Alavian SM et al. 2. Public Health Implications of HCV; the Rising Concerns and Growing Hopes for HCV Eradication 2.1. The Global and Local Image of Hepatitis C Hepatitis C is considered as a major cause of liver-re- lated morbidities and mortalities worldwide. Global re- cords and estimations show that the occurrence of end stage liver disease caused by HCV (Cirrhosis, fibrosis, Hepatocellular carcinoma and) will likely peak around the year 2020. Today, there are around 170-200 million in- dividuals living with HCV worldwide. The analyzed data reported from the United States show that HCV is seen as the etiologic factor for acute hepatitis (20%), chronic hepatitis (70%), liver cirrhosis (40%), hepatocellular car- cinoma (60%) and liver transplants (40%) in a noticeable number of liver disease patients (1). In a systematic re- view, HCV prevalence in general population of Iran was reported less than 1%. Tehran and Guilan provinces with the prevalences of 1.3 % and 0-0.16 % respectively were con- sidered as the most and the least prevalent geographic ar- eas for HCV (2). Statistics show that intravenous drug use (IDU) accounts for 50% of HCV transmission routes in our country. Other less important risk factors are male gen- der (OR = 10), tattooing (OR = 8.1), unmarried status (OR = 6.9), living in rural areas (OR = 3.4) and history of transfu- sion (OR = 1.1). In the countries under the Eastern Mediter- ranean Regional Office of WHO, nearly 32% (95% CI: 31-33) of hemodialysis patients are currently infected with HCV (3). In Iran, however, there are promising recent statistics with regard to specific transmission modes. In end stage renal disease patients, prevalence was 25% in a late 2009 study report, which decreased to 7.61% in the year 2010. Prevalence of HCV among spouses is 1.33% which is not higher than controls statistically. Therefore intra-familial contacts are not considered as an important route of HCV transmission. In a phylogenic study done on 125 Iranian patients, the most prevalent subtype of HCV in Iran was 1a (47%). The 3a, 1b and 4 genotypes were reported in 36%, 8% and 1% of HCV patients respectively (4). 2.2. The Natural History of Hepatitis C Following acute HCV infection, roughly 80% of patients will have the persistent infection and fail to experience recovery. Among the persistent infected patients, some will have a stable chronic hepatitis (30%), some will expe- rience variable progression (40%) and others will prog- ress to severe stages (30%) (5). Of those with chronic HCV infection, 80% would remain stable, while 20% would ultimately have cirrhosis from which 5% will develop end stage of liver failure or hepato- cellular carcinoma (5). Considering the HCV prevalence and the country population of Iran, there will be over 5000 patients estimated to need liver transplantation over next 10 to 20 years. HCV; the Rising Concerns and Growing Hopes 2.3. Reducing the HCV Related Liver Complications Preventing liver injury caused by HCV is normally done in four different levels, primordial to tertiary. Primary preventions include all measures to help preventing new HCV infections to occur. Since there are no vaccines avail- able for HCV (primary prevention), these efforts mainly focus on risk behaviors reduction (primordial preven- tion). This is partly done by primarily increasing public awareness and particularly alert those high risk popula- tions about transmission routes and subsequent burden of HCV (6). Secondary and tertiary preventions include all measures exercised to reduce complications of liver dis- ease in those with chronic infection. This will be achieved firstly by identifying infected individuals and reversing or eliminating factors which accelerate the rate of fibro- sis progression. There are therapies to stabilize or reverse liver injury and fibrosis (6, 7). 2.4. Screening for HCV and Cirrhosis in Infected Cases The high risk population, visited in our daily practice, is believed to have at least one of the following risk factors (8). 1. People who ever injected illegal drugs, even who did it once many years ago. 2. People with selected medical conditions including those: a. Receiving clotting factor concentrates made before 1990. b. On hemodialysis or “ever had it”. c. With history of organ transplant (recipient) or trans- fusion before 1992. 3. Healthcare providers, emergency medical and public safety workers after needle sticks, or mucosal expo- sure to HCV contaminated blood or body fluids. 4. Children born to HCV positive women. Patients who are already afflicted with hepatitis C, some have factors which predispose development of cirrhosis. These factors include, later age, male gender, ethnicity, higher body mass index, alcohol intake(> 40-50 mg/day), genotype (GT) 1, high GT quasispecies diversity, viral co- infection (HBV and HIV), cigarette smoking and being genetically prone to alpha-1 antitrypsin deficiency, use of steroids, and genetic polymorphism (8). There is a newly developed genetic test to predict fibrosis progres- sion probability in patients with chronic HCV. In this as- say certain single nucleotide polymorphisms (SNPs) are assessed in seven genes and then the pattern of SNPs is converted to a numerical score known as CRS (Cirrhosis Risk Score) (9, 10). CRS identifies patients who will more rapidly progress to cirrhosis. Patients with quite high CRS need not undergo liver biopsy and can be considered for HCV treatment (Figure 1). This assay does not seem to be commercially available in our settings; however its prognostic value and ability to bypass liver biopsy before 424 Hepat Mon. 2012