Review the latest recommendations with

Katherine S. Kohari, MD, FACOG

Dr. Kohari, a Maternal-Fetal Medicine specialist, is an Assistant Professor and the Medical Director for MFM Outpatient Services in the Department of Obstetrics and Gynecology at the Yale School of Medicine in New Haven, CT

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Learning Objectives: Upon completion of this activity, participants should be better able to

• Screen and diagnose Hepatitis C (HCV) in pregnancy
• Understand risks of and to pregnancy complicated by HCV
• Manage laboring patients with HCV
• Recommend postpartum care for follow-up and treatment

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• The Case
• Part 1: Screening
• Part 2: Pregnancy Implications
• Part 3: HCV In Laboring Patients
• Part 4: Postpartum Care and Treatment
• The Wrap-Up

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The Case

• 31 yo G2P1001, with a history of full term VD presents for initial prenatal visit @ 11 weeks of pregnancy
  • History significant for polysubstance abuse in her early 20’s
  • She is on methadone and admits to daily tobacco use

Chief Complaint

• Has been feeling well but is nervous about the pregnancy as she thinks she was recently told she has hepatitis C
• Reports compliance with her methadone and regularly attends rehabilitation program

Synopsis – HCV Overview

The incidence of hepatitis C in the United States among pregnant women is on the rise partly due to the opioid epidemic and the use of illicit intravenous drugs. It is estimated that approximately 1 to 2.5% of pregnant women in the US are HCV positive. While 15 to 45% of patients who contract hepatitis C will go on to completely clear the virus, the remainder will have chronic infection, increasing their risk for cirrhosis and subsequent hepatocellular carcinoma. In fact, HCV is the most common cause of chronic liver disease in the US. In pregnancy there is a 5% risk for vertical transmission.

Recent developments in pharmaceutical discovery have resulted in direct acting antivirals (DAAs) whose use effectively cures hepatitis C. The following are key points that are helpful in the diagnosis and management of hepatitis C in pregnancy and the postpartum period.

Part 1: Screening

Professional Recommendations

• American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA)
  • Recommend universal screening for HCV in pregnant women, ideally at the first prenatal visit
  • Recommendations aimed at improving linkage to care and supported by a recent cost effectiveness study
• USPSTF
  • The USPTF updated its guidelines to reflect routine screening of all adults ages 18-79, including pregnant women
  • Because of the increasing prevalence of HCV in women aged 15 to 44 years and in infants born to HCV-infected mothers, clinicians may want to consider screening pregnant persons younger than 18 years
• CDC
  • All pregnant women should be screened for HCV during each pregnancy (except in settings where the prevalence of HCV infection is <0.1%)

ACOG & SMFM Guidance

• ACOG has released a Practice Advisory, endorsed by SMFM that aligns with other professional bodies. The document reviews the USPSTF and CDC guidance (above) and states the following

The American College of Obstetricians and Gynecologists is updating its hepatitis C screening guidance to recommend screening for all pregnant individuals during each pregnancy

Hepatitis C screening during the first prenatal blood assessment obtained in every pregnancy is recommended to identify pregnant individuals with HCV infection and infants who should receive testing at a pediatric visit.

Screening Tests

• HCV is tested by evaluating the presence of anti-HCV antibodies in the plasma
  • If this results as positive, additional quantitative HCV RNA should be performed to confirm HCV infection and establish a baseline value
• Genotype testing may also be performed to help guide later treatment
• If a high-risk patient tests negative, consider repeat testing later in the pregnancy
• The presence of HCV antibodies may indicate any of the following situations
  • Prior acute HCV infection, now cleared or treated
  • Ongoing acute infection
  • Chronic infection
• Patients being tested for HCV should also be evaluated for
  • Infections: Hepatitis B | HIV | Gonorrhea | Chlamydia | Syphilis
  • Hepatic assessment: Liver function tests | Platelet count | Coagulation profile

Note: There is no role for serial viral loads or liver function tests for the purposes of HCV monitoring

Part 2: Pregnancy Implications

• HCV in pregnancy has been associated with adverse pregnancy outcomes including
  • Poor fetal growth | Preterm birth | Need for respiratory support in the neonatal period
• However, it is often difficult to distinguish the isolated risk for adverse pregnancy outcomes with HCV compared with the often-present confounding variables of the patient population most associated with HCV infection
  • Examples
    • Methadone use, and tobacco exposure have both been linked to low birthweight
    • Pregnant women with HCV are at a significantly higher risk for developing intrahepatic cholestasis of pregnancy | Therefore, it is important to screen for clinical symptoms of ICP
• Impact of pregnancy on HCV prognosis
  • Data do not indicate that pregnancy worsens the prognosis for HCV
  • In fact, some data suggest hepatocellular damage due to HCV decreases in pregnancy
    • Alanine aminotransferase levels typically decrease in the second and third trimester likely owing to the immunomodulation associated with pregnancy
  • Similarly, the delay to treatment until the postpartum period does not appear to worsen long term outcomes
• Referral and Care Plan
  • Women with a diagnosis of HCV in pregnancy should be referred to a hepatologist or infectious disease specialist if not already under their care
  • Pregnancy is often the only time women in their reproductive years seek healthcare therefore an Obstetrician/Gynecologist should facilitate access to healthcare providers to manage this and other chronic medical conditions
  • Consultation with a Maternal-Fetal Medicine subspecialist to assist with management during pregnancy and to help coordinate multidisciplinary postpartum follow up should considered

Part 3: HCV In Laboring Patients

• Vertical transmission risk
  • The risk of vertical transmission is approximately 5% | Risk increased if the patient is coinfected with untreated HIV | Unclear if the value of the viral load affects the rate of transmission
• Mode of delivery
  • Does not appear to prevent vertical transmission of HCV, regardless of viral load
  • Allow patients to labor unless otherwise contraindicated
• Procedures and interventions on L&D
  • The use of fetal scalp electrodes, and operative vaginal delivery should be discouraged
  • Prolonged rupture of membranes and the use of episiotomy have been associated with increased rates of vertical transmission
  • Universal precautions should be followed | Delivering providers should wear a face mask, gown and gloves to prevent occupational transmission

Part 4: Postpartum Care and Treatment

Breastfeeding

• Breastfeeding should be encouraged in women with HCV
• If cracked or bleeding nipples are noted
  • Expressed milk should be discarded until nipples heal

Direct Acting Antiviral (DAA) HCV Therapy

• DAA has now made chronic HCV a curable condition
  • These medications have replaced the previously used pegylated interferon and ribavirin
  • Compared to their predecessors, DAA medications are
    • Better tolerated
    • More efficacious: Sustained virologic response rates are >95%
• DAA medications are direct inhibitors of HCV replication
  • DAA medications act on one of three target proteins
  • There are 6 different genotypes for HCV
  • Therefore, DAA is combined with a second DAA to provide distinct modes of action, multi-genotype coverage and non-overlapping resistance profiles
  • Additionally, only second generation DAA medications are recommended for treatment of HCV owing to improved side effects profiles

• DAA and pregnancy
  • There is no safety data regarding the use of these medications in pregnancy
  • Therefore, defer HCV treatment until after delivery
  • Phase 1 trials underway to evaluate the safety and efficacy of DAA therapy in pregnancy with the goal of avoiding delay of treatment to the postpartum period

Transition of Care

• Due to changing treatment recommendations and required expertise
  • All women in the postpartum period should establish hepatology or infectious disease care to follow their genotyping and to initiate treatment
  • Coordination of care in the postpartum period is essential for the long-term care and management

The Wrap-Up

• The above patient would be considered high risk due to history of polysubstance abuse and should be screened for HCV
  • If she tests positive, appropriate referrals should be made to initiate work-up and develop a care plan for pregnancy and treatment postpartum
• Incidence of HCV is on the rise due to multiple factors, primarily due to increasing opiate crisis in the United States
• Pregnancies in women with HCV often proceed without major complication but obstetricians should view this diagnosis as an opportunity to enhance access to medical care
• There is no current treatment for HCV in pregnancy, but with the advent of DAA’s, chronic HCV can be considered curable
  • Therefore, Ob-Gyns or MFMs should assist their patients in establishing care with a hepatologist for long term follow up and initiation of treatment
• Given the changing landscape of management for patients with HCV, it is essential that those caring for HCV patient be current and knowledgeable regarding all aspects of care
• A multidisciplinary team is felt to be most successful in achieving comprehensive and up to date care for these patients, possibly including Ob/Gyn, MFM, Infectious Disease, Hepatology, and GI

Learn More – Primary Sources

AASLD/IDSA: HCV in Pregnancy 

ACOG Clinical Practice Guideline 6: Viral Hepatitis in Pregnancy | ACOG

AASLD/IDSA: Hepatitis C Guidance 2019 Update – American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

CDC: Hepatitis C FAQs for Health Professionals 

CDC Recommendations for Hepatitis C Screening Among Adults — United States, 2020

Reported Prevalence of Maternal Hepatitis C Virus Infection in the United States 

USPSTF: Screening for Hepatitis C Virus Infection in Adolescents and Adults US Preventive Services Task Force Recommendation Statement 

Short-term Effects and Long-term Cost-Effectiveness of Universal Hepatitis C Testing in Prenatal Care (Tasillo et al. Obset Gynecol, 2019)

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Commercial Support

This educational activity is supported by an independent educational grant from Gilead Sciences

Faculty Disclosures

Dr. Kohari reports that she has no relevant financial relationships to disclose

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