Hepatitis C:The Complexities

Hepatitis C: A Brief History

The hepatitis B virus was identified in the early 1970’s (first called Australia Antigen) and testing for hepatitis B (antigens and antibodies) became available at this time. In the early 1980’s the hepatitis A virus was identified and testing for the antibodies became available. There were many patients with neither hepatitis A nor B who were then called “non-A non-B” hepatitis. Since some patients seemed to develop hepatitis after a blood transfusion, some workers referred to this type of hepatitis as “post transfusion” hepatitis. The virus for hepatitis C was cloned in 1989 and testing became available in early 1990. Many of the patients previously diagnosed as either non-A non-B or post transfusion hepatitis were retested, (or stored serum was tested) and found to be hepatitis C. We now recognize hepatitis C as one of the most common types of hepatitis with up to 1.5% of the population being positive.

Basic Research Limited

Unfortunately, there is no good animal model for hepatitis C and the virus has not been grown in tissue culture. Thus, basic studies of the virus are not possible and studies are limited to gene sequencing and clinical studies. This fact also is one of the reasons a vaccine is very difficult to develop.

The Screening Test Is An Antibody

The screening test for hepatitis C is an antibody test to detect the antibodies to hepatitis C (anti-HCV). This test does not differentiate between the 20% who have recovered from the 80% with chronic hepatitis, nor do the antibodies indicate the degree of activity. Sera is usually tested with a second generation ELISA test, and if positive, confirmed with a second generation RIBA test. The presence of the virus must be confirmed by showing the hepatitis C RNA in the blood, and this is best done by PCR (polymerase chain reaction). Although quantitative measures may be done, it is usually adequate to simply determine the virus qualitatively (further discussion in a later issue of the newsletter).

Many Types and Subtypes

The hepatitis C virus is not one single homogenous virus, but rather, there are differences in the gene sequence resulting in 4 major genotypes. Within each genotype there are a number of subtypes, and within the subtypes a number of quasispecies. The frequency of the genotypes are different in different parts of the world, and genotype 1b is the most common in North America. There may be different genotypes relating to the route of infection, and some genotypes such as 1a, 3a and 4 may be more common in younger persons and type 2a associated with older age. It is still controversial whether genotype is related to severity and pathogenicity of the hepatitis, although it has always been reported that type 1b responds less well to treatment than other types. There is no correlation between genotype and pathology or enzymes elevation. Each genotype and subtype may be antigenically different, another factor making the development of a vaccine very difficult.

Acute Hepatitis C Extremely Mild

Acute hepatitis C is very mild and often not clinically apparent. It accounts for less than 15% of all cases of acute hepatitis in the USA. Only about 15 – 25% of persons are jaundiced. Thus, many patients have no idea when they contracted hepatitis C. The antibodies to hepatitis C may take up to three months to detect and so early diagnosis may be difficult. The HCV RNA is positive early but this test is not done without the antibody tests being done first and being positive.

The Course Is Slow and Insidious

About 20% of persons with acute hepatitis C fully recover and are felt to clear the virus, 80% develop some form of chronicity. On average, it takes 10 years before chronic hepatitis is apparent or diagnosed. Of those with chronic hepatitis, 22% will be mild in severity, 15% moderate, and 11% severe. Twenty-five percent of patients with chronic hepatitis will develop cirrhosis after 20 years and of these, 5% will develop liver cell cancer and 5% decompensated cirrhosis.

A Number of Factors May Influence the Clinical Course

There are both host and viral factors that influence the progression of hepatitis C. The major factors promoting progression are:

» alcohol consumption
» viral load at infection (transfusion acquired)
» body iron stores (increased iron)
» at age of infection (older)
» male gender

There May Be Associated Conditions

Chronic hepatitis C infection causes chronic immune stimulation and autoimmune diseases are more frequent in hepatitis C. Thus, many autoimmune diseases may be seen either as presenting conditions or in association with hepatitis C. Some of these are:

diabetes, mixed cryoglobulinemia, thyroiditis, erythema nodosum, erythema multiforme, glomerulonephritis, hypothyroidism, lichen planus, polyarteritis, urticaria, porphyria cutanea tarda, polymyalgia, B-cell lymphoma, Mooren corneal ulcers

Symptoms Unrelated to Findings

Symptoms such as fatigue, anorexia and right upper quadrant discomfort are not related to the degree of enzyme elevation, the level of virus in the blood or even the degree of inflammation or fibrosis in the liver. At least 30-50% of patients are totally asymptomatic even with fairly active disease.

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