It is well established now that HCV is the major etiological agent of parenterally transmitted non-A, non-B hepatitis (PT-NANBH), [1][2][3] and that it has a worldwide distribution. Studies on HCV infection have led to three striking observations. First, there is a high frequency of chronic infection in a significant number of infected individuals. It is estimated that at least 50% of HCV infections lead to chronic liver disease, including chronic active hepatitis with or without concurrent cirrhosis. [4][5][6] Second, HCV has been implicated as one of the major causative agents of primary hepatocellular carcinoma (HCC) in Japan 7 , Saudi Arabia, 8 and other parts of the world. [9][10] Third, approximately 45% of HCV cases have no obvious risk factors, including parenteral exposure, 4-6 leaving unanswered the question of virus transmission via as yet unidentified routes of exposure. The aim of this article is to review the literature about the extent of HCV infection in Saudi Arabia and see what can be concluded from the studies conducted so far. However, since there have been dramatic advances in the serologic diagnosis of HCV during the past six to seven years, we would first like to briefly review those serologic tests used and their reliability in diagnosing HCV infection.
Diagnosis of HCV Infection
Anti-HCV enzyme immunoassay (EIA) testsHCV infection, once a diagnosis of "exclusion" based on the absence of markers of acute infection with hepatitis A virus (HAV) or hepatitis B virus (HBV) can now be specifically diagnosed by using serodiagnostic assays for virus-specific antibodies.11 A first-generation anti-HCV EIA test was developed by using recombinant c100-3, derived from the NS3/NS4 region of the genome of HCV, as antigen (Figure 1). The test was used widely and although important data was generated, the test suffered from major drawbacks. These included failure to discover all patients with HCV infection, 12 long "window-phase" before seroconversion (could be up to 12 months), 13 in addition to a high rate of false-positive reactions. [14][15][16][17][18][19][20] To circumvent the drawbacks of the anti-HCV c100-3 test, recombinant or synthetic antigens derived from other regions of the HCV genome were included in the test and this is what is referred to as second-generation anti-HCV EIA tests. The additional antigens c22 and c33 were derived from two conserved regions: the structural region (core) and NS3 region, respectively (Figure l). 21,22 In patients with posttransfusion NANBH, the seroconversion rate improved from 54% with the first-generation to 82% with a second-generation test and the time lag to seroconversion decreased from a mean of 6.1 weeks after the onset of hepatitis with the first-generation test to a mean of 2.3 weeks with the second-generation test.23 Thus, the second-generation test reduces the "window-phase" to seroconversion and increases the sensitivity in diagnosing HCV infection, with a dramatic reduction in the number of false-positive reactions seen with the first-generation ...