Essay: Epidemiology of HCV Genotypes Worldwide:

The most repeatedly encountered genotypes worldwide are genotypes 1, 2, and 3. When the subtype distribution is inspected the significant differences are observed. Genotype 1a is the most widespread subtype in the Northern Europe and North America followed by the 2b and 3a (Mahaney et al., 1994). The genotype 1b is most common subtype in Southern and Eastern Europe followed by the genotypes 2 and 3. Moreover, North America and Europe are relatively common with HCV subtypes 2a and 2b, In Northern Italy subtype 2c is found commonly (Jeevitha et al., 2015). In Tunisia, the largely dominant subtype is 1b and followed by 1a, 2a, 2b, 3a, and 4. In the North Africa, Eastern and Southern Europe situation are analogous; HCV subtype 1b seems to be most prominent. In the Middle East and Central Africa, genotype 4 seems to be the predominant genotype (Ray et al., 2000). Almost exclusively in South Africa HCV genotype 5 has been isolated. In Hong Kong, Vietnam and throughout the South East Asia genotype 6 has been isolated (Jeevitha et al., 2015). Figure (3) shows the distribution of the predominant genotype for each country worldwide.
Figure (3): The most common HCV genotype for each country worldwide (Missena et al., 2015).
2.1.5 HCV in Egypt:
Hepatitis C is found worldwide. The most affected regions are Africa and Central and East Asia. Egypt has by far the highest national-level HCV prevalence in the world, with more than 14% of the Egyptian adult population having been exposed to the virus and 5 to 7 million having active infections (i.e., HCV-RNA positive) (Graham and Swan, 2015). These high rates are due to the mass campaign of intravenous tartar emetic (anti-schistosomiasis treatment) in the 1960s– (Strickland, 2006). This mode of infection has now resulted in a high incidence of hepatic morbidity from the late complications of HCV infection, such as chronic hepatitis, cirrhosis and hepatocellular carcinoma (Strickland et al., 2002; El Zayadi et al., 2005).
Estimates of HCV prevalence in Egypt range from11% to 14% with 8 to 10 million having anti-HCV and 5 to 7 million having active infections (i.e., HCV-RNA positive). The lowest rates are in Cairo and Alexandria (<8%), highest in rural areas of the Nile Delta (>15%), and intermediate (8%-16%) in rural areas along the Nile south of Cairo.  Prevalence increases with age and is higher in males (Strickland, 2006). Blood transfusion, before screening for HCV was started in the early 1990s, infected many Egyptians (Strickland, 2006). In addition to unsafe injection practices, lack of attention to appropriate cleaning and disinfection of equipment used in hospital and dental settings also may be a source for HCV transmission. Because chronic liver disease may develop many years after infection, the past incidence is a major determinant of the future burden of HCV-associated complications (Alter, 2007).
2.1.5 Natural History of Hepatitis C Virus:
There has long been evidence that hepatitis C can lead to persistent infection in a high proportion of infected individuals, and can progress to chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). The transition from acute to chronic hepatitis C is usually sub-clinical. Chronic infection with HCV is the leading cause of end-stage liver disease, hepatocellular carcinoma (HCC) and liver related death in the Western world. The natural history of the chronic disease remains incompletely defined. It is generally a slowly progressive disease characterized by persistent hepatic inflammation, leading to the development of cirrhosis in approximately 10–20% of patients over 20–30 years of HCV infection (Westbrook and Dusheiko, 2014).
2.1.5.1 Acute hepatitis C infection:
Inoculation of HCV will lead to acute hepatitis. The incubation period of HCV is approximately 50 days (range 15-150 days) before symptoms occur. However, the majority of acute HCV patients (60% to 75%) are asymptomatic while 20% to 30% become jaundiced and 10% to 20% have symptoms (Thomas and seef, 2005). Usually, HCV RNA can be detected in blood within 1 to 3 weeks. However, the average time period to seroconversion is 8-9 weeks, with more than 97% of individuals seroconverting within 6 months of exposure. Once symptoms start in HCV patients HCV antibodies can be detected by enzyme immunoassay (EIA) in only 50% to 70% (Zein, 2003; Maheshwari et al., 2008).
Within an average of 4 to 12 weeks, liver cell injury is showed by elevation of serum alanine aminotransferase (ALT) levels. Acute infection can be severe but is rarely fulminant. Symptoms are uncommon, but can include fatigue, nausea and vomiting malaise, weakness, anorexia, and jaundice. Symptoms usually subside after several weeks as ALT levels decline (Hoofnagle, 2002).
Spontaneous viral clearance appears to occur fairly rapidly, usually between 6 and 24 months after initial exposure. Additionally, some patients have been shown to lose all markers of previous HCV infection, including anti-HCV (Alter et al., 1999).
2.1.5.2 Chronic HCV infection:
Previous data showed that approximately 15% of patients clear acute infection, while 50%–85% of acute HCV patients develop chronic infection (Muir, 2000 and Thomas et al., 2000). Also, studies indicated that this percentage of spontaneous clearance may be higher in women and children (Seeff, 2002; de Bruijne et al., 2009).
Most patients with chronic hepatitis C have few if any symptoms, the most common being fatigue, which is typically intermittent. Right upper quadrant pain (liver ache), nausea, and poor appetite occur in some patients. Serum ALT levels are usually continuously or intermittently elevated, and at least one third of infected people have persistently normal ALT levels (Hoofnagle, 2002).
2.1.5.3 Cirrhosis and Hepatocellular Carcinoma:
Chronic HCV infected patients may have progressive liver fibrosis leading to cirrhosis, end-stage liver disease and HCC. The proportion of chronically infected people who develop cirrhosis 20 years after initial infection vary widely, from 2%–4% in studies of children and young women to as high as 20%–30% in middle-aged transfused subjects (Alberti et al., 1999 and Seeff, 2002). The actual risk is probably between these two ranges, perhaps 2%–20%. Once Cirrhosis develops 2-5% of HCV infected patients decompensate and go into liver failure within 5 years. Also, it has been reported that the rate of HCC development in cirrhotic HCV patients is 1-4% per year (El-Serag and Mason, 2000 and Seeff, 2002). Figure (4) shows the natural history of Hepatitis C Virus HCV (Seef, 2002).