From the Guidelines
A positive hepatitis C antibody test with negative RNA indicates past infection that has either resolved spontaneously or been successfully treated, and no treatment is needed in this situation. The antibody test detects previous exposure to the hepatitis C virus, while the RNA test confirms active infection. When RNA is negative, it means there is no virus currently replicating in your body. This pattern is common and represents either natural clearance (which occurs in about 15-25% of infected individuals) or successful treatment with antiviral medications 1. You should inform future healthcare providers about your positive antibody status, but you are not infectious to others and do not need hepatitis C treatment. The antibodies will likely remain positive for life, so repeat antibody testing is unnecessary. However, if you have ongoing risk factors for hepatitis C (such as injection drug use), periodic RNA testing may be warranted to detect possible reinfection 1. Liver health monitoring is still important, especially if you had the infection for a long time before clearance.
Some key points to consider:
- The third-generation EIA uses recombinant core, NS3, NS4, and NS5 HCV proteins, and its sensitivity and specificity are 97.2-99% and 99.8-100%, respectively, when tested in immune-competent individuals 1.
- Average time between HCV infection and seroconversion is 8-9 weeks, and anti-HCV is detectable in >97% of patients with HCV infection within 6 months 1.
- A qualitative PCR test is recommended in immunodeficient patients with suspected HCV infection 1.
- Measurement of HCV RNA concentrations in serum and determination of HCV genotype are recommended and should be used to determine the duration of treatment 1.
It is essential to note that the management of hepatitis C infection has evolved over time, and the current guidelines recommend a more personalized approach to treatment, taking into account the patient's viral load, genotype, and liver disease severity 1.
From the Research
Hepatitis C Diagnosis and Treatment
- A positive hepatitis C antibody test with negative RNA result can occur in some individuals, as seen in 18% of cases in a study published in 1998 2.
- This discrepancy may be due to the presence of HCV-RNA in peripheral blood mononuclear cells (PBMC) even when plasma viremia is negative, as detected in 10.5% of plasma viremia-negative HCV-seropositive subjects 2.
- The current screening recommendations for hepatitis C virus (HCV) infection involve universal screening with an anti-HCV antibody test, followed by reflex HCV RNA polymerase chain reaction testing for positive results to confirm active disease 3.
- Treatment guidelines for HCV infection recommend a simplified treatment regimen consisting of eight weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir for treatment-naive adults without cirrhosis or with compensated cirrhosis, resulting in greater than 95% cure rates 3.
Implications of Positive Antibody and Negative RNA Results
- The presence of anti-HCV antibody without viremia was shown in 72.7% of asymptomatic subjects and 17.6% of chronic hepatitis subjects without interferon treatment 2.
- The detection of HCV-RNA in PBMC in anti-HCV-positive subjects without viremia could reduce false-negative results of HCV-RNA testing by RT-PCR in serum or plasma 2.
- A sustained virologic response, defined as undetectable HCV RNA 12 weeks after completing therapy, is associated with lower all-cause mortality and improves hepatic and extrahepatic manifestations, cognitive function, physical health, work productivity, and quality of life 3.