Hepatitis C Virus - HCV

Diagnosis

Indications for Testing

  • New onset of jaundice, anorexia or dark urine
  • Known exposure to hepatitis
  • Suspicion of chronic hepatitis (elevated liver enzymes)

Laboratory Testing

  • Initial testing – rule out hepatitis A (HAV) or B (HBV) in acute presentation
    • Perform HAV antibody IgM, HBV core antibody IgM, HBV surface antigen, and HCV antibody testing
      • Positive HCV from hepatitis panel – perform HCV RNA PCR (quantitative or qualitative)
        • Quantitative or qualitative PCR test negative – infected but recovered or false-positive screen  
        • Quantitative or qualitative PCR test positive – currently infected (chronic HCV) 
          • Perform HCV genotyping – genotype affects rate of treatment success
          • Consider interleukin 28 B (IL28B) typing to predict therapeutic response in patients infected with HCV genotype 1
          • Consider biopsy (liver) – if patient is genotype 1, response rate to treatment is low and degree of fibrosis may determine whether to treat the patient

Prognosis

  • HCV RNA PCR quantitative – viral load predicts likelihood of treatment response
    • Lower viral load at therapy initiation suggests better therapeutic response

Differential Diagnosis

Screening

  • Patients from high-risk populations (eg, IV-drug use, immigrant from endemic areas)
    • U.S. Preventative Services Task Force found insufficient evidence to recommend screening
    • CDC, American Gastroenterological Association, National Gastroenterology Society (2009), National Hepatology Society (2003) – all recommend screening
      • Initial screening for HCV antibodies by CIA, EIA, ELISA
      • Flu testing required for positive result
    • For pregnant females, routine HCV screening is not recommended

Monitoring

  • HCV RNA PCR quantitative test – monitor effectiveness of treatment and perform when treatment is complete
    • Monthly until week 12 of treatment
    • Negative result confirms treatment success

Clinical Background

Hepatitis C is a virally mediated disease of the liver with a propensity to cause chronic infection leading to cirrhosis and an increased risk of hepatocellular carcinoma.

Epidemiology

  • Prevalence – 2% of U.S. population is infected  
    • >50% of new cases are caused by IV drug use
    • 19,000 estimated new cases in 2006
  • Age – peaks in 30s-40s
  • Sex – M:F, equal
  • Transmission – parenteral (only 50% have one of these known routes)

Organism

  • Single-stranded RNA virus; member of Flaviviridae family (genus Hepacivirus)
  • Six major genotypes with multiple subtypes (1a, 1b, 1c, etc)
    • Genotype is an important predictor of virologic response to HCV treatment
      • Type 1 is predominant genotype in U.S.
      • Types 2 and 3 are less aggressive and easier to treat

Risk Factors

  • Transfusion with blood or blood products prior to 1990
    • Risk is 1/400,000 units transfused
  • Infected with another blood-borne pathogen (eg, HBV, HIV)
  • History of IV drug or intranasal cocaine use
  • HCV-positive sexual partner
  • Organ transplant recipient

Clinical Presentation

  • HCV typically asymptomatic in acute infection
    • Infection may be identified when patient has positive anti-HCV in a blood donor screen or has high alanine aminotransferase in blood chemistry testing for flu-like symptoms (10-20 times the upper limit of normal)
  • Chronic asymptomatic hepatitis may manifest with other systemic symptoms
    • Mixed cryoglobulinemia – systemic vasculitis involving skin, kidneys, nervous system
    • Sjögren syndrome – anti-SSA and SSB antibodies are usually absent or present in low levels
    • Lichen planus – violaceous papules on any skin site; oral most common
    • Porphyria cutanea tarda
    • Non-Hodgkin lymphoma – B-cell type most common
  • Chronic disease states occur in ~10-20% of patients
    • Cirrhosis (20%) and hepatocellular carcinoma (1-5%)
  • Pregnant females
    • Not transmitted to infant via breast feeding 
    • Pregnancy not contraindicated

Treatment

  • Moderately effective
  • Genotypes 2 and 3 have more favorable prognosis and treatment response

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Hepatitis Panel, Acute with Reflex to HBsAg Confirmation 0020457
Method: Qualitative Chemiluminescent Immunoassay/Qualitative Enzyme Immunoassay

Order when patient has had clinical acute hepatitis of unknown origin for less than 6 months

Panel includes HAV IgM, HBV core antibody IgM, HBV surface antigen, HCV antibody

Positive HAV IgM shows current or recent infection with 98% sensitivity and specificity

    
Hepatitis A Virus Antibody, IgM 0020093
Method: Qualitative Chemiluminescent Immunoassay

Rule out acute HAV

    
Hepatitis B Virus Core Antibody, IgM 0020092
Method: Qualitative Chemiluminescent Immunoassay

Rule out HBV

    
Hepatitis B Virus Surface Antibody 0020090
Method: Quantitative Chemiluminescent Immunoassay

Determine immunity to HBV

    
Hepatitis C Virus Antibody by CIA 2002483
Method: Qualitative Chemiluminescent Immunoassay

Screen individuals at risk for HCV infection

  

For positive results, order HCV RNA PCR (quantitative or qualitative)

Order genotyping once diagnosis is established
Hepatitis C Virus RNA Quantitative, Real-Time PCR 0098268
Method: Quantitative Real-Time Polymerase Chain Reaction

Diagnose HCV infection in anti-HCV positive patients

Provide baseline for monitoring treatment efficacy

Determine length of treatment

Guide therapy by early identification of patients unlikely to have sustained therapeutic response (failure to lower HCV quantitative levels during the first 12 weeks of therapy strongly predicts a sustained therapeutic response will not be achieved)

Assess transmission of HCV in newborns from HCV-positive mothers

Quantification limit for this assay is 1.6 log IU/mL (43 IU/mL)

If the assay DID NOT DETECT the virus, the result will be reported as “<1.6 log IU/mL (<43 IU/mL)”; if the assay DETECTED the presence of the virus but was not able to accurately quantify the number of copies, the test result will be reported as “Not Quantified"

False positive may occur

  
Hepatitis C Virus RNA Qualitative PCR 0098264
Method: Qualitative Polymerase Chain Reaction

Quantitative test generally preferred 

Monitor ongoing viral response to therapy when quantitative test is negative

Assess transmission of HCV in newborns from HCV-positive mothers

Negative result does not rule out the presence of PCR inhibitors in the patient sample or the presence of HCV RNA concentrations below the level of detection by the assay

False positives may occur

  
Hepatitis C Virus RNA Quantitative bDNA 0051811
Method: Quantitative Branched Chain DNA

Diagnose HCV infection in anti-HCV positive patients

Provide a baseline viral load for monitoring treatment efficacy

Determine length of treatment

Guide therapy by early identification of patients who are unlikely to have sustained therapeutic response (failure to lower HCV quantitative levels during the first 12 weeks of therapy strongly predicts that sustained therapeutic response will not be achieved)

Negative result does not rule out the presence of PCR inhibitors in the patient sample or the presence of HCV RNA concentrations below the level of detection by the assay

Low-positive values may occasionally be seen in specimens from patients who are not infected

  
Hepatitis C Virus Genotyping 0055593
Method: Polymerase Chain Reaction/Sequencing
 Identify genotypes to determine therapeutic regimens

Test may be unsuccessful if HCV RNA viral load is <log 2.8 or 600 IU/mL

  
Interleukin 28 B (IL28B)-Associated Variants, 2 SNPs 2004680
Method: Qualitative Polymerase Chain Reaction/Qualitative Fluorescence Monitoring

Identify therapeutic response in genotype 1 patients

SNPs other than those targeted will not be detected

For HCV genotypes other than type 1, the usefulness of these SNPs for predicting response to therapy is unknown

  
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Hepatitis C Virus RNA Quantitative bDNA with Reflex to Hepatitis C Virus RNA Quantitative, Real-Time PCR 2002682
Method: Quantitative Branched Chain DNA/Polymerase Chain Reaction

Use for diagnostic purposes
Hepatitis C Virus RNA Quantitative bDNA with Reflex to Genotype 2002681
Method: Quantitative Branched Chain DNA/Sequencing

Diagnose HCV infection in anti-HCV positive patients and determine genotype

Provide baseline viral load for monitoring treatment efficacy

Determine length of treatment
Hepatitis C Virus RNA Quantitative Real-Time PCR with Reflex to Genotype 2002685
Method: Quantitative Real-Time Polymerase Chain Reaction/Sequencing

Quantification limit for this assay is 1.6 log IU/mL (43 IU/mL)

If the assay DID NOT DETECT the virus, the test result will be reported as “<1.6 log IU/mL (<43 IU/mL)”; if the assay DETECTED the presence of the virus but was not able to accurately quantify the number of copies the test result will be reported as “Not Quantified”

Diagnose HCV infection in anti-HCV positive patients and determine genotype

Provide baseline viral load for monitoring treatment efficacy and determine length of treatment
FibroSURE 2004745
Method: Semi-Quantitative Immunologic/Colorimetry/Kinetic/Nephelometry

Provide assessment of liver status following diagnosis of HCV as well as baseline determination of liver status before initiating HCV therapy

Also use for post-treatment assessment of liver status six months after completion of therapy and noninvasive assessment of liver status in patients who are at increased risk of complications from a liver biopsy