Blood Tests
Testing the level of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood is one way of assessing if liver cells are dying. However, in most people with chronic infection the liver function tests fluctuate and may vary from normal to markedly raised over the space of a few days. Raised ALT levels are present in around two thirds of those infected but one-third show no evidence of elevated levels at all. Hence the traditional liver function tests are not very effective predictors of liver damage in chronic hepatitis C. Currently the most reliable way to assess the extent of liver damage is by liver biopsy (see below).
There are also some new blood tests, made by a variety of different companies hence with different names Fibrotest, Fibrosure, Actitest, that are starting to be used in the UK as markers of liver damage. They are possibly better at showing cirrhosis than fibrosis. Some UK hospitals are also using a scanner called a Fibroscan as a non-invasive alternative to biopsy. It measures the elasticity of the liver: the less elastic, the more scarring there is. It is particularly good at grading the different ranges of cirrhosis. Another way some doctors use to determine the presence of cirrhosis is by looking over time at the AST/ALT ratio. It seems that if the ratio of AST to ALT is >/=1 it is highly suggestive of cirrhosis, i.e. if the AST is consistently higher than ALT or equal to it.
Biopsy
Currently the most accurate way to check the extent of damage to the liver is by biopsy. A liver biopsy is a test in which small pieces of liver tissue are removed and examined under a microscope. This is done via a long needle inserted usually between 8th and 9th ribs under the right arm. The tissue will be assessed to see the extent of inflammation and fibrosis. (A biopsy will also reveal other abnormalities such as damage to bile ducts and the presence of fat).
The degree of inflammation is described in terms of inflammatory grade. Fibrosis is described by fibrotic grade. Confusingly there are several different scoring and grading systems for liver biopsies, and the same numbers are not comparable with another system. The systems used in the UK are the Ishak HAI, the Metavir and the Knodell systems and the Child-Pugh grading system for cirrhosis. The biopsy will indicate which stage of inflammation and fibrosis (scarring) are present in the liver. Inflammatory grade will range from none to extensive inflammation. Fibrotic grade will range from minimal scarring, scarring that has developed outside of the portal tracts (see below), fibrosis that has spread or is bridging towards neighbouring portal tracts is advanced scarring or cirrhosis.
In hepatitis C active fibrosis begins around the portal areas in the liver. The portal areas are tiny tracts of connective tissue within the liver that contain branches of the portal vein, (the main blood supply of the liver linking through the small intestine, stomach, pancreas and spleen).
As the fibrosis worsens, it may extend from one portal zone to adjoining portal zones; this is called bridging fibrosis. Bridging fibrosis is the stage before cirrhosis and ranges from early to marked bridging fibrosis. Cirrhosis is characterized by serious scarring that alters the livers structure and its ability to function.
The most extensive study of the rate of progression of fibrosis that has been done split people into three groups - "rapid fibrosers ", intermediate fibrosers " and " slow fibrosers " The largest group in the study, just over a third, were intermediate fibrosers who would be expected to develop cirrhosis in around thirty years after initial infection with HCV. 33% of patients were expected to develop cirrhosis in less than 20 years (rapid fibrosers). Just under a third would progress to cirrhosis in more than 50 years, if ever (slow fibrosers)
