Investigations
1st investigations to order
hepatitis C virus (HCV)-antibody enzyme immunoassay (EIA)
Test
Recommended for initial diagnosis.[66]
If the antibody test is positive, it should be followed immediately by sequential HCV RNA testing to confirm HCV viraemia.[66]
A negative (or non-reactive) result indicates no current HCV infection, and no further testing is required. A repeat test should be considered 6 months or longer after exposure in patients with HCV exposure in the past 6 months.[66]
Occasional false-negative results may occur in immunocompromised patients or those undergoing dialysis.[63] False positives are rare, but may occur in the setting of autoimmune disease. Suspicion of a false-positive or false-negative result should lead to HCV RNA testing.
A recombinant immunoblot assay (RIBA) is more specific than an EIA and helps to rule out false-positive antibody, but is rarely used as a supplemental test. It may be used in non-clinical settings or for those who test positive on EIA and negative for HCV RNA.[63]
Testing with a different HCV antibody assay can help to differentiate between a past, resolved infection and a false-positive result.[66]
Point of care tests may be available in some countries.[73]
Result
positive: indicates current infection (either acute or chronic) or a past resolved infection
hepatitis C virus (HCV) RNA polymerase chain reaction (PCR)
Test
Reflex HCV RNA PCR testing is recommended after a positive HCV antibody result to confirm the initial diagnosis. A negative result indicates no current HCV infection and no further testing is required, unless indicated.[66] Patients with a negative HCV RNA test and a positive antibody test do not have evidence of current infection, but are not protected from re-infection.[66]
HCV RNA testing should be considered as the initial test (rather than HCV antibody testing) in patients who are immunocompromised or those with possible HCV exposure in the prior 6 months (particularly those with risk factors) as these patients may be HCV-antibody negative due to failed (or delayed) seroconversion.[66]
HCV RNA testing is required to detect re-infection after previous viral clearance as HCV antibody testing will be positive in this situation.[66]
It is important to remember that 15% to 45% of people exposed may ultimately clear the virus without treatment.[29] In these patients, the HCV antibody test will remain positive, but because they are no longer viraemic, the HCV RNA test will become negative.
Quantitative HCV RNA testing is recommended prior to initiating antiviral therapy to determine baseline viraemia.[66]
Rapid point of care HCV RNA assays are available in some countries, including the US. They may be used as an alternative approach to laboratory-based assays to diagnose viraemic infection, and as a test of cure.[67] These tests allow a patient to be linked to care and potentially start on treatment in the same healthcare visit.
Result
positive: indicates presence of current (or active) infection
serum aminotransferases
Test
Serum aminotransferases, particularly alanine aminotransferase (ALT), can be used to measure disease activity, although the sensitivity and specificity are low.
There is only a weak association between the ALT level and the degree of chronic liver disease, although serial estimates may be useful in monitoring disease activity and response to therapy in some patients.
ALT level does not reflect disease progression to cirrhosis.
Result
may be elevated
Investigations to consider
viral genotyping
Test
Should be considered in patients for whom it may alter treatment recommendations only (e.g., evidence of cirrhosis, previous unsuccessful treatment).[66]
Not recommended for patients who are starting on pangenotypic treatment regimens.[66]
May rarely reveal a mixed genotype.[66]
Result
may predict response to antiviral therapy in certain patients
hepatitis C virus (HCV) core antigen assay
Test
HCV core antigen appears approximately 2-3 weeks after contact with the virus, almost simultaneously with HCV RNA. It may be used as an alternative approach to HCV RNA testing to diagnose viremic infection.[66]
As the sensitivity is lower than that for HCV RNA testing, antibody-positive samples that test negative for HCV core antigen should have confirmatory testing with HCV RNA to exclude false-negative core antigen results.[66]
Result
positive
non-invasive tests of liver fibrosis or elasticity
Test
Non-invasive tests of liver fibrosis (fibromarkers in serum and transient elastography that uses ultrasound and low-frequency waves to measure liver elasticity) may be able to suggest or to exclude advanced fibrosis.[66][69]
Simple blood-based non-invasive tests are recommended as an initial test to detect fibrosis or cirrhosis in patients with chronic HCV who require staging prior to antiviral therapy. Simple, readily-available tests such as FIB-4 are recommended over complex proprietary tests. A sequential combination of blood-based markers may perform better than a single biomarker.[70]
Imaging-based non-invasive tests (ultrasound-based or magnetic resonance elastography, depending on local availability and expertise) should be incorporated into the initial fibrosis staging process as they are more accurate than blood-based non-invasive tests.[71]
Blood-based and imaging-based non-invasive tests may be combined, particularly for the detection of significant and advanced fibrosis.[71]
In Europe, non-invasive tests such as elastography have been more accepted as replacements for liver biopsies; however, elastography may not be adequate on its own to rule in or rule out significant fibrosis.[72]
In the US, liver elastography is approved and, along with serum tests of fibrosis, has essentially replaced the need for liver biopsy for disease staging.
Transient elastography accurately predicted liver cirrhosis in people with hepatitis C with a sensitivity of 84% and specificity of 90%.[74]
Result
may suggest or exclude advanced fibrosis
aspartate aminotransferase-to-platelet ratio index (APRI)
Test
In resource-limited settings, APRI is recommended as the preferred non-invasive test to assess for significant fibrosis or cirrhosis.[70]
Result
score >0.5 indicates significant fibrosis; score >1.0 indicates cirrhosis
liver biopsy
Test
Not used to diagnose hepatitis C infection, but is useful in staging fibrosis and the degree of hepatic inflammation. However, because direct-acting antiviral therapy is now considered to be so effective, a biopsy is rarely warranted.
Another potential reason to obtain a biopsy is to evaluate the possibility of cirrhosis and thus the risk for hepatocellular carcinoma.
May also be considered if the patient and provider want the prognostic information of a fibrosis score or to make a decision regarding treatment.[66]
Risks associated with biopsy include bleeding and puncture of other organs; however, these are rare.
Result
may indicate inflammation or fibrosis
testing for co-infection
Test
Appropriate testing for hepatitis B and HIV infection is recommended.[66]
Result
may be positive for hepatitis B or HIV
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