Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (188 page)

HCV risk may also be increased in noninjection illicit drug use, like intranasal cocaine use, patients with tattoos or body piercing, patients with a history of STD or multiple sex partners, patients with a long-term sexual relationship with an HCV-positive partner.

   The acute phase of HCV infection usually occurs 2 months after exposure (range: 2–26 weeks) and is typically mild; 70–80% of patients remain anicteric and asymptomatic. ALF is very rarely seen as a complication of acute HCV infection.

   The reported rate of spontaneous recovery after acute HCV infection has varied between 14% and 50%; the variability is likely due to the patient population studied and mode of acquisition of infection. Reinfection after spontaneous clearance, in some patient populations, may also be misinterpreted as chronic infection. Patients with symptomatic infection during the acute phase are more likely to spontaneously recover; most patients who recover after acute HCV infection do so within 3 months after the onset of acute infection. Because the HBV RNA viral load may vary over time, even to undetectable levels, a single negative value should not be relied on as a marker of recovery; several repeat laboratory evaluations to confirm recovery should be performed at 3-month intervals.

   Chronic HCV infection develops in 75–85% of infected patients, but in most patients, it is associated with relatively mild clinical disease, in spite of progressive hepatic damage. Risk factors for more severe disease and rapid progression include alcohol abuse (or other hepatotoxin exposure); coexisting liver disease; immunocompromised status, especially HIV infection; and genetic and other factors. The risk of progression to cirrhosis is markedly increased in patients with hypogammaglobulinemia. Transaminase elevations are typically lower than in HBV infection; episodic fluctuations are common. Occult HBV infection is present in about one third of patients with chronic HCV liver disease.

   
Initial HCV Diagnostic Tests

   
Serology
: Patients with suspected HCV infection should first be tested for HCV antibody. Current “second-generation” EIA assays are very sensitive; tests are positive at presentation in half of patients and within 1 month of presentation in approximately 95% of patients. False-negative results may be seen in dialysis, transplant, or immunocompromised patients (e.g., HIV-infected patients) in spite of circulating HVC RNA. The specificity of HCV serology tests is also very high (>99%), but false-positive reactions must be ruled out in asymptomatic patients with a low prior probability of infection, as in blood donor screening.

   The FDA has approved several waived, rapid diagnostic tests for HCV antibody detection. These tests have sensitivities comparable to laboratory-based EIA tests. These assays may improve care by providing direct testing with immediate results at the point of patient encounter, like a physician’s office, clinic, or emergency room.

   A negative result for HCV antibody rules out infection in immunologically intact patients. In patients who might not mount a solid antibody response, testing for HCV RNA should be performed.

   A positive result for HCV serology testing indicates HCV infection or a false-positive result. In antibody-positive patients with a low prior probability of HCV infection, like healthy blood donors, unexpectedly positive HCV serology screens should be followed by repeat HCV antibody testing using a different test method from the one used for initial testing.

   Positive HCV serology tests cannot distinguish between resolved versus active infection, which requires testing for HCV RNA.

   
Molecular diagnostic testing
: Molecular testing for HCV RNA should be performed on all patients with positive HCV serology to determine the presence of active HCV replication. The recombinant immunoblot assay (RIBA HCV) is no longer available for routine diagnostic testing.