At a Glance

Most acute cases of hepatitis C virus (HCV) are asymptomatic and anicteric, but, because of the high incidence of HCV in the United States, 20% of acute viral hepatitis is caused by HCV. The signs and symptoms of acute symptomatic hepatitis C may include fever, chills, fatigue, myalgias, anorexia, nausea, and right upper quadrant pain or discomfort. Jaundice is present in less than 25% of patients. Duration of symptoms is 2-12 weeks; liver failure due to acute HCV is rare but may be more common with other causes of liver injury, such as pre-existing hepatitis B (HBV) infection.

Between 60 and 80% of infected persons develop chronic hepatitis, with elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Slowly progressive liver disease develops over 10 or more years of chronic infection. Chronic HCV is an insidious, asymptomatic condition. Centers for Disease Control and Prevention (CDC) recommendations for screening are as follows:

Screening is indicated for persons who have:

Continue Reading

ever injected illegal drugs

received clotting factors made before 1987

received blood/organs before July 1992

ever been on chronic hemodialysis

evidence of liver disease (elevated ALT)


The need for testing is uncertain for persons who:

were recipients of transplanted tissue after 1992

have used intranasal cocaine or other non-injecting illicit drug

have a history of tattooing, body piercing

have a history of sexually transmitted diseases or multiple sex partners

have been long-term steady sexual partners with HCV-positive persons

Testing should be performed for exposure management for:

healthcare, emergency, and public safety workers after needle stick/mucosal exposure to HCV-positive blood

children born to HCV-positive women

Routine testing is not recommended, unless an additional risk factor is identified, in:

healthcare, emergency medical and public safety workers

pregnant women

household (non-sexual) contacts of HCV-positive persons

the general population

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Most patients with acute HCV infections are asymptomatic. Of symptomatic patients, only one-half are HCV antibody positive. HCV RNA can be used to detect acute HCV; the clinical distinction between acute and chronic HCV, in the presence of ongoing risk factors, may not be simple to make.

A HCV antibody screening is the test of choice for chronic HCV. Patients with low-positive or equivocal HCV antibody tests may need further evaluation with a recombinant immunoblot assay (RIBA) to clarify their serostatus and/or with HCV viral load, which may be required in any case to make decisions concerning therapy (Table 1).

Table 1.
Test Clinical Use and Intepretation
Elevated liver indicators; ALT, AST, bilirubins, alkaline phosphatase These markers of hepatic injury are not specific to HCV but indicate hepatitis is present.
HCV antibody This test is used for primary diagnosis of acute and chronic HCV infection, although a “window period” exists between infection and seroconversion.
HCV RIBA RIBA stands for recombinant imunoblot. This test is used to assess serostatus in patients with low-positive and equivocal HCV antibody determinations, as a supplemental test.
HCV Viral Load This test is used in combination with other tests and clinical assessment to determine whether to treat HCV infection and to monitor the effectiveness of therapy.
HCV Genotype This test is used to determine treatment strategy and prognosis. HCV genotypes 1 and 4 are more difficult to treat successfully than other genotypes.
Liver biopsy This test is used to assess stage of liver disease associated with HCV and contributes to treatment decisions.
IL-28B polymorphism This test is used to determine treatment strategy in patients with HCV genotype 1 infection. Patients with favorable IL-28B genotype CC have a significantly higher rate of sustained virological response to peginterferon/ribavirin therapy than patients with unfavorable genotypes.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

As with all laboratory tests, false-positive results are seen in low-risk populations.

Only 70-90% of seropositive patients have detectable HCV RNA. A RIBA can be used to confirm seropositivity in antibody-positive RNA-negative patients, if needed.

Transplant recipients, patients with advanced HIV disease, and patients on hemodialysis may have a negative HCV antibody, despite being infected; screening with HCV RNA is recommended in such patients with unexplained elevations of ALT/AST.

How are Tests Used to Evaluate Patients for Treatment?

To be candidates for HCV therapy, patients must have detectable HCV RNA.

Treatment is more valuable in patients with evidence of disease activity from elevations of ALT/AST or inflammation and fibrosis seen on liver biopsy.

Uncompensated liver disease reflected in low albumin, elevated INR, or elevated bilirubin is a relative contraindication to treatment, though some centers treat these patients.

The complete evaluation of patients for HCV treatment is complex and includes both laboratory and nonlaboratory factors. Current guidelines are published by the American Association for the Study of Liver Diseases (AASLD).

IL-28B genotyping is useful primarily in patients with genotype 1 disease who are otherwise candidates for therapy. Good-prognosis genotype patients are likely to be successfully treated with conventional peginterferon-ribavirin; poorer prognosis patients may benefit from adding one of the novel, expensive HCV antivirals.

How is Treatment Monitored

In patients with genotype 1, HCV RNA is measured following 12 weeks of treatment. Patients with no viral response (less than a 2-log decrease) are unlikely to respond to further treatment, so therapy should be discontinued. Patients with a partial response; 2 log decrease or greater but still-detectable HCV RNA should have HCV RNA measured again at 24 weeks; if virus is detectable at 24 weeks, treatment is stopped. Those with undetectable HCV RNA at either 12 or 24 weeks should be treated for 48 weeks. HCV RNA is measured at 48 and at 72 weeks to assess sustained virological response.

In patients with genotype 2 or 3, HCV RNA is measured at the end of the 24 week treatment period. If HCV RNA is detected after 24 weeks, treatment has failed. If HCV VL is undetectable, it is measured again at 48 weeks to assess sustained virological response.