USPSTF Recommends Universal Screening for Hepatitis C

SUMMARY:

  • USPSTF has reviewed available evidence and has updated its hepatitis C screening guidance. HCV is the most common chronic blood-borne pathogen in the US with potential for significant morbidity and mortality if left untreated. The prevalence of chronic HCV infection in the US is approximately 1.0% (2013 to 2016), with 44,700 new HCV infections in 2017. There has been an increase in acute infections over the last decade primarily due to increased injection drug use and better surveillance.
  • The USPSTF recommends screening for HCV infection in adults aged 18 to 79 years
  • Population: All asymptomatic adults aged 18 to 79 years without known liver disease
  • B level recommendation
    • Offer or provide this service
    • There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial

The USPSTF concludes with moderate certainty that screening for HCV infection in adults aged 18 to 79 years has substantial net benefit

Risk Assessment

  • Screen all adults ages 18 to 79 years
  • Risk factors to consider
    • Injection drug use: Consider screening adolescents <18 years or >79 years
      • Young adults (ages 18 to 30): Approximately 30% are infected
      • Older adults: 70% to 90% are infected
  • Pregnancy
    • Screen pregnant adults  

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

Screening Test

  • Anti-HCV antibody testing followed by polymerase chain reaction testing for HCV RNA
    • HCV infection can be detected by anti-HCV screening tests (enzyme immunoassay) 4 to 10 weeks after infection
    • Delayed seroconversion may occur in immunocompromised individuals (e.g., those with HIV infection)

Screening Intervals

  • “Most adults need to be screened only once”
    • Consider more frequent screening for individuals with ongoing risk (e.g., ongoing injection drug use)
    • Data is limited to determine optimal screening interval for those at continued risk or whether pregnancy impacts need for additional screening

KEY POINTS:

Hepatitis C Overview

  • Acute Hepatitis C occurs within the first 6 months after exposure to HCV
  • Many individuals will remain asymptomatic
  • 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 | 20 to 30% will exhibit symptoms
    • Symptoms will usually appear within 2 to 12 weeks (range: 2–26 weeks) 
  • 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 

Hepatitis C Treatment

Acute

  • No treatment required
  • Consider treatment if HCV RNA persists after 6 months

Chronic

  • Current antiviral therapies can result in sustained virologic response (SVR; absence of detectable virus 12 weeks after completion of treatment)
    • SVR is indicative of a cure of HCV infection
    • Over 90% of HCV infected persons can be cured of HCV infection regardless of HCV genotype with 8-12 weeks of oral therapy
    • CDC provides a link to currently approved FDA therapies to treat hepatitis C (see ‘Learn More – Primary Sources’ below)

Other Professional Recommendations

  • AASLD/IDSA
    • One-time, routine, opt out HCV testing is recommended for all individuals aged 18 years and older
    • One-time HCV testing should be performed for all persons less than 18 years old with behaviors, exposures, or conditions or circumstances associated with an increased risk of HCV infection
    • Periodic repeat HCV testing should be offered to all persons with behaviors, exposures, or conditions or circumstances associated with an increased risk of HCV exposure
    • Annual HCV testing is recommended for all persons who inject drugs and for HIV-infected men who have unprotected sex with men
    • As part of prenatal care, all pregnant women should be tested for HCV infection, ideally at the initial visit
  • CDC
    • All adults 18 years and older (except in settings where the prevalence is > 0.1%)
    • All pregnant persons should be screened for HCV during each pregnancy (except in settings where the prevalence of HCV infection is > 0.1%)
    • All persons with risk factors (eg., persons with HIV, prior recipients of blood transfusions, persons who ever injected drugs and shared needles, and persons who are born to an HCV-infected mother) should be tested for HCV, with periodic testing while risk factors persist
  • SMFM (see ‘Related ObG Topics’ below) has released new guidance supporting the USPSTF/CDC recommendations and states

…we recommend that obstetrical providers screen all pregnant patients for HCV by testing for anti-HCV antibodies in every pregnancy

The timing of when to screen during pregnancy is somewhat arbitrary; screening in the first trimester would theoretically bring the most patients to attention at the earliest time

Learn More – Primary Sources:

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

AASLD / IDSA: HCV Testing and Linkage to Care

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

CDC link to FDA therapies to treat hepatitis C

Hepatitis C Questions and Answers for Health Professionals

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

SMFM Consult Series #56: Hepatitis C in pregnancy—updated guidelines

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