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

• The same regimens recommended for chronic HCV infections are recommended for acute infection

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 considerations

• Advise abstinence from alcohol and acetaminophen during acute infection                
• Evaluate for hepatitis B and HIV infection
• Vaccinate against Hepatitis A and Hepatitis B
• Evaluation for advanced hepatic fibrosis with
  • Elastography or liver imaging (US or CT Scan)
  • FIB-4 Score (see ‘Learn More – Primary Sources’ below for calculator)
  • Lab tests: ALT | AST | Albumin | Bilirubin | INR | CBC
• Provide education on how to prevent HCV transmission to others

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

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

Fibrosis-4 (FIB-4) Calculator – Clinical Calculators – Hepatitis C Online (uw.edu)

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

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