Hepatitis C—New Guidelines Expand Screening Recommendations 

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. It is associated with more deaths than the top 60 other reportable infectious diseases combined, including HIV infection.1,2 While almost all people with hepatitis C can now be cured, a large portion of people with chronic HCV infection do not know they have it.1

This newsletter will discuss HCV infection and new screening guidelines. The guidelines reflect the changing demographics of high-risk populations, which have been influenced by the opioid epidemic in recent years. Laboratory testing identifies individuals with HCV infection and guides treatments that are effective in nearly 100% of patients.
HCV Infection 
HCV is a single-stranded RNA virus with 7 major genotypes. It is most often transmitted through blood, historically (prior to 1992) from contaminated blood products received during transfusions and currently via sharing needles for injection drug use.3

Soon after exposure to HCV, people may develop acute infection. Most people with acute infection don’t have symptoms, but about 30% experience symptoms such as fever, jaundice, and abdominal pain.3

For about 15% to 25% of adults with acute HCV infection, the infection goes away on its own.3 Others develop chronic HCV infection, defined as the presence of detectable HCV RNA at least 6 months after the acute infection.3

People with chronic HCV infection are at risk of developing liver complications including fibrosis with subsequent cirrhosis and decompensation; hepatocellular carcinoma (HCC); extrahepatic manifestations such as diabetes mellitus, B cell lymphoma, and membranoproliferative glomerulonephritis; and chronic fatigue.3 
HCV Prevalence and Incidence
Approximately 4.1 million persons in the United States are estimated to have past or current infection with HCV; of these, 2.4 million have current infection.1 Approximately 45,000 new cases of HCV were estimated to have occurred in the United States in 2017, and cases of acute HCV infection have increased approximately 3.8-fold over the last decade (2010 to 2017). The increases reflect improved surveillance and increasing injection drug use.1
An Important Risk Group for HCV Infection—People Who Inject Drugs 
Prior screening recommendations acknowledged that being born between 1945 and 1965, a generation known as “baby boomers”, was an important risk factor for HCV infection.4 The epidemiology of HCV infection has changed over the past 2 decades and now the most important risk factor for HCV infection is past or present injection drug use—a reflection of hepatitis C incidence increasing in parallel with injection opioid use during the ongoing opioid epidemic.5

Although the incidence of hepatitis C infection has increased across all age groups, the increase has been most rapid among adults younger than 40 years and in nonurban settings.6

Approximately one-third of people who inject drugs (PWID) aged 18 to 30 years are infected with HCV and 70% to 90% of older PWID are also infected.1 Because many PWID are women of reproductive age, perinatal transmission of HCV has also increased.7
Screening Guidelines
Guidelines from the United States Preventive Services Task Force (USPSTF) recommend screening all adults 18 to 79 years of age for HCV infection.1 In addition to injection drug use, other factors also increase the risk of contracting HCV (see Sidebar).8 The guidelines also suggest that clinicians consider screening at-risk adolescents younger than 18 years and at-risk adults older than 79 years.

The guidelines indicate that most adults need to be screened only once in their lifetime and that persons with continued risk for HCV infection (eg, PWID) should be screened periodically.1 However, there is limited information about optimal screening intervals for people who continue to be at risk for new HCV infection or how pregnancy changes the need for additional screening.1

Screening all adults has been shown to be cost-effective,5 and the USPSTF grade B recommendation means that insurance companies will provide reimbursement for hepatitis C testing without cost-sharing by patients.9

The updated USPSTF screening guidelines are consistent with those of the American Association for the Study of Liver Diseases/Infectious Diseases Society of America (AASLD/IDSA) and the Centers for Disease Control and Prevention (CDC), with minor differences:
  • The AASLD/IDSA guidelines include a lower graded recommendation for annual screening for PWID and for men with HIV who have unprotected sex with men.8
  • The CDC recommends screening all adults aged ≥18 years once in their lifetime, but includes an exception in settings where the prevalence of HCV infection is <0.1% (no state currently meets this threshold) and repeat screening with each pregnancy due to the risk of vertical transmission.5
HCV Treatment Is Effective in Nearly 100% of Patients
Direct antiviral agents (DAAs) were introduced in 2014 as a treatment for HCV infection.10 DAAs interrupt HCV replication by targeting the HCV NS3/4A protease, the NS5B polymerase, or the NS5A protein.10 They are orally administered over a course of 8 to 12 weeks and have sustained virological response (SVR) rates (cure rates) of ≥95% in persons with HCV infection.10 The high cure rates include persons with HIV, end-stage renal disease, and cirrhosis.8 Pan-genotypic regimens are now recommended as first-line treatment for people with chronic HCV infection and are now the standard of care.8,11

Results of randomized clinical trials showed that newer all-oral regimens are associated with SVR rates of up to 99% after 8 to 12 weeks of treatment.12 Observational studies found that a wide variety of patient populations, including PWID, had similarly high SVR rates.12 The USPSTF reported that SVR was associated with decreased risk of liver-related mortality (pooled hazard ratio [HR] = 0.11), decreased risk of hepatocellular carcinoma (pooled HR = 0.29), and decreased all-cause mortality (pooled HR = 0.40).12 These results formed the basis for the USPSTF’s expanded screening recommendations.

The AASLD/IDSA published comprehensive management guidelines for persons with HCV8 and simplified treatment guidelines for those with uncomplicated infections.13








References
  1. US Preventive Services Task Force. Screening for hepatitis C virus infection in adolescents and adults: US Preventive Services Task Force Recommendation Statement JAMA. 2020;323(10):970-975. doi:10.1001/jama.2020.1123
  2. Ly KN, Hughes EM, Jiles RB, et al. Rising mortality associated with hepatitis C virus in the United States, 2003-2013. Clin Infect Dis. 2016;62(10):1287-1288. doi:10.1093/cid/ciw111
  3. Millman AJ, Nelson NP, Vellozzi C. Hepatitis C: review of the epidemiology, clinical care, and continued challenges in the direct-acting antiviral era. Curr Epidemiol Rep. 2017;4(2):174-185. doi:10.1007/s40471-017-0108-x
  4. The urgency of hepatitis C screening for baby boomers. National Viral Hepatitis Roundtable. Accessed September 17, 2020. http://nvhr.org/sites/default/files/.users/u27/NVHR%20Urgency%20Fact%20Sheet_One%20Pager%20Final.pdf
  5. Schillie S, Wester C, Osborne M, et al. CDC Recommendations for hepatitis C screening among adults—United States, 2020. MMWR Recomm Rep. 2020;69(2):1-17. doi:10.15585/mmwr.rr6902a1
  6. Suryaprasad AG, White JZ, Xu F, et al. Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006-2012. Clin Infect Dis. 2014;59(10):1411-1419. doi:10.1093/cid/ciu643
  7. Koneru A, Nelson N, Hariri S, et al. Increased hepatitis C virus (HCV) detection in women of childbearing age and potential risk for vertical transmission–United States and Kentucky, 2011-2014. MMWR Morb Mortal Wkly Rep. 2016;65(28):705-710. doi:10.15585/mmwr.mm6528a2
  8. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. HCVGuidelines.org. Updated August 27, 2020. Accessed August 27, 2020. https://www.hcvguidelines.org/sites/default/files/full-guidance-pdf/AASLD-IDSA_HCVGuidance_August_27_2020.pdf
  9. Graham CS, Trooskin S. Universal screening for hepatitis C virus infection: a step toward elimination. JAMA. 2020;323(10):936-937. doi:10.1001/jama.2019.22313
  10. Asselah T, Marcellin P, Schinazi RF. Treatment of hepatitis C virus infection with direct-acting antiviral agents: 100% cure? Liver Int. 2018;38(suppl 1):7-13. doi:10.1111/liv.13673
  11. Zoratti MJ, Siddiqua A, Morassut RE, et al. Pangenotypic direct acting antivirals for the treatment of chronic hepatitis C virus infection: a systematic literature review and meta-analysis. EClinicalMedicine. 2020;18:100237. doi:10.1016/j.eclinm.2019.12.007
  12. Chou R, Dana T, Fu R, et al. Screening for hepatitis C virus infection in adolescents and adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2020;323(10):976-991. doi:10.1001/jama.2019.20788
  13. American Association for the Study of Liver Diseases, Infectious Diseases Society of America. Simplified HCV treatment for treatment-naive adults without cirrhosis. HCVGuidelines.org. Updated August 27, 2020. Accessed August 27, 2020. https://www.hcvguidelines.org/treatment-naive/simplified-treatment   

Populations at Increased Risk of HCV Infection

Other groups are also at increased risk of HCV infection, and screening frequency should be based on the clinician’s assessment of risk for infection or reinfection.8 The at-risk groups include
  • Individuals with a history of
  • Using illegal drugs intranasally
  • Incarceration
  • Being tattooed in an unregulated setting
  • Long-term hemodialysis
  • Receiving blood transfusions or organ transplants before 1992
  • Receiving clotting factor concentrates made before 1987
  • Receiving blood or organs from a donor who later tested positive for HCV
  • HIV infection
  • Unexplained chronic liver disease
  • Chronic hepatitis including elevated alanine aminotransferase levels
  •  Healthcare workers accidentally exposed to HCV-infected blood (eg, via needlestick injury)
  • Children born to an HCV-infected mother
  • HIV-infected men who have unprotected sex with men (at least annually)
How the Laboratory Can Help

Quest Diagnostics offers testing to screen for infection, detect ongoing viral replication, and determine status of liver fibrosis including
  • An HCV antibody test that is used to screen for infection (all positive test results need to be confirmed by HCV RNA testing: when sufficient sample remains after a positive HCV antibody test, Quest will automatically reflex that sample for HCV RNA testing at additional cost and CPT code)
  • HCV RNA tests that are used to confirm active infection and measure viral load
  • Other blood tests that are used for evaluating the extent of liver damage and inflammation

To guide therapy, Quest also offers
  • HCV genotyping to determine if drug-resistant variants are present
  • Comprehensive testing for hepatitis B virus (HBV) infection and other viral infections of the liver, and other infectious diseases that must be ruled out prior to beginning treatment for HCV.8
  • HCV RNA tests and routine blood tests that monitor treatment response

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Content reviewed 11/2020

Disclaimer: Images are used for illustrative purposes; those pictured are models.