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Hepatitis C - The latest public health risk
Michigan HIV News, Fall 1999 Issue (Note this article is now fairly
outdated, see below)
Another bloodborne virus
has gained the attention of public health officials as a serious health
threat. Hepatitis C virus (HCV) has emerged as a major cause of chronic liver
diseases worldwide since its discovery in 1988. Hepatitis, inflammation of the
liver, is most commonly caused by viral infection and hepatitis C is one of
now four types of hepatitis (B, C, D and G) that are blood borne.
The clinical importance of
hepatitis C was recognized only in the last couple of years. According to the
Centers for Disease Control and Prevention (CDC), it is now the leading cause
of liver transplants and there are an estimated 4 million people in this
country infected. About 8,000 to 10,000 people in the United States die
annually as a result of infection with it. Hepatitis C is much more virulent
than HIV, and there is no vaccination.
Hepatitis C is transmitted
primarily through sharing contaminated injection equipment but can be
transmitted sexually (with the presence of blood) as well as perinatally (from
mother to unborn child), although apparently not by breast milk. It can be
transmitted through mucous membranes as well as direct blood-to-blood contact
and can be contracted through the nasal passages when inhaling or snorting
cocaine. Further research is needed to define the epidemiology and relative
risk for sexual partners, tattooing and acute hemodialysis (blood cleansing
process.)
Historically, transfusion
of contaminated blood and blood products and the reuse or sharing of
contaminated equipment during the course of both traditional and
nontraditional medical procedures were largely responsible for HCV
transmission. Blood banks have screened the blood supply since 1992, so
transfusions with hepatitis C are rare. (See testing.) Blood products are now
also treated with heat and detergent solvents, which kill viruses.
An estimated 10,000 people
in Michigan are being notified they may have received an infected blood
transfusion before screening was available in June 1992. This targeted “lookback”
program reviews the records of blood donors who test positive for hepatitis C
to locate prior blood and blood product recipients. These recipients are then
notified that they may be at risk for hepatitis C.
Among adults with bleeding
disorders, 70 to 90 percent are estimated to be infected with hepatitis B
and/or C, according to the Hemophilia Foundation of Michigan (In Focus,
Spring 1997). The CDC is currently gathering data to get an accurate number.
Now injection drug use
poses the highest risk for HCV infection.
Where
HIV and hepatitis C paths merge
There are many
similarities between HIV and hepatitis C. Like HIV, hepatitis C is a blood
borne virus that mutates during viral replication, making it difficult for the
body’s immune system to combat. This allows the virus to establish and
maintain persistent infection, which can go undiagnosed until severe liver
problems emerge possibly 20 to 30 years later.
The incubation period for
hepatitis C averages six to seven weeks, but may range from two to 26 weeks.
Children and adults with acute hepatitis C are typically either asymptomatic
or have mild clinical illness. The vast majorities of people who contract
hepatitis C infection become persistently infected, and most develop chronic
liver disease.
Similar to HIV,
individuals with hepatitis C may not realize they are infected with the virus
for years and unwittingly transmit it to others. Of the estimated 4 million
Americans infected, it is estimated that 95 percent are unaware of their
infection, according to David L. Thomas, an infectious disease specialist at
Johns Hopkins University.
“The hepatitis C
epidemic is an iceberg, and we’ve only just discovered the tip,” Thomas
said. “When first infected, only one in five people ever exhibit acute
symptoms such as fatigue, jaundice, appetite loss, abdominal pain, nausea and
vomiting, and they may be attributed to flu.”
According to Thomas, 75%
of those infected eventually develop chronic disease. (Another source said
85%.) “However, even those with persistent infection usually won’t have
symptoms until there is complete liver failure, and then it’s too late to
treat.” Over time hepatitis C can lead to advanced liver disease, cirrhosis
and liver cancer.
“When we look at the
challenges of HIV and hepatitis C prevention and control, there are more
similarities than differences, especially in disease transmission, populations
at risk, and the required programmatic response,” said Randall S. Pope,
former manager of the HIV/AIDS Prevention and Intervention Section of the
Michigan Department of Community Health.
At a meeting with the CDC
in July, 1998, Pope said, “For many of us involved with the HIV epidemic, it
was obvious that many of the elements of the HIV model have applicability to
addressing the hepatitis C epidemic, including health education and risk
reduction, outreach strategies, public information programs, counseling and
testing — especially reducing barriers to knowledge of serostatus — and
care and treatment on the Ryan White CARE Act experience.”
The CDC is now in the
process of developing a broad nationwide prevention and control plan which —
because it involves the same populations at risk —
will probably in some ways utilize the HIV model and infrastructure.
And the new MDCH Division of HIV/AIDS and STDs (DHAS) Director, Loretta
Davis-Satterla, is already working on a plan for Michigan.
Testing
for HCV
A reliable test for
hepatitis C was developed in 1990, the year after the virus was identified.
Since then, 200,000 people in the United States have been
diagnosed either because they became sick or because it was discovered while
they were being treated for another illness.
The present testing
methods for hepatitis C include blood tests for antibody and virus. As with HIV, there are times when a test for
antibodies will not provide accurate results.
For HCV, this testing method
does not differentiate between acute, chronic or past infection. There is a
high false-positive rate for EIA in low prevalence populations.
Also, HIV and HCV co-infected individuals may not test positive for HCV using
this testing method. (see diagnosis in co-infected.)
Another traditional
test for hepatitis, ALT levels, which tests for liver enzymes, is not always
an accurate measure of HCV infection, according to two Michigan
gastroenterologists. According to Dr. Kim Brown at Henry Ford Hospital in
Detroit, 20% of those infected with HCV have normal liver enzymes.
The HCV PCR
(polymerase chain reaction) assays are currently the most sensitive lab tests
for HCV and can provide both qualitative and quantitative information.
Presence of virus is detectable within two weeks of exposure using methods
that detect viral RNA. These assays can be used for accurate and early
diagnosis in individuals who are at high risk and are immunocompromised to
confirm antibody tests and to monitor efficacy of therapy. Followed by
genotyping assays, these are important tools for therapy. Patients with HCV
genotypes other than type 1 respond better to interferon therapy.
According to the American Red Cross web site, a new
test – a nucleic acid “multiplex
assay” or NAT -- has been added to the Red Cross testing of the blood
supply. On March 1, 1999 Red Cross
added NAT to the tests that are performed on donated blood, under an
FDA-approved research protocol, IND. The
new test is able to detect parts of both HIV and Hepatitis C virus.
Early estimates suggest that NAT may annually detect an additional 6
HI-infected donations and 50 HCV-infected donations that
otherwise would not have been identified by standard testing.
Treatment
for HCV
Note: This section of the article is dated; please see care news for the most recent treatment advances.
However, there is important information regarding the use of ribavarin.
The National Institutes of
Health Consensus Development Conference Panel recommended that therapy for
hepatitis C be limited to those patients who have histological evidence of
progressive disease.
Until recently, the
primary treatment for hepatitis C was a drug called alpha interferon. In July
1998 the Federal Drug Agency (FDA) approved a new drug called ribavarin. This
new drug is now being used in combination with alpha interferon and appears to
be increasing treatment success rates. According to a report in the July 1998
National Alliance of State and Territorial AIDS Directors (NASTAD) HIV
Prevention Community Planning Bulletin, the combination therapy has been
shown to be up to 50 percent effective, increased from 20 percent with alpha
interferon alone. However, the February 1999 NASTAD Bulletin
indicated that the FDA approved combination packaged as Rebetron is a
relatively expensive treatment with a retail price of up to $1,440 a month.
The optimal duration
of treatment varies depending on whether interferon monotherapy or combination
therapy is used, as well as on HCV genotype. For more details see the National
Digestive Diseases Information Clearinghouse, “Chronic Hepatitis C: Current
Disease Management.”
According to this source
the common side effects of alpha interferon are fatigue, muscle aches,
headaches, nausea, low-grade fever, weight loss, irritability, hair loss
(reversible), mild bone marrow suppression and depression. Most of these side
effects are mild to moderate in severity and can be managed. The side effects
of ribavirin are anemia, fatigue and irritability, itching and skin rash,
nasal stuffiness, sinusitis and cough.
Possible serious side
effects: With combination therapy, ribavarin can cause a sudden drop in
hemoglobin, which can precipitate angina pectoris in susceptible people. The
Clearinghouse article stated, “fatalities from acute myocardial infarction
and stroke have been reported in patients receiving combination therapy.
“Ribavarin should not be
used in patients with preexisting anemia or with significant coronary or
cerebral vascular disease. Ribavirin causes birth defects in animal studies
and should not be used in women who are not practicing adequate means of birth
control.”
An important factor to consider in the treatment of
hepatitis C with alpha interferon is the psychological make-up of the patient.
Alpha interferon has multiple neuropsychiatric effects, again according to the
National Digestive Diseases Information Clearinghouse article.
It stated, “Prolonged therapy can cause marked irritability, anxiety,
personality changes, depression, and even suicide or acute psychosis.”
Robert B. Ferguson, M.D. a gastroenterologist at North
Oakland Medical Center in Pontiac, stated that before putting patients on
alpha interferon it is important to do a psychological evaluation “because
interferon is known to cause severe depression, not just mild depression,
where you actually have the suicidal (thoughts).” He said underlying
psychiatric disorders will be brought out with interferon.
HIV and Hepatitis C Co-Infection
Many persons with bleeding
disorders, as well as injection drug users, are infected with both HIV and
hepatitis C. While there is
epidemiologic data showing a higher incidence of hepatitis C among men who
have sex with men, the risk of sexual transmission for hepatitis C is still
not evidenced. There is risk of transmission in the presence of blood.
However, infection with
HIV may increase risk of sexual transmission of Hepatitis C, said Stuart
Gordon M.D., a hepatologist at Beaumont Hospital in Royal Oak. And,
while maternal to infant transmission is not common, the risk rises with the
amount of HCV in the mother’s blood; and the risk increases if the mother is
co-infected with HIV.
Also, people with HIV who
are co-infected with hepatitis C tend to have a more rapid decline in health.
Diagnosis of Hepatitis C in HIV Infected Persons
HIV and HCV co-infected individuals may not test
positive for HCV using the EIA screening method. Dr. Ferguson suggests using
the PCR test for hepatitis C RNA test. “It’s
very important to do the Hep C RNA on HIV infected patients,” he said. While
a more expensive test, this tests for the actual virus. Someone who is HIV positive may have hepatitis C but not test
positive for HCV antibodies. The other side of this is a false positive
diagnosis. “Hep C antibody can stay around much longer than the Hep C RNA, so
if they have antibody but no RNA they are not hep C positive,” said
Ferguson. “You are not going to treat those patients. Also, if you are going
to treat the patient, you will need an RNA level. With HIV - hep C co-infected
patients the hep C RNA is really the way to go. To me it’s the gold
standard.”
Treatment for the Co-Infected
Because HCV is a relatively new virus, there are no
official guidelines yet for treatment of individuals co-infected with HIV. And
it is impossible to get a consensus from physicians.
The FDA has not issued any guidelines for the
treatment of individuals who are co-infected with both HCV and HIV, said Dr.
Gordon, who is well known in Michigan for the treatment of hepatitis. “Due
to the possible drug interactions,” he said, “treatment of the co-infected
should be done within the context of clinical trials.” However, Dr. Gordon
noted and other physicians have supported that this treatment is done in
clinical practice.
“In people with both
HCV and HIV infection, benefits of therapy for hepatitis C have not been
shown. The decision to treat people co-infected with HIV must also take into
consideration the concurrent medications and medical conditions. If CD4 counts
are normal or minimally abnormal (>400mL), responses are similar in
frequency to those in patients who are not infected with HIV. The efficacy of
combination therapy has not been documented in HIV-infected people, and
ribavarin may have significant interactions with other antiretroviral drugs,”
according to the National Digestive Diseases Information Clearinghouse, “Chronic
Hepatitis C: Current Disease Management.
According to the
Hemophilia Foundation of Michigan, “(P)ersons with HIV and hepatitis C
co-infection should closely monitor the health of their liver, especially
before beginning powerful new drugs such as protease inhibitors, and should
consult a specialist to determine a treatment plan.” Lancet reported
in its 1998 Review that studies now show nucleoside analogues inhibit viral
replication and improve liver enzymes and histology in HBV-infected
co-infected individuals.
Martin Delaney, Founder of
Project Inform in San Francisco and a member of the national advisory panel
for the HIV Treatment Guidelines, is concerned about the misunderstanding of
Hepatitis C by some physicians who treat co-infected individuals. “Using
viral levels as a marker for treatment is not as good as liver enzyme tests,”
he said. High viral loads of HPV are not as threatening as the same levels of
HIV. He is also concerned about the toxic affects of using the
combination of HIV antiretrovirals with HCV drugs. This a very complex
treatment issue and Delaney does not expect a consensus for the guidelines
soon. If HCV treatment is necessary, he suggests that a short time off of HIV
antiretrovirals for the duration of the HCV treatment could be considered.
The American Foundation
for AIDS Research is conducting a national study to determine whether the new
combination therapy for hepatitis C works as well in those infected with both
HIV and hepatitis C.
The July 1998 NASTAD Bulletin
noted that there are significant treatment implications for injection drug
users who are infected with HIV and hepatitis C. Paul Loberti, chief of the
Office of Communicable Diseases at the Rhode Island Department of Health, said
the standard of care for injection drug users who are co-infected is not to
provide treatment for hepatitis C, because there is a considerable risk of
developing complications such as kidney failure and liver disease with the
treatment.
Current Resources
"Hepatitis C: What Clinicians and Other Professionals Need to Know
", an interactive web-based training on the Hepatitis Branch
web site http://www.cdc.gov/hepatitis
Also, visit the CDC
website www.cdc.gov/ncidod/diseases/hepatitis.
For a copy of the National Digestive Diseases Information Clearinghouse
publication “Chronic Hepatitis C: Current Disease Management, visit the
NIDDK website www.niddk.nih.gov/health/digest/pubs/chrnhepc.htm.
For follow-up information on the most recent international HCV Conference, see the HCV Global Foundation website www.hcvglobal.org.
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