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Hepatitis C Manual
http://www.medicineau.net.au/clinical/hepatitis/hepatiti1508.html
Hepatitis C Infection
Introduction
The hepatitis C virus was identified in 1989 and it is
estimated that three hundred million people
worldwide have been infected with the virus. Studies of
blood donors suggest the prevalence of
anti Hepatitis C Virus antibodies is low in northern Europe, the USA
and Australia, higher in southern Europe
and
Asia and highest in Africa.
The virus's recent spread is thought to be due to
receipt of blood products before the introduction
of testing (Feb 1990) and to an increase in injecting
drug use (IDU) in Western countries.
Hepatitis C is probably the most common life
threatening infection in Australia. Over the last 20
years, an estimated 130,000 people have been infected,
with an estimated 6000 new infections
annually
from IDU alone. Of those infected, 80-85% develop chronic
liver disease. Of these,
10-20% develop cirrhosis within 20 years, and of those
with cirrhosis, 5% will develop
hepato-cellular carcinoma.
Universal testing by blood banks has minimised the risk
of transmission via blood products.
However, there is little evidence that the campaign
that successfully reduced the spread of HIV
(via
IDU) through education, needle exchanges and methadone
clinics, has had much impact on
the spread of hepatitis C.
The large numbers of people infected, together with the
chronicity of the disease, makes Hepatitis C Virus a
major health challenge. GPs, with their skills in long
term management of chronic illness, are at the
forefront of this challenge and also have an
opportunity to educate IDUs about the dangers of
hepatitis
C.
Hepatitis C - the Virus
Hepatitis C is an RNA virus. It is a very effective
viral pathogen. It is estimated that 80- 85% of
patients who are infected with the virus will develop
chronic infection. This happens despite a
healthy immune system. There is no evidence to indicate
that most patients with Hepatitis C Virus have any
immune defect. The virus appears to subtly alter its
genetic structure over time and this is one of
the theories on how it evades immune clearance. The
virus can be found within the liver cell
(hepatocyte) and in the blood.
Generally there are low titres of the virus in the
serum of infected patients. It is very difficult to
grow in cell culture, and no one has ever seen the
virus with electron microscopy. Viral antigens
have not been classified nor are they measurable
(compare this with hep B surface antigen). A
positive Hepatitis C Virus antibody test indicates infection with the
virus at some stage (past and/or current).
The Hepatitis C Virus-RNA test via the PCR technique is consistently
improving and a positive test indicates
the presence of active infection. At the current time
there is no rebate for this test and most
laboratories charge about $60.
Epidemiology of Hepatitis C
From the available data the prevalence of hepatitis C
in Australia is about 0.3%. This figure is
obtained from studies of potential blood donors and
because of risk factor screening, may be
lower than that of the general population.
Direct parenteral exposure is the major risk factor in
transmission of hepatitis C
Transfusion of blood products from infected donors;
people transfused with blood prior to
universal testing of all blood products in February
1990 are at risk.
Regular transfusion of blood products; 85-90% of
haemophiliacs in Australia
are Hepatitis C Virus antibody +ve. Blood products are now treated by
a process that destroys Hepatitis C Virus.
IDUs sharing contaminated drug injecting equipment.
The infection rate is highest among people
participating in high risk behaviours
IDUs
have the highest risk rate, studies showing 75% are infected
after five years rising to
nearly 100% at 10 years.
Sex industry workers have a higher rate than the
general population 5-8%, but this may be
more a reflection of IDU use than sexual transmission.
Body piercing and tattooing using contaminated
equipment.
Household and sexual contacts of patients with
hepatitis C have an increased risk of
infection. Sexual transmission is thought to occur
rarely, in less than 5% of couples. Transmission
may be more likely during acute phase of infection.
Vertical transmission from mother to fetus occurs, but
breast feeding is safe unless there is
bleeding from the nipple. Maternal hepatitis C
antibodies are transmitted passively to the fetus but
disappear from circulation by 18 months. 5-10% of
children acquire the virus. This is most likely
to happen when there is a high viral titre, such as
when hepatitis C is acquired during pregnancy,
or if the mother is HIV positive.
Endoscopy before 1990 may be a risk factor.
Natural History
On current evidence, most patients will not have their
life span altered by Hepatitis C Virus infection. On
current evidence, most patients will not have their
life span altered by Hepatitis C Virus infection.
About 1/4 patients may develop significant liver
diseases including:
20% cirrhosis after 20 years
10%
hepatocellular carcinoma after 30 years
Many patients will be asymptomatic. Many patients
describe symptoms including lethargy, RUQ
pain, malaise, headache.
The challenge of therapy is to treat patients to
prevent cirrhosis and hepato cellular carcinoma
(HCC) without unduly disturbing those who will have
mild chronic hepatitis only.
If 100 people catch the hapatitis C virus at the same
time:
15 - 20 people get rid of the virus within two to six
months ( but will continue to carry
antibodies for some time).
80 - 85 people have chronic (long - term) hepatitis C
infection.
Around 20 people will never develop any liver damage or
physical symptoms.
Between 60 to 65 people will develop some level of long
term symptoms or signs of
liver
damage ( after an average 13 years )
Between 20 to 25 of these people will develop cirrhosis
of the liver (over an
average 20 year period)
Bewteen
5 to 10 of those people will experience liver failure of liver
cancer (after an average 25 to 30 years, all up)
Hepatitis C Virus Prevelance
Hepatitis C Virus prevalence in different population groups.
NSW North Coast hepatitis C study
This study, conducted by the North Coast Public Health
Unit, examined how hepatitis C was
being transmitted on the North Coast. All people who
were notified to the North Coast Public
Health Unit during a 21 month study period (1993-94)
were invited to complete a survey. 465
questionnaires were completed (46% of notified cases).
Direct
exposure to blood could be demonstrated for almost all
subjects. Risks associated with
household, sexual and other contact where blood
exposure was avoided appeared to be minimal.
83 sexual partners of Hepatitis C Virus positive subjects were Hepatitis C Virus
positive (36% of those tested).
When 57 of these positive partners were followed up
only 5% (3) had no independent blood
exposure. Approximately half of the Hepatitis C Virus negative sexual
partners reported having unsafe sex
with their Hepatitis C Virus positive partner, further illustrating
the lack of sexual transmission.
Management of hepatitis C antibody positive patients
Checklist
PRETEST COUNSELLING
SELECTION OF PATIENTS FOR TESTING
INTERPRETATION AND CONFIRMATION OF TESTS
POST TEST COUNSELLING
ASSESSING CLINICAL DISEASE
MONITORING DISEASE PROGRESS
SELECTION OF PATIENTS FOR ANTIVIRAL THERAPY
ONGOING SUPPORT AND COUNSELLING FOR THE PATIENT
ASSESSING RESPONSE TO ANTIVIRAL THERAPY
MANAGEMENT
OF PATIENTS WITH CHRONIC HEPATITIS, CIRRHOSIS AND
HEPATOCELLULAR CARCINOMA
EDUCATION TO PREVENT SPREAD OF DISEASE
PreTest Counselling
Counselling should be undertaken whenever a test for
Hepatitis C Virus is being considered. This should be
carried out in private, leaving sufficient time to
enable discussion of the issues.
Pretest check list
Natural history of Hepatitis C Virus
Transmission
Nature and interpretation of tests
Assessment of level of risk
Significance of positive result
Management
and treatment of Hepatitis C Virus
Assessment of psychological status
Confidentiality and notification
Informed consent
Information material
Pretest counselling should include:
Assessment of the patient's risk factors and the
likelihood of a positive result.
The significance of a positive result. A positive
result does not necessarily indicate
progressive liver disease.
Transmission sexually and from mother to infant is low,
but transmission to household
members is possible via toothbrushes and razors.
An outline of the management of hep C including
monitoring, antiviral therapy and lifestyle
changes.
A brief psychological assessment to gain some insight
into the patient's possible reaction to
a positive result.
Confirmation that confidentiality will be respected but
that positive results are notifiable to
the NSW Health Department.
Allow
the patient to give informed consent before testing.
Provision of written information (see back of book for
details).
Who Should Be Tested
Population screening or screening of all pregnant women
is not recommended, but HIGH RISK
patients should be offered testing. Diagnosis can lead
to disease modification through lifestyle
changes and antiviral therapy, and counselling can be
given to prevent further transmission.
Testing should be offered to the following:
People who have EVER injected drugs
People who were transfused with blood or blood products
(especially prior to February
1990)
People with abnormal liver function tests or evidence
of liver disease with no apparent
cause
People with occupational exposure to Hepatitis C Virus
People with extra hepatic manifestations eg.
Cryoglobulinaemia glomerulonephritis
Renal dialysis patients
People with a history of imprisonment
Testing should be considered in the following:
People who have had tattoos, body piercing or
acupuncture in a situation where infection
control guidelines may not have been followed
People from countries where there is a high prevalence
(the Mediterranean, Middle East,
Asia, Africa, South America)
Children, sexual and household contacts of persons with
Hepatitis C Virus
Health care workers
Those requesting the test who may have a hidden agenda
Travellers who have received medical care, injections,
or transfusions in countries where
Hepatitis C Virus
has a high prevalence or where blood is not tested prior to
transfusion.
The window period (seroconversion) ranges from 2-26
weeks (average 10 weeks)
The Tests
ANTI-Hepatitis C Virus (Hepatitis C Virus ANTIBODY)
Measures antibody response to virus.
2nd and 3rd generation tests with confirmatory test are
generally quite accurate but still
have a low false positive rate..
Antibody levels indicate the positivity of the test (ie
level above cutoff) but are no guide to
the severity of hepatitis.
LIVER ENZYMES
ALT is the best indicator of hepatitis.
Commonly fluctuates in Hepatitis C Virus.
If consistently normal (with positive anti-Hepatitis C Virus and
negative Hepatitis C Virus-RNA) may suggest
resolved past exposure.
VIRAL
SUBTYPES
There are known to be six different subtypes of the
virus. The most common subtypes in
Australia are types 1 and 3. Most patients are infected
with one subtype only but infection with
two
or more subtypes has been recorded. It does appear that
patients with type 3 virus respond
better to antiviral therapy (Interferon) than those
with type 1, 4 or 5. Currently, virus subtyping in
the individual patient is not routinely done in
clinical practice. The test costs about $150 and there
is no rebate. It can be performed through a reference
laboratory in Brisbane or Sydney.
VIRAL LOAD
The
quantity of virus in the peripheral blood can be quantified.
There is evidence to support the
assertion that patients with persistently low levels of
virus have a greater chance of responding to
antiviral therapy compared to those with persistently
high levels of the virus. The viral load test is
performed through reference laboratories, costs about
$300 and there is no rebate.
PCR (POLYMERASE CHAIN REACTION)
A sensitive technique for detecting viral RNA.
Even small amounts of RNA can be amplified and
detected.
Is a marker of viral replication and infectivity if
positive.
The
commonly available test gives a non-qualitative result (ie.
detected or not detected).
The test is not currently funded under Medicare and
costs about $60.
The PCR test can be very useful, as in the following
situations:
If the anti-Hepatitis C Virus and confirmatory test are equivocal and
the ALT consistently normal, a
negative PCR strongly suggests that the patient does
not have hepatitis C.
If a patient has normal LFTs during Interferon therapy
but has a positive PCR 6-12
months into therapy, they are likely to relapse when
therapy ceases.
If the anti-Hepatitis C Virus test is positive and the ALT
consistently normal, and the PCR negative on
two occasions over six to 12 months, then the patient
has probably recovered after past
infection.
If the patient has several possible causes for liver
disease and is anti-Hepatitis C Virus positive, a
positive PCR suggests that Hepatitis C Virus is playing a role in the
liver disease.
TEST
RESULTS
INTERPRETATION
RECOMMENDATION
anti-Hepatitis C Virus
positive
chronic hepatitis, chronic
hepatitis C recovered, recent
acute hepatitis C, or false
positive test
further
evaluation
anti-Hepatitis C Virus
ALT
EIA
positive
normal
positive
possible
chronic Hepatitis C Virus or
recovered infection
further evaluation
anti-Hepatitis C Virus
ALT
EIA
positive
elevated
positive
presume chronic hepatitis C
further
evaluation/ consider
Interferon therapy
anti-Hepatitis C Virus
ALT
EIA
positive
normal
negative or
indeterminate
presume false positive
anti-Hepatitis C Virus or recovered
further evaluation by Hepatitis C Virus-RNA
PCR test
anti-Hepatitis C Virus
ALT
EIA
positive
elevated
negative
presume false positive
anti-Hepatitis C Virus,
false negative
supplemental test unlikely
further evaluation for liver
disease
other then hepatitis C +
Hepatitis C Virus RNA PCR
ALT (no
other +ve
tests)
elevated
other
liver diseases
further evaluation
Definitions:
anti-Hepatitis C Virus - antibody to hepatitis C virus.
ALT
- Liver enzyme released from liver cells that are injured, eg.
by virus, alcohol, fat,
drug, etc.
Indeterminate means one of four antigens positive.
Hepatitis C Virus-RNA test by polymerase chain reaction (PCR)
determines whether the virus is
multiplying.
EIA - Elisa immune assay - Supplemental test to detect
antibody to hepatitis C virus.
Post Test
Counselling
The results of a Hepatitis C Virus test should always be given in
person. You should have enough time to give
a full explanation and to provide support to the
patient with a positive result.
A
positive result often causes psychological trauma and this may
be reduced by
appropriate counselling at the time of diagnosis.
Counselling issues
Pre test counselling prepares for a positive result
Pre test counselling may help to reduce an anxious or
angry reaction to a positive test result. A
person with a significantly high risk history can be
prepared to deal with a positive result by
sensitive counselling.
Present or past IDU - a sensitive issue
Many people testing positive for Hepatitis C Virus have a history of
injecting drug use. This may have been
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