Hepatitis C Antibody Positive, RNA Negative

You are providing a clinic consult for a 68‐year‐old man who is otherwise healthy who underwent birth cohort screening by his primary care physician. His results show a positive hepatitis C virus (HCV) antibody and HCV RNA negative. He is a new patient in the clinic. What do you recommend?

Discussion

HCV infection is common, with an estimated prevalence of 3.5 million individuals in the United States, of whom approximately 50% are unaware of their infection.1, 2 Epidemiological data demonstrate a higher prevalence of HCV infection in individuals born between the years 1945 and 1965 because of a significantly increased incidence of HCV transmission in the 1970s and 1980s compared with more recent years. Thus, the Centers for Disease Control and Prevention and the US Preventive Services Task Force both recommend one‐time HCV screening of asymptomatic individuals from this birth cohort in addition to directed testing on the basis of traditional risk factors, behaviors, and exposures associated with increased risk for HCV infection.3 This strategy has been shown to significantly increase the rate at which infected individuals are detected as compared with the conventional risk factor–based approach, which alone misses greater than 50% of infections.4 The recommendations for HCV testing are based on data showing that screening decreases all‐cause mortality and reduces the risk for hepatocellular carcinoma in addition to promoting public health benefits, such as decreasing viral transmission, initiating early treatment to limit HCV‐associated morbidity and mortality, and reducing risk behaviors.3

Initial HCV screening is performed with an HCV antibody test. A positive result indicates one of three scenarios: (1) current, active HCV infection, either acute or chronic; (2) prior HCV infection that has resolved, which is estimated to occur in approximately 20% to 37% of acute infections5; or (3) a false‐positive test result.6 A positive or equivocal/indeterminate HCV antibody test should be followed with an HCV nucleic acid test to assess for active viremia, which, if positive, would confirm a diagnosis of active HCV infection and warrant further testing for genotype identification and initiation of HCV‐directed treatment. A positive HCV antibody test followed by a negative HCV nucleic test is consistent with no laboratory evidence of active HCV infection.

Fig. presents a recommended algorithm to follow if an asymptomatic patient presents to clinic with a positive HCV antibody test and a negative HCV nucleic acid test. First, a careful history should be obtained to assess for risk factors, behaviors, or potential exposures associated with increased risk for HCV transmission. Then, a physical examination should be performed to assess for clinical evidence of HCV infection and/or complications related to infection. Baseline hepatic enzyme testing should also be done. If there is concern for HCV exposure within the last 6 months or HCV infection on a clinical basis from the history, examination, and initial laboratory evaluation, repeat HCV nucleic acid testing should be completed. In addition, if there is concern regarding the integrity, quality, handling, and/or storage of the sample obtained for initial nucleic acid testing, repeat nucleic acid testing should be performed.7

In most cases, if the clinical assessment and baseline hepatic enzyme testing do not suggest HCV infection or recent HCV exposure, no additional testing is needed, and the patient can be reassured that there is no evidence of active or current HCV infection. Additional testing to determine whether the initial positive HCV antibody represents clearance of a prior infection or a false‐positive test result can be considered and pursued, if desired, based on shared decision making between the clinician and patient. The false‐positive rate of HCV antibody testing depends on the background prevalence of HCV of the tested patient population because false‐positive rates are more likely if the background prevalence is low.8 If differentiation between clearance of prior infection and false‐positive initial testing is desired, repeat HCV antibody testing using an approved HCV antibody assay different from that used during initial testing should be performed. A second positive result using a separate laboratory assay suggests clearance of prior infection.9

In the case of this particular patient, the results are most likely consistent with false‐positive antibody testing. If the history, physical examination, and/or laboratory results suggest recent exposure, repeat confirmatory testing can be obtained within 6 months. Otherwise, if there is no other clinical suspicion for active infection, he can be reassured of the benign nature of the results with no further testing recommended.