Showing posts with label HCV pregnancy. Show all posts
Showing posts with label HCV pregnancy. Show all posts

Tuesday, November 6, 2018

Over 2 Million Americans Have Hepatitis C; Affects nearly every generation

CDC Press Release
CDC Estimates Nearly 2.4 Million Americans Living with Hepatitis C
New data highlight urgent need to diagnose and cure more Americans, and to address rising infections due to U.S. opioid crisis.

Nearly 2.4 million Americans – 1 percent of the adult population – were living with hepatitis C from 2013 through 2016, according to new CDC estimates published today in the journal Hepatology.

** Link to full-text journal article provided below

Medications that cure hepatitis C offer the hope of eliminating the disease in the U.S., yet, today’s report suggests that millions are infected and have not benefited from these new treatment options. Expanded testing, treatment, and prevention services are urgently needed, especially in light of the surge in new infections linked to the opioid crisis.

Every American who has been cured of hepatitis C is living proof that ending this epidemic is possible,” said CDC Director Robert R. Redfield, M.D. “Hundreds of thousands of Americans have already been cured. In order to achieve our goal, we must commit to ensuring that everyone living with hepatitis C is tested and treated.”

To estimate total hepatitis C prevalence in the United States, researchers analyzed blood test results from the nationally representative National Health and Nutrition Examination Survey (NHANES) from 2013 through 2016. They also analyzed data from other studies of groups not surveyed in the NHANES, including active duty members of the military, and people who are incarcerated or homeless.

Opioid crisis puts new generations at risk of hepatitis C infections 
Adding to the burden of those already living with hepatitis C, separate CDC surveillance data indicate that the number of new infections each year in the United States is disturbingly high and on the rise. Acute hepatitis C cases reported to CDC more than tripled from 2010 to 2016, with most new hepatitis C infections due to increased injection drug use associated with the nation’s opioid crisis. Based on these data, CDC estimates that more than 41,000 Americans were newly infected with hepatitis C in 2016 alone.

Seeing an undiagnosable infection become a curable disease has been a public health highlight of the past 30 years. But the shadow of the opioid crisis puts our nation’s progress at risk,” said Jonathan Mermin, M.D., director of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. “Tackling hepatitis C requires diagnosing and curing people living with the virus and cutting off new infections at the source.”

Hepatitis C affects nearly every generation 
Hepatitis C now poses a serious health threat to three generations of Americans, all of whom need to be reached with prevention services, testing, and treatment:
Baby boomers (born between 1945 and 1965) account for a large portion of all chronic hepatitis C infections in the United States and currently have the highest rate of hepatitis C-related deaths. CDC recommends that all adults born between 1945 and 1965 get a one-time test for hepatitis C, but only a small fraction have done so. 

Adults under 40 have the highest rate of new infections, largely because of the opioid crisis.

Infants born to mothers with hepatitis C are a growing concern. The overall risk of an HCV-infected mother transmitting infection to her infant is approximately 4 percent to 7 percent per pregnancy. From 2011 through 2014, national laboratory data indicate that the rate of infants born to women living with hepatitis C increased by 68 percent. 

Eliminating hepatitis C requires substantial national commitment 
Even though new treatments can cure hepatitis C virus infections in as little as two to three months, far too many Americans have not been effectively treated. They may be unaware of their infection or they are unable to access medication because they lack healthcare coverage or have financial restrictions.

In addition to expanding testing and removing barriers to treatment, authors of the new report stress that intensified programs to prevent, track, and respond to new hepatitis C infections are also essential to reducing the number of infections. Prevention efforts to address new infections include support for comprehensive community-based prevention services. Such services focus on drug treatment and recovery and reducing transmission of viral hepatitis and HIV through hepatitis A and B vaccination, testing, linkage to care and treatment, and access to sterile syringes and injection equipment. 

“Until we as a nation remove the barriers to hepatitis C testing and treatment, it will continue to cost us dearly – both in terms of dollars and American lives,” said Dr. Mermin. “Every death from hepatitis C is a reminder of a promise not yet realized for far too many.” 

For more information from CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, visit

Read More From The CDC:
Hepatitis C Prevalence Estimates 2013-2016

In The Journal Hepatology
Full-Text Article
First published: 6 November 2018 - In Hepatology
Estimating Prevalence of Hepatitis C Virus Infection in the United States, 2013‐2016
Hepatitis C virus (HCV) infection is the most commonly reported bloodborne infection in the United States, causing substantial morbidity and mortality and costing billions of dollars annually. To update the estimated HCV prevalence among all adults aged ≥18 years in the United States, we analyzed 2013‐2016 data from the National Health and Nutrition Examination Survey (NHANES) to estimate the prevalence of HCV in the noninstitutionalized civilian population and used a combination of literature reviews and population size estimation approaches to estimate the HCV prevalence and population sizes for four additional populations: incarcerated people, unsheltered homeless people, active‐duty military personnel, and nursing home residents. We estimated that during 2013‐2016 1.7% (95% confidence interval [CI], 1.4‐2.0%) of all adults in the United States, approximately 4.1 (3.4‐4.9) million persons, were HCV antibody‐positive (indicating past or current infection) and that 1.0% (95% CI, 0.8‐1.1%) of all adults, approximately 2.4 (2.0‐2.8) million persons, were HCV RNA–positive (indicating current infection). This includes 3.7 million noninstitutionalized civilian adults in the United States with HCV antibodies and 2.1 million with HCV RNA and an estimated 0.38 million HCV antibody‐positive persons and 0.25 million HCV RNA–positive persons not part of the 2013‐2016 NHANES sampling frame. Conclusion: Over 2 million people in the United States had current HCV infection during 2013‐2016; compared to past estimates based on similar methodology, HCV antibody prevalence may have increased, while RNA prevalence may have decreased, likely reflecting the combination of the opioid crisis, curative treatment for HCV infection, and mortality among the HCV‐infected population; efforts on multiple fronts are needed to combat the evolving HCV epidemic, including increasing capacity for and access to HCV testing, linkage to care, and cure.
Continue to article:

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- This full-text research article was downloaded and shared today by @HenryEChang on Twitter.

In The Media
Over 2 Million Americans Have Hepatitis C; Opioids Help Drive Spread
By Amy Norton
HealthDay Reporter
TUESDAY, Nov. 6, 2018 (HealthDay News) -- More than 2 million Americans have hepatitis C -- and the opioid epidemic is a major contributor to the problem, according to a new government study.

The study, by the U.S. Centers for Disease Control and Prevention, does highlight progress against the potentially fatal liver disease. It also shows how much more work remains, CDC officials said.

Between 2013 and 2016, the agency estimated, nearly 2.4 million Americans had hepatitis C infections.

That's a small decline from previous years. And the CDC said that may indicate the effects of new therapies that have changed the face of hepatitis C treatment in the past several years.

Monday, November 5, 2018

Listen-Pregnancy guidelines: Hepatitis C testing, preferably at the start of prenatal care.

Pregnancy guidelines around vitamin D, hepatitis C testing updated
Dr. Norman Swan, the host of Health Report, along with his guest Professor Jeremy Oats, discuss the new guidelines for hepatitis C testing for pregnant women, preferably at the start of prenatal care.

Listen here....
Monday 5 November 2018 5:52PM (view full episode)
Source: Health Report

Further Information
Med J Aust 2018; 209 (9): 409-412. || doi: 10.5694/mja18.00286
Published online: 5 November 2018
Updated clinical practice guidelines on pregnancy care

HCV Guidelines - Updated to include universal screening for pregnant women
Last update: May 24, 2018
The guidelines were developed by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America.

In The Media
Infectious Disease Advisor
Universal vs Risk-Based Screening in Pregnancy: An Expert Weighs In 
Tori Rodriguez, MA, LPC 
November 06, 2018
Infectious Disease Advisor interviewed Dr Espinosa for additional insights on the topic of universal HCV screening in pregnancy.

Infectious Disease Advisor: What are some of the issues and potential benefits pertaining to universal HCV screening for pregnant women?

Dr Espinosa: Several studies have shown that risk-based screening misses many cases of infection. Several reasons account for that — for example, the screening tools are not perfect, patients do not trust the provider or just do not want to admit risks factors, and many may just not want the risk factors to be permanently part of their medical record.

These factors are not unique to hepatitis C risk factors, as we have seen it happening with other infectious diseases such as HIV. It was not until universal screening for HIV was implemented for pregnant women that the rates of perinatal transmission dramatically decreased.

Universal screening in pregnant women will destigmatize hepatitis C and increase awareness. The United States is [in the midst of] an epidemic that should be controlled, and transmission will not decrease unless several actions are taken. We will not know the true burden of the disease if we do not increase screening. 

On This Blog
Monday, October 22, 2018
Hepatitis C Virus in Women of Childbearing Age, Pregnant Women, and Children

Monday, October 22, 2018

Hepatitis C Virus in Women of Childbearing Age, Pregnant Women, and Children

Of Interest
Recent increases in hepatitis C among women of child-bearing age have led public health advocates to call for universal HCV screening in all pregnant women, regardless of reported risk factors. Read our new fact sheet for an overview of the reasons why HCV screening should be expanded. 
View and download the fact sheet here.

The American Journal of Preventive Medicine
Am J Prev Med. 2018 Nov;55(5):633-641. doi: 10.1016/j.amepre.2018.05.029.
Hepatitis C Virus in Women of Childbearing Age, Pregnant Women, and Children.
Schillie SF1, Canary L2, Koneru A2, Nelson NP2, Tanico W3, Kaufman HW4, Hariri S2, Vellozzi CJ2.
Full-text article online:
Download PDF

This study identified trends in hepatitis C virus testing and positivity in women of childbearing age, pregnant women, and children aged less than 5 years. Among women who delivered live births in 2015, hepatitis C virus–infected women were more likely to be aged 20–29 years, white, non-Hispanic, covered by Medicaid, and living in rural areas. From 2011 to 2016, hepatitis C virus testing increased by 39% among women of childbearing age, 135% in pregnant women, and 25% among children. Hepatitis C virus positivity increased by 36% among women of childbearing age, 39% in pregnant women, and 13% among children. 

Perinatal transmission is an increasingly important mode of hepatitis C virus transmission. The authors characterized U.S. births among hepatitis C virus-infected women and evaluated trends in hepatitis C virus testing and positivity in women of childbearing age, pregnant women, and children aged less than 5years.

In 2017, National Center for Health Statistics birth certificate data (48 states and District of Columbia) were analyzed to assess the number of hepatitis C virus-infected women delivering live births in 2015, and commercial laboratory data were analyzed to assess hepatitis C virus testing and positivity among women of childbearing age, pregnant women, and children aged <5years from 2011 to 2016.

In 2015, a total of 0.38% (n=14,417) of live births were delivered by hepatitis C virus-infected women. Births delivered by hepatitis C virus-infected women, compared with births overall, occurred more often in women who were aged 20-29years (60.7% vs 50.9%); white, non-Hispanic (80.2% vs 52.8%); covered by Medicaid or other government insurance (79.2% vs 43.9%); and had rural residence (26.0% vs 14.0%). From 2011 to 2016 laboratory data, among women of childbearing age, hepatitis C virus testing increased by 39%, from 6.1% to 8.4%, and positivity increased by 36%, from 4.4% to 6.0%. Among pregnant women, hepatitis C virus testing increased by 135%, from 5.7% to 13.4%, and positivity increased by 39%, from 2.6% to 3.6%. Among children, hepatitis C virus testing increased by 25%, from 0.47% to 0.59%, and positivity increased by 13%, from 3.6% to 4.0%.

The potential for perinatal hepatitis C virus transmission exists. Expanded hepatitis C virus testing guidelines may address the burden of disease in this population.

Wednesday, August 29, 2018

Perinatal Transmission of Hepatitis C Virus: Defining the Cascade of Care

Perinatal Transmission of Hepatitis C Virus: Defining the Cascade of Care
Rachel L. Epstein, MD, Vishakha Sabharwal, MBBS, Elisha M. Wachman, MD,
Kelley A. Saia, MD, Claudia Vellozzi, MD, MPH, Susan Hariri, PhD, Benjamin P. Linas, MD, MPH


Complete article shared by @HenryEChang via twitter

The US National Viral Hepatitis Action Plan calls for major efforts to expand hepatitis C virus (HCV) diagnosis and treatment; prenatal care settings are potential venues for expanding HCV testing. We aimed to characterize the HCV diagnostic cascade for women and infants and investigate factors associated with linkage and follow-up.

Study design
We used electronic health records for a 10-year cohort of 879 women with opioid use disorder from an obstetric clinic serving women with substance use disorders.

Altogether, 744 women (85%) were screened for HCV; 510 (68%) were seropositive, of whom 369 (72%) had nucleic acid testing performed and of these 261 (71%) were viremic. Of 404 infants born to HCV-seropositive women, 273 (68%) were tested at least once for HCV, 180 (45%) completed the American Academy of Pediatrics-recommended perinatal HCV screening, and 5 (2.8%) were diagnosed with HCV infection and linked to care. More recent delivery date (2014-2015) was associated with maternal linkage to care (aOR, 2.5; 95% CI, 1.4-4.7). Maternal coinfection with HIV (aOR, 9.0; 95% CI, 1.1-72.8) and methadone maintenance therapy, compared with buprenorphine (aOR, 1.5; 95% CI, 0.9-2.5), were associated with higher rates of infant HCV testing.

HCV prevalence among pregnant women with opioid use is high and infant HCV screening is imperfect. Programmatic changes to improve both mother and infant follow-up may help to bridge identified gaps in the cascade to cure.

Thursday, July 26, 2018

HCV antiviral drugs during pregnancy?

Perspective > Medscape Gastroenterology > DDW 2018

Antiviral Therapy for HCV During Pregnancy to Prevent Transmission: 6 Reasons in Favor of a Controversial Concept
July 23, 2018
Nancy Reau 
During this year's Digestive Disease Week in Washington, DC, I was asked to present an argument in favor of the controversial concept of giving antiviral therapy to pregnant patients with HCV to disrupt mother-to-child transmission (MTCT). I must clearly state that this concept is neither evidence-based nor is it recommended by any of the current treatment guidelines. Universally, national and societal guidelines, as well as experts and patient advocates, recommend viral eradication of HCV prior to conception—not during pregnancy. There are, however, several reasons that support the use of HCV antiviral drugs during pregnancy
Read the article:
HCV: 6 Reasons in Favor of Antiviral Therapy During Pregnancy 
Dr Nancy Reau discusses factors that could potentially support the use of antiviral therapy during pregnancy to prevent mother-to-child transmission of hepatitis C virus infection.
Medscape Gastroenterology, July 23, 2018 
Free registration may be required.

Saturday, March 10, 2018

HCV in Pregnant Women on Rise Increased risk of HCV infected infants

AGA Reading Room 03.08.2018
HCV in Pregnant Women on Rise Increased risk of HCV infected infants
by Pippa Wysong
Contributing Writer, MedPage Today

An estimated 1% to 2.5% of pregnant women in the United States are infected with hepatitis C virus (HCV), which translates to about 4,000 new cases yearly. This also comes packaged with about a 6% risk of mother-to-infant transmission.

Worrisomely, the rates are increasing, with various studies adding to the discussion about screening for at-risk pregnant women and related to managing and treating them.

According to Raymond Chung, MD, director of Hepatology and the Liver Center at Massachusetts General Hospital in Boston and a recent co-Chair of the American Association for the Study of Liver Diseases-Infectious Diseases Society of America HCV Guidance Panel, screening with an HCV antibody assay is recommended for pregnant women with known or suspected risk factors for HCV infection.

"Confirmatory HCV RNA testing is recommended for women with a positive screening test," he told MedPage Today.

Continue reading @ MedPage Today

On This Blog

Monday, February 26, 2018

Podcast: What happens when a pregnant woman has hepatitis C

Host: Amber Smith

What happens when a pregnant woman has hepatitis C
Rates of hepatitis C infections are on the rise among adults in the United States, and some of those adults are pregnant women. Helene Bernstein, MD, PhD, explains how the disease can easily be diagnosed through a blood test and treated with medication. (Click here for a paper she published on this topic.) She’s an associate professor of obstetrics and gynecology and of microbiology and immunology at Upstate.

Listen here:
Podcast: Play in new window | Download
Thursday, February 22nd, 2018
Upstate University Hospital

Friday, December 22, 2017

Blog Updates & Reports: Chronic Illness and Expectations - Hepatitis B Experimental Treatments - Treatment for acute HCV infection

2017 December: Blog Updates & Reports
For your reading pleasure, check out a few blog updates and reports released this week on the topic of viral hepatitis.

Blog Updates
A number of modeling experts the agency works with are predicting that this year’s flu season will peak around the end of this month, Dr. Daniel Jernigan, head of the agency’s influenza division, told STAT. That means lots of people will be sick over the holidays; lots already are. And the multi-generational family gatherings that are part and parcel of the holidays will fuel the spread of the nasty virus.

It’s Flu Season! Did you get your shot?
Flu season is upon us! It usually ranges from the winter into early spring. It’s important that you get your flu shot, especially if you or a family member has a chronic disease such as hepatitis B.

The Latest Issue: Weekly Bull
Did you know that there are now 8 genotypes and 84 subtypes of HCV, all of which respond to Vosevi? Also in the news, Telemedicine, transplanting infected livers, and treating seniors.

INHSU 2017 Recap
At the International Symposium on Hepatitis Care in Substance Users held in New Jersey in September 2017, Dr. Jason Grebely provided an excellent debrief summarizing the main themes of the conference which we will try to summarize in this blog post.

Top 10 HIV and hepatitis C stories of 2017
Negotiations with Canada’s provincial and territorial governments this year brought down the price of new and effective hepatitis C drugs, making it possible to end the practice of “rationing” treatment to those with severe liver damage.

2017 Top Hepatitis Treatment Stories
Hepatitis treatment news stories with the most views this year over at Hep blogs.

Investment in hep C treatment programs needed to support elimination goal
Hepatitis Australia is urging government to invest in programs designed to increase the uptake of PBS-listed direct acting antivirals that cure hepatitis C.

Another Inspiring Story from Texas
By Greg Jefferys
Every story is precious and every person feels such relief and joy at having cleared this wicked disease.

Hepatitis C Treatment: What does it really cost?
By Greg Jefferys
I received a press release from MSF saying they had access to Hepatitis C treatment for the price of US$120 for a 12 week treatment.

How Hepatitis C Damages Your Health
By Greg Jefferys
A closer look at how HCV damages the body.

What I Don’t Want for Christmas: Hepatitis A
By Lucinda K. Porter, RN
Hepatitis A outbreaks are occurring all over the world, including in the United States. However, hepatitis A can be easily prevented.

Weekly Special: Harm Reduction – Alcohol
Alcohol is one of the most addictive and destructive substances. Our fact sheet discusses how to apply harm reduction strategies to alcohol use.

Celebrating the Holidays with Hepatitis B
The holidays are a joyous time as family and friends gather for parties, dinners and get-togethers. However, they can also be a difficult, stressful time on so many levels, and especially for those who might not yet have disclosed their hepatitis B to loved ones

Facing Changes During the Holidays
By Karen Hoyt - December 21, 2017
With each season of life, there are bound to be changes. Some of them are felt more during the holidays. When we’re weighed down with health decisions from a sick liver, we...

By Carleen McGuffey - December 20, 2017
When I first found out I had hepatitis C I only told James, my husband of 20 years. He has been and currently is an excellent support, caretaker, strength, and provider throughout...

By Kimberly Morgan Bossley - December 19, 2017
My Grateful Heart A grateful heart does not mean it comes from a perfect life, great health, or monitory riches. A grateful heart is one that has fought through the pits of...

Preventing overdose deaths is not one-size-fits-all
December 22, 2017,
Scott Weiner, MD, Contributor
By now, we all know that the number of opioid-related deaths in the United States has reached epidemic proportions. Despite the Centers for Disease Control and Prevention declaring an epidemic in 2011, the death rate has continued to increase every year, with more than 30,000 deaths per year now attributed to opioids.

Related: Opioid crisis trims U.S. life expectancy, boosts hepatitis C: CDC

Boston-area paramedics on front lines of U.S. opioid crisis
The paramedics find them everywhere - slumped over car steering wheels, barely breathing in doughnut shop bathrooms or dead in derelict apartments and expensive mansions.

The Weekly Special is our Harm Reduction Fact Sheet – Opioids. Learn about opioids–the effects they have on the body, the side effects and why they are addictive.

Answer these 5 questions to help make your New Year’s resolutions stick
Marcelo Campos, MD
t’s that time of the year again when we start thinking about the (in)famous New Year’s resolutions. Change can be a frustrating experience for many. So, I decided to investigate what may increase your chances of success.

When to get tested for hepatitis C after exposure
Learn what the window period is for hepatitis C infection, and when someone should consider testing. We look at available tests and when symptoms appear.

A healthy liver is crucial for maintaining a person's overall health, but expensive cleanses or diets are just not necessary. In some cases, they may even be dangerous. A healthy lifestyle, balanced diet, and regular consultations with a doctor are far more valuable to the health of the liver than any fad diet or cleanse. Liver cleanses offer no proven benefits. To protect liver health, people can adopt a more comprehensive, long-term health strategy.

In The Journals
Hepatitis C virus (HCV) mainly replicates in the cytoplasm, where it easily establishes persistent infection, resulting in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Due to its high rate of mutation, HCV forms viral quasispecies, categorized based on the highly variable regions in the envelope protein and nonstructural 5A protein. HCV possesses seven major genotypes, among which genotype 1 is the most prevalent globally. The distribution of HCV genotypes varies based on geography, and each genotype has a different sensitivity to interferon treatment. Recently-developed direct-acting antivirals (DAAs), which target viral proteases or polymerases, mediate drastically better antiviral effects than previous therapeutics. Although treatment with DAAs has led to the development of drug-resistant HCV mutants, the most recently approved DAAs show improved pan-genomic activity, with a higher barrier to viral resistance.
View Full-Text

SVR Reduced HCC by 71%
from Jules: there never was any doubt that SVR would reduce or eliminate risk for HCC. In this study cirrhosis prior to treatment had a higher HCC risk then for those without cirrhosis, but that is to be expected and merely reinforces how crucial it is to treat HCV as early as possible...
Full Text

Diagnosing Liver Fibrosis and Cirrhosis: Serum, Imaging, or Tissue?
When assessing a patient with chronic liver disease, one of the foremost questions in a clinician’s mind is the stage of fibrosis. The degree of fibrosis predicts risk of complications and guides management, including hepatocellular carcinoma and variceal surveillance. Traditionally, the liver biopsy has staged fibrosis. Recently, several serum tests and imaging modalities have become available to assess fibrosis noninvasively. Clinicians now have options to consider for fibrosis assessment.
Full Text

For Your Viewing Pleasure
A critical review of endpoints for non-cirrhotic NASH therapeutic trials 
Prof. Vlad Ratziu discusses his article "A critical review of endpoints for non-cirrhotic NASH therapeutic trials" for the upcoming NAFLD special issue of the Journal of Hepatology

Webinar - Hepatitis C Among Pregnant Women
This webinar is now archived.
Click here for the slides. Click here for the recording.
(Click the link and then enter name and email address to view the webinar).


December 2017 infohep bulletin
Latest treatment news and information for patient advocates and people working in hepatitis in Europe.

Hepatitis C Coalition 
Hepatitis C Coalition new report on the Operational Delivery Networks
How Hepatitis Services are delivered
Relevant policies
Project process and topics discussed
List of ODN visits
Overview of findings
Run rates
Finances and CQUIN
Delivering the clinical service and MDTs
Data and sharing of information with NHS England
Prisons and outreach
Diagnosis and referral
Future of the ODNs 
Begin here....

Wishing you all a Very Merry Christmas!

Monday, November 4, 2013

AASLD- Risk-based screening misses hepatitis C in many pregnant women

Risk-based screening misses hepatitis C in many pregnant women

By: DENISE FULTON, Internal Medicine News Digital Network

WASHINGTON – Programs to screen pregnant women for hepatitis C infection could go far to reduce a host of adverse outcomes, according to an analysis of a large national sample.

"Targeted HCV screening may overlook many pregnant women with chronic HCV infections, and that may contribute to the underdiagnosis of pediatric hepatitis C in the United States," study investigator Dr. Po-Hung Chen said at the annual meeting of the American Association for the Study of Liver Diseases.

"Chronic hepatitis C is associated with adverse maternal/fetal consequences. In light of these findings, there seems to be a need to further evaluate universal hepatitis C screening as a part of antepartum care," he added.

Dr. Chen of the division of gastroenterology at Johns Hopkins University, Baltimore, and colleagues collected data on all births and spontaneous abortions recorded in the National Inpatient Sample between 2003 and 2010.

More than 28,000 of the 32 million deliveries or miscarriages recorded in the National Inpatient Sample were to mothers infected with HCV, he reported.

Of HCV-positive mothers, 72% had no traditional risk factors for the disease.

HCV-positive mothers were significantly more likely to experience obstetric pulmonary embolism (adjusted OR, 3.05), thyroid dysfunction (aOR, 1.37), and maternal death (aOR, 2.49). They also were significantly more likely to be white, less affluent, on Medicaid, substance abusers, and have more comorbidities.

Women who were HCV positive were significantly more likely to have labor before 37 weeks’ gestation (aOR, 1.36), antepartum hemorrhage (aOR, 1.44), and poor fetal growth (aOR, 1.61).

Cost of care and length of stay were significantly greater for mothers who were HCV positive, Dr. Chen said.

Previous analysis using data from the National Health and Nutrition Examination Survey (NHANES) showed that the prevalence of hepatitis C virus infection in women aged 20-39 years was 1%-1.6% in the period between 1999 and 2002. Dr. Chen noted that this could be an underestimation because NHANES is based on home health surveys and therefore does not include prison populations and homeless women, who are at high risk for HCV infection.

Currently, no definitive guidelines exist on how to manage chronic HCV in pregnant women, likely because of a dearth of suitable proven management options, Dr. Chen said, adding that ribavirin is contraindicated in pregnancy, interferon is generally not recommended, and the currently approved protease inhibitors are not options for single-drug management.

The American College of Obstetricians and Gynecologists does not recommend routine prenatal screening for HCV; instead, the college recommends screening only in women who are at high risk based on Centers for Disease Control and Prevention criteria.

Dr. Chen did not report financial conflicts of interest.

Monday, October 28, 2013

Hepatitis C - Pregnant women may pass heartier viral strain to newborns

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. The findings, from a team in The Research Institute at Nationwide Children's Hospital, are the first to describe how a virus that has infected 180 million people worldwide takes advantage of immune changes during pregnancy.

About 1 percent of all pregnant women worldwide have hepatitis C, caused by a highly adaptable virus known as HCV that infects liver cells. In 3 to 5 percent of these pregnancies, the virus is passed to the newborns, accounting for the majority of new childhood HCV infections. Between 15 and 45 percent of people infected with HCV are able to mount an immune response sufficient to eradicate the virus. But in most cases, the virus eludes immunity, leading to a chronic infection that increases the risk of liver failure or liver cancer.

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."

HCV persists in the general population, in part, because the virus outwits the immune system with mutations that can render it undetectable to CD8+ T-cells, important weapons in the body's antiviral immune arsenal. Although these viral variations—called immune escape mutations—protect the virus from attack by T-cells, they sometimes slow the virus replication machinery.

During pregnancy, T-cells are restrained to prevent the body from attacking the fetus as foreign tissue. Viral levels of HCV have also been known to increase during pregnancy, but whether this was related to changes in T-cell function was unknown. Working closely with Chris Walker, director of the Center for Vaccines and Immunity, and colleagues at Emory University and the University of North Carolina, Dr. Honegger found that during pregnancy, certain T-cell escape mutations were lost, resulting in a virus that could replicate far more quickly.

"This surprised us because the virus' immune escape mutations are usually stable in a patient," Dr. Honegger says. "The loss of these immune escape mutations from HCV during pregnancy provided strong evidence that the immune changes of pregnancy, intended to protect the fetus, significantly impaired the ability of CD8+ T-cells to exert pressure on the virus."

Loss of the escape mutations also meant that the babies got a version of the virus that was optimized for viral replication, Dr. Honegger adds. In the children they studied, the virus persisted and did not mutate in a way to suggest that it was under significant attack by their CD8+ T-cells.

"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.

Researchers now are following a larger group of pregnant women with HCV, hoping to learn more about how viral mutations affect the way the body controls hepatitis C in pregnant women and infants.

"We believe that better understanding of the natural history of the infection in these patients will be critical for designing rational strategies to treat or prevent HCV in these populations."


Full citation: Honegger JR, Kim S, Price AA, Kohout JA, McKnight KL, Prasad MR, Lemon SM, Grakoui A, Walker CM. Loss of Immune Escape Mutations During Persistent HCV Infection in Pregnancy Enhances Replication of Vertically Transmitted Viruses. Nature Medicine. 2013 Oct 27. doi: 10.1038/nm.3351 [Epub ahead of print]

Funding: This work was supported by the US National Institutes of Health (R37-AI47367 to C.W, R56-AI096882 and R01-AI096882 to C.W and J.H., RO1-DA024565 and R01-AI95690 to S.L., R01-AI070101 and R01-DK083356 to A.G., T32-HD043003 and K12-HD043372 to J.H., and the Yerkes Research Center Base Grant P51RR-000165 (A.G.)), The Research Institute at Nationwide Children's Hospital (C.W. and J.H.), and the University of North Carolina University Cancer Research Fund (S.L.).

Nationwide Children's Hospital
2013 Oct 27. doi: 10.1038/nm.3351. [Epub ahead of print]
Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses.
1] The Center for Vaccines and Immunity, Nationwide Children's Hospital, Columbus, Ohio, USA. [2] Department of Pediatrics, The Ohio State University School of Medicine, Columbus, Ohio, USA.

Globally, about 1% of pregnant women are persistently infected with the hepatitis C virus (HCV). Mother-to-child transmission of HCV occurs in 3-5% of pregnancies and accounts for most new childhood infections. HCV-specific CD8+ cytotoxic T lymphocytes (CTLs) are vital in the clearance of acute HCV infections, but in the 60-80% of infections that persist, these cells become functionally exhausted or select for mutant viruses that escape T cell recognition. Increased HCV replication during pregnancy suggests that maternofetal immune tolerance mechanisms may further impair HCV-specific CTLs, limiting their selective pressure on persistent viruses. To assess this possibility, we characterized circulating viral quasispecies during and after consecutive pregnancies in two women. This revealed a loss of some escape mutations in HLA class I epitopes during pregnancy that was associated with emergence of more fit viruses. CTL selective pressure was reimposed after childbirth, at which point escape mutations in these epitopes again predominated in the quasispecies and viral load dropped sharply. Importantly, the viruses transmitted perinatally were those with enhanced fitness due to reversion of escape mutations. Our findings indicate that the immunoregulatory changes of pregnancy reduce CTL selective pressure on HCV class I epitopes, thereby facilitating vertical transmission of viruses with optimized replicative fitness.

Thursday, October 10, 2013

Human breast milk inactivates hepatitis C virus infectivity

Human breast milk inactivates hepatitis C virus infectivity

Wednesday Oct 09, 2013 | Reuters


Last Updated: 2013-10-09 12:35:30 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - A new study shows why breastfeeding is generally safe even when mothers are infected with the hepatitis C virus (HCV).

The reason is that human breast milk inactivates hepatitis C virus (HCV) infectivity by disrupting its envelope, researchers from Germany have found.

"This study provides a novel mechanism for the protective properties of human mother's milk against HCV," Dr. Eike Steinmann from the TWINCORE Center for Experimental and Clinical Infection Research in Hannover told Reuters Health by email. "A new finding is that lipases in human milk generate free fatty acids that damage the viral envelope and render them non-infectious."

In an editorial published with the paper online September 24 in The Journal of Infectious Diseases, Dr. Ravi Jhaveri from the University of North Carolina in Chapel Hill says "the results provide a plausible explanation for why breastfeeding is not a risk factor for HCV transmission. This is reassuring for us as practitioners when we counsel our HCV patients that it is safe for them to breastfeed."

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.

The anti-viral activity was not destroyed by heat treatment, the authors reported.

In a series of experiments, the researchers showed that lipases in human milk generated fatty acids that disrupted the viral envelope, resulting in the loss of viral infectivity.

"Similar processes concerning the release of free fatty acids take place upon digestion of human breast milk by the infant," the investigators note. "Therefore, milk digestion products, like free fatty acids, released in the stomach might be able to inactivate residual viral particles which otherwise could be transmitted upon breastfeeding."

Human breast milk also had significant antiviral effects against other enveloped viruses (influenza, herpes simplex, and vesicular stomatitis virus) but no pronounced effect on non-enveloped viruses (murine norovirus, rotavirus).

"As there are far more enveloped viruses known than tested in this study, further investigations are necessary," Dr. Steinmann said.

"Human breast milk efficiently inactivates HCV in vitro and neither the Centers for Disease Control nor the American Association for the Study of Liver Diseases argues against breastfeeding from HCV infected women unless they have cracked or bleeding nipples," Dr. Steinmann concluded.

Dr. Jhaveri's editorial concludes, "After reading this article, when we clinicians next encounter an HCV infected patient that just delivered a healthy infant and wants to breastfeed, we have yet another reason to say 'Breast is Best.'"


J Infect Dis 2013.

Copyright © 2013 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.

Monday, January 14, 2013

Reducing Risk for Mother-to-Infant Transmission of Hepatitis C Virus: A Systematic Review for the U.S. Preventive Services Task Force

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Reducing Risk for Mother-to-Infant Transmission of Hepatitis C Virus: A Systematic Review for the U.S. Preventive Services Task Force

Erika Barth Cottrell, PhD, MPP; Roger Chou, MD; Ngoc Wasson, MPH; Basmah Rahman, MPH; and Jeanne-Marie Guise, MD, MPH

[+] Article and Author Information

Background: Mother-to-infant transmission is the leading cause of childhood hepatitis C virus (HCV) infection, with up to 4000 new cases each year in the United States.

Purpose: To evaluate effects of mode of delivery, labor management strategies, and breastfeeding practices on risk for mother-to-infant transmission of HCV.

Data Sources: MEDLINE (1947 to May 2012), the Cochrane Library Database, clinical trial registries, and reference lists.

Study Selection: Randomized trials and observational studies on mode of delivery, labor management strategies, and breastfeeding practices and risk for mother-to-infant transmission of HCV.

Data Extraction: Investigators abstracted and reviewed study details and quality using predefined criteria.

Data Synthesis: Eighteen observational studies evaluated the association between mode of delivery, labor management strategies, or breastfeeding practices and risk for mother-to-infant HCV transmission. Fourteen studies (2 good-quality, 4 fair-quality, and 8 poor-quality studies) found no clear association between mode of delivery (vaginal versus cesarean delivery) and risk for transmission. Two studies (1 good-quality and 1 poor-quality study) reported an association between prolonged duration of ruptured membranes and increased risk for transmission. Fourteen studies (2 good-quality, 2 fair-quality, and 10 poor-quality studies) found no association between breastfeeding and risk for transmission.

Limitations: Only English-language articles were included. Studies were observational, and most had important methodological shortcomings, including failure to adjust for potential confounders and small sample sizes.

Conclusion: No intervention has been clearly demonstrated to reduce the risk for mother-to-infant HCV transmission. Avoidance of breastfeeding does not seem to be indicated for reducing transmission risk.

Primary Funding Source: Agency for Healthcare Research and Quality.

An estimated 40 000 children are born to hepatitis C virus (HCV)–positive women each year (1). Mother-to-infant (vertical) transmission is the main route of childhood HCV infection (2). Estimates for the rate of vertical transmission range from 3% to 10% (2 - 5). Risk for transmission is highest among women with a high viral load at delivery (2 - 6) and those co-infected with HIV (5,7). Although antiviral therapies are contraindicated in pregnancy because of teratogenic risks, prenatal HCV screening to identify HCV-infected women unaware of their status might lead to other interventions during labor and delivery or in the perinatal period that reduce risk for mother-to-infant transmission (8).

The purpose of this review was to synthesize the evidence on the effects of mode of delivery, labor management strategies, and breastfeeding practices on risk for mother-to-infant transmission. This review was performed as part of a larger report on HCV screening (9) and will be used by the U.S. Preventive Services Task Force (USPSTF) to inform its prenatal HCV screening recommendations.

Discussion Only
Full Text Available @ Annals Of Internal Medicine

Vertical transmission is the leading cause of childhood HCV infection, and identification of effective management strategies to reduce risk for transmission is an important clinical and public health concern. However, the primary finding of this review as summarized in the Table is that no perinatal management strategy has clearly been shown to reduce risk for HCV transmission. Observational studies consistently found no evidence of an association between breastfeeding and risk for vertical transmission, consistent with data suggesting that transmission typically occurs in utero (23,33). Evidence on the effects of labor management strategies and mode of delivery on risk for transmission was somewhat conflicting. Two studies (5,24) reported increased risk for HCV transmission with more prolonged duration of ruptured membranes, similar to findings for other infectious agents transmitted vertically (such as group B streptococcus and HIV). However, other studies did not find vaginal delivery associated with increased risk for vertical transmission versus cesarean delivery, and the largest single study (15) reported a non–statistically significant trend toward decreased risk, even though vaginal delivery is associated with longer duration of ruptured membranes. Possible explanations for the failure to find an association between vaginal delivery and increased risk for transmission could include threshold or modifying effects related to the duration of rupture, viral load, or other factors. Cohort studies that focus on women with longer rupture of membranes or high viral load and perform statistical adjustment on other potential confounding factors could help clarify the effects of mode of delivery on transmission risk. Randomized trials are less susceptible to confounding but would involve potential challenges related to the acceptability of randomly assigning HCV-infected women to elective cesarean delivery versus planned vaginal birth....

Full Text Available @ Annals Of Internal Medicine

Friday, August 26, 2011

Maternal hepatitis B and hepatitis C carrier status influences perinatal outcomes

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Maternal hepatitis B and hepatitis C carrier status influences perinatal outcomes

A study in the latest issue of Liver International investigates the influence of maternal hepatitis B and hepatitis C carrier status on perinatal outcomes.

Dr Laura Connell and colleagues from Florida, USA examined the association between maternal hepatitis B and C mono- and co-infections with singleton pregnancy outcomes in the state of Florida.

The research team analyzed all Florida births from 1998 to 2007 using birth certificate records linked to hospital discharge data.

The team's main outcomes of interest were selected pregnancy outcomes including preterm birth, low birth weight, small for gestational age, fetal distress, neonatal jaundice and congenital anomaly.

Women with Hep B were less likely to have infants born small gestational age
Liver International

The study sample consisted of 1,670,369 records. Human immunodeficiency virus co-infection and all forms of substance abuse were more frequent in mothers with hepatitis B and C infection.
The research team found that important socio-demographical variables and obstetric complications, women with hepatitis C infection were more likely to have infants born preterm, with low birth weight and congenital anomaly.
In addition, women with hepatitis B infection were less likely to have infants born small gestational age.

Dr Connell's team concluded, "Our findings provide further understanding of the association between maternal hepatitis B or C carrier status and perinatal outcomes."
"Infants born to women with hepatitis C infection appear to be at risk for poor birth outcomes, including preterm birth, low birth weight and congenital anomaly."

Liver Int 2011: 31(8): 1163–1170
29 August 2011

Monday, July 25, 2011

Women with hepatitis have an increased risk for complications during pregnancy

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Women with hepatitis have an increased risk for complications during pregnancy

The latest issue of the Journal of Viral Hepatitis examines pregnancy outcomes associated with viral hepatitis.

Dr Keisha Reddick and colleagues from North Carolina, USA examined the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to pregnancy-related complications including gestational diabetes mellitus, preterm birth, intrauterine growth restriction, pre-eclampsia, antepartum hemorrhage and cholestasis.

The Nationwide Inpatient Sample was queried for all pregnancy-related discharges, pregnancy complications and viral hepatitis from 1995 to 2005.

The research team used logistic regression to examine the association between HBV, HCV, HBV + HCV and pregnancy-related complications including gestational diabetes mellitus, preterm birth, intrauterine growth restriction, pre-eclampsia, antepartum hemorrhage, cholestasis and cesarean delivery.

Model covariates included maternal age, race, insurance status, substance use and medical complications including liver complication, hypertension, HIV, anaemia, thrombocytopenia and sexually transmitted infections.
Of 297,664 pregnant women data available for analysis, 1446 had a coded diagnosis of HBV, HCV or both. High-risk behaviors, such as smoking, alcohol and substance use were higher in women with either HBV or HCV.

The researchers found that women with HBV had an increased risk for pre-term birth but a decreased risk for caesarean delivery.

The team observed that individuals with HCV had an increased risk for gestational diabetes mellitus.

Individuals with both HBV and HCV co-infection had an increased risk for antepartum hemorrhage.

The research team found no association of viral hepatitis with intrauterine growth restriction or pre-eclampsia.

Dr Reddick's team commented, "Women with hepatitis have an increased risk for complications during pregnancy."

"Research to determine the efficacy and cost-effectiveness of counselling patients about potential risks for adverse outcomes is warranted."

J Viral Hep 2011: 18(7): e394–e398
25 July 2011

Thursday, May 26, 2011

Hepatitis C Virus Infection During Pregnancy and the Newborn Period

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M. Arshad; S. S. El-Kamary; R. Jhaveri

From Journal of Viral Hepatitis

Hepatitis C Virus Infection During Pregnancy and the Newborn Period
Are They Opportunities for Treatment?

Posted: 05/26/2011; J Viral Hepat. 2011;18(4):229-236. © 2011 Blackwell Publishing

The worldwide prevalence of hepatitis C virus (HCV) infection in pregnant women is estimated to be between 1 and 8% and in children between 0.05% and 5%. While parenteral transmission is still common in children living in developing countries, perinatal transmission is now the leading cause of HCV transmission in developed countries. The absence of an HCV vaccine or approved therapy during pregnancy means that prevention of vertical transmission is still not possible. However, a low vertical transmission rate of 3–5%, a high rate of spontaneous clearance (25–50%) and delayed morbidity have resulted in HCV being overlooked in pregnant women and their infants. Yet a study of the natural history in mothers and children demonstrates that the prognosis of HCV can vary greatly and should be taken seriously. Factors known to increase the risk of perinatal transmission include HIV coinfection and higher maternal viral loads, while elective C-section and withholding breastfeeding have not been demonstrated to reduce vertical transmission. Current guidelines for the diagnosis of persistent perinatal infection require a positive anti-HCV test in infants born to infected mothers after 12 months or two positive HCV RNA tests at least 6 months apart. Current HCV treatment options using pegylated interferon and ribavirin are both unsuitable for use in pregnancy and infancy. However, new agents currently in preclinical phases of development, along with the recently identified association between single-nucleotide polymorphisms within the IL28 gene and treatment response, may serve to create a therapeutic window for these patients.

It is well known that hepatitis C virus (HCV) chronic infection is a major cause of liver disease among adults worldwide[1] and is the leading indication for adult liver transplantation in the United States.[2] There are over 170 million people infected with the virus worldwide, and only half of patients treated with the current standard therapies achieve a sustained viral response.[3] Among the groups less often discussed when considering the burden of HCV infection are pregnant women and their infants. Much remains unknown about the dynamics of chronic HCV infection during and after pregnancy, as well as in the neonatal period. It is clear, however, that chronic HCV infection does have a modified course during these times of tremendous physiological changes. This review will summarize what is known about HCV infection during pregnancy and infancy and offer some perspectives on possible treatment opportunities that may arise during these times as new therapies for HCV become available

Worldwide, the seroprevalance of HCV in pregnant women is thought to be anywhere from 0.15% to 2.4% in the United States and European countries and much higher in countries like Egypt where it is estimated to be as high as 8.6%.[4–8]
The prevalence of HCV infection in children ranges from 0.05% to 0.36% in studies carried out in the United States and Europe[9–11] and is much higher in developing countries where it can range from 1.8% to 5%.[12,13] Insufficient screening of transfused blood and blood products and parenteral exposure continue to be the major causes of HCV transmission in developing countries.[14] In the United States and other developed countries, vertical transmission is the major route of HCV infection. In the United States, an estimated 240 000 children have antibodies to HCV, with seroprevalences of 0.1–0.2%.[11,15,16] A tenfold higher seroprevalence of 2% was reported in incarcerated juveniles, and rates of 10–20% have been reported among children with a variety of other potential exposures such as malignancy, haemodialysis, extracorporeal membrane oxygenation or surgery for congenital heart disease.[17–19] Almost all children who remain viremic after several years have chronic hepatitis,[20] and decompensated HCV-associated cirrhosis in children as young as 4 years has been reported.[21] Given that most perinatal HCV infections are silent with long-term complications that present later in adulthood, it is a considerably underestimated childhood disease with a predicted significant economic and health burden on society. At the current rate of HCV infection in children, it is estimated that in the next decade, 26 million dollars will be spent in screening, 117–206 million dollars in monitoring and 56–104 millions dollars in treatment. The total cost was calculated to be between 199 and 335 million.[22]

Natural History of HCV in Pregnancy
The intensity of HCV infection varies during pregnancy as demonstrated by the varying level of viral loads and HCV-specific T-cell responses that correspond with the progression of pregnancy. Some studies have shown that there is a decrease in serum alanine transferase levels (ALT) in the 2nd and 3rd trimesters of pregnancy,[23,24] along with a corresponding increase in HCV RNA during these trimesters. It is hypothesized that this may be seen because of a relative suppression of immunity as pregnancy proceeds. Oestrogen has shown to suppress intrathymic T-cell differentiation while activating the extrathymic pathways,[25] a phenomenon that has also been noted during pregnancy.[26] The modulation of cytokines as a result of this is important in maintaining tolerance of the paternal antigens in the foetus. This may also increase the proliferation of HCV resulting in higher HCV RNA titres in the 2nd and 3rd trimesters. The seemingly paradoxical decrease in liver enzymes and hepatic inflammation is explained by the decrease in immune-mediated hepatocellular destruction seen in chronic HCV.[23]
Conversely, HCV RNA titres tend to decrease in the postpartum period.[27,28] A study from Japan on 22 pregnant HCV RNA-positive women noted that some women may have spontaneous resolution of viremia following parturition.[28] They also noted significantly greater rates of clearance compared to the nonpregnant control group. In addition, the HCV core protein levels at 3 months postpartum were much lower among patients who cleared their viremia versus those who had persistent HCV elevation. It is thought that the loss of physiological pregnancy-induced immunosuppression after birth leads to a surge in maternal cellular immune activation that results in viral clearance.[27,29] Interestingly, pregnancy is associated with a decrease in Th-1 activity and a corresponding increase in Th-2 activity leading to a greater humoral immunity.[30] One advantage of the weakened Th-1 responses is the reduction in the number of viral quasispecies that usually develop by the rapidly mutating HCV to escape host immunity.[31] The postpartum reversal of this phenomenon with a decrease in Th-2 activity and a surge in Th-1 postpartum, combined with fewer viral quasispecies, may explain the increased ability of some mothers to clear persistent viremia. Some authors have also recommended that this may be an optimal time to initiate antiviral treatment, which can augment the natural defence mechanism.
Recent studies have confirmed that a tremendous surge in HCV-specific T cells in the third trimester and postpartum period is accompanied by a corresponding drop in HCV RNA. Honegger et al. demonstrated that in nine chronically infected women, a 1.4 log drop in HCV RNA titres occurred when the HCV-specific interferon-γ responses increased by more than 100% as measured by ELISpot. Depletion studies confirmed that this surge consisted of both CD4+ and CD8+ T cells, indicating a broad and potent response.[32]
Risks of obstetrical complications in HCV-infected pregnant women are varied. A study on 506 patients in the United States showed that the infants born to such mothers were more likely to be low in birth weight, small for gestational age, be admitted to the intensive care nursery or require assisted ventilation of some sort.[33] However, a smaller study carried out on mothers who were infected by contaminated anti-D immunoglobulin in Ireland did not show any adverse outcomes in the study group versus the control group.[34]
In a five-year study on 208 women, Locatelli et al. [35] showed that the risk of cholestasis increased in pregnant women who are also HCV antibody positive, and this tends to occur earlier in the gestation compared to HCV-negative mothers. This has also been noted in other studies.[36] While gestational cholestasis is a common complication of pregnancy, it has been suggested that HCV alters the epithelial cells in a way that predisposes women to cholestasis.[35] Berkley et al. [37] noted that neonates born to HCV antibody-positive mothers were more likely to have neonatal abstinence syndrome when adjusted for the dose of methadone used. The authors speculate that this may be because of poor metabolism of methadone in an HCV-infected liver; hence, a considerably higher dose is transferred transplacentally compared to women who are not infected.

The Pathogenesis of HCV Vertical Transmission
Studies on the pathogenesis of HCV have been numerous, diverse and, in many cases, yielded conflicting results. Studies to examine the timing of transmission indicate that many infants who are infected with HCV have PCR tests that are positive at or soon after delivery, suggesting in utero transmission.[38] Testing of amniotic fluid for HCV did not demonstrate evidence of detectable virus, which suggests that transmission may occur directly through the placenta.[39] This is supported by numerous studies that have demonstrated no significant differences with mode of delivery.[40,41] Case reports of divergent outcomes in monochorionic, diamniotic twins suggest that this placental infection is likely a sporadic event.[42] Studies of the hypervariable regions of HCV from infants demonstrated limited diversity, which indicates that transmission is likely restricted to a few virions.[43–46] Maternal factors that have been cited as playing a significant role in HCV vertical transmission are certain HLA types, as well as the presence of HCV RNA in maternal peripheral blood mononuclear cells.[47,48] The presence of maternal neutralizing antibodies was studied and found to have no role in promoting or protecting against HCV vertical transmission.[49]
One can make some general conclusions from the results of these disparate studies. In cases where vertical transmission occurs, it is likely that HCV is transmitted in utero at an early or middle stage of pregnancy. The event likely consists of a few virions with limited or no diversity crossing the placenta through direct infection in an inefficient manner given the low rate of transmission. This may be influenced by maternal genetic or immune factors.

Modifiers of and Risk Factors for HCV Vertical Transmission
Perinatal transmission is thought to be the leading cause of mother to baby transmission.[50] Both intrauterine and intrapartum transmission are possible. It is estimated that up to one-third of the infected children acquire the infection in utero, as evidenced by the positive PCR testing within the first 3 days of life, and up to one-half as late intrauterine or intrapartum and are PCR positive after 3 days of life.[38] Other studies have shown that HCV RNA reaches detectable levels several weeks after birth in infants born to infected mothers, raising the likelihood that HCV can also be transmitted perinatally and postnatally.[46,51,52]
Several factors have been studied as potential modifiers of the frequency of HCV vertical transmission. Multiple obstetric, immunological and virologic factors may influence perinatal transmission of HCV. These include maternal HCV RNA levels (at viral titres beyond 105 to 106 copies/mL), HIV coinfection, HCV genotype, neutralizing antibodies, cytokine modulation, amniocentesis, foetal blood monitoring, prolonged membrane rupture and type of delivery.[53,54]

HIV Coinfection
Maternal HCV and HIV coinfection has consistently been shown to be associated with higher transmission rates. Studies have shown that vertical transmission is 3- to 4-fold higher compared to maternal HCV alone [40,55–57]. Polis et al. in a meta-analysis of 10 articles showed that HIV and HCV coinfection increase the odds of vertical transmission by 90%. The incidence of HCV vertical transmission is approximately 3–5% in HCV RNA-positive-monoinfected mothers, but can be as high as 19% in HIV-coinfected mothers. Even when controlling for HIV, presence of HCV viremia increases the odds of vertical transmission by 2.82-fold.[55] Studies have shown a 0% transmission, when maternal HCV RNA is negative.[40,58]

Prolonged Rupture of Membranes
Rupture of membranes for more than 6 h has been significantly associated with viral transmission.[40,59] However, there is lack of any statistically significant data on the impact of obstetrical procedures on intrapartum HCV exposure. There is some suggestion that use of scalp electrodes may lead to HCV exposure.[40] Another study demonstrated a potential increase in HCV infection in infants following amniocentesis.[60] Benefits of doing elective C-section in mothers with HCV viremia are controversial. Gibb et al. [51] in a study on 441 mother–infant pairs in United Kingdom and Ireland reported a transmission rate of 7.7% among infants delivered vaginally, 5.9% among those delivered via an emergent C-section and 0% among those delivered by elective C-section (i.e. prior to membrane rupture). Paccagnini et al. [61] in a study on 70 high-risk mother–infant pairs (HIV positive and/or a history of drug use) showed a 32% rate of vertical transmission in infants born vaginally compared to 6% in those who were born by C-section. There were only two infants who were HIV positive, and both were born by caesarean section. However, most studies have not found any association between route of delivery and a decrease in transmission rates.[56,62,63] The European Paediatric Hepatitis C Virus Network showed in a study carried out on 1758 mother–infant pairs that there was no significant difference (P = 0.16) in vertical transmission between elective C-section, vaginal delivery or emergent C-section.[64]

Severity of Maternal HCV Disease
The effects of maternal HCV disease activity on vertical transmission are not completely understood. Two recent studies showed that mothers with HCV infection of the peripheral blood monocytes have a higher rate of transmission to their infants.[48,65] This is similar to what is noticed in the vertical transmission of other viruses, e.g. HIV. It has also been noted that persistently high ALT levels in the year preceding pregnancy or during pregnancy are associated with higher rates of vertical transmission.[66] This is likely related to the higher viral loads that may cause the more extensive hepatic damage and subsequent elevated ALT. Elevated ALT is also associated with certain HCV genotypes that are more likely to be transmitted like 1a or 1b.[67]
A small study carried out on 12 HCV seropositive mothers and their infants and a control group of 16 healthy mothers and their infants showed an increase in the natural killer (NK) cells in the placenta of HCV-positive mothers compared to the control group.[68] It also showed that these cells had greater cytotoxicity in the HCV-positive mothers. This may be an explanation for the relatively low rates of vertical transmission; though, the increased cytotoxicity of the NK cells may also lead to a higher risk of preterm delivery in HCV-positive mothers.

Breastmilk/Breastfeeding Transmission
HCV RNA has been detected in breast milk and colostrum.[69,70] However, there are only isolated studies that show some indication of HCV infection of the infant secondary to breastfeeding in mothers with a high viral load.[69] Most studies indicate that even though theoretical transmission may be possible, the viral count in breast milk is extremely low and likely becomes inactivated in the digestive tract of the infant [51,54,70–72]. Infants in several of the aforementioned studies had a single positive HCV RNA, which could be explained by vertical transmission and not necessarily breastfeeding itself. The European Paediatric Hepatitis C Virus Network noted no difference in infection rates in breast- vs formula-fed infants in a study carried out on 1758 infants.[64] The risk of transmission is higher if the mother has cracked or bleeding nipples. Mothers who are coinfected with HIV and HCV are recommended to follow the current guidelines for the prevention of HIV transmission

HCV Infection in Children: Short- and Long-term
As noted earlier, the most common cause of chronic hepatitis in children is HCV infection. With the improvements in HCV detection in transfused blood products and the prevention of other modes of parenteral transmission, the most common method of transmission in children is maternal–infant perinatal transmission. Conservative estimates suggest that 10 000–60 000 infants can be infected with HCV per year worldwide because of vertical transmission.[54] Current CDC guidelines recommend testing for anti-HCV in infants born to infected mothers after 12 months.[73] Passively acquired antibodies from the mother fall below detectable levels at this time. If earlier testing is required, CDC recommends RT-PCR for HCV RNA 1–2 months after birth.
The European Pediatric HCV network prospectively studied 357 HCV-exposed infants and found that the sensitivity of PCR for HCV RNA was 22% at birth and increased dramatically to 70–85% after 1 month of age.[74] This study also showed that the PPV of the PCR test was 33% at birth and increased to 78% at 9 months of age, while NPV ranged from 96% to 99%. While these results could be attributed to very low and undetectable viral loads in the first month of life, they could also be explained by the widely variable incubation period of HCV that can range from 2 weeks to 6 months. These results suggest that negative testing at birth using PCR is not an adequate predictor of the infant's HCV infection status at a later date. Conversely, a negative PCR test after 12 months of age should be confirmed with the 'gold' standard of anti-HCV to detect children who were previously infected and successfully cleared their viremia.
Spontaneous clearance of HCV can occur in up to 25–30% of children.[75,76] Rates of clearance are not different among those who are infected via vertical transmission or parenteral transmission. However, a younger age at follow-up and normal ALT levels favour HCV clearance.[76] Another prospective study with seven infants was carried out in Italy and showed constant viremia in all of the subjects at least in the first few years of life.[77] They all had initial elevation of ALT, with some subsequently recovering from it. Liver biopsies showed varying degrees of chronic persistent hepatitis. Most other studies reviewed showed similar low rates of HCV RNA clearance and a high rate of chronicity in the paediatric population.[78–80] Although most patients continued to have only mild elevations of their liver enzymes, liver biopsies showed evidence of mild to moderate hepatitis. Data from the adult population suggest that approximately 10–20% of patients with HCV can go on to develop cirrhosis and hepatocellular carcinoma.[81] Currently, there are no long-term studies to show the rates of cirrhosis or hepatocellular carcinoma in adults who acquired HCV through vertical transmission.

What Potential Treatment Opportunities Exist?
The current standard of care in HCV therapy is the combination of pegylated interferon and ribavirin. These medications have several drawbacks that are magnified during pregnancy and in the neonatal period. Pegylated interferon would be problematic given its psychiatric side effects in these women given the high background rate of postpartum depression. Addition of an agent that could promote these symptoms would not be tolerated. Similarly, ribavirin is a known teratogen and could not be used during pregnancy. Likewise, in the neonatal period, given the low rates of vertical transmission, relatively high rate of spontaneous resolution and lack of symptoms, one ought to be highly selective in who would be treated. Given the concern for growth suppression seen with pegylated-interferon treatment in older children, using it in any infant during a period of intense growth could have devastating effects. Thus, any consideration of treatment during this period could only occur once new anti-HCV agents are approved and have a demonstrated long-term safety profile.

A first strategy would be to select who would most benefit from therapy. The recent association of single-nucleotide polymorphisms within the IL28B gene being significantly associated with treatment response is highly provocative.[82] Obviously, these data are based on interferon being the primary agent used in treatment, which has already been discussed as problematic. However, perhaps IL28B profiling could be used in a broader campaign to treat those young women infected with HCV who intend to become pregnant, thus resolving their infection prior to conception. This could be carried out immediately now that IL28B testing is commercially available.
Another strategy would be to follow the model used for the interruption of HIV vertical transmission. Initial strategies centred around use of an antiviral agent, in this case zidovudine, for the last 6 weeks of pregnancy, as an infusion intrapartum and then for the first 6 weeks of the infants life. This strategy when it was first applied reduced the transmission rate of HIV from 25% to 8%.[83] Over the years, other agents have been added so that antiviral use has reduced transmission to <2% in developed nations. Obviously, HCV vertical transmission does not have the immediate consequences that HIV does, so the need to be so aggressive in prevention is not there. However, if it was possible to use short-term treatment with a combination of an HCV protease and polymerase inhibitor to coincide with the natural drop in HCV RNA in the pregnant woman postpartum, combined with treatment in those infants that demonstrated viremia soon after birth, this could be a viable strategy. Obviously, the costs associated with this kind of regimen would have to be considered.
To most effectively design treatment strategies, more research on HCV infection during pregnancy and infancy needs to be conducted. Further understanding of the influence of pregnancy on the immune response to HCV within the liver as well as how HCV infects the foetal liver as it matures is needed. This knowledge would allow better selection of treatment candidates as well as agents used for therapy.

HCV infection during pregnancy and the post-partum period appears to be a highly unique period in the interaction between virus and host. These periods of intense physiological change appear to force some adaptation of the virus that may offer a therapeutic window when more suitable agents come into use. Further studies of how and when the virus is transmitted from mother to child will only enhance the ability for prevention and treatment in the future.

Update June 20 2011

Pregnancy After Liver Transplant Raises Risk of Graft Loss

PHILADELPHIA – Women who become pregnant after receiving a transplanted liver face an elevated risk of graft rejection, especially during or immediately following the pregnancy, based on a review of 161 U.S. cases.

"The data suggest poorer outcomes for both mothers and their newborns in female liver recipients with risk factors for graft loss within 5 years post pregnancy," Dr. Carlo B. Ramirez said at the American Transplant Congress. "The findings highlight the high-risk nature of this group, warranting closer follow-up of both mother and child," said Dr. Ramirez, a transplant surgeon at Thomas Jefferson University, Philadelphia.
Of the 161 women who became pregnant following a liver transplant and were enrolled in the National Transplantation Pregnancy Registry (in place since 1991), 16 (10%) lost their graft within 5 years following their first posttransplant pregnancy. The pregnancy and the 3 months following pregnancy posed a particular risk, with half of the women who eventually lost their graft experiencing rejection during that time. In a multivariate model that took into account baseline risk factors, women with a liver transplant faced a 14-fold increased risk for graft loss during the pregnancy, Dr. Ramirez said.

"A lot of patients who have a stable equilibrium with their graft may destabilize under stress. It is possible that there is low-grade, clinically insignificant rejection in some of these patients prior to pregnancy" that then becomes exacerbated by the stress of pregnancy, commented Dr. Jean C. Emond, professor of surgery and director of transplantation at Columbia University in New York. Dr. Emond suggested that a liver biopsy prior to pregnancy might be warranted to assess the stability of the transplant.

Other risk factors for graft loss included younger age of the mother and low gestational age at the time of delivery. In the multivariate analysis, the risk for graft loss fell by a statistically significant 26% for each additional year of age for the mother. Graft loss fell by a statistically significant 5% for each additional week of gestational age when delivery occurred.

Among the 16 women who lost their graft during pregnancy or the following 5 years, their average age when they conceived was 22 years old, compared with an average age of 28 years old among the 145 women who did not lose their graft. Average gestational age at delivery was 33 weeks among the women who lost their graft, and 37 weeks among the women who did not lose their graft.

The average age of the women at the time they received their liver transplant was 18 years among those who later lost their grafts, and 23 years among those who retained their grafts. However, the average time between transplantation and conception was an identical 4.3 years in both groups.

The only other risk factor for graft loss that approached statistical significance in the multivariate model was viral hepatitis as the etiologic agent for the liver failure that led to the transplants. Viral hepatitis was the cause of liver failure for six (38%) of the women who lost their grafts following pregnancy, and for 23 (16%) of the women who did not lose their grafts. In the multivariate model, viral hepatitis as the cause of liver failure was linked with a nearly fourfold increased risk for women losing their graft during or after pregnancy, but this relationship failed to meet the standard criterion for statistical significance, Dr. Ramirez said.
The congress was sponsored by the American Society of Transplant Surgeons. Dr. Ramirez said he had no disclosures. The National Transplantation Pregnancy Registry has been supported by grants from Novartis, Astellas, Genentech, Pfizer, Teva, and Sandoz.