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Women and Hepatitis C
Host factors such as age, alcohol and obesity influence liver disease progression in both men and
women with HCV. However, host factors that are unique to women influence both disease
progression and treatment response. The female hormone estrogen has been shown to have an
effect on SVR rates and fibrosis progression.
The effect of female gender on the course and outcomes of chronic hepatitis C remains a
controversial topic, literature into various aspects of infection, such as spontaneous clearance,
progression of fibrosis, response to interferon-based therapy favor women but vary in different
study cohorts, and have been found to be highly influenced by two female host factors; age and
menopausal status.
In this slide-set we explore all of the above, HCV transmission and gender specific host factors that
can influence disease progression using recent literature published in the Journal of Viral Hepatitis,
and Hepatology, as well as the article; “Women With Chronic Hepatitis C Virus Infection
Recommendations for Clinical Practice,” found in the July 2013 issue of Southern Medical Journal.
2014 - Women And Chronic Hepatitis C
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The U.S. Centers for Disease Control and Prevention (CDC) reports the global hepatitis C
epidemic is estimated to include 130–170 million people, in the United States an estimated 2.7–
3.9 million are living with the virus and close to half are women. Out of the 3.9 million
Americans infected more than 2 million are baby boomers, with 75 percent unaware they have
contracted the virus.
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Who Should Get Tested For HCV?
In 2012 the CDC released the recommendation that all baby boomers should be tested one
time for hepatitis C. The US Preventive Services Task Force followed suit with updated
recommendations which include hepatitis C screening among all persons born between 1945
and 1965.
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The natural history of hepatitis C remains controversial and depending on host factors can vary
between men and women. The prognosis for hepatitis C depends on fibrosis progression, some
studies indicate fibrosis progression is more rapid in men than it is in women.
Sexual Transmission Of Hepatitis C
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In heterosexual couples, the transmission of HCV from an infected partner during sex
is rare according to research published in the November 23, 2012 issue of Hepatology,
a journal published by Wiley on behalf of the American Association for the Study of
Liver Diseases (AASLD). In the study; Sexual transmission of hepatitis C virus among
monogamous heterosexual couples: The HCV partners study, researchers concluded:
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“Sexual transmission of HCV among monogamous heterosexual couples is an
extremely infrequent event. The maximum prevalence of HCV infection among sexual
partners of persons with chronic HCV infection was only 1.2%, and the maximum
incidence of HCV transmission by sex was 0.07% per year or ~1 per 190,000 sexual
contacts.”
AASLD Podcast - Drs. Stephen A. Harrison and Norah A. Terrault discuss
the article: The HCV partners study.
Click Here To Listen To Podcast
Spontaneous clearance rates tends to be higher among women than men
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A meta-analysis published in the
Journal of Viral Hepatitis 2006,
indicates spontaneous clearance rates
tend to be higher among women than
men, 40% vs 19%, and among
individuals who experience acute
hepatitis C symptoms, which is thought
to signal a more robust immune
response. Clearance, if it occurs,
usually happens within 4 to 6 months,
but may take up to 18 months, or
possibly even longer. A more recent
study published in Hepatology 2014,
reported female patients and those
with HCV genotype 1 and/or IL28B CC
genotype were about two times more
likely than men to get rid of the virus
on their own.
HCV transmission from mother to child
There are an estimated 23,000 to 46,000 children in the United States living with the
hepatitis C virus.
Overall, the risk of HCV transmission from an infected mother
to her newborn infant is only about 3 to 7 percent. The risk of transmission increases
to about 15 percent for women with both hepatitis C and HIV
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Mothers with hepatitis C are usually anti-HCV positive and frequently pass this
antibody to their offspring. However, most anti-HCV positive newborns are not
actually infected with the hepatitis C virus. The hepatitis C antibodies showing
up in the newborn’s blood are most often the mother’s antibodies that were
passed to the baby before birth. HCV antibodies gradually decline and are
usually gone when the infant is 18 months of age. Testing of a baby born to a
woman infected with hepatitis C virus should happen at 18 months of age. Up
to 40 percent of children with hepatitis C will clear the virus spontaneously
without treatment, while others may need medical treatment.
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Of Interest: Reducing Risk for Mother-to-Infant Transmission of Hepatitis C
Virus: A Systematic Review for the U.S. Preventive Services Task Force - This
review was performed as part of a larger report on HCV screening and will be
used by the U.S. Preventive Services Task Force to inform its prenatal HCV
screening recommendations.
Pregnant women with hepatitis C may pass heartier viral strain to
newborns, study suggests
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Infants who get hepatitis C from their mothers during childbirth may inherit a viral strain
that replicates more quickly than strains found in non-pregnant hosts, according to a
new study published Oct. 27 in Nature Medicine. As part of a larger study of HCV in
pregnant women and infants, researchers at Nationwide Children's followed two women
with hepatitis C over a five-year period. Both women had two children during this time,
and researchers were able to track the virus before, during and after pregnancy. Their
analysis revealed surprising changes in HCV genomes that not only allowed the virus to
thrive, but also ensured that the strain passed on by one of the women during childbirth
was particularly good at replication, says Jonathan R. Honegger, MD, an infectious
disease specialist and principal investigator in the Center for Vaccines and Immunity at
Nationwide Children's.
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"We found that better replicating versions of the virus emerged during pregnancy, and
these 'fit' viruses were passed to the babies." Dr. Honegger says. "The findings actually
provide unique insight into the impact of pregnancy on the mothers' control of viral
infections, and also a striking illustration of this virus' ability to adapt to changing
environmental pressures."
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"We don't yet know whether getting the fast-replicating, immune-susceptible version of
the virus would be an advantage for the baby or the virus," says Dr. Honegger, who also
is an assistant professor of pediatrics at The Ohio State University. "We suspect that if
the baby doesn't mount a swift and strong immune response, then fast viral replication
may increase the risk of persistent infection in the baby."
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On the other hand, viral loads in the mothers dropped more than 1,000 fold by 12 weeks
after delivery and viral genetic analysis showed that immune escape mutations had
returned. "We interpreted this to mean that T-cell activity against hepatitis C in the liver
increased sharply after delivery," Dr. Honegger says.
Breastfeeding does not transmit the hepatitis C virus
According to both the Centers for Disease Control and Prevention (CDC) and the American
Academy of Pediatrics (AAP), breastfeeding does not increase the risk for mother-to-infant
HCV transmission. According to a 2013 Systematic Review, published in Annals of Internal
Medicine, there is no association between breastfeeding and risk for HCV transmission.
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In an editorial published online in the September 2013 issue of The Journal of Infectious
Diseases, authors reported why breastfeeding is generally safe even when mothers are infected
with the hepatitis C virus; The study found that human breast milk inactivates the hepatitis C
virus infectivity by disrupting its envelope.
Reported by Reuters Health
► An Excerpt ; Using breast milk from healthy HCV-negative women, the research team found
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that even short preincubation periods of HCV in the milk brought consistent reductions of HCV
infectivity by 2 to 3 orders of magnitude.
The breast milk inactivated HCV infectivity independent of the viral genotype, and antiviral
activity was concentration dependent. Concentrations between 4% and 6% milk were sufficient
to reduce HCV infectivity, whereas higher dilutions abolished the antiviral effect.
The antiviral activity was specific to human milk. It was not found in milk from horses, cows, or
commercial infant formula.
Gender specific medicine in liver diseases:
A point of view
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Recently an article; Gender specific medicine in liver diseases: A point of view,
published in the March 2014 issue of World J Gastroenterol, examined gender
differences in chronic diseases of the liver, including viral hepatitis. The review
included the influence gender may have on the immune system, and
autoimmune diseases.
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For those interested, in an older study; Autoimmune Diseases Co-Existing with
Hepatitis C Virus Infection, information on a number of different autoimmune
manifestations related to the hepatitis C virus is available; cryoglobulinemia,
Sjögren's syndrome, autoimmune thyroid disorders, rheumatoid arthritis,
systemic lupus erythematosus, neurological disorders and autoimmune
hepatitis.
Host Factors Associated With Disease Progression
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Hepatitis C generally requires decades to progress to advanced liver disease, and is
influenced by several host factors, such as age, alcohol consumption, and gender.
As mentioned, most studies describing the progression of chronic hepatitis C
suggest women have a lower risk of cirrhosis and liver cancer compared to men.
Research indicates the reason may be the female hormone estrogen; estrogen has
been shown to have a protective effect against liver damage, but only until
menopause. Once estrogen levels decline the risk for liver cancer increases.
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According to a study published in Southern Medical Journal, available at Medscape,
some experts propose the female hormone estrogen is a factor in disease
progression, offering a protective effect on the liver. However, this effect has
previously been evaluated at time of infection and over the course of the disease,
rather than according to different reproductive stages over a woman's lifetime. For
instance, we know women who have had one or more pregnancies exhibit lower
stages of fibrosis than women who have never been pregnant. But that all changes
after menopause when the production of estrogen begins to decrease. This
supports the concept that in women the progression of fibrosis is an interrupted
process: very slow during reproductive age and accelerating rapidly after
menopause.
HCV Disease Progression In Women:
Natural History
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Researchers often reference a unique cohort of HCV patients when describing
the natural history of hepatitis C. Never has there been a more perfect
natural history study, in that, the known dates of infection were clear and
precise. This for the most part is difficult to achieve since the time of acute
HCV infection is often impossible to establish. The somewhat famous and
tragic cohort included 704 Irish women and 917 German women who were
exposed to hepatitis C from contaminated Anti-D immunoglobulin in 1977–
1978. Researchers have studied the aging population of women at 17, 20, 25
and 35 years after infection. Offering an interesting comparison of data. In
the German women, a study published in Hepatology - 2000, reported that
only four women out of over 1,000 developed cirrhosis after 20 years from
the time of infection. In the most recent study, published again in Hepatology
- January 2014, researchers reported on the overall mortality of the German
cohort, 35 years after infection. In total, 30 patients (4.2%) of the actual
study cohort died since 1979.
View The Table In Next Slide….
► Full text article; Hepatology Volume 59, Issue 1, pages 49–57, January 2014
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35 years after HCV infection:
In the group of HCV RNA-negative patients, 10 died, among them 2 who were classified
as patients without hepatitis, 7 with spontaneous recovery from HCV infection, and 1 with SVR
after treatment who died of a malignant disease other than HCC.
In the group of HCV RNA-positive patients, 20 died, among them 9 who succumbed to definite
HCV-related end-stage liver complications, such as esophageal variceal bleeding or hepatic coma.
The remaining 11 died from additional non-liver-related causes, such as cardiac failure, nonliver
malignancy, apoplectic insult, or accident.
The effects of alcohol on disease progression
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Multiple studies have shown progression of hepatitis C to advanced liver disease is
generally slow, but once again is influenced by several host factors. Three potential
contributory factors independently associated with increased rates of fibrosis include;
Age at infection (more then 40 years of age) male gender, and daily alcohol consumption
of more than 50 grams per day.
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In the U.S., one drink is usually considered to be 12 ounces of beer, 5 ounces of wine, or
1½ ounces of spirits (hard liquor such as gin or whiskey). Each delivers about 12 to 14
grams of alcohol.
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According to a study published in Clinical Liver Disease, Volume 2, Issue 2, pages 72–75,
April 2013;
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Even small doses of alcohol intake (below 30 g/day) can promote liver fibrogenesis.
Thus, it appears that there is no “safe alcohol consumption” among patients with HCV
infection. Chronic alcohol consumption in HCV-infected patients stimulates not only
fibrogenesis but also hepatocarcinogenesis. Patients with chronic HCV infection who
actively consume alcohol have a higher relative risk of hepatocellular carcinoma (HCC)
compared with abstainers (54 versus 19, respectively). This risk also appears to be dosedependent. In one study, alcohol consumption >80 g/day increased the risk for HCC
significantly by a factor of 7.3 when compared with <40 g/day. Finally, there are data
showing that alcoholics have inferior rates of response to HCV therapy. However, the
question about a possible inhibitory effect of alcohol on therapy rather than patient
noncompliance requires further research.
Women And Alcohol
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Women infected with hepatitis C who drink heavily die more than a decade earlier than
HCV-infected women who only drink moderately - or not at all, according to Chiung M.
Chen, M.A., and colleagues; Alcohol and hepatitis C mortality among males and females
in the United States: a life table analysis, published in Alcoholism: Clinical and
Experimental Research-2007.
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Investigators wrote; "Findings suggest that alcohol affects men and women with HCV
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Women with hepatitis C who were not heavy drinkers died at an average age of 61, but
women with both hepatitis C and alcoholism died at an average age of 49. Among men
with HCV, the mean age at death for heavy alcohol users was 50, compared with 55.1 for
non-heavy users.
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As noted; "While HCV alone showed a disproportionate effect on premature death in
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Primary source: Alcoholism: Clinical and Experimental Research Source reference: Chen
CM et al. "Alcohol and hepatitis C mortality among males and females in the United
States: a life table analysis." Alcohol Clin Exp Res 31(2), 2007. Article source; HeavyDrinking Women with HCV Infection Cut Decade Off Life
differently, and provides further evidence that heavy drinking contributes to HCV-related
disease progression and death."
males, heavy alcohol use presented a stronger effect in females, resulting in a 'catchingup' effect that diminished the gender difference in age of HCV death."
Treatment Response
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Overall men and women appear to equally respond to pegylated interferon and
ribavirin, although, when including age as a factor, SVR rates were much lower
in older women (postmenopausal), then in older men. Again, similar to the
protective effects of estrogen has on the progression of liver disease, higher
levels of the hormone are thought to promote SVR.
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Table 1. Studies that stratified sustained virologic response to interferon-based
therapies by sex and age
Staying Healthy
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People living with hepatitis C, regardless of gender, should avoid alcohol at
all cost and other substances that can cause liver damage. Discuss any
prescription drugs, or over-the-counter (non-prescription) medications you
may be using with your physician, as well as any herbs you are taking,
some herbal remedies can also be harmful to the liver.
Links
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Hepatitis C New Drug Research And Liver Health
Pregnancy, Childbirth, and Breastfeeding
Hepatitis C: The Basics
Women With Chronic Hepatitis C Virus Infection
Your Best Friends Guide To Hepatitis C
Blog - Lucinda Porter,,RN
Karen Hoyt: Your Best Friends Guide To Hepatitis C
HCV Advocate
Severity of Fibrosis in Women with Hepatitis C
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All Content provided on this website or through this slide-set is provided for informational purposes
only, and is not a substitute for professional medical advice, care, diagnosis or treatment, nor is it
designed to promote or endorse any medical practice, program or agenda or any medical tests, products
or procedures.
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THE CONTENT OF THIS SITE IS NOT INTENDED TO BE A SUBSTITUTE FOR PROFESSIONAL MEDICAL
ADVICE, DIAGNOSIS, OR TREATMENT. ALWAYS SEEK THE ADVICE OF YOUR DOCTOR OR OTHER
QUALIFIED HEALTHCARE PROVIDER WITH ANY QUESTIONS YOU MAY HAVE REGARDING HCV OR A
MEDICAL CONDITION THAT YOU OR THOSE YOU ARE CARING FOR MAY SUFFER FROM.