Hepatitis C
By Howard J. Worman, M. D.
The Hepatitis C Virus (HCV)
HCV was discovered in 1989 by investigators at Chiron, Inc. Portions of
the HCV genome were isolated by screening cDNA expression libraries made
from RNA and DNA from chimpanzees infected with serum from a patient with
post-transfusion non-A, non-B hepatitis. [Prior to the discovery of HCV,
hepatitis following blood transfusion that was not caused by hepatitis A
or hepatitis B was referred to as non-A, non-B hepatitis]. To identify
portions of the genome that encoded viral proteins, the libraries were
screened with antibodies from patients who had non-A, non-B hepatitis.
These investigators went on to show that the virus they identified was
responsible for the vast majority of cases of non-A, non-B hepatitis.
They called the new virus hepatitis C virus (HCV). Subsequently, the
complete genomes of various HCV isolates were cloned and sequenced by
several groups.
HCV is a positive, single-stranded RNA virus in the Flaviviridae
family. The genome is approximately 10,000 nucleotides and encodes a
single polyprotein of about 3,000 amino acids. The polyprotein is
processed by host cell and viral proteases into three major structural
proteins and several non-structural protein necessary for viral
replication. Several different genotypes of HCV with slightly different
genomic sequences have since been identified that correlate with
differences in response to treatment with interferon alpha.
Despite the discovery of HCV by molecular biological methods and the
sequencing of the entire genome, a permissive cell culture system for
propagating HCV has yet to be established. A non-primate animal model
also does not exist. As a result, the production of specific drugs
against HCV has been impeded although excellent diagnostic methods for
have been developed.
Risk Factors for HCV Infection
Approximately 170,000,000 people worldwide and 4,000,000 in the
United States are infected with HCV.
The virus is transmitted primarily by blood and blood products. The
majority of infected individuals have either received blood transfusions
prior to 1990 (when screening of the blood supply for HCV was implemented)
or have used intravenous drugs. Sexual transmission between monogamous
couples is rare but HCV infection is more common in sexually promiscuous
individuals. Perinatal transmission from mother to fetus or infant is
also relatively low but possible (less than 10%). Many individuals
infected with HCV have no obvious risk factors. Most of these persons
have probably been inadvertently exposed to contaminated blood or blood
products.
Consequences of HCV Infection
About 85% of individuals acutely infected with HCV become chronically
infected. Hence, HCV is a major cause of chronic (lasting longer than six
months) hepatitis. Once chronically infected, the virus is almost never
cleared without treatment. In rare cases, HCV infection causes clinically
acute disease and even liver failure, however, most instances of acute
infection are clinically undetectable.
The natural history of chronic HCV infection can vary dramatically between
individuals. Some will have clinically insignificant or minimal liver
disease and never develop complications. Others will have clinically
apparent chronic hepatitis. Of these, some go on to develop cirrhosis, however, the exact percentages is
not known. About 20% of individuals with
hepatitis C who do develop cirrhosis will develop end-stage liver disease.
Cirrhosis
caused by hepatitis C is presently the leading indication for orthotopic
liver transplantation in the United States. Individuals with cirrhosis
from hepatitis C are also at an increased risk of developing hepatocellular carcinoma (primary liver cancer).
A major problem in discussing prognosis in patients with chronic hepatitis
C is that it is difficult to predict who will have a relatively benign
course and who will go on to develop cirrhosis or cancer. One fairly
clear factor for progression to cirrhosis is concurrent alcohol abuse.
Certain findings on liver biopsy can also be helpful in predicting a
relatively benign or progressive course. Viral genotype may also play a
role. Additional research is urgently needed to identify host factors
that are important in determining prognosis in chronic hepatitis C.
Diagnosis
The diagnosis of chronic hepatitis C is made by history, serological
testing and liver biopsy. Most patients with chronic hepatitis C will be
asymptomatic or have non-specific symptoms such as fatigue. In some
individuals, the diagnosis will be suspected from the results of blood
tests obtained for other reason (usually elevations in the serum alanine and aspartate aminotransferase activities).
Individuals suspected of having chronic hepatitis C include:
- Those with symptoms of chronic liver disease
- Those with risk factors such as past or current intravenous drug use
or blood transfusions prior to 1990
- Those with abnormal laboratory tests suggesting liver disease
Such individuals should be tested for the presence of serum antibodies
against HCV. The presence of anti-HCV antibodies in a person with a risk
factor or evidence of liver disease strongly suggests the diagnosis of
chronic hepatitis C. The absence of anti-HCV antibodies generally rules
out the diagnosis. Tests for HCV RNA in blood should be done in those
individuals with anti-HCV antibodies to confirm the diagnosis and in the
rare patient who does not have anti-HCV antibodies but in whom the
diagnosis is still strongly suspected on clinical grounds. Such testing
shuld also be performed in patients who will undergo treatment. After making
the diagnosis, a liver biopsy is usually indicated to assess the degree of
liver inflammation and fibrosis and the presence or absence of
cirrhosis.
Treatment
All patients with
chronic hepatitis C should be evaluated by a specialist for possible
treatment with these agents. In general, adults less than 70 years old
with evidence of active inflammation on liver biopsy and without advanced
cirrhosis are good treatment candidates. Indications for treatment of
patients with very mild disease on liver biopsy are less clear. Such
individuals should be
considered for possible participation in clinical studies. Patients with
advanced cirrhosis secondary to hepatitis C should be referred
referred for evaluation for possible liver
transplantation.
Click here for information on current
treatments for chronic hepatitis C. Considerable research is also
devoted toward new treatments for chronic hepatitis C.
Other Sources of Information on Hepatitis C
-
- By Howard J. Worman, M. D.
- National
Institutes of Health Consensus Statement on Management of Hepatitis C
- A consensus statement on the management of hepatitis C prepared by a
nonadvocate, non-Federal panel of experts.
- Hepatitis C
- From the U.S. Centers for Disease Control and Prevention.
- Hepatitis C: An Epidemic for
Anyone
- From the Koop Institute at Dartmouth College.
- Hepatitis C: Current Treatment
- From Howard J. Worman, M. D.
- Evolving Treatments for Chronic Viral Hepatitis
C
- From Howard J. Worman, M. D.
- Hepatitis Foundation
International
- Information about an organization established to reduce suffering
caused by hepatitis.
Diseases of the Liver Home Page
Copyright, 1995, 1998, 2001, 2002, Howard J. Worman, M. D. All rights
reserved. Printing or other reproduction is prohibited without
the written authorization of Howard J. Worman.
Diseases of the Liver/Howard J. Worman, M. D./hjw14@columbia.edu
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