| Abstract|| |
Infection with hepatitis C virus (HCV) is a common global cause of chronic liver disease, which is also true in Saudi Arabia. HCV prevalence in Saudi Arabia varies in different provinces being highest in the Western and Southern provinces. Most of the studies among blood donors documented a decrease in HCV prevalence, probably due to increase awareness and improved socioeconomic status. Genotype 4 is the commonest genotype in Saudi patients infected with HCV which unfortunately is least likely to respond to the standard interferon therapy though recent studies using pegylated interferon demonstrated promising results. Liver transplantation for patients with end stage liver disease was started in 1994 but the cases currently done are still less than that required
Keywords: Hepatitis C, prevalence, Saudi Arabia
|How to cite this article:|
Akbar HO. Hepatitis C virus infection in Saudi Arabia. Saudi J Gastroenterol 2004;10:127-31
Until 1989 patients with hepatitis who were tested negative for hepatitis A and B were labeled as having non A non B (NANB) hepatitis  . In 1989 Chiron diagnostic in cooperation with the Centers for Disease Control and Prevention (CDC) developed the first test for detection of antibodies to hepatitis C virus (HCV) using enzyme linked immunosorbent assay (ELISA-1 first generation)  . After the universal use of these ELISA tests it became clear that HCV accounted for more than 90% of patients with NANB hepatitis  . In Saudi Arabia HCV antibody testing was used then for research purpose-tests for detection of HCV antibodies were implemented as a mandatory prescreening assay in blood banks in late 1992.
| Epidemiology|| |
The World Health Organization (WHO) estimates that 3% of the global population is currently infected with HCV  . Hence more than 170 million people are infected with HCV with 3-4 million people newly infected each year. In the Eastern Mediterranean region with a population of 446 millions, WHO estimates that HCV prevalence is 1-4.6% with 21.3 million people infected with HCV. Prevalence of HCV (1993-1997) among Saudi blood donors was reported as 2.74 % (27907 out 1017303) with more than 500,000 Saudis being already infected with HCV. The Riyadh Central Blood Bank reported that HCV prevalence among Saudi blood donors in 1997 was 1.3% (199 out 15,008), this dropped to 1.2% in 1998 (177 out 15,197) and 0.8% in 1999 (126 out 15,904)  . Similar changes in HCV prevalence among Saudi blood donors has also been reported; prevalence of HCV in 1995 was 2.5% (75 out 3001), 2.0% in 1996 (74 Out 3724), 1.6% in 1997 (54 out 3379) and 1.5% in 1998 (49 out 3379)  . The decrease in HCV prevalence among Saudi blood donors in the absence of effective HCV vaccine could be related to the use of more specific screening assays for detection of HCV antibodies and hence less HCV transmission from false negative individuals, together with improved socioeconomic conditions and general public awareness.
Most of HCV seroprevalance studies were performed on blood donors and results may differ between different blood banks depending on inclusion of persons with different nationalities (Saudi habitants vs. Saudi citizens) or with abnormal liver enzymes  . This was observed by Al Tamimi et al, who found HCV prevalence to be 1 % among blood donors with normal liver enzymes and 5% among donors with increased liver enzymes at King Fahad National Guard Hospital, Riyadh  . Hepatitis C Virus seroprevalence among Saudi blood donors is highest in Gizan (Southern province). In Riyadh HCV seroprevalence (1997-2001) was 0.9%, in Al-Hasa (1992-1999) was 0.67%, in Qunfudah (2000) was 0.7% and in Gizan (1996-1999) HCV seroprevalence was 1.9%. Recently the reported prevalence of HCV among Saudi blood donors (2002) was: Eastern province (0.6%), Western province (1%), Central province (0.4%), Northern province (0.7%) and Southern province (0.9%). Prevalence rates were also different between age group of individuals studied. Seroprevalence increased with age, being highest among persons older than 50 years (3.5%-5.4%) and this was found both in hospital and community based studies ,, . HCV prevalence among Saudi school children was 0.2% and 0.9% among Saudi pregnant women  Differences in HCV seroprevalence in Saudi children (1-9years) were also observed indifferent provinces, being lowest in the Eastern province (0%), 0.4% in the Northwestern province, 0.6% in Central province, 0.9% in the Southwest province and highest in the Southern province (1.9%) ,
| Prevalence in high risk groups|| |
Transmission of HCV is mainly parentral through blood or blood products transfusion and puncture with infected needles. More than 45% of patients with HCV infection have no identifiable risk factors. Prevalence of HCV among high risk groups such as patients with chronic renal failure on hemodialysis is 43.2%-72.3% among adults ,, and 45% among children  . Other high risk group patients such as patients with thalassemia major and hemophiliacs have a prevalence rate of 70% and 78.6% respectively , . In patients with sexually-transmitted diseases HCV prevalence of 15.9% was reported  .
| Hepatitis C virus genotypes|| |
Hepatitis C virus exhibits extensive heterogenicity and currently there are six major genotype worldwide. Genotypes 1, 2, and 3 accounts for more than 90% in the Americas, Europe and Asia. Genotype 4 is the predominant genotype in the Middle East, Egypt, central and west Africa  Several studies in Saudi Arabia have proven that HCV genotype 4 followed by genotype 1 were the most prevalent genotypes ,, . In a recent multicenter national study by Shobokshi et al, on patients with HCV 59.6% had genotype 4, 25.1% had genotype 1, 8.3% had genotype 2 and 6.4% had genotype 3 [Table - 1].
| Natural history|| |
Hepatitis C is a major cause of chronic liver disease where up to 80% of patients infected with HCV develop chronic liver disease. Among a group of patients with chronic liver disease in the Western region of Saudi Arabia (653 patients), HCV was responsible for 35.4% of these cases among Saudis, 74.2% among Egyptians, 28.6% among Yemenis, and 24% among Palestinians  [Table - 2]. Patients with post necrotic liver cirrhosis secondary to HCV are also liable to develop hepatocellular carcinoma with an annual rate of 1 to 4%  . HCV was found in 88 patients out of 223 patients with Hepatoma (39.5%) in the Western region  .
| Treatment|| |
Alpha interferon and ribavirin were the first drugs approved by FDA for treatment of patients with chronic hepatitis C. Most of the studies using combination treatment with alpha interferon and ribavirin have shown that HCV genotype was an independent factor for patient's response where genotypes 2 and 3 had a better treatment response  . Considering that the most prevalent HCV genotypes in Saudi Arabia are least likely to respond to the standard combination therapy (alpha interferon and ribavirin) ,,, , our patients currently infected with HCV would probably be treated with more effective drugs i.e. pegylated interferon in combination with ribavirin. This combination is currently being studied in two different multicentral trials in Saudi Arabia. Preliminary results of one of these studies showed early virological response of 77% (EVR) and end therapy response of 67% (ETR) among Saudi patients with genotype 4 using pegylated interferon and ribavirin , This promising response to pegylated interferon in patients with genotype 4 in comparison with regular interferon has also been observed elsewhere  .
Patients with decompensated post necrotic cirrhosis secondary to hepatitis C are beyond antiviral treatment and require liver transplantation. The first liver transplant in Saudi Arabia was performed in 1990. However there was a lag period then until 1994 when several other centers started liver transplant programs. Decompensated chronic liver disease secondary to HCV is the commonest indication for liver transplantation in Saudi Arabia. It is estimated that more than 400 cases with chronic HCV require liver transplantation annually; however only few cases are transplanted due to poor donor pool  .
In conclusion: Until the discovery of a potent HCV vaccine and a more effective treatment of infected individuals, HCV infection will continue to be a major medical problem in our community despite decrease in reported prevalence rate. Beside measures currently taken by the Ministry of Health; more community education and better disinfection of medical equipments (i.e.: Dental) in certain institution, may further help elimination of possible denovo infection source.
| References|| |
|1.||Choo QL, Kuo G,Weiner AJ, Overby LR, Bardley DW, Henghton M: Isolation of a c DNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989: 244: 359-62. |
|2.||Kuo G, Choo QL, Alter H, Gritnick GL, Redeker AG, Purell RH, et al: An assay for circulating Antibodies to a major Etiologic Virus of Human Non-A, Non-B Hepatitis. Science 1989; 244: 362-4. |
|3.||Kao JH, Chen DS: Transmission of hepatitis C virus in Asia: Past and present perspectives. J Gastroenterol Hepatol 2000; 15: 91-6. |
|4.||World Health Organization. Weekly Epidemiological Record 49, 1999. |
|5.||Shobokshi OA, Serebour FE, Skakni L: Chronic Hepatitis C Treatment: A Review. Ann Saudi Med 2000; 20: 402-8. |
|6.||Ankra-Badu GA, Ahmad M, Sowayan S, Bashawri L: Demographic Characteristics of Seropositive donors in Al-Khobar. Ann Saudi Med 2001; 21: 113-9. |
|7.||Al-Bahrani A, Panhorta BR: Prevalence of HBsAg and Anti-HCV Antibodies in Blood Donors of the Al Hasa Region of Saudi Arabia. Ann Saudi Med 2001; 21: 234-5. |
|8.||Al Tamimi W, Al Traif I, El Shaikh M, Al Kashan A, Qasem L, Sohaibani M: Prevalence of HBsAg and Anti HCV in Saudi Blood Donors. Ann Saudi Med 1998; 18: 60-2. |
|9.||Al Faleh FZ, Ramia S, Arif M, Ayoola EA, A1 Rashed RS, Al Jeffry M, et al: Profile of hepatitis C virus (HCV) and the possible mode of transmission of the virus in Gizan area, Kingdom of Saudi Arabia: a community-based study. Ann Trop Med Parasitol 1995: 89: 431-7. |
|10.||Al Nasser MN: Interfamilial Transmission of hepatitis C virus (HCV): a major mode of spread in the Saudi Arabian population. Ann Trop paediatr 1992; 12: 211-5. |
|11.||Bakir TMF: Age-specific prevelance of antibody to hepatitis C virus (HCV) among the Saudi population. Saudi Med J 1992; 13: 321-4. |
|12.||Shobokshi OA: Key note address: Overview of viral hepatitis A through TT virus. The Sixth Saudi Gastroenterology Association meeting, Jeddah, 1999. Saudi J Gastroenterol 2000; 6: 102-3. |
|13.||Al Faleh FZ, Ayoola EA, Al Jeffry M, Al Rashed R, A1 Mofareh M, Arif M, et al: Prevalence of antibody to hepatitis C virus among Saudi Arabian children: a communitybased study. Hepatology 1991; 14: 215-8. |
|14.||Al Faleh FZ, Ramia S: Hepatitis C virus (HCV) infection in Saudi Arabia: A Review. Ann Saudi Med 1997; 17: 77-81. |
|15.||Huraib SO: Hepatitis C in dialysis patients. Saudi J Kidney Dis Transplant 1995: 6: 197-205. |
|16.||AI-Muhanna FA: Hepatitis C virus infection among Hemodialysis patients in the Eastern region of Saudi Arabia. Saudi J Kidney Dis Transplant 1995; 6: 125-7. |
|17.||Al Mugeiren M, Al Faleh FZ, Ramia S, Al Rasheed S, Mahmoud MA, At Nasser M. Seropositivity to hepatitis C virus (HCV) in Saudi children with chronic renal failure maintained on hemodialysis. Ann Trop Paediat 1992; 12: 217-9. |
|18.||Bahakim H, Bakir TMF, Arif M, Ramia S: HCV antibodies in high-risk Saudi groups. Vox Sang 1991; 60: 162-14. |
|19.||El Zayadi A, Simmonds P, Dabbous H, Prescott L, Selim 0, Ahdy A: Response to interferonalpha of Egyptian patients infected with hepatitis C virus genotype 4. J Viral Hepat 1996 -1 3: 261-4. |
|20.||Osoba AO, Ibrahim M, Abdelaal MA, Al Mowallad A, At Shareef B, At Haj Hussein B: 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: 394-7. |
|21.||Al Faleh FZ, Huraib S, Sbeih F, Al Karawi M, Al Rashed R, Al Mofleh IA, et ai: Hepatitis C virus genotypes in patients with chronic liver disease and haemodialysis patients from Saudi Arabia. J Viral Hepat 1995, 2: 293-6. |
|22.||Shobokshi OA, Serebour FE, Skakni L, Al Safy YH, Ahdal MN. Hepatitis C genotypes and subtypes in Saudi Arabia. J Med Virol 1999; 58: 44-8. |
|23.||Shobokshi OA. Serebour FE, Skakni Lt. Hepatitis C genotypes/subtypes among chronic hepatitis patients in Saudi Arabia. Saudi Med J 2003: 24: S87-S91. |
|24.||Di Bisceglie AM: Hepatitis C and hepatocellular carcinoma. Hepatology 1997; 26(3 suppl 1): 34S-38S. |
|25.||Shobokshi OA, At Safi Y, Zaharna J, Mohammad A: The prevalence of hepatitis C virus in patients with established primary hepatocellular carcinoma in the western region of Saudi Arabia. Saudi Med J 1996; 17: 570-5. |
|26.||Poynard T, McHutchinson J, Goodman Z, Ling MH, Albercht J. Is an "a la carte" combination interferon alfa 2b plus ribavirin regimen for the first line treatment in patients with chronic hepatitis C? The ALGOVIRC Project group. Hepatology 2000; 31: 211-8. |
|27.||Akbar HO: Effect of induction therapy on Hepatitis C. Saudi Med J 2002; 23: 773-6. |
|28.||Al Faleh FZ, Al Jumah A. Rezeig M, Al Kanawi B, At Otaibi M, Al Ahdal M, et al: Treatment of chronic hepatitis C genotype IV with interferon-ribavirin combination in Saudi Arabia: a multicenter study. J Viral Hepat 2000; 7: 287-91. |
|29.||Al Faleh FZ, Sbeih F, Al Karawi M, Al Mofieh IA, Al Rashed RS, Ayoola A, et al: Treatment of chronic hepatitis C genotype 4 with alphainterferon in Saudi Arabia: a multicenter study. Hepatogastroenterology 1998; 45(20): 488-491. |
|30.||El Zayadi A, Selim O, Haddad S. Simmonds P. Hamdy H, Badran HM, et al: Combination treatment of interferon alpha-2b and ribavirin in comparison to interferon monotherapy in treatment of chronic hepatitis C genotype 4 patients. Ital J Gastroenterol Hepatol 1999:31: 472-5. |
|31.||Shoboksi O, Serebour F, Skakni L, Tantawi T. Dinish M, At Quwaiz M, et al: Efficacy of Pegylated (40 KDA) IFN alpha-2a (Pegasys) plus ribavirin in the treatment of hepatitis C genotype 4 chronic active patients in Saudi Arabia. J Hepatol 2002: 36(Sl): 173 (Abstract 612). |
|32.||Shoboksi O, Serebour E, Skakni L, Tantawi T, A1 Quwaiz M, Sandokji A, et al: PEG-IFN alfa-2a (40 KDA) as a monotherapy or in combination with ribavirin significantly improved end of treatment response rate in HCV genotype 4 chronic active hepatitis (CAH). Hepatology 2002; 36-Abstract 797. |
|33.||Diago M, Hadziyannis S, Bodenheimer H, Hassanein T, Uchman S, Marcellin P, et al: Optimized virological response rates with genotype 4 chronic hepatitis C treated with peg interferon alfa-2a in combination with ribavirin. Hepatology 2002: 36(4): 364A (Abstract 804). |
|34.||Al Sebayel MI: Starting a liver transplant program: Experience at King Fahad National Guard Hospital in Riyadh. Ann Saudi Med 1998: 18: 330-333. |
Hisham Osman Akbar
Department of Medicine, King Abdulaziz University Hospital, P 0 Box 80215 Jeddah 21589
Source of Support: None, Conflict of Interest: None
[Table - 1], [Table - 2]