CAM 127

Hepatitis C testing

Category:Laboratory   Last Reviewed:July 2019
Department(s):Medical Affairs   Next Review:July 2020
Original Date:January 2016    

Description/Background
Hepatitis C virus (HCV) infection is relatively common in the United States, with an estimated 1% – 1.5% of all Americans (nearly 3 million people) currently infected. Prevalence of the infection is highest in individuals born between 1945 and 1965, at 3.25%. This rate is approximately 5 times higher than that seen in other adult age groups.

Nearly 17,000 new infections occur each year, and over three-fourths of infected individuals have detectable viremia, which is indicative of chronic infection. HCV infection is the most common reason for liver transplantation in adults in the United States and is the most common cause of hepatocellular carcinoma.

It is estimated that 20% of people with HCV infection will develop cirrhosis, and nearly 5% will die from liver disease resulting from HCV infection.

Although HCV infection is common, most individuals who are infected are unaware of their infection, and, therefore, do not receive the care and treatment that can mitigate progression to severe liver disease and possible death.

HCV is spread through exposure to blood of infected individuals. Such exposure includes injection drug use, blood transfusions (prior to 1992) and, to a lesser extent, high-risk sexual behaviors. Additionally, being born to an HCV-infected mother, hemodialysis, intranasal drug use, tattoos, incarceration, needle sticks and invasive procedures (prior to implementation of universal precautions) are also associated with increased risk of HCV infection.

Acute HCV infection often is asymptomatic, resulting in many infected individuals being unaware that they acquired the virus. In nearly 80% of infected individuals, there is a chronic infection that can result in serious conditions such as liver cirrhosis or hepatocellular carcinoma many years after the initial infection.

HCV was first identified in 1988, and in 1992, routine testing of the blood supply for HCV was initiated. Therapy for HCV historically has included pegylated interferon, with or without ribavirin. In 2011, two direct-acting antiviral agents (DAAs), telaprevir and boceprevir, were approved in the United States for use along with pegylated interferon and ribavirin for treatment of HCV. The addition of either of these drugs to the treatment regimen was shown to be more effective in achieving a sustained virologic response (i.e., undetectable HCV RNA) than that achieved without the DAAs.

There are six different genotypes of HCV, with genotype 1 being the most common in the United States. Individuals with genotype 1 are nearly three times less likely than those with genotypes 2 or 3 to respond to standard therapy. The length of treatment with pegylated interferon and ribavirin is dependent on HCV genotype, with genotype 1 requiring a longer treatment time. Given that the new DAAs are approved for use only in individuals with genotype 1, identification of the HCV genotype helps determine the type of therapy and its duration.

In addition to the HCV genotype, certain host factors are correlated with a sustained virologic response (SVR). One of these, the CC genotype of the interleukin 28 B (IL28B) gene rs12979860 SNP, is associated with a higher likelihood of rapid response and SVR in patients infected with genotype 1 HCV than are the TT or CT genotypes. European-Americans are more likely than African-Americans to have the CC polymorphism, which accounts for much of the increased treatment success seen in European-Americans infected with genotype 1 HCV. Determination of IL28B genotype status may be useful in determining the treatment strategy for individuals infected with HCV genotype 1.

Ideally, individuals with HCV infection would be identified prior to onset of severe complications and be provided appropriate care to avoid such complications. The Centers for Disease Control and Prevention (CDC) estimates that only 55% of people infected with HCV had known exposure risks. As a result, testing strategies that focus on testing only those considered at risk have not been successful in identifying many infected individuals. Studies have shown that over twice as many HCV-infected individuals are identified when a birth-cohort testing protocol is used as compared to testing only those who have known risks.

Policy

  1. A one-time screening for Hepatitis C infection is considered MEDICALLY NECESSARY for adults born between 1945 and 1965.
  2. Testing for Hepatitis C infection is considered MEDICALLY NECESSARY in the following situations:
    • Illicit drug use: injection (current or ever, including those who injected only once)
    • Illicit drug use: intranasal
    • Receipt of clotting factor concentrates produced before 1987
    • History of or current hemodialysis
    • Evidence of liver disease (based on clinical presentation or persistently abnormal alanine aminotransferase (ALT) levels)
    • Presence of HIV infection
    • Receipt of an organ transplant
    • Receipt of a blood transfusion or blood component before 1992
    • History of incarceration
    • Receipt of a tattoo in an unregulated setting.
  3. HCV testing based on a recognized exposure is considered MEDICALLY NECESSARY and meets coverage criteria for:
    • Health care, emergency medical, and public safety workers after needle sticks, sharps, or mucosal exposures to HCV-positive blood
    • Children born to HCV-positive women
    • Current sexual partners of HCV-infected persons.
  4. One-time testing for HCV genotype is considered MEDICALLY NECESSARY prior to initiation of treatment to guide selection of the most appropriate antiviral regimen.
  5. For patients with acute HCV infection, monitoring HCV RNA is considered MEDICALLY NECESSARY to determine spontaneous clearance of HCV infection versus persistence of infection. Testing can be performed every 4 to 8 weeks for 6 to 12 months.
  6. Testing for HCV viral load, using a quantitative nucleic acid test, is considered MEDICALLY NECESSARY in the following situations:
    • prior to initiation of HCV therapy, AND
    • after 4 weeks of therapy AND
    • at the end of treatment AND
    • 12 weeks and 24 weeks after completion of treatment.

Rationale 
The Centers for Disease Control and Prevention (CDC) recommends testing for HCV in all individuals at risk for infection, as well as one-time testing for adults born in 1945 – 1965, without regard for HCV risk.

The CDC defines those at risk for infection, who should be routinely tested, to include HIV-infected patients, individuals who ever injected illegal drugs (regardless of how long ago or how many times), individuals who received clotting factor concentrates before 1987; individuals who were ever on long-term hemodialysis; people with persistently elevated alanine aminotransferase levels; individuals who received a blood transfusion or organ transplant before July 1992; health care, emergency medical and public safety workers after needle sticks, sharps or mucosal exposures to HCV-positive blood; and children born to HCV-positive women.

The CDC also notes that the initial HCV test should be "with an FDA-approved test for antibody to HCV." A positive result for the HCV antibody indicates either a current infection or previous infection that has resolved. For those individuals, the CDC recommends testing by an FDA-approved HCV nucleic acid test (NAT) to differentiate between active infection and resolved infection. "Persons who test anti-HCV positive or have indeterminate antibody test results who are also positive by HCV NAT should be considered to have active HCV infection; these persons need referral for further medical evaluation and care."

The CDC also recommends repeat testing for individuals with ongoing risk behaviors.

The United States Preventive Services Task Force (USPSTF) recommends HCV screening in persons at high risk for infection, as well as a one-time screening for individuals born between 1945 and 1965. The USPSTF also indicates that follow-up of positive HCV antibody testing with "polymerase chain reaction testing for viremia is accurate for identifying patients with chronic HCV infection."

The American Association for the Study of Liver Diseases (AASLD) and the Infectious Disease Society of America (IDSA) also recommend HCV testing "at least once for persons born between 1945 and 1965."

The AASLD and IDSA recommendations also note that "one-time testing should be performed for all persons with behaviors, exposures and conditions associated with an increased risk of HCV infection." Additionally, individuals with HIV and those who have unexplained chronic liver disease should be tested. They also recommend annual testing for HCV for injection drug users and for HIV-seropositive men who have unprotected sex with men. Others with ongoing risk factors should also be tested periodically.

The AASLD and IDSA recommend an anti-HCV test as the initial screen, followed by confirmation with a sensitive RNA test when the antibody screen is positive. Additionally, for "persons with a negative anti-HCV test who are suspected of having liver disease, testing for HCV RNA or follow-up testing for HCV antibody is recommended if exposure to HCV occurred within the past 6 months; testing for HCV RNA can also be considered in persons who are immunocompromised."

For those individuals who are suspected of reinfection following viral clearance, "HCV-RNA testing is recommended because an anti-HCV test is expected to be positive."

The AASLD and IDSA recommend quantitative HCV RNA testing prior to the initiation of antiviral therapy to determine the baseline viral load. Also, testing for HCV genotype should be done to help guide the selection of an antiviral regimen.

The AASLD and IDSA also note that there may be instances when a positive anti-HCV is followed by a negative HCV RNA test, and further information is "desired to distinguish between true positivity and biologic false positivity for HCV antibody." In that situation, they recommend testing "with a second FDA-approved HCV antibody assay that is different from the assay used for initial antibody testing."

The AASLD also recommends evaluation for HCV infection in individuals being considered for liver transplant.

The American Gastroenterological Association (AGA) indicates that HCV RNA testing "should be performed in: patients with a positive anti-HCV test; patients for whom antiviral treatment is being considered, using a sensitive quantitative assay; patients with unexplained liver disease whose anti-HCV test is negative and who are immunocompromised or suspected of having acute HCV infection."

The AGA specifies that "HCV RNA should be tested by a highly sensitive quantitative assay at the initiation of or shortly before treatment and at week 12 of therapy." Also, for the diagnosis of acute hepatitis C, HCV RNA testing "is required since HCV RNA appears before anti-HCV antibodies may be detectable." The AGA also recommends testing for HCV RNA "at weeks 4, 12 and 24 of treatment, 4 to 12 week intervals thereafter, the end of treatment and 24 weeks after stopping treatment."

Also, the AGA notes that "HCV genotyping should be performed … prior to interferon-based treatment in order to plan for the dose and duration of therapy and to estimate the likelihood of response."

The World Health Organization (WHO) recommends "HCV serology testing be offered to individuals who are part of a population with high HCV seroprevalence or who have a history of HCV risk exposure/ behaviour." It also indicates "that nucleic acid testing for the detection of HCV RNA be performed directly following a positive HCV serological test to establish the diagnosis of chronic HCV infection, in addition to nucleic acid testing for HCV RNA as part of the assessment for starting treatment for HCV infection."

With regard to treatment selection, the AASLD guidelines note that "IL28B genotype is a robust pretreatment predictor of SVR to peginterferon alfa and ribavirin as well as to protease inhibitor triple therapy in patients with genotype 1 chronic hepatitis C virus infection. Testing may be considered when the patient or provider wish additional information on the probability of treatment response or on the probable treatment duration needed."

The package inserts for both Victrelis (beceprevir) and Incivek (telaprevir) note that the drugs are for treatment of HCV genotype 1. They also recommend monitoring of HCV RNA levels periodically during treatment to assess the effectiveness of the treatment.

The package insert for ribavirin indicates that the duration of therapy is dependent on the HCV genotype. Patients with genotype 2 or 3 are recommended for 24 weeks of therapy, whereas other genotypes are recommended for 48 weeks of therapy.

References 

  1. Chou R, Barth Cottrell E, Wasson N, Rahman B, Guise J. (2012). "Screening for Hepatitis C virus infection in adults: A systematic review for the U.S. Preventive Services Task Force." Annals of Internal Medicine, 158, 101-108. Retrieved on 5.5.2014 from file:///C:/Users/ba.markley/Downloads/0000605-201301150-00004.pdf
  2. Centers for Disease Control and Prevention, "Recommendations for the identification of Chronic Hepatitis C virus infection among persons born during 1945-1965." (2012). MMWR, 61 (RR04); 1-18. Retrieved on 5.5.2014 from http://www.cdc.gov/mmwr/pdf/rr/rr6104.pdf
  3. American Gastroenterological Association, "Hepatitis C screening and evaluation clinical decision support tool." Retrieved on 5.5.2014 from http://www.gastro.org/practice/practice-management/395-005PNQ_13-1_HCV_Branded_Algorithm_Web.pdf
  4. The American Association for the Study of Liver Diseases and the Infectious Disease Society of America, "Recommendations for testing, managing, and treating Hepatitis C." (2014). Retrieved on 5.5.2014 from http://www.hcvguidelines.org/fullreport
  5. United States Preventive Services Task Force, "Screening for Hepatitis C Virus Infection." (2013). Retrieved on 5/5/2014 from http://www.uspreventiveservicestaskforce.org/uspstf12/hepc/hepcfinalrs.pdf
  6. World Health Organization, "Guidelines for the screening, care and treatment of persons with Hepatitis C infection." (2014). Retrieved on 5.5.2014 from http://apps.who.int/iris/bitstream/10665/111747/1/9789241548755_eng.pdf?ua=1&ua=1
  7. U.S. Preventative Services Task Force, The Guide to Clinical Preventative Services 2014. AHRQ Pub. No. 14-05158 May 2014. Available at www.ahrq.gov

Coding Section 

Codes Number Description
CPT 86803 Hepatits c antibody
  86804 Hepatits c antibody; confirmatory test (eg, immunoblot)
  87520 Infectious agent detection by nucleic acid (dna or rna); hepatitis c, direct probe technique
  87521 Infectious agent detection by nucleic acid (dna or rna); hepatitis c, amplified probe technique
  87522 Infectious agent detection by nucleic acid (dna or rna); hepatitis c, quantification, includes reverse transcription when performed
  87902 Infectious agen genotype analysis by nucleic acid (dna or rna); hepatitis c virus
  0001M Infectious disease, hcv, six biochemical assays (alt, a2-macroglobulin, apolipoprotein a-1, total bilirubin, ggt, and haptoglobin) utilizing serum, prognostic algorithm reported as scores for fibrosis and necroinflammatory activity in liver
ICD 10 Diagnoses Code B18.2

Chronic hepatitis C

  E920.5 Accidents caused by hypodermic needle
  F11.10-F11.99 Opioid related disorders (injecting drug users)
  F13.10-F13.99 Sedative, hypnotic, or anxiolytic related disorders (injecting drug users)
  F14.10-F14.99 Cocaine related disorders (injecting drug users)
  F19.20  Other psychoactive substance dependence, uncomplicated 
  K75.2  Nonspecific reactive hepatitis 
  K75.81  Nonalcoholic steatohepatitis (NASH) 
  K76.81-K76.89  Other specified diseases of liver 
  K76.9  Liver disease, unspecified 
  L81.8  Other specified disorders of pigmentation, Tattoo pigmentation 
  N25.0  Renal osteodystrophy 
  R74.0 Nonspecific elevation of levels of transaminase and lactic acid dehydrogenase (LDH)
 

R74.8 

Abnormal levels of other serum enzymes 
  R74.9  Abnormal serum enzyme level, unspecified 
  T80.61XA - T80.61XS Complications following infusion, transfusion and therapeutic injection
  W46.1XXA-W46.1XXS  Contact with contaminated hypodermic needle 
  Z11.59  Encounter for screening for other viral diseases 
  Z20.5 Contact with and (suspected) exposure to viral hepatitis
  Z21, B20, B97.35 HIV
  Z65.1  Imprisonment and other incarceration 
  Z72.51-Z72.53 High risk sexual behavior
  Z72.89  Other problems related to lifestyle 
  Z77.21 Contact with and (suspected) exposure to potentially hazardous body fluids
  Z79.01 Long term (current) use of anticoagulants
  Z79.899  Other long term (current) drug therapy 
  Z99.2 Dependence on renal dialysis

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.  

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved"  

History From 2016 Forward     

07/11/2019 

Annual review, no change to policy intent. 

07/18/2018 

Interim review to change review date to July. No other changes made. 

02/14/2018 

Annual review, updating policy verbiage for clarity and to address testing frequency for HCV. Also expanding ICD10 code range. 

06/19/2017 

Updated coding section. No other changes. 

04/26/2017 

Updated category to Laboratory. No other changes.

01/04/2017 

Annual review, no change to policy intent. 

01/07/2016

NEW POLICY


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