New guidelines for managing hepatitis C
- Contemporary OB/GYN� Archive
Oct. 1, 2002
New guidelines for managing hepatitis C
Recognizing the infectionWhat constitutes effective treatment?Who
should be treated?
By Paul Cerrato, Managing Editor
The latest NIH Consensus Development Statement on the disease offers
some important advice for ob/gyns on perinatal transmission.
Once upon a time, hepatitis C was considered somewhat of an oddity,
an unclassifiable disorder given the stepchild designation "non-A,
non-B hepatitis." In 1989, however, researchers discovered the
specific virus that caused hepatitis C, and shortly after that, they
realized that the majority of patients with non-A, non-B disease were
in fact infected with the newly discovered microbe. Now it's
estimated that nearly 4 million Americans have hepatitis C and it's
believed to be the leading cause of liver disease in this country.
In 1997, the NIH convened the first consensus development conference
to make recommendations on managing the disorder. But in the last 5
years, our knowledge of hepatitis C has increased dramatically,
prompting the government to convene another conference. Here are the
highlights from their consensus statement.
Recognizing the infection
There are six major genetic variants of the hepatitis C virus (HCV),
and 70% to 75% of Americans who are infected have genotype 1, which
responds relatively poorly to treatment. By one conservative
estimate, 69% of the 3.9 million Americans with HCV have a chronic
Persons at greatest risk for the disease include IV drug users,
infants born to infected mothers, transplant patients, and those who
received blood products before 1992.
In the words of the NIH consensus panel: "The risk of perinatal
transmission is approximately 2% for infants of anti-HCV-seropositive
women. When a pregnant woman is HCV RNA positive at delivery, this
risk increases to 4% to 7%. Higher HCV RNA levels appear to be
associated with a greater risk. HCV transmission increases to up to
20% in women co-infected with HCV and HIV. There are no prospective
studies evaluating the use of elective cesarean section for the
prevention of mother-to-infant transmission of HCV. However, avoiding
fetal scalp monitoring and prolonged labor after rupture of membranes
may reduce the risk of transmission to the infant. There are
currently no data to determine whether antiviral therapy reduces
perinatal transmission. Ribavirin and interferons are contraindicated
during pregnancy. Breastfeeding does not appear to transmit HCV.
Infants born to HCV-positive mothers should be tested for HCV
infection by HCV RNA tests on two occasions between the ages of 2 and
6 months and/or have tests for anti-HCV after 15 months of age.
Positive anti-HCV in infants prior to 15 months of age may be due to
transplacental transfer of material anti-HCV antibody."
Typically viral RNA will appear in a woman's blood within 1 to 3
weeks of exposure. Within 4 to 12 weeks, the patient will usually
have elevated serum alanine aminotransferase (ALT). It's uncommon for
patients to have symptoms during this acute phase but some will
present with malaise, weakness, anorexia, and jaundice. ALT levels
usually drop after several weeks.
The older a patient is when she contracts the infection, the more
likely it will progress into a chronic condition. Other risk factors
for chronic disease include being male or immunosuppressed, heavy
alcohol use, and the use of hepatotoxic drugs.
In the words of the NIH consensus development statement: "The
diagnosis is often suggested by abnormalities in ALT level and is
established by EIA [enzyme immunoassay] followed by confirmatory
determination of HCV RNA."1 The NIH report also states that chronic
infection is diagnosed if HCV RNA is detected in a patient's blood at
least intermittently for 6 months or more.
EIA, which measures antibodies to the virus, is suitable for
screening patients who are at risk for the infection and is
recommended as the initial test for those with clinical liver
disease. A negative EIA rules out chronic infection in an
immunocompetent patient but the test can on rare occasion be falsely
negative among patients with immune deficiencies and those on
What constitutes effective treatment?
One of the most important advances in the treatment of hepatitis
since the last NIH conference has been the use of combined
interferon/ribavirin therapy. In chronic sufferers, three large
clinical trials have shown that pegylated interferon plus ribavirin
is more effective than either standard interferon plus ribavirin or
pegylated interferon alone. Pegylated interferon (either alpha 2a or
alpha 2b) attaches polyethylene glycol to the interferon molecule,
producing a sustained effect. Such longer-acting formulations allow
clinicians to replace three injections a week with one, improving
In the three trials that used this drug combination, researchers saw
a response rate between 42% and 46% for patients with genotype 1
disease who were treated for 48 weeks. The response rate was 76% to
82% among type 2 and 3 patients. It also appears that these latter
two groups do well on a 24-week regimen that incorporates a lower
dose of ribavirin.
On the downside, however, adverse effects of interferon/ribavirin
cause about 10% to 14% of patients to stop treatment. Major reactions
include flu-like symptoms, hematologic abnormalities, and
neuropsychiatric symptoms. Severe hemolysis has also been reported in
patients with renal insufficiency and lactic acidosis in HIV-infected
Who should be treated?
The NIH consensus panel devoted a great deal of attention to this
issue. To quote the consensus statement: "Treatment is recommended
for patients who are at increased risk for progression to cirrhosis."
Those at risk have detectable HCV RNA, their liver biopsy indicates
portal or bridging fibrosis, and they have at least moderate
inflammation and necrosis. Most also have persistently elevated ALT
One of the most problematic groups, however, are patients with
chronic hepatitis C who have normal or only mildly elevated ALT
levels. While most of these patients have a histologically mild form
of the disease, some will likely progress to advanced fibrosis and
cirrhosis. Experts continue to debate whether they should be treated.
Among the factors to weigh when deciding whether to treat these
patients are how motivated they are, the viral genotype, symptoms,
the presence of hepatic fibrosis, the patient's age, and the severity
of co-existing disorders.
The NIH statement recommends periodic monitoring for those with mild
liver disease, that is, those who have persistently elevated ALT
levels but no fibrosis and minimal necroinflammatory changes.
The role of interferon and ribavirin in patients with decompensated
cirrhosis is uncertain and these patients should be referred to
clinical trials until the drugs are proven safe and effective. The
other option, of course, is liver transplantation.
The jury is still out on how to treat acute hepatitis C as well.
Since it often goes undetected, study populations have been small,
making it hard to generalize. The NIH panel sums up the situation
this way: "Although high [response rates] have been seen in small,
uncontrolled trials with interferon monotherapy, recommendations on
whether treatment is necessary, the timing of therapy, and which
regimen to use remain open."
National Institutes of Health Consensus Development Conference
Statement. Management of Hepatitis C: 2002, June 10-12, 2002. (For a
copy of the statement and supporting materials, see
Paul Cerrato. New guidelines for managing hepatitis C. Contemporary
Copyright � 2002 and published by Medical Economics Company at
Montvale, NJ 07645-1742. All rights reserved.
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