Individuals who are currently infected with HCV have HCV RNA detectable in their serum. The levels of HCV RNA typically found with human infection are not easily detected using standard hybridization assays and require amplification of either the target (by PCR) or signal. As few as 50 copies of viral RNA per ml of serum can be detected with some modern assays.
The amount of HCV RNA in the circulation is readily quantifiable and is on average 2 to 3 million copies per ml. The level of HCV RNA may however vary considerably from patient to patient but is generally consistent over time in individual patients. The level of HCV RNA in serum does not appear to correlate with the severity of liver disease assessed either by serum aminotransferase activities or liver histopathology.
Finally, the serum level of HCV RNA appears to be a good predictor of response to antiviral therapy. Assays to determine HCV genotype are now widely available although they lack standardization. Commonly used assays are based on amplification and sequencing or a line probe hybridization assay.
Patient histories are often unreliable and serologic tests do not accurately distinguish acute from chronic HCV infection. Jaundice is uncommon with acute hepatitis C. The Liver biopsy plays a major role in the management of chronic hepatitis C. The histologic features of chronic hepatitis C commonly include an infiltrate of chronic inflammatory cells within portal areas, interface hepatitis, lobular hepatocellular injury and hepatic steatosis.
Less commonly, the portal infiltrates take on the form of lymphoid aggregates or sometimes even lymphoid follicles. Progression of chronic hepatitis C is marked by progressive increases in hepatic fibrosis, consisting largely of collagen. Hepatic fibrosis due to HCV infection begins within the portal triads but may form bridges between portal areas or with terminal hepatic venules (bridging fibrosis).
Cirrhosis represents the most advanced form of hepatic fibrosis.
Several systems for scoring the severity of chronic hepatitis C have been developed. They have in common assigning a grade to the degree of necrosis and inflammation and a stage to the degree of fibrosis.
These scoring systems have proved to be very useful in clinical trials as a means of measuring improvement in liver histopathology as a result of antiviral therapy, but are also valuable in clinical practice as a means of assessing and following the severity and possible prognosis of liver disease. Commonly used systems include those described by Knodell and colleagues, Scheuer, Ishak and a French collaborative group (METAVIR) Brunt (01)).