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HEPATITS C AND PREGNANCY
Prof. ABOUBAKR ELNASHAR
Benha University Hospital, Egypt
Email: elnashar53@hotmail.com
ABOUBAKR ELNASHAR
CONTENTS
1. Epidemiology & Aetiology
2. Diagnosis
3. Transmission
4. Hepatitis and pregnancy
1. Effect of pregnancy on hepatitis
2. Effect of hepatitis on pregnancy: Maternal risk, Fetal risk
5. Management
a. Preconception
b. Antenatal
Prenatal testing
Prenatal management
Maternal prevention
Maternal TT
c. Delivery
d. Postpartum:
neonatal
breast feeding
Mat follow up
Infant follow up
Prevention of transmission
ABOUBAKR ELNASHAR
1. EPIDEMIOLOGY& ETIOLOGY
 In Egypt: Major health problem
•20-40%: of the all-viral hepatitis.
•Carrier state: High prevalence.
•UK: 0.01–0.1%
•Egypt:
17–26% (Wasley & Alter,2000)
16 % (Mohamoud et al.2013)
 Assuit and Benha: 8%
 Rural villages of the Nile Delta: 16%
 The Ministry of Health revealed that the prevalence rate of Hepatitis
C in 2021 reached 2 percent, marking a drop compared to 7 percent
in 2018
ABOUBAKR ELNASHAR
•70%: progress to chronic infection
•30% of ch infection: develop cirrhosis over 10-30 y.
•3%: annual development of hepatcellular carcinoma
•92% infected population had HCV genotype 4 (Egyptian
Ministry of Health. Annual report 2007)
ABOUBAKR ELNASHAR
CDC have detected alarming trends in incident HCV rates:
1. Rate of new HCV infections in 2018 was 4 times as high as
2010
2) People of reproductive age born between 1975&2000 are
responsible for 60% of new diagnosis
3) Injection drug use is the primary route of HCV transmission.
CDC 2020, broaden HCV screening recommendations to all
pregnant women and adolescents during each pregnancy, except
in settings where the prevalence of HCV infection is less than
0.1%.
ABOUBAKR ELNASHAR
 AETIOLOGY:
 Family: Flaviviridae
 Nucleic Acid Structure: single stranded (+) RNA
 Genome Size (kb): 10–12
 Envelop: yes
ABOUBAKR ELNASHAR
2
ABOUBAKR ELNASHAR
2. DIAGNOSIS
 Symptoms
 Most are asymptomatic
 Non-specific symptoms associated with raised transaminase
 Serological diagnosis:
 IgG Anti-HCV, IgM Anti-HCV by 2nd or 3rd generation
enzyme immunoassay (ELISA)
 Identification of HCV RNA as antibodies are not detected
until late in the disease.
 ACOG, CDC, USPSTF recommend universal screening in pregnancy.
 If HCV Ab positive
 HCV RNA PCR testing to assess for active infection.
 Genotype testing can also be considered
ABOUBAKR ELNASHAR
 Outcome of acute HCV infection
ABOUBAKR ELNASHAR
3. TRANSMISSION
 HCV RNA has been detected in
 Blood
 Saliva
 Urine
 Menstrual fluid
 Breast milk
 Semen
 Methods primarily by contact with infected blood but not with
other body fluid
1. Blood: Parenteral
2. Sexual: very uncommom
3. MTCT: Vertical: 3 – 10 % Related to maternal Virous Load
ABOUBAKR ELNASHAR
 Needle sticks and sharp injuries
 Incidence:
 1.8% [Alter 1997; CDC 1998b].
 Transmission rarely occurs from mucous membrane exposures to
blood
 Management:
 No vaccine exists to prevent HCV infection
 Neither immunoglobulin nor antiviral therapy is
recommended [CDC, 1998].
 Follow-up: at baseline & 6 mons for seroconversion.
 Antivirals:
 when HCV RNA first becomes detectable
 {±prevent development of chronic infection}.
ABOUBAKR ELNASHAR
 Sexual transmission:
 Incidence:
 Very uncomm on with vaginal sex in serodiscordant
heterosexual couples.
 <5% of long-term sexual partners become infected. Due
to direct contact with infected body fluids (mostly blood).
 HCV should
 not viewed as STD from the perspective of population
health strategies (Giles et al, 2003)
 If pregnancy is not required, barrier methods are not
recommended in stable monogamous sexual partners
(National Institutes of HealthBacq & Lee, UpToDate , March 2015)
ABOUBAKR ELNASHAR
3
 Sexual partners of infected patients
 should be tested for HCV antibodies.
 Safe sexual practices
 Condom for those not trying to conceive (ASRM,2004).
 Minimize the extent of blood contact
 Covering open wounds
 Precautions:
 No need to avoid:
 close contact with family members or
 sharing meals or
 eating utensils.
ABOUBAKR ELNASHAR
 MTCT:
 Incidence:
 Rare 5% transmission risk in women with viraemia
 increased to ~10% in women with HIV co- infection
 Risk of V. transmission is enhanced by:
1. High level of HCV RNA titers:
> 106 copies/ml: 36%
<104 copies/ml: No transmission
2. Concomitant HIV.
3. Multiple risk factors
4. Invasive procedures e.g.
 Chorionic villous biopsy
 Fetal blood sampling
 Scalp electrode (Mazza et al,1998).
5. Membrane rupture >6 h prior to delivery (Resti et al., 1998)
Vertical
transmission (%)
Serostatus of the mother
<1
HCV RNA-
HCV Ab+
11
+
HCV RNA
HCV Ab+
16
and HIV
HCV RNA
+
Ab
HCV Ab+
ABOUBAKR ELNASHAR
Mother-to-child transmission of virus in women with chronic viral hepatitis. Potential opportunities for
transmission of viral infection from mother to infant can occur in utero, or during the peripartum and postpartum
periods.Data on in- utero transmission of hepatitis viruses are limited and based on detection of viraemia in
newborns within days of birth. As prenatal invasive procedures can theoretically lead to transfer of infectious blood
or body secretions from the maternal to the fetal compartment, this risk needs to be considered when
contemplating their use. Mother- to- child transmission (MTCT) requires the mother to be viraemic. Thus, the risk
period in mothers experiencing acute hepatitis (from any of the hepatitis viruses) will be shorter than in mothers
with chronic hepatitis (hepatitis B virus (HBV), hepatitis C virus (HCV) or hepatitis D virus infection). In women
with chronic HBV or chronic HCV infection, the most common period of transmission is during the peripartum
ABOUBAKR ELNASHAR
No association between V. transmission and
1. Gestational age
2. Type of delivery
3. Chorioamnionitis (Ohto et al,1994; Alter,1995).
4. Subsequent pregnancies.
5. Breast feeding.
6. The viral genotype
Preventing VT: Reducing maternal VL with
therapy
ABOUBAKR ELNASHAR
 Assisted conception: (ASRM,2004)
 HCV can be found in the semen (low levels of HCV RNA)
 Transmission of viral hepatitis in ART is possible, but the
magnitude of the risk is unknown
 Recommendation of ASRM,2004
1. Testing for HCV of high-risk infertile couples seeking fertility
therapy.
2. Testing for HCV of couple prior to cryopreservation of semen
or embryos
3.Semen and embryos from HCV patients should be stored in
HCV designated storage tanks
ABOUBAKR ELNASHAR
4. HEPATITIS C & PREGNANCY
1. Effect of pregnancy on HCV
No deleterious effect of pregnancy on the course of HCV
infection (Chard et al., 1986)
Course in pregnancy: Acute & chronic infections
2. Effect of HCV on pregnancy:
•Maternal risks
Increased rates of GDM, APH, PPH, PRO
20- fold increased risk of intrahepatic cholestasis
•Fetal risks: Increased rates of IUFG, preterm
delivery, SFGA and low birthweight
ABOUBAKR ELNASHAR
4
5. MANAGEMENT
a. Preconceptional
 Cure reproductive aged women prior to conception with
direct acting antiviral (DAA): improve health and eliminate
the risk of vertical transmission.
 Women who become pregnant while on DAA therapy (with
or without ribavirin) should discuss the risks versus benefits
of continuing treatment with their physicians.
ABOUBAKR ELNASHAR
b. Antenatal
1. Screening
 Benefits of screening: Detect at an early stage
asymptomatic adults:
1. Education and tt: Modify their alcohol intake, sexual
behavior and views on tissue and organ donation.
2. Mothers and children with ch hepatitis C should be
immunized against hepatitis A and B
{super infection may have a more severe course}
3. Identify children at risk of acquiring HCV
ABOUBAKR ELNASHAR
 How:
 Detection of HCV antibody implies persistent infection rather
than immunity.
 Anti-HCV, and if positive HCV RNA
ABOUBAKR ELNASHAR
 Types:
1. Universal=Routine
not justified in areas with low HCV prevalence e.g UK.
{lack of measures to prevent transmission and to treat the
infection efficiently}.
2. Selective: only
high risk categories or
if positive hepatitis B virus or HIV.
Disadvantages:
miss more than half of HCV positive pregnant women.
 Universal screening of pregnant women is better than risk
factor- based screening if prevalence of anti- HCV in
pregnant women is 0.03% or higher.
ABOUBAKR ELNASHAR
 Women in Whom Prenatal Screening for HCV Is Recommended
 Women who ever injected illegal drugs (even once)
 Users of intranasal illicit drugs
 Women ever on long-term hemodialysis
 Women with percutaneous/parenteral exposures in an unregulated
setting (eg, tattoos received outside licensed parlors or medical
procedures done in settings without strict infection control policies)
 Recipients of transfusions or organ transplants before July 1992
 Recipients of blood products from a donor who later tested positive for
HCV
 Women with a history of incarceration
 Women seeking evaluation or care for a sexually transmitted infection,
including HIV
 Women with unexplained chronic liver disease (including persistently
elevated ALT)
ABOUBAKR ELNASHAR
 Management of HCV-Positive Women in Pregnancy
 Prenatal testing
 Measure HCV RNA level to determine viral load
 Measure ALT, AST, bilirubin, prothrombin time, albumin,
and platelet to evaluate extent of liver disease
 Test for HCV genotype
 Screen for HIV, HBV, and HAV
 Prenatal management
 If susceptible to HBV or HAV, vaccinate
 Refer to a hepatologist
 Serial growth scans to monitor for f growth restriction
 AST indicates aspartate aminotransferase; HAV, hepatitis A virus.
ABOUBAKR ELNASHAR
5
 Maternal prevention:
 No maternal vaccination available
 Risk reduction or avoidance of drug use and/or sex partners
with HCV.
 Maternal TT:
 Supportive Care
 Antiviral therapy: Direct-acting antiviral (DAA)
 Now recommended for nearly all patients with ch HCV
infection.
 Use during pregnancy under investigation
 reduced risk of liver-related and all-cause mortality.
 Preventing VT: Reducing maternal VL with therapy
ABOUBAKR ELNASHAR
 There are few clinical trials evaluating the safety &efficacy of
DAAs in pregnancy.
 ledipasvir/sofosbuvir limited experience to a recently published
phase 1 trial with 100% cure and no safety concerns.
 Pangenotypic, There are no data yet
 Sofosbuvir/velpatasvir early studies are active
 Ribavirin is contraindicated in pregnancy due to teratogenicity
risk which persists for up to 6 months after cessation.
ABOUBAKR ELNASHAR
c. Intraparum
1. Elective Cesarean section
 not recommended
 {Role in reducing vertical transmission is uncertain}.
2. Vaginal delivery: Avoid
 internal fetal monitoring
 fetal blood sampling
 episiotomy
 prolonged rupture of membrane
 ventouse
ABOUBAKR ELNASHAR
 MTCT prevention
• Cure reproductive aged women prior to conception with direct
acting antiviral (DAA)
• DAA therapy during pregnancy to prevent mother- to- child
transmission (MTCT) is probably effective but safety studies
are lacking.
• Caesarean delivery not recommended but avoid intrapartum
invasive monitoring.
ABOUBAKR ELNASHAR
d. Postpartum
1. Breast feeding provided there are no cracked maternal nipples
Although HCV RNA can be found in breast milk, infection
through breastfeeding has not been demonstrated.
1. Found in tiny amount: Unable to infect newborn
2. Easily inactivated by gastric juices
3. The integrity of the oral and gastrointestinal
mucosa.
4. If nipples are not traumatized
ABOUBAKR ELNASHAR
Maternal follow- up:
 Mothers with hepatitis C virus (HCV) viraemia
should be offered antiviral therapy after delivery
and breastfeeding is complete.
Infant follow- up
 Early HCV RNA testing after 2 months has some
utility, but there are false- positives due to transient
viraemia
 Delay anti- HCV testing until 12–18 months to avoid
false- positives from passively transferred maternal
antibody.
ABOUBAKR ELNASHAR

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  • 1. 1 HEPATITS C AND PREGNANCY Prof. ABOUBAKR ELNASHAR Benha University Hospital, Egypt Email: elnashar53@hotmail.com ABOUBAKR ELNASHAR CONTENTS 1. Epidemiology & Aetiology 2. Diagnosis 3. Transmission 4. Hepatitis and pregnancy 1. Effect of pregnancy on hepatitis 2. Effect of hepatitis on pregnancy: Maternal risk, Fetal risk 5. Management a. Preconception b. Antenatal Prenatal testing Prenatal management Maternal prevention Maternal TT c. Delivery d. Postpartum: neonatal breast feeding Mat follow up Infant follow up Prevention of transmission ABOUBAKR ELNASHAR 1. EPIDEMIOLOGY& ETIOLOGY  In Egypt: Major health problem •20-40%: of the all-viral hepatitis. •Carrier state: High prevalence. •UK: 0.01–0.1% •Egypt: 17–26% (Wasley & Alter,2000) 16 % (Mohamoud et al.2013)  Assuit and Benha: 8%  Rural villages of the Nile Delta: 16%  The Ministry of Health revealed that the prevalence rate of Hepatitis C in 2021 reached 2 percent, marking a drop compared to 7 percent in 2018 ABOUBAKR ELNASHAR •70%: progress to chronic infection •30% of ch infection: develop cirrhosis over 10-30 y. •3%: annual development of hepatcellular carcinoma •92% infected population had HCV genotype 4 (Egyptian Ministry of Health. Annual report 2007) ABOUBAKR ELNASHAR CDC have detected alarming trends in incident HCV rates: 1. Rate of new HCV infections in 2018 was 4 times as high as 2010 2) People of reproductive age born between 1975&2000 are responsible for 60% of new diagnosis 3) Injection drug use is the primary route of HCV transmission. CDC 2020, broaden HCV screening recommendations to all pregnant women and adolescents during each pregnancy, except in settings where the prevalence of HCV infection is less than 0.1%. ABOUBAKR ELNASHAR  AETIOLOGY:  Family: Flaviviridae  Nucleic Acid Structure: single stranded (+) RNA  Genome Size (kb): 10–12  Envelop: yes ABOUBAKR ELNASHAR
  • 2. 2 ABOUBAKR ELNASHAR 2. DIAGNOSIS  Symptoms  Most are asymptomatic  Non-specific symptoms associated with raised transaminase  Serological diagnosis:  IgG Anti-HCV, IgM Anti-HCV by 2nd or 3rd generation enzyme immunoassay (ELISA)  Identification of HCV RNA as antibodies are not detected until late in the disease.  ACOG, CDC, USPSTF recommend universal screening in pregnancy.  If HCV Ab positive  HCV RNA PCR testing to assess for active infection.  Genotype testing can also be considered ABOUBAKR ELNASHAR  Outcome of acute HCV infection ABOUBAKR ELNASHAR 3. TRANSMISSION  HCV RNA has been detected in  Blood  Saliva  Urine  Menstrual fluid  Breast milk  Semen  Methods primarily by contact with infected blood but not with other body fluid 1. Blood: Parenteral 2. Sexual: very uncommom 3. MTCT: Vertical: 3 – 10 % Related to maternal Virous Load ABOUBAKR ELNASHAR  Needle sticks and sharp injuries  Incidence:  1.8% [Alter 1997; CDC 1998b].  Transmission rarely occurs from mucous membrane exposures to blood  Management:  No vaccine exists to prevent HCV infection  Neither immunoglobulin nor antiviral therapy is recommended [CDC, 1998].  Follow-up: at baseline & 6 mons for seroconversion.  Antivirals:  when HCV RNA first becomes detectable  {±prevent development of chronic infection}. ABOUBAKR ELNASHAR  Sexual transmission:  Incidence:  Very uncomm on with vaginal sex in serodiscordant heterosexual couples.  <5% of long-term sexual partners become infected. Due to direct contact with infected body fluids (mostly blood).  HCV should  not viewed as STD from the perspective of population health strategies (Giles et al, 2003)  If pregnancy is not required, barrier methods are not recommended in stable monogamous sexual partners (National Institutes of HealthBacq & Lee, UpToDate , March 2015) ABOUBAKR ELNASHAR
  • 3. 3  Sexual partners of infected patients  should be tested for HCV antibodies.  Safe sexual practices  Condom for those not trying to conceive (ASRM,2004).  Minimize the extent of blood contact  Covering open wounds  Precautions:  No need to avoid:  close contact with family members or  sharing meals or  eating utensils. ABOUBAKR ELNASHAR  MTCT:  Incidence:  Rare 5% transmission risk in women with viraemia  increased to ~10% in women with HIV co- infection  Risk of V. transmission is enhanced by: 1. High level of HCV RNA titers: > 106 copies/ml: 36% <104 copies/ml: No transmission 2. Concomitant HIV. 3. Multiple risk factors 4. Invasive procedures e.g.  Chorionic villous biopsy  Fetal blood sampling  Scalp electrode (Mazza et al,1998). 5. Membrane rupture >6 h prior to delivery (Resti et al., 1998) Vertical transmission (%) Serostatus of the mother <1 HCV RNA- HCV Ab+ 11 + HCV RNA HCV Ab+ 16 and HIV HCV RNA + Ab HCV Ab+ ABOUBAKR ELNASHAR Mother-to-child transmission of virus in women with chronic viral hepatitis. Potential opportunities for transmission of viral infection from mother to infant can occur in utero, or during the peripartum and postpartum periods.Data on in- utero transmission of hepatitis viruses are limited and based on detection of viraemia in newborns within days of birth. As prenatal invasive procedures can theoretically lead to transfer of infectious blood or body secretions from the maternal to the fetal compartment, this risk needs to be considered when contemplating their use. Mother- to- child transmission (MTCT) requires the mother to be viraemic. Thus, the risk period in mothers experiencing acute hepatitis (from any of the hepatitis viruses) will be shorter than in mothers with chronic hepatitis (hepatitis B virus (HBV), hepatitis C virus (HCV) or hepatitis D virus infection). In women with chronic HBV or chronic HCV infection, the most common period of transmission is during the peripartum ABOUBAKR ELNASHAR No association between V. transmission and 1. Gestational age 2. Type of delivery 3. Chorioamnionitis (Ohto et al,1994; Alter,1995). 4. Subsequent pregnancies. 5. Breast feeding. 6. The viral genotype Preventing VT: Reducing maternal VL with therapy ABOUBAKR ELNASHAR  Assisted conception: (ASRM,2004)  HCV can be found in the semen (low levels of HCV RNA)  Transmission of viral hepatitis in ART is possible, but the magnitude of the risk is unknown  Recommendation of ASRM,2004 1. Testing for HCV of high-risk infertile couples seeking fertility therapy. 2. Testing for HCV of couple prior to cryopreservation of semen or embryos 3.Semen and embryos from HCV patients should be stored in HCV designated storage tanks ABOUBAKR ELNASHAR 4. HEPATITIS C & PREGNANCY 1. Effect of pregnancy on HCV No deleterious effect of pregnancy on the course of HCV infection (Chard et al., 1986) Course in pregnancy: Acute & chronic infections 2. Effect of HCV on pregnancy: •Maternal risks Increased rates of GDM, APH, PPH, PRO 20- fold increased risk of intrahepatic cholestasis •Fetal risks: Increased rates of IUFG, preterm delivery, SFGA and low birthweight ABOUBAKR ELNASHAR
  • 4. 4 5. MANAGEMENT a. Preconceptional  Cure reproductive aged women prior to conception with direct acting antiviral (DAA): improve health and eliminate the risk of vertical transmission.  Women who become pregnant while on DAA therapy (with or without ribavirin) should discuss the risks versus benefits of continuing treatment with their physicians. ABOUBAKR ELNASHAR b. Antenatal 1. Screening  Benefits of screening: Detect at an early stage asymptomatic adults: 1. Education and tt: Modify their alcohol intake, sexual behavior and views on tissue and organ donation. 2. Mothers and children with ch hepatitis C should be immunized against hepatitis A and B {super infection may have a more severe course} 3. Identify children at risk of acquiring HCV ABOUBAKR ELNASHAR  How:  Detection of HCV antibody implies persistent infection rather than immunity.  Anti-HCV, and if positive HCV RNA ABOUBAKR ELNASHAR  Types: 1. Universal=Routine not justified in areas with low HCV prevalence e.g UK. {lack of measures to prevent transmission and to treat the infection efficiently}. 2. Selective: only high risk categories or if positive hepatitis B virus or HIV. Disadvantages: miss more than half of HCV positive pregnant women.  Universal screening of pregnant women is better than risk factor- based screening if prevalence of anti- HCV in pregnant women is 0.03% or higher. ABOUBAKR ELNASHAR  Women in Whom Prenatal Screening for HCV Is Recommended  Women who ever injected illegal drugs (even once)  Users of intranasal illicit drugs  Women ever on long-term hemodialysis  Women with percutaneous/parenteral exposures in an unregulated setting (eg, tattoos received outside licensed parlors or medical procedures done in settings without strict infection control policies)  Recipients of transfusions or organ transplants before July 1992  Recipients of blood products from a donor who later tested positive for HCV  Women with a history of incarceration  Women seeking evaluation or care for a sexually transmitted infection, including HIV  Women with unexplained chronic liver disease (including persistently elevated ALT) ABOUBAKR ELNASHAR  Management of HCV-Positive Women in Pregnancy  Prenatal testing  Measure HCV RNA level to determine viral load  Measure ALT, AST, bilirubin, prothrombin time, albumin, and platelet to evaluate extent of liver disease  Test for HCV genotype  Screen for HIV, HBV, and HAV  Prenatal management  If susceptible to HBV or HAV, vaccinate  Refer to a hepatologist  Serial growth scans to monitor for f growth restriction  AST indicates aspartate aminotransferase; HAV, hepatitis A virus. ABOUBAKR ELNASHAR
  • 5. 5  Maternal prevention:  No maternal vaccination available  Risk reduction or avoidance of drug use and/or sex partners with HCV.  Maternal TT:  Supportive Care  Antiviral therapy: Direct-acting antiviral (DAA)  Now recommended for nearly all patients with ch HCV infection.  Use during pregnancy under investigation  reduced risk of liver-related and all-cause mortality.  Preventing VT: Reducing maternal VL with therapy ABOUBAKR ELNASHAR  There are few clinical trials evaluating the safety &efficacy of DAAs in pregnancy.  ledipasvir/sofosbuvir limited experience to a recently published phase 1 trial with 100% cure and no safety concerns.  Pangenotypic, There are no data yet  Sofosbuvir/velpatasvir early studies are active  Ribavirin is contraindicated in pregnancy due to teratogenicity risk which persists for up to 6 months after cessation. ABOUBAKR ELNASHAR c. Intraparum 1. Elective Cesarean section  not recommended  {Role in reducing vertical transmission is uncertain}. 2. Vaginal delivery: Avoid  internal fetal monitoring  fetal blood sampling  episiotomy  prolonged rupture of membrane  ventouse ABOUBAKR ELNASHAR  MTCT prevention • Cure reproductive aged women prior to conception with direct acting antiviral (DAA) • DAA therapy during pregnancy to prevent mother- to- child transmission (MTCT) is probably effective but safety studies are lacking. • Caesarean delivery not recommended but avoid intrapartum invasive monitoring. ABOUBAKR ELNASHAR d. Postpartum 1. Breast feeding provided there are no cracked maternal nipples Although HCV RNA can be found in breast milk, infection through breastfeeding has not been demonstrated. 1. Found in tiny amount: Unable to infect newborn 2. Easily inactivated by gastric juices 3. The integrity of the oral and gastrointestinal mucosa. 4. If nipples are not traumatized ABOUBAKR ELNASHAR Maternal follow- up:  Mothers with hepatitis C virus (HCV) viraemia should be offered antiviral therapy after delivery and breastfeeding is complete. Infant follow- up  Early HCV RNA testing after 2 months has some utility, but there are false- positives due to transient viraemia  Delay anti- HCV testing until 12–18 months to avoid false- positives from passively transferred maternal antibody. ABOUBAKR ELNASHAR