Negative baseline HCV RNA
Individuals who have negative HCV RNA at baseline are at risk for new HCV infection following an exposure. In such patients, we repeat testing to monitor for HCV infection:
•Four weeks after exposure: HCV RNA and serum aminotransferases (anti-HCV antibody is not expected to be detectable at this time if it was negative at baseline)
•Three to four months after exposure: HCV RNA, anti-HCV antibody (if not previously positive), and serum aminotransferases
•Six months after exposure: HCV RNA, anti-HCV antibody (if not previously positive)
Elevated aminotransferases at the above time points would be a trigger to check HCV RNA sooner if not already detectable.
•HCV RNA becomes detectable – If the HCV RNA becomes detectable at one of the time points above, acute HCV infection is diagnosed. We then recheck anti-HCV antibody (if not already detected at one of these time points) 12 weeks later to confirm seroconversion and acute HCV. For such patients, we also repeat HCV RNA testing to evaluate for spontaneous clearance or initiate treatment. (See 'Spontaneous viral clearance' below and 'Management' below.)
•HCV RNA remains undetectable
-For patients who have a baseline positive anti-HCV antibody (suggestive of prior spontaneously cleared or treated HCV infection), if HCV RNA remains negative throughout the testing period outlined above, HCV reinfection has not occurred, and testing can be stopped. If there is ongoing risk of exposure (eg, continued injection drug use or sexual exposure, particularly HIV-positive men who have sex with men), repeated screening for reinfection can be performed with HCV RNA testing [5].
-For patients who had a baseline negative anti-HCV antibody, if HCV RNA and anti-HCV antibody remain negative during the testing period, then HCV infection has not occurred, and testing can be stopped. In some cases, the anti-HCV antibody becomes reactive over time but the HCV RNA remains undetectable. This suggests acute HCV infection with spontaneous clearance and is confirmed when HCV RNA remains negative over 12 weeks and for at least six months after exposure. In rare instances, anti-HCV antibody may not become detectable after an acute infection, either because of a low inoculum with spontaneous clearance or an immunocompromising condition (eg, advanced HIV infection or hemodialysis), even if chronic infection ensues. With the newest generation HCV antibody assays, however, false-negative results are rare.
These recommendations for post-exposure testing are generally similar to those suggested by other expert guidelines, with slight differences in testing intervals [5,24,25]. As an example, in the United States, the Centers for Disease Control and Prevention recommend that, following an HCV exposure, health care personnel who have negative baseline HCV testing be tested with HCV RNA three to six weeks later [24]. If that HCV RNA test is negative, they should be tested again with anti-HCV antibody with reflex HCV RNA testing at four to six months; health care personnel who are immunocompromised or have underlying liver disease can be re-tested with HCV RNA at that time even if the anti-HCV antibody is negative. (See "Prevention of hepatitis B virus and hepatitis C virus infection among health care providers".)
Pre-exposure or post-exposure prophylaxis treatment is not recommended.
●Detectable baseline HCV RNA – Individuals with a detectable HCV RNA are HCV infected. If the anti-HCV antibody is also positive, this likely indicates preexisting chronic infection, although it can also represent an acute reinfection after prior spontaneous clearance or successful treatment. Aside from history, the level of ALT and other features mentioned above can help distinguish preexisting chronic infection from an acute reinfection. If the anti-HCV antibody is negative with a detectable baseline HCV RNA, this suggests acute HCV infection, particularly if the exposure was more than a few days prior. In such cases, we recheck the anti-HCV antibody at 12 weeks to confirm seroconversion and repeat HCV RNA testing to evaluate for spontaneous clearance. A small proportion of immunocompromised individuals (eg, those with advanced HIV infection or on hemodialysis) may not develop antibodies; however, this is rare with the newest generation HCV antibody tests. (See 'Spontaneous viral clearance' below.)
HCV RNA timing and patterns — HCV RNA is first detectable in serum by PCR within days to eight weeks following exposure, depending, in part, upon the size of the inoculum [26,27]. In a series of 14 needle-stick injuries, a negative HCV PCR at two weeks post-exposure had a high negative predictive value (100 percent) [28]. However, the minimal interval following suspected exposure after which a persistently negative HCV PCR test excludes infection has not been definitely established. For patients with a discrete exposure, we typically test HCV RNA at baseline, at week 4, at weeks 12 to 16, and at 6 months. (See 'Patients with discrete HCV exposure' above.)
HCV RNA may remain detectable in the liver even in patients in whom it is undetectable in serum, although its clinical significance is uncertain [29].
HCV antibody timing and patterns — Enzyme-linked immunosorbent assay (ELISA) tests detecting anti-HCV antibodies become positive as early as eight weeks after exposure, with most patients seroconverting between two and six months after exposure (figure 2 and figure 3) [16,27]. Approximately one-half of patients with symptomatic acute infection have detectable anti-HCV antibodies by ELISA when first presenting [26]. Rare patients who are severely immunocompromised or on chronic dialysis do not mount a detectable anti-HCV antibody. (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Nonreactive anti-HCV antibody'.)
A positive anti-HCV antibody does not distinguish acute or early infection from chronic infection or from a prior infection that has spontaneously cleared or was successfully treated. In addition, some patients with prior infection may have negative antibody testing because HCV antibody levels may eventually drop below detection limits in patients who have cleared the infection [30-32]. As a result, population-based studies that estimate spontaneous resolution rates of HCV infection using the prevalence of anti-HCV antibody positivity and HCV PCR negativity in untreated patients may underestimate spontaneous resolution rates.