MRC Conference

 

The Natural History of Hepatitis C

By Dr. Averell Sherker

Sir Mortimer B. Davis, Jewish General Hospital,, 3755 Cote Ste- Catherine, Chambre G 327, Montreal, Quebec, H3T 1E3. Tel: 514.340.8223 Fax: 514.340.8282

 

It is possible for people with acute hepatitis C to recover however the majority of infection persists and goes on to chronicity. From chronicity a percentage will go on to develop cirrhosis and a percentage of those cirrhotics will develop Hepatocellular Carcinoma. The normal progression we see is chronic portal HCV going to chronic active periportal HCV which then is followed by cirrhosis. The cirrhosis takes about 20 years to develop and 20 percent of the cirrhotics will develop Hepatocellular Carcinoma within 10 years.

 

We have seen with the Irish example that this progression is not so severe. It is possible to study this group for that reason and this should be done.

 

Factors that affect the natural progression include:

Route of infection

Age at time of contracting the disease

Alcohol consumption

Gender

Co-infection with other viruses

Quasispecies diversity (this may be a surrogate marker for the duration of infection)

Genotypes

 

 

Predictors of natural progression

The baseline histology is the best indicator of progression. In a one example of 57 individuals who had serial biopsies performed with 11 years to repeat biopsy - 25% developed moderate chronic active hepatitis, 15% had severe active hepatitis, and 10% had cirrhosis.

 

Grading relates to the degree of inflammation.

1=Limited to portal track

2=Spill out of portal track

3=Piecemeal necrosis

4=Bridging

 

 

Staging relates to the degree of scarring

1=Portal

2=Beyond portal

3=Bridging, portal to portal, portal central

4=Cirrhosis

 

 

Rate of progression

In a study with 2235 individuals fibrosis was scored from 0 to 4 and the duration of infection was based on the median. Fibrosis progression was equal to 0.133 fibrosis units per year. It took approximately eight years to progress to the next stage. Increased rate of progression was due to age 40 at infection, alcohol above three to four drinks a day, and male gender.

 

Inflammation progression is affected by:

  1. age
  2. gender- males show a more rapid prgression
  3. route of exposure- transfusion seems to increase the rate of progression
  4. alcohol
  5. genotype 1b
  6. viral load- no correlation between disease severity and symptoms and viral load.

 

We need a much more reliable method for documenting fatigue. Many of the symptoms are nonspecific and correlate less well with stage of disease. Nonspecific symptoms include depression, anxiety, sleep disorders and fatigue. Are they due to the HCV or another disease process? Many of the individuals are older and have other problems.

Specific Symptoms: Include jaundices, ascites, portal hypertension among others. One third of these individuals will have normal transaminases.

Exta hepatitic Manifestations Include:

Mixed cryoglobulinemia, glomulernephritis, keratoconjunctivitis sicca, lichen planus, non hodgkins lympoma and IASS.

Essential Mixed Cryoglobulinemia (EMC) can lead to arthralgias, Raynaud's Syndrome, Purpura, Mononeurtitis Multiplex. Type II is the most common although there is some Type III. 54% of people with HCV will have mixed cryoglobulinemia.

*EMC may be a precursor to Non Hodgkin's Lymphoma and may reflect infection in the lymphocytes.

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