Is it Time for Universal Prenatal Hepatitis C Screening?

BACKGROUND AND PURPOSE:

  • SMFM recommends screening for hepatitis C in pregnancy in women who are at high risk (see ‘Related ObG Topics’ below)
  • New medications can result in 95–99% Hepatitis C virus (HCV) cure
  • Due to opioid epidemic, incidence of HCV is rising in younger individuals
  • Tasillo et al. (Obstetrics & Gynecology, 2019) sought to determine the clinical effects and cost-effectiveness of universal prenatal hepatitis C screening using computer modeling

METHODS:

  • Stochastic individual-level micro-simulation model to simulate the lifetimes of 250 million pregnant women
  • Women were matched at baseline with the U.S. childbearing population for
    • Age
    • Injection drug use behaviors
    • Hepatitis C virus (HCV) infection status
  • Modeled outcomes included
    • Hepatitis C diagnosis | Treatment | Cure | Lifetime health care costs | Quality-adjusted life years (QALY) | Incremental cost-effectiveness ratios comparing universal prenatal hepatitis C screening to current practice
  • Authors also modeled the identification of neonates exposed to maternal HCV at birth

RESULTS:

  • Universal prenatal hepatitis C screening compared to current practice resulted in
    • Pregnant women with hepatitis C infection living 1.21 years longer and 16% lower HCV-attributable mortality
    • an incremental cost-effectiveness ratio of $41,000 per QALY gained
  • Incremental cost-effectiveness ratios remained below $100,000 per QALY gained in most additional analyses
    • Notable exceptions included
      • Incremental cost-effectiveness ratios above $100,000 when assuming mean time to cirrhosis of 70 years
      • A cost greater than $500,000 per false positive diagnosis
      • Population HCV infection prevalence below 0.16%
    • Universal prenatal hepatitis C screening increased identification of neonates exposed to HCV at birth from 44% to 92%

CONCLUSION:

  • Universal prenatal hepatitis C screening would result in
    • Improved health outcomes in women with HCV infection
    • Improved identification of at risk HCV-exposed newborns
  • The authors demonstrated that universal hepatitis C screening is cost effective and further state

Universal prenatal HCV testing should be considered in plans for the elimination of viral hepatitis C as a public health threat.

Learn More – Primary Sources:

Short-Term Effects and Long-Term Cost-Effectiveness of Universal Hepatitis C Testing in Prenatal Care

SMFM Releases Guidelines on Screening and Management of Hepatitis C in Pregnancy 

SUMMARY:

SMFM has released guidance on the screening, treatment and management of women infected with hepatitis C virus (HCV) in pregnancy. HCV is a global problem with at least 1% to 2.5% of women infected in the US alone. 8% of pregnant women are infected and there is a risk of transmission to the fetus.

KEY POINTS:

  • Acute Hepatitis C  occurs within the first 6 months after exposure to HCV
  • Most women will remain asymptomatic, with only 25% exhibiting symptoms | Symptoms typically appear within 2 to 12 weeks (range of 2 to 26 weeks) 
  • 15% of patients will spontaneously clear the virus within 6 months
  • Signs and symptoms of acute HCV infection
    • Fever | Fatigue | Dark urine | Clay-colored stool | Abdominal pain | Loss of appetite | Nausea and vomiting | Joint pain | Jaundice
    • Most individuals with newly acquired HCV infection will be asymptomatic 
  • Signs and of chronic HCV infection
    • Most people are asymptomatic or have non-specific symptoms (e.g., chronic fatigue and depression)
    • Many eventually develop chronic liver disease, which can range from mild to severe, including cirrhosis and liver cancer
    • Chronic HCV infection is typically not recognized until asymptomatic people are identified as HCV-positive when screened for blood donation or liver function tests return an abnormal result (e.g., elevated ALT), often during routine evaluation 

HCV and Pregnancy 

  • Pregnancy may be associated with a decrease in HCV liver damage, however data is conflicting 
  • HCV is associated with poor pregnancy outcomes 
    • Small for gestational age 
    • Fetal growth restriction  
    • Low birthweight 
    • Increased NICU admissions  
    • Preterm birth 
    • Intrahepatic cholestasis of pregnancy (odds with HCV are increased 20-fold over non-HCV population)
  • Congenital anomalies and GDM have also been reported 
  • Above findings are associations only and more research is required to determine causation

HCV and Vertical Transmission 

  • The risk of transmission is approximately 5%  
  • Risk only for women with detectable HCV RNA during pregnancy 
  • A pooled meta-analysis of 17 studies demonstrated the following risks in women with chronic HCV 
    • HIV neg: 5.8% 
    • HIV pos: 10.8% but may be lower in women using modern antiretroviral therapies 

Screening for HCV in Pregnancy 

SMFM recommends risk-based HCV screening in pregnancy

  • Screen high risk women at the first prenatal visit 
    • Past or current injection drug use (even once) 
    • Blood transfusion or transplants before July 1992 
    • Unregulated tattoo 
    • Long-term hemodialysis 
    • Intranasal drug use and other percutaneous exposures 
    • Long-term hemodialysis 
    • Recipients of clotting factor concentrates produced before 1987 
    • Recipients of blood products from donor who later tested positive for HCV 
    • History of incarceration 
    • Women seeking evaluation or care for sexually transmitted infection including HIV 
    • Unexplained chronic liver disease (including persistently elevated ALT) 

SMFM recommendations (Grade 1B) 

  • Test for anti-HCV antibodies at their first prenatal visit 
  • Negative anti-HCV antibodies 
    • Repeat later in pregnancy in women with persistent or new risk factors 
    • If HCV exposure < 6 months, perform HCV RNA as patient may not have seroconverted  
    • Positive anti-HCV antibodies: Follow up with HCV RNA 
  • Universal HCV screening is not recommended 

Obstetrical Management 

  • Invasive prenatal diagnosis 
    • Data on risk of invasive testing appears ‘reassuring but limited’ 
    • Amniocentesis recommended over CVS (Grade 2C) 
  • HCV is not an indication for cesarean section in isolation (Grade 1B) 
  • Avoid internal fetal heart monitoring, prolonged rupture of membranes and episiotomy (Grade 1B) 

Treatment  

  • Screen for other for other STDs (Grade 1B) 
    • Overlapping risk factors between HCV and HBV  
  • Counsel patients to avoid alcohol (Best Practice)  
  • No antiviral therapies for HCV infection are approved in pregnancy 
    • Direct-acting antiviral (DAA) agents should only be used in pregnancy in the setting of a clinical trial or defer to postpartum (Grade 1C) 
  • Ribavirin is contraindicated in pregnancy due to potential teratogenicity 

Postpartum  

  • Breast feeding should NOT be discouraged (Grade 1A) 
  • Presence of anti-HCV antibodies in newborn is not diagnostic 
  • The CDC recommends that  
    • Children should be tested for anti-HCV > age 18 months because anti-HCV from the mother might last until this age 
    • If diagnosis is desired before the child turns 18 months, testing for HCV RNA could be performed at or after the infant’s first well-child visit at age 1–2 months 
      • HCV RNA testing should then be repeated at a subsequent visit, independent of the initial HCV RNA test result 

Other Guidance on Prenatal Screening for HCV

  • ACOG also currently advise risk-based screening
  • USPSTF recommends universal screening, including pregnant women,  between ages 18 and 79|The USPSTF guidelines include the following data and rationale for potentially offering screening to pregnant women <18 years of age
    • HCV prevalence has doubled in women aged 15 to 44 years (2006 to 2014)
    • 0.73% of pregnant women tested had an HCV infection (2011 to 2014), with a 68% increase in the proportion of infants born to HCV-infected mothers
    • Approximately 1700 infected infants are born annually to 29,000 HCV-infected mothers
    • “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 recommends universal screening for HCV
  • AASLD and IDSA (2018) recommend universal screening in pregnancy, ideally at the initiation of prenatal care (see ‘Learn More – Primary Sources’ below)

Learn More – Primary Sources:  

SMFM Consult Series #43, Hepatitis C in pregnancy: screening, treatment, and management

AASLD / IDSA: HCV in Pregnancy

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

What is the Effect of Hepatitis C on Fertility and Pregnancy Outcomes?

BACKGROUND AND PURPOSE:

  • Hepatitis C in premenopausal women can lead to failing ovarian function
  • Karampatou (Journal of Hepatology, 2017) assessed fertility and adverse pregnancy outcomes in HCV+ women

METHODS:

  • 3 different cohorts were studied:
    • 100 HCV+ women with chronic liver disease (CLD), were age matched in a 2:1 proportion with 50 HBV+ women with CLD and 1:1 proportion with 100 healthy women (Italian GI unit)
    • 1,998 HCV+ women enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER)
    • 6,085 HCV+; 20,415 HCV-/HIV-; 305 HCV+/HIV+ women from a large de-identified insurance database from US
  • Total fertility rate (TFR) was defined as the average number of children that a woman would bear during her lifetime
  • Anti-mullerian hormone (AMH) and 17β-Estradiol were used to define reproductive stage

RESULTS:

  • Data from group 1
    • HCV+ and HBV+ women had similar CLD and age at first pregnancy
    • HCV+ women had higher risk of miscarriage than HBV+ (odds ratio [OR] 6.905; 95% CI 1.771-26.926)
    • HCV infection alone (OR 9.363; 95% CI 2.569-34.123, P<0.001) was significantly associated with miscarriage (multivariate analysis)
    • HCV+ women more likely to have AMH levels in the menopausal range compared to HBV+ women
    • Achieving sustained virologic response after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723) compared to women who failed antiviral therapy
  • PITER cohort
    • Miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages)
  • TFR for HCV+ women between 15 and 49 years was 0.7 vs. 1.37 of Italian population of the same age range
  • US cohort
    • HCV+ compared to HCV- women had a significantly higher probability of
      • Infertility (OR 2.439; 95% CI 2.130-2.794)
      • Premature birth (OR 1.34; 95% CI 1.06-1.69)
      • Gestational diabetes (OR 1.24; 95% CI 1.02-1.51)
      • Less likely to report a live birth (OR 0.754; 95% CI 0.622-0.913)

CONCLUSION:

  • HPV+ women are more likely to suffer from a number of adverse pregnancy outcomes and impaired fertility and miscarriage
  • These outcomes may be positively influenced by the newer generation of antiviral drugs

Learn More – Primary Sources:

Premature ovarian senescence and high miscarriage rate impair fertility in women with hepatitis C virus infection