From the Guidelines
A positive anti-hepatitis C virus (HCV) IgG antibody with negative HCV RNA indicates past infection with hepatitis C that has either resolved spontaneously or was successfully treated, and the individual is not considered infectious to others. This pattern means the person was exposed to HCV at some point, developed antibodies against the virus, but currently has no detectable virus in their bloodstream 1. Approximately 15-25% of people infected with HCV clear the virus naturally without treatment. This result does not indicate active infection, and the individual is not at risk of transmitting the virus to others. However, the antibodies will likely remain positive for life, even though the infection is gone.
Key Points to Consider
- No specific treatment is needed for this pattern, but the person should be informed about their prior HCV exposure 1.
- If there's any uncertainty about whether treatment occurred in the past, a one-time follow-up HCV RNA test in 3-6 months can confirm the absence of virus.
- The person remains susceptible to reinfection if exposed again, so risk reduction counseling may be appropriate depending on individual circumstances 1.
Testing and Follow-Up
- According to the 2020 guidelines, persons found to have a positive HCV-antibody test and negative results for HCV RNA by polymerase chain reaction should be informed that they do not have evidence of current (active) HCV infection but are not protected from reinfection 1.
- Quantitative HCV-RNA testing is recommended prior to initiation of antiviral therapy to document the baseline level of viremia, but this is not necessary in this case since the HCV RNA is negative 1.
From the Research
Interpretation of Anti-Hepatitis C IgG Positive but RNA Negative Results
- The presence of anti-hepatitis C IgG antibodies indicates that the individual has been exposed to the hepatitis C virus (HCV) at some point in their lives 2, 3, 4.
- A negative HCV RNA result suggests that the virus is not currently active in the individual's bloodstream 2, 3, 4.
- However, it is possible for HCV RNA to persist in peripheral blood mononuclear cells (PBMC) even in the absence of viremia, which could lead to false-negative results of HCV RNA testing by RT-PCR in serum or plasma 3.
- The detection of anti-HCV IgG antibodies without viremia is more common in asymptomatic subjects (72.7%) than in chronic hepatitis subjects without interferon treatment (17.6%) 3.
- The relationship between HCV infection, risk group, and clinical diagnosis should be studied further to understand the implications of anti-HCV IgG positive but RNA negative results 2, 3.
- It is essential to note that HCV can now be eradicated with minimal side effects using oral direct-acting antivirals (DAAs), but the development of a safe prophylactic vaccine remains a medical priority 5, 4.
- The use of molecular tools, such as nucleic acid tests, is crucial for diagnosing and following chronic HCV infection, but the cost of these tools can be a major obstacle in resource-limited countries 5, 4.