Thursday, November 11, 2010

Hepatitis C in Pregnancy



Updates Here

The chances of a infant
or baby getting hepatitis
C from its mother is
low – most studies have
only found that about 4%
or 5% of babies (that’s 4 or
5 babies out of 100) born to
hepatitis C infected mothers
are infected with hepatitis
C. The infection happens
during the birth of the baby,
and is called perinatal transmission
.
....
Hepatitis C transmission not reduced by C-sections
. November 2008

Planned cesarean sections do not help to reduce the chances of a pregnant mother with Hepatitis C (HCV) transmitting the infection to her unborn baby, according to new scientific findings by the UCD School of Medicine and Medical Science and the National Maternity Hospital in Dublin.
Hepatitis C is the most common cause of chronic viral infection in the Western World today. It affects an estimated 170 million people worldwide. It is a viral infection of the liver which is mainly transmitted through contact with contaminated blood or blood products.
Infant infection rates are linked to the number of mothers infected with the viral infection and the risk factors associated with the transmission of the infection to their unborn children in the womb.

The results of a new 5-year study of 559 mother-child pairs in Ireland, one of the largest such studies of its kind, published in the American Journal of Obstetrics & Gynaecology, show that vaginal delivery and planned cesarean among mothers infected with Hepatitis C display almost equal transmission rates of Hepatitis C from mother to child (4.2% and 3% respectively).
“The mode of delivery itself was not shown to have a significant influence on the transmission rate of hepatitis C from mother to child,” says Professor Fionnuala McAuliffe from the National Maternity Hospital and the UCD School of Medicine and Medical Science, one of the co-authors of the report.

“The main risk factor associated with the vertical transmission of hepatitis C was the presence of detectable hepatitis C virus in the mother’s bloodstream, a condition where viruses enter the bloodstream and hence have access to the rest of the body.”

“Mothers who demonstrated detectable hepatitis C virus had a significantly higher transmission rate (7.1%) to their infants compared to the transmission rate (0%) for those in whom the hepatitis C virus was undetectable during pregnancy,” explains Professor McAuliffe.
“According to these new findings, if the Hepatitis C virus is undetectable antenatally despite the mother being antibody positive the patient can be reassured that the risk of vertical transmission to their child is minimal, and this is a significant development for patient counseling.”


http://www.ucd.ie/news/2008/11NOV08/061108_hep.html


Hepatitis in Pregnancy

Author: Stephen A Contag, MD, Assistant Professor, Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine; Attending Physician, Institute for Maternal-Fetal Medicine, Sinai Hospital of BaltimoreCoauthor(s): Pedro P Arrabal, MD, Director, Division of Maternal-Fetal Medicine, The Institute for Maternal-Fetal Medicine, The Louis and Henrietta Blaustein Women's Health Center, Sinai Hospital of Baltimore

Contributor Information and Disclosures
Updated: Oct 15, 2010

The information below is only for hepatitis C. For information on all viral hepatitis in Pregnancy

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Introduction

Hepatitis C virus (HCV) was first identified in 1989.12,13 It is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma around the world.14 HCV infection has a slow onset with symptoms in about 25% of patients.15 Approximately 40% of patients infected with HCV recover completely and the remainder become chronic carriers. Twenty percent of the carriers develop cirrhosis and of those, up to 20% develop liver cancer.16


Pathophysiology

Hepatitis C Hepatitis C is a partially double-stranded RNA virus, one that mutates frequently secondary to changes in the structural proteins of the viral envelope. The development of antibodies against HCV does not produce immunity against the disease like it does with most other organisms.28


After an individual is infected, hepatitis C virus replicates with rates up to a trillion copies per day. It is constantly genetically mutating within the host. The mutated forms are frequently different enough from their predecessors that when the immune system is capable of identifying and eradicating one form, the mutant forms continue to cause ongoing disease and take over as the predominant strain. For this reason humoral immune responses have little effect on viral clearance and no specific antibody response can predict the outcome of infection.31 On the other hand, cellular immune responses seem to have an important role in determining the outcome of acute HCV infection.


The CD4 and CD8 cellular response mediated by a Th1 lymphocytic response is associated with a cytokine profile leading to viral clearance.32,33 Of the individuals chronically infected with HCV, 80% progress to chronic disease. The disease is an indolent and slowly progressive one. Most infected individuals carry the virus for life and remain infective for life.34 Spontaneous viral clearance is higher in symptomatic acute HCV infection.14


There are 11 major genotypes of HCV, with 15 different subtypes, which vary in prevalence in different regions of the world.34,35,16 Each of these major genotypes can differ significantly in their biological effects. The most important biological differences are their replication rates, mutation rates, and severity of damage they can cause. Most importantly, clinically these different genotypes vary in their response to currently available therapies.36,28

Frequency
United States

Hepatitis C
HCV-related end stage liver disease is the most common chronic bloodborne infection and the leading reason for liver transplantation in the United States. New HCV infections have decreased by more than 80% since 1990.55 There are an estimated 4 million cases of chronic liver disease and 2.7-3.4 million cases of HCV infection.56,57 There are 25,000-38,000 new cases of HCV diagnosed every year with a prevalence of 1.6%.58,56 Of the newly diagnosed cases, only 6,300 (17%) are symptomatic.59


Acute HCV infection leads to symptomatic hepatitis in fewer than 20% of patients; 15% of acute liver disease in the United States is due to HCV.60 HCV infection occurs among persons of all ages, but the highest incidence of acute HCV is found among persons aged 20-39 years.61 In the pregnant population, the prevalence of HCV is estimated to be between less then 1-5%
Approximately 75% of patients are chronically infected and may not be aware of their infection because they are not clinically ill. These individuals serve as a source of transmission to others and are at risk for chronic liver disease or other HCV-related chronic diseases.
. Approximately 60% of all new infections are believed to occur via intravenous (IV) drug use64 , 10-20% by sexual transmission65 , <6 data-blogger-escaped-href="javascript:showcontent(">66 The transmission risk from needlestick injury is approximately 3%.66 Only 25% of pregnant women report receiving blood products or IV drug use when HCV infection is diagnosed.67 Concurrent alcoholism, IV drug use (38%), and coexisting HIV infection (33%) are important associated risk factors.66,68 The decline observed in the incidence and prevalence of HCV is attributed to needle exchange programs among intravenous drug users and improved blood donor screening.14 This has led to a relative increase in the importance of accidental needle sticks, and sexual and perinatal transmission in the incidence of HCV infections.14
.
.
The World Health Organization (WHO) estimates that about 3% of the world’s population has been infected with HCV and that there are more than 170 million chronic carriers who are at risk of developing liver cirrhosis and/or liver cancer.16 The highest prevalence is in Egypt (18-22%) and the lowest in Sweden (0.003%).14,16 As many as 2-4 million persons may be chronically infected in the United States, 5-10 million in Europe, and about 12 million in India. Of these, about 25% are symptomatic, but 60-80% may progress to chronic liver disease, and 20% of these develop cirrhosis.16

Transmission

Hepatitis CTransfer of HCV infection occurs as a result of vertical or horizontal transfer. The prevalence of HCV among pregnant women is approximately 1% (0.1-2.4%) and the rate of mother- to-infant transmission is 4-7% per pregnancy among women with detectable viremia.83 Vertical or perinatal transfer could potentially occur prior to or during delivery. Currently, no evidence is available upon which to base any practice recommendations regarding planned cesarean section versus vaginal delivery for preventing mother–to-infant hepatitis C virus transmission.84


The most current evidence from large multicenter trials does not support elective cesarean delivery for prevention of vertical HVC transmission.85 Vertical transfer appears to be highly dependent on viral load and HIV status, both of these independent of each other.86 High viral loads of more 100,000 copies/ mL are associated with an increased risk of vertical transmission. Concurrent HIV infection increases the risk of transmission by 15-22%, probably due to a higher viral load.14,87,88


The role of cesarean section to prevent vertical transmission is questionable and results have been conflicting, particularly in patients with isolated HCV infection.89,90 Cesarean delivery based on viral load is not advocated. Infection prior to delivery has been shown to occur in as many as 33% of patients.91 An elective cesarean section has been suggested for patients co-infected with HIV, since transmission rates in this cohort appear to be higher. Elective surgery in these patients has been shown to reduce maternal-fetal transmission by up to 60%.88,92 Transmission during breastfeeding occurs more often in patients infected with HIV.88 Breastfeeding alone does not appear to increase transmission.88 Chronic HCV infection appears to be the exception among infected newborns.


Some data suggest that fewer than 10% develop chronic infection and that fewer than 5% develop cirrhosis.66 Chronicity rates appear to depend on the mode of infection and the age at which patients acquire infection, with increased rates among transfusion or intravenous drug recipients.14 The risk of HCV infection from accidental needle stick exposure is reported to be 0.2-0.4%.93,94 Co-infection with HIV increases the risk of needle-stick transmission. Transfer to female infants may be twice as high as transfer to male infants.90 The frequency of sexual transmission of HCV is much lower than that observed for HIV or HBV.95,96 Barrier precautions do not impact viral transmission rates in stable monogamous couples, but co-infection with other sexually transmitted diseases and HIV does increase sexual transmission.(97

Blood transfusions in an unscreened population, reuse of disposable medical supplies, and unsafe therapeutic procedures are the major modes of transmission in the developing world.14 The screening rates for HCV in blood bank donors in developing nations is lower than that for HIV, ranging from 6-23%.98,99 Unsafe medical procedures are responsible for a substantial number of cases of HCV worldwide, accounting for 2-3 million new cases of HCV infections per year.100

Most cases of transmission occur from infected blood or infected needles. The infection may also occur after accidental exposure to infected blood. Nonparenteral transmission does not occur frequently.

Sexual transmission has been documented in stable heterosexual couples at a rate of 1.5-3%101 and between male homosexual exposures at a rate of 3%. The factors that facilitate transmission between partners are concurrent HIV infection, traumatic sexual practices, and concurrent sexually transmitted disease.102

Vertical perinatal transmission occurs in women who are HCV-RNA positive at the time of delivery. The average rate of infection is approximately 6%, although it is higher (17%) if a woman is co-infected with HIV.16 The role of a viral titer is unclear. There does not appear to be an association with method of delivery. The infected infants tend to do well and severe hepatitis is rare.16

Workup

seroconversion= (development of antibodies in blood serum as a result of infection)
IgM-(IgM is the class of antibodies found in circulating body fluids. IgM antibodies are the first antibodies to appear in response to an initial exposure to an antigen)


Hepatitis C No definite test diagnoses acute HCV infection.14 Most patients are identified by a known exposure, documented seroconversion= (development of antibodies in blood serum as a result of infection), unexplained increases in liver enzymes, and exclusion of other causes of liver disease.14

The only conclusive method to diagnose an acute or recent-onset HCV infection is to demonstrate seroconversion in a previously seronegative individual. This is most likely to occur after an acute event or when following a high-risk individual. Attempting to establish infection based on the presence of antibodies is not a reliable way to confirm the diagnosis since many individuals may continue to be antibody negative for 6-12 months. Therefore the absence of antibodies does not preclude infection in the acute setting.14

Up to 30% of patients will have delayed seroconversion (especially those who are immunocompromised).110 HCV RNA can be very unreliable for up to a year after infection due to fluctuations and levels below a detectable concentration. This requires serial measurement of HCV RNA for at least a year after documented exposure or seroconversion.

Occasionally, the infection resolves and HCV RNA either clears before seroconversion occurs111,112 or up to 10% of individuals lose their serologic markers.111 Among patients who do develop serological markers, measuring IgM=(IgM is the class of antibodies found in circulating body fluids. IgM antibodies are the first antibodies to appear in response to an initial exposure to an antigen) has not shown to be useful, as their concentrations remain stable in acute and chronic disease.113


Various methods are available to detect HCV RNA. The most sensitive are reverse transcriptase PCR, branched DNA assays, and transcription mediated amplification.


They are reliable with detection limits of 5IU/mL and a sensitivity of more than 95%. Despite their high sensitivity, these tests are not recommended for screening for chronic HCV infection because of their cost.111,114


Clear postexposure guidelines are not available. The CDC recommend measuring HCV antibodies and serum transaminase concentration at baseline. Subsequent testing schedules have been proposed that include testing for HCV RNA at 0, 1, 2, and 3 months after exposure and for antibodies at 0, 3, and 6 months after exposure.115


Progression of liver disease are recommended to be monitored every 6 months by checking blood counts and liver enzymes. In patients with more advanced liver disease, level of α -fetoprotein and ultrasonography should be added.16

Hepatitis C

The CDC do not recommend testing all pregnant women for HCV infection, only those at high risk. Care during pregnancy is not modified by HCV infection.147 The objectives for treatment of chronic hepatitis are to reduce inflammation; prevent progression to fibrosis, cirrhosis, and HCC through the eradication of the virus; decrease infectivity and control the spread of the disease.16 Spontaneous resolution occurs in one third of infected persons.14


Medical treatment is unlikely to have a significant impact on disease as most infected individuals remain undiagnosed and have limited resources and access to care.14 Antibiotics are of no value in the treatment of the infection.


Antiviral agents, as well as corticosteroids, have no effect in the management of the acute disease. Genotype determinations influence treatment decisions. In patients with genotype 2 or 3, the duration is 24 weeks, while patients with genotype 1 need 48 weeks of treatment.125


Currently the best indicator of effective treatment is a sustained viral suppression, defined by the absence of detectable HCV RNA in the serum as shown by a qualitative HCV RNA assay with lower limit of detection of 50 IU/mL or less by 24 weeks after the end of treatment.15 The most widely used form of treatment is a combination of pegylated interferon and ribavirin in cases of chronic HCV infection.

The use of pegylated interferon leads to a suppression of viral replication in more than 50% of cases.126

Its use in pregnancy is contraindicated secondary to conflicting reports of decreased birth weight and increased fetal loss.127,128

The FDA labels ribavirin as category X, although reports exist of its use during pregnancy without adverse outcomes.129,128 Transplantation is an option for patients with cirrhosis and end-stage liver disease. Despite transplantation, the donor liver almost always becomes infected, and the risk of progression to cirrhosis reappears.130

Follow Up

Hepatitis C

Testing and counseling for HCV should be offered to women with known risk factors. Currently no pre-exposure prophylaxis, vaccine, or post-exposure prophylaxis is available for HCV.14,82 Post-exposure prophylaxis with IG is not effective in preventing infection.16


Primary prevention activities to reduce the risk of contracting the infection and secondary prevention activities to reduce the risk of liver disease and other HCV-related chronic diseases among those infected with HCV are required to reduce the burden of HCV infection and HCV-related disease in the United States.61


The prevention of HCV transmission and acquisition depends on preventing exposure to infected blood or blood products as well as implementation of universal precautions. It also requires avoidance of high-risk sexual behavior.


The most common form of transmission in the United States is through IV drug use. Needle-exchange programs for injecting drug users may help to limit the spread of HCV infection as well as of HIV and HBV.15 Patients who are HIV positive also have a higher risk of acquiring the disease.

Women with HCV infection should avoid alcohol consumption and be vaccinated against hepatitis A and B.134

The HCV is susceptible to heating at 60°C for 10 h or 100°C for 2 minutes in aqueous solution, formaldehyde (1:2000) at 37°C for 72 h, ß-propiolactone, and UV irradiation.

HCV is relatively unstable when exposed to storage at room temperature and repeated freezing and thawing. National Institutes of Health recommend follow-up testing for exposed infants on 2 different occasions between 2-6 months with HSV RNA testing or HCV antibody testing after 15 months of age.125

Complications

In addition to the known complications of chronic hepatitis B and C, which are cirrhosis and hepatocellular carcinoma, there are complications specific to several of the hepatitis viruses.

Prognosis

Hepatitis C Patients with a sustained virological response remain HCV RNA negative for at least 5 years after stopping therapy and experience a long-term biochemical and histological outcome with a decrease in total inflammatory activity and a decrease in the reversible components of fibrosis.16 Nevertheless, sustained virological responders have a highly reduced risk of disease progression.142

Patient Education

HCV is not spread by breastfeeding, sneezing, coughing, hugging, sharing eating utensils, or drinking from the same glass, other normal social contact, food, or water.28
. Special Concerns
. Blood transfusions Transfusion-related HBV infection occurs in approximately 1 in 200,000 transfusions. Some evidence shows that the rate may be lower, however this is still higher than the HIV and HCV-related risk of approximately 1 in 2,000,000.144,145,146 Current rates for HBV are thought to be around 1 in 280,000 to 1 in 350,000, partially due to improved immunization and a decrease of infected products in the donor pool.144
. References

. Prospective cohort study of mother-to-infant infection and clearance of hepatitis C in rural Egyptian villages
. Fatma M. Shebl1,2, Samer S. El-Kamary1, oa'a A. Saleh3, Mohamed Abdel-Hamid1,4,
Nabiel Mikhail4, Alif Allam2, Hanaa El-Arabi2, Abrahim Elhenawy2, Sherif El-Kafrawy2,4,
Mai El-Daly2,4, Sahar Selim2, Ayman Abd El-Wahab2, Mohamed Mostafa2, Soraya Sharaf2,
Mohamed Hashem1, Scott Heyward1, . Colin Stine1 Laurence S. Magder1, Sonia Stoszek1,
G. Thomas Strickland1,*

. Article first published online: 20 APR 2009
DOI: 10.1002/jmv.21480

. Abstract
Although persistent transmission of hepatitis C virus (HCV) from infected mothers to their infants is reported in 4–8%, transient HCV perinatal infection also occurs.
. This prospective cohort study determined perinatal HCV infection- and early and late clearance-rates in 1,863 mother-infant pairs in rural Egyptian villages.
. This study found 15.7% and 10.9% of pregnant women had HCV antibodies (anti-HCV) and HCV-RNA, respectively. Among 329 infants born of these mothers, 33 (10.0%) tested positive for both anti-HCV and HCV-RNA 2 months following birth—29 (12.5%) having HCV-RNA positive mothers and 4 (with transient infections) having mothers with only anti-HCV.
. Fifteen remained HCV-RNA positive at one and/or 2 years (persistent infections), while 18 cleared both virus and antibody by 1 year (transient infections). Among the 15 persistent cases, 7 cleared their infections by 2 or 3 years. At 2- to 6- and at 10- to 12-month maternally acquired anti-HCV was observed in 80% and 5% of infants, respectively.
. Four perinatally infected and one transiently infected infant were confirmed to be infected by their mothers by the sequence similarity of their viruses. Viremia was 155-fold greater in mothers of infants with persistent than mothers of infants with transient infections.
. Maternal-infant transmission of HCV is more frequent than generally reported. However, both early and late clearance of infection frequently occurs and only 15 (4.6%) and 8 (2.4%) infants born of HCV-RNA positive mothers had detectable HCV-RNA at one and 2–3 years of age. Investigating how infants clear infection may provide important information about protective immunity to HCV. J. Med. Virol. 81:1024–1031, 2009. © 2009 Wiley-Liss, Inc.

http://onlinelibrary.wiley.com/doi/10.1002/jmv.21480/abstract

How should you manage children born to hepatitis C positive Women?
. Evidence-based answers from the
Family Physicians Inquiries Network
. jfp online .com Vol 59, No 5 MAY 2010 The Journa l of Family Practi ce 289
. Evidence-based answer . A for starters, don’t be overly concerned with the mode of delivery; it doesn’t influence the rate of transmissionof hepatitis C virus (HCV), except in women who are also infected with human immunodeficiency virus (HIV) (strength of recommendation [SOR]: B, consistent retrospective cohort studies).
. Avoid internal fetal monitoring and prolonged rupture of membranes
. Advise patients that it’s OK to breastfeed.
. Breastfeeding doesn’t affect transmission. Check HCV RNA and serum anti-HCV on 2 occasions between 2 and 6months of age and 18 and 24 months of age. Perinatal transmission of HCV is rare. It occurs only when serum HCV RNA is detectable; transmission rates may be related to higher levels (>106 copies/mL).
. HCV is transmitted to 2% of infants of anti-HCV seropositive women and 4% to 7% of infants born to mothers who are HCV RNA-positive at delivery. Spontaneous clearance of the virus occurs in approximately 20% of infants. Most remain asymptomatic if HCV persists, but have mild elevation of liver function tests.
. Routine screening for HCV in mothers is not recommended, but pregnant women at high risk for HCV infection should be screened for anti-HCV.
. Route of delivery:
. Only a concern for HIV-positive mothers
. The mode of delivery doesn’t influence the rate of HCV transmission, except in mothers with HIV. Retrospective analysis of 503 HCV-positive mothers coinfected with HIV showed a decreased risk of transmission during cesarean delivery (odds ratio [OR]=0.36;P=.01; number needed to treat [NNT]=10)
. One study suggested an increased rate of vertical HCV transmission during vaginal delivery compared with cesarean delivery (32% vs6%; P<.05). The study didn’t account for the percent of mothers coinfected with HIV, however.
.
A meta-analysis of 11 studies showed similar rates of transmission for vaginal and cesarean delivery: adjusted rates were 4.3%and 3%, respectively. Internal monitoring is an issue. Avoid internal fetal monitoring to minimize HCV transmission, based on a single retrospective cohort of 244 infants born to HCV positivemothers (relative risk [RR]= 7.7; 95% confidence interval ; number needed to harm [NNH]=6).7
.
The same study showed an increased risk with membrane rupture longer than 6 hours (RR=9.9; 95% CI,1.2-81; NNH=13)
.
Breastfeeding doesn’t significantly affect HCV transmission.
.
Transmission rates for breast fed and nonbreast fed infants are 3.7% and 3.9%, respectively Routine screening for HCV isn’t recommended, but screen pregnant women at high risk of HCV infection foranti-HCV. Defer postpartum lab testing. Because about 20% of infants exposed to HCVclear the virus spontaneously, and maternal antibodies can confound laboratory results, deferring postpartum diagnostic testing is appropriate.
.
A study of 1104 children in whom vertical transmission didn’t occur after exposureto HCV showed that 95% of the children were anti-HCV antibody negative by12 months age. A prospective study of 23 infants documented spontaneous clearance of HCV RNA by 6 months in all patients.
.
Recommendations The National Institutes of Health 2002 Consensus Statement recommends:
• avoiding fetal scalp electrodes and prolongedrupture of membranes
• serum testing for HCV RNA at 2 monthsand 6 months of age
• anti-HCV antibody testing after 15months of age.
.
The American College of Obstetricians and Gynecologists supports breastfeeding, recommends against routine HCV screening, and recommends that cesarean delivery be reserved for obstetric indications.
.
The American Association for the Studyof Liver Diseases recommends serum testing and liver biopsy on the same schedule as adult patients and endorses considering treatment after 3 years of age.
.
The US Food and Drug Administration has approved treatment after 3 years of age for children with detectable HCV RNA levels higher than 50 IU/mL and who have had a liver biopsy with portal or bridging fibrosis and at least moderate inflammation and necrosis.
.
The American Gastroenterological Association recommends considering treatment with PEG-interferon and ribavirin after 3 years of age.

References

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