Q. How is HCV diagnosed?

A. The diagnosis of HCV is established by the enzyme-linked immunosorbent assay (ELISA), which detects the presence of HCV antibodies (anti-HCV). The ELISA test is recommended for first-line screening in at-risk populations due to its high sensitivity and specificity. A positive anti-HCV indicates exposure but does not signify current or past infection. The best diagnostic approach is a polymerase chain reaction (PCR) test, which qualitatively detects HCV RNA. The HCV RNA appears in the blood within two weeks following initial exposure. Serum aminotransferase levels may also increase several weeks after exposure. These levels may exceed 1,000 units/L in 20 percent of cases and typically follow a fluctuating pattern during the first few months of infection. If jaundice develops, serum bilirubin levels are usually <12 mg/dL and will resolve within a month.

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Quantitative assay should not be used as a primary diagnostic test. It measures the concentration, or “viral load,” of HCV RNA. The quantitative HCV viral load is used to assess response to antiviral therapy. Several quantitative assays have been developed, each with a different standard in measuring viral concentration. Most PCR assays have a lower limit of detection between 100 and 1,000 viral genome copies/mL. However, there is an ongoing effort to establish a uniform standard of measuring viremia in international units/mL.

Q. What are the various “types” of HCV?

A. There are six HCV genotypes and more than 90 subtypes. Genotypes 1, 2, and 3 are the most common in the United States. Genotypes 4, 5, and 6 are common in Europe, Asia, and Africa. Approximately 70% of HCV-infected patients in the United States have genotype 1, with subtype 1a predominating over subtype 1b. Clinical features and progression to cirrhosis or hepatocellular carcinoma are the same in patients with different genotypes. However, patients with genotype 1 require longer treatment with antiviral therapy (48 weeks) and demonstrate lower response rates in clearing the virus.

Q. What happens after diagnosis of HCV?

A. Patients who test positive for HCV should be referred to a hepatologist/gastroenterologist or infectious disease specialist for further evaluation and management. Additional diagnostic testing may include a complete blood count (CBC), metabolic panel, PT, quantitative HCV viral load, genotyping, hepatitis A and B immunity panel, abdominal imaging, and liver biopsy. 

A CBC may provide insight into advanced liver disease. Patients may have leukopenia and/or thrombocytopenia secondary to hepatocellular damage, which can result from portal hypertension and/or hypersplenism. Ù A prolonged PT, decreased albumin, and elevated aminotransferase suggest impaired hepatic function. In chronic HCV, increases in the alanine and aspartate aminotransferases may range from zero to 20 times the upper limit of normal but are usually less than five times normal.

Liver biopsy assesses the presence and severity of liver damage. Some patients may refuse biopsy; they should not be denied treatment. If the infection is recent or the patient is infected with genotype 2 or 3, a biopsy is not always necessary.4 Liver biopsy should be obtained prior to initiation of treatment in patients without evidence of decompensated cirrhosis. In patients with HCV infection and elevated aminotransferases, biopsy is mandatory.6 

Biopsy can also rule out other liver diseases that may be responsible for liver damage or a false-positive anti-HCV, such as hemochromatosis, alcoholic liver disease, or autoimmune hepatitis. Other conditions that may be confused clinically with chronic HCV are sclerosing cholangitis, Wilson’s disease, a1-antitrypsin deficiency, and drug-induced disease.