Volume 1 issue 4
Hep C: Progression, Pathology
Hepatitis C is still a recently diagnosed disease recognized only nine years ago. For this reason, patients have not been able to be followed long enough prospectively to truly know the natural history. Statistics are gained from retrospective analysis and some small short-term prospective studies but the statitstics are still somewhat uncertain.
The course may fluctuate in activity. Specialists in the field of Hep C recognize that enzyme levels fluctuate and the degree of hepatic inflammation may well fluctuate (similar to other chronic viral illnesses such as Herpes Simplex).
The host and environmental factors that influence the course and progression
Factor: Duration of infection
Influence on Outcome: Longer duration may increase rate of progression
Factor: Age of infection
Influence on Outcome: Persons infected over age 50 may have more active disease
Influence on Outcome: Women may have less active course than men
Factor: Route of infection
Influence on Outcome: Transfused-related Hep C acquired may have more active course than IVDU acquired
Influence on Outcome: Some limited studies suggest less fibrosis in hemophiliacs
Influence on Outcome: Increased risk of acquiring Hep C
Factor: Iron overload
Influence on Outcome: Increased rate of progression of Hep C
Factor: Alcohol use/abuse
Influence on Outcome: Increased rate of progression
Factor: HBV co-infection
Influence on Outcome: No increased progression to cirrhosis but increase in hepatocellular carcinoma (HCC)
Factor: HIV co-infection
Influence on Outcome: Faster progression to cirrhosis and higher rate of cirrhosis
Influence on Outcome: Possible increased risk of HCC
Influence on Outcome: Steroids do not seem to make Hep C more active
According to present knowledge, the rate of progression is as follows:
- number of acute cases becoming chronic: 80 - 85%
- number of chronic cases developing cirrhosis:
- at 10 years post infection = 5 - 6%
- at 20 years post infection = 12 - 15%
- at 30 years post infection = 18 - 25%
- number of cirrhotics (from Hep C) developing decompensation:
- at 10 years post infection = 0.7%
- at 20 years post infection = 3 - 4%
- at 30 years post infection = 5 - 7%
- number developing Hep C related HCC:
- usually only occurs in patients after development of cirrhosis
- occurrence rate after development of cirrhosis is approximately:
* 3 years: 4% developing HCC
* 5 years: 7% developing HCC
* 10 years: 14% developing HCC
- average time to development is 28 years after infection
What about a liver biopsy?
A liver biopsy is currently the most accurate way of determining activity of disease, extent of fibrosis and assessing prognosis. The CASL (Canadian Association for the Study of the LIver) consensus statement is that "A liver biopsy is not mandatory but is strongly recommended". Because of imperfect treatment, a liver biopsy can assist greatly in making the decision about treatment. If the time of infection is known, the progression from that point to the time of the biopsy will give valuable information about previous and probably future progression. A liver biopsy is relatively safe, particularly the ultrasound guided biopsy.
Statistics relative to biopsy are:
risk of pain: 1/30
risk of serious bleeding: 1/1,000 - 1/3,000
risk of death: 1/10,000 - 1/17,000
Risk of death in the past tended to occur in patients with cirrhosis and with the use of a larger biopsy needle. With ultrasound guidance, pre-biopsy group and screen and smaller needles, death from bleeding should not occur.
The important features in the liver biopsy are the amount of inflammation and the degree of fibrosis. While a number of classifications are used, a practical one is the Ludwig Classification. Note: what was formerly called piecemeal necrosis or limiting plate necrosis is now usually called "interface hepatitis".
Grade 0 no inflammation
Grade 1 peri-portal inflammation no hepatocellular necrosis
Grade 2 inflammation with mild interface hepatitis
Grade 3 severe portal inflammation with moderate interface hepatitis
Grade 4 marked inflammation with severe interface hepatitis
Grade 0 no inflammation
Grade 1 minimal, no necrosis (inflammatory cells within the lobule)
Grade 2 moderate inflammatory cells with occasional liver cell necrosis
Grade 3 marked inflammation with severe focal liver cell necrosis
Grade 4 extensive inflammation with bridging necrosis
Stage 1 none or mild peri-portal fibrosis
Stage 2 peri-portal fibrosis with/without extension and portal-portal bridging
Stage 3 portal-central bridges but no nodular formation
Stage 4 probable or definite cirrhosis
- lymphoid nodules - fairly specific to Hep C
- damage to small bile ducts
- fatty deposition - fairly frequent
The Hepatitis Knowledge Newsletter is edited by F.H. Anderson, MD., FRCP(C), Natalie Rock, BSN, RN, Susan Campbell, RN. Room B-206, Dept. of Medicine, Van. Gen. Hosp. 855 W 12th. Vancouver V5Z 1M9. Phone:(604)209-9976 Fax: (604)875-4429.
The Newsletter is supported by an educational grant from Schering Canada Inc.
and GlaxoWellcome Canada.
Some of our most commonly asked questions and our answers to them.
Learn about the Hepatitis C Virus (HCV).
Information about the transmission of Hepatitis C.
You'll find links to a comprehensive symptoms list, as well as various studies and discussions about Hepatitis C symptoms.
Learn about the conventional medical treatments used to fight Hepatitis C.
Numerous links to studies, info sheets, FAQs, and analysis of Ribavirin/Rebetron medicines.
Alternative methods of treatment due to side effects and dissatisfication with current medical treatments.
A number of herbal products useful in the management of liver disease.
Receive the latest news on hepatitis treatments, clinical trials, social issues and important breakthroughs.
Learn about Hepatitis C Genotypes and their variants.
A state-by-state and worldwide reference listing physicians who treat HCV, including an email link to submit your physician for inclusion.
Convenient links to other sites external to Hepatitis-Central.
A Bulletin Board for discussions on hepatitis, treatments, etc.
An easy way to get involved in urging our government to do more for Hepatitis C awareness and treatment research.
Numerous links to various Hepatitis B related information, including transmission, symptoms and treatment.
A comprehensive resource of information relating to the liver biopsy.
Many discussions and analyses of cirrhosis, including causes, complications, pathology, symptoms, and much more.
Commonly used medical terms and definitions.
What they are and what they mean. Helps you interpret & understand all the various hepatitis lab tests likely to be encountered.
Liver Cancer/Hepatocellular Carcinoma studies, info sheets, FAQs, and analysis.
An exhaustive list of links to studies, info sheets, FAQs, and analysis of the various drugs used to treat liver disease.
Provides information regarding the best known liver supporting supplements.
Provides information regarding the best known milk thistle supplements.
Provides detailed information on how to analyze and interpret viral load numbers as well as a link to a convenient Viral Load Chart.
Learn more about various Hepatitis C related topics, including HCV, Ascites, Biopsies, and much more.
Recommended reading for those interested in hepatitis information.