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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 ► 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. ► 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. ► 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 ► 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: ► “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 ► 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 ► 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. ► 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 ► 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. ► "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." ► "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." ► 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. ► 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 ► 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 ► 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. ► 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 ► 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. ► 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 ► 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 ► 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 ► 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. ► 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. ► According to a study published in Clinical Liver Disease, Volume 2, Issue 2, pages 72–75, April 2013; ► 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 ► 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. ► Investigators wrote; "Findings suggest that alcohol affects men and women with HCV ► 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. ► As noted; "While HCV alone showed a disproportionate effect on premature death in ► 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 ► 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. ► Table 1. Studies that stratified sustained virologic response to interferon-based therapies by sex and age Staying Healthy ► 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 ► ► ► ► ► ► ► ► ► 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 ► 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. ► 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.