO) data, the highest HCV prevalence rates were reported in Africa, Eastern Mediterranean, South-East Asia and the Pacific regions compared with North American and European countries. [4],[5] In Saudi Arabia, the prevalence of HCV among blood donors is estimated to be between 0.6 and 1%. [6] Worldwide, HCV infection in hemodialysis (HD) patients varies geographically, and both within and between countries, ranging from 3% in the USA to more than 70% in some other countries. [7],[8],[9],[10],[11],[12] HCV infection in Saudi HD patients varies between different regions and provinces, ranging from 15% to 95%. [13] Genotype-4, followed by genotypes-1a and -1b, are predominant in Saudi patients, whereas genotypes-2, 3, 5 and 6 are rare. [13],[14],[15],[16] Mixed infections (co-infection) with more than one genotype were observed in some studies. In this study, we investigated the prevalence of multiple (mixed) HCV genotypes in Saudi patients recently diagnosed with HCV, referred for genotyping to our institute.


   Materials and Methods Top


Patients

Plasma samples from 1,292 newly diagnosed patients with HCV infection (HCV-RNA positive) who were referred to the molecular pathology laboratory were studied between January 2006 and July 2009. Two tubes of isolated EDTA plasma were processed within two hours of collection from each patient and stored at -80°C prior to performing the requested test. [17] HCV-RNA viral load and its genotypes were studied to assist in the management of the HCV-infected patient undergoing antiviral therapy. Before genotyping, detection of HCV RNA was mandatory to reconfirm the current HCV infection. Clinical and other laboratory data were collected on all patients.

HCV-RNA Viral Load Assay

A total HCV nucleic acid (RNA) was extracted from 1,050 μL of plasma from the patients and controls using the automated extraction Cobas AmpliPrep instrument (Roche Molecular Systems, Pleasanton, USA) and according to the manufacturer's instructions. HCV RNA amplification and detection were performed using the real-time Cobas TaqMan 48 analyzer (Roche Molecular Systems, Pleasanton, USA) manufacturer's recommendations. The final HCV viral load was reported in international units (IU)/mL.

HCV RNA Genotyping Assay

A 5 μL sample of the extracted RNA was added to 20 μL of each HCV Genotyping II kit master mix as per the manufacturer's instructions. Amplification and detection were performed using the m2000 real-time system (Abbott Molecular Diagnostics, Abbott Park, IL, USA).


   Results Top


A total of 1,292 newly diagnosed HCV-positive cases, confirmed by HCV-RNA, between January 2006 and July 2009, were analyzed for genotyping prior to management. Only 22 (1.7%) cases of the 1,292 cases revealed presence of more than one HCV genotype (mixed). All the 22 cases were mainly associated with chronic hepatitis and other medical history, including age and sex distribution is shown in [Table 1]. Three cases were associated with chronic hepatitis and not related to any direct risk factors, although link to drug abuse was considered.
Table 1: Summary of correlation between patient's clinical features and demographics with mixed HCV genotype.

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In 19 cases (86%), genotype-4 was seen to be associated with genotype-1, genotype-3 and genotype-2 (68.4%, 26.3% and 5.3%, respectively). Three cases (13.6%) of genotype-1 had associated genotype-2 and genotype-5 (66.7% and 33.3%, respectively). Presence of three mixed genotypes was seen in one case, and was associated with genotype-1, genotype-4 and genotype-5.

It was also important to note that mixed genotypes were more frequently seen in males (63.6%) as compared with females (36.5%).


   Discussion Top


It is well known that HCV is a major cause of chronic liver disease that may lead to liver cirrhosis and HCC. [3],[18],[19] In 1998, Poynard et al reported that between 20 and 30% of HCV cases will eventually progress to liver cirrhosis and, subsequently, to HCC. [20] This has been well documented in five of our patients (23%) who developed HCC or cirrhosis or both. According to our data, we anticipate that HCC and cirrhosis are more common among patients with co-existence of mixed HCV genotype.

Transmission of HCV is influenced by several risk factors, such as intravenous drug use, surgery, transplantation, dialysis, blood transfusion, liver diseases and diabetes mellitus. [1],[2],[5],[7],[12],[16],[19] Certain medications, chemicals, exposure to poisons and other toxins as well as alcohol abuse may influence the progress of HCV infection. [13] Only 19 cases (86%) with mixed HCV genotype were proven to be associated with various risk factors.

Three cases of mixed HCV genotype (13.6%) were shown to have chronic hepatitis, with the source of HCV transmission being unknown. The prevalence of HCV infection is increased in patients with type-2 diabetes mellitus, [12],[21],[22] and this was noticed in five of our patients (22.7%), compared with 21.2% in a study by Akbar in Saudi patients from the Western Province. [22]

Mixed HCV with more than one genotype was observed in some studies with higher prevalence rates in multiple-exposure groups such as hemophiliacs, patients on chronic HD and injection-drug users. [14],[16],[23],[24] In this study, the prevalence of mixed HCV genotype was seen in 22 of the 1,292 patients (1.7%), compared with 5.3% in an Egyptian study, [23] 6% among Serbian patients, [24] 4% in Honk Kong and 18% in China. [25]

The prevalence rate of mixed HCV genotype in the cohort of newly infected Saudi patients was 1.7%, indicating the contribution and association of various risk factors to the clinical profile and disease progression in different patients.

 
   References Top

1.National Institutes of Health Consensus Deve lopment Conference Panel statement: management of hepatitis C. Hepatology 1997;26(3 Suppl 1):2S-10S.  Back to cited text no. 1
    
2.The C. Everett Koop Institute. Hepatitis C: an epidemic for anyone: Worldwide Prevalence, Dartmouth Medical School 2009.  Back to cited text no. 2
    
3.Perz JF, Alter MJ. The coming wave of HCV-related liver disease: Dilemmas and challenges. J Hepatol 2006;44(3):441-3.  Back to cited text no. 3
    
4.Sy T, Jamal MM. Epidemiology of hepatitis C virus (HCV) infection. Int J Med Sci 2006;3 (2):41-6.  Back to cited text no. 4
    
5.WHO. Hepatitis C. Fact Sheet No.164 Revised October 2000 WHO, 2000.  Back to cited text no. 5
    
6.Tamimi W, Hajeer A, Qasem L, et al. Expansion of Saudi blood donor pool by better screening and vaccination practices. Clin Diagn Lab Immunol 2003;10(6):1159-60.  Back to cited text no. 6
    
7.Freitas SZ, da Cunha RV, Martins RM, Teles SA, Ibanhes ML, Motta-Castro AR. Prevalence, genotypes and risk factors associated with hepatitis C virus infection in hemodialysis patients in Campo Grande, MS, Brazil. Mem Inst Oswaldo Cruz 2008;103(4):405-8.  Back to cited text no. 7
    
8.Huraib S, al-Rashed R, Aldrees A, Aljefry M, Arif M, al-Faleh FA. High prevalence and risk factors for hepatitis C in haemodialysis patients in Saudi Arabia: a need for new dialysis strategies. Nephrol Dial Transplant 1995;10 (4):470-4.  Back to cited text no. 8
    
9.Huraib SO. Hepatitis C in dialysis patients. Saudi J Kidney Dis Transpl 1995;6(2):197-205.  Back to cited text no. 9
    
10.Al-Jiffri AM, Fadag RB, Ghabrah TM, Ibrahim A. Hepatitis C virus infection among patients on hemodialysis in jeddah: a single center experience. Saudi J Kidney Dis Transpl 2003;14 (1):84-9.  Back to cited text no. 10
    
11.Alavian SM. A shield against a monster: Hepatitis C in hemodialysis patients. World J Gastroenterol 2009;15(6):641-6.  Back to cited text no. 11
    
12.Iwasa Y, Otsubo S, Sugi O, et al. Patterns in the prevalence of hepatitis C virus infection at the start of hemodialysis in Japan. Clin Exp Nephrol 2008;12(1):53-7.  Back to cited text no. 12
    
13.Karkar A. Hepatitis C in dialysis units: the Saudi experience. Hemodial Int 2007;11(3): 354-67.  Back to cited text no. 13
    
14.Osoba AO, Ibrahim M, Abdelaal MA, Al-Mowallad A, Al Shareef B, Hussein BA. Hepatitis C virus genotyping by polymerase chain reaction and DNA enzyme immunoassay among Saudi patients in the Western Province, Saudi Arabia. Ann Saudi Med 2000;20(5-6):394-7.  Back to cited text no. 14
    
15.Alzahrani AJ, Obeid OE, Al-Ali A, Imamwardi B. Detection of Hepatitis C virus and Human immunodeficiency virus in expatriates in Saudi Arabia by antigen-antibody combination assays. J Infect Developing Countries 2009;3(3):235-8.  Back to cited text no. 15
    
16.al-Faleh FZ, Huraib S, Sbeih F, et al. Hepatitis C virus genotypes in patients with chronic liver disease and haemodialysis patients from Saudi Arabia. J Viral Hepat 1995;2(6):293-6.  Back to cited text no. 16
    
17.Grant PR, Kitchen A, Barbara JA, et al. Effects of handling and storage of blood on the stability of hepatitis C virus RNA: implications for NAT testing in transfusion practice. Vox Sang 2000;78(3):137-42.  Back to cited text no. 17
    
18.Nousbaum JB, Pol S, Nalpas B, Landais P, Berthelot P, Brechot C. Hepatitis C virus type 1b (II) infection in France and Italy. Collaborative Study Group. Ann Intern Med 1995; 122(3):161-8.  Back to cited text no. 18
    
19.Akbar HO. Hepatitis C virus infection in Saudi Arabia. Saudi J Gastroenterol 2004;10:127-31.  Back to cited text no. 19
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20.Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet 1998;352 (9138):1426-32.  Back to cited text no. 20
    
21.Rudoni S, Petit JM, Bour JB, et al. HCV infection and diabetes mellitus: influence of the use of finger stick devices on nosocomial transmission. Diabetes Metab 1999;25(6):502-5.  Back to cited text no. 21
    
22.Akbar DH, Siddique AM, Ahmed MM. Prevalence of Type-2 diabetes in patients with hepatitis C and B virus infection in Jeddah, Saudi Arabia. Med Princ Pract 2002;11(2):82-5.  Back to cited text no. 22
    
23.Omran MH, Youssef SS, El-Garf WT, et al. Phylogenetic and Genotyping of Hepatitis C Virus in Egypt. Aust J Basic Appl Sci 2009;3 (1):1-8.  Back to cited text no. 23
    
24.Stamenkovic G, Zerjav S, Velickovic ZM, et al. Distribution of HCV genotypes among risk groups in Serbia. Eur J Epidemiol 2000;16 (10):949-54.  Back to cited text no. 24
    
25.Zhang YY, Lok ASF, Chan DT, Widell A. Greater Diversity of Hepatitis C Virus Genotypes Found in Hong Kong than in Mainland China. J Clin Microbiol 1995;33(11):2931-34.  Back to cited text no. 25
    

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Correspondence Address:
Mohammed A Al Balwi
Department of Pathology and Laboratory Medicine, MC 1122, King Abdulaziz Medical City, P.O. Box 22490, Riyadh 11426
Saudi Arabia
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PMID: 21743215

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