Abstract
The sustained virologic response and elimination of HCV is widely viewed as a true cure of chronic hepatitis C as it associates with amelioration of histological liver damage and improved clinical outcomes. Therefore, the existence and clinical burden of occult HCV infection (OCI) has been a controversial issue for many years. In this review, we summarize recently published data that adds new information on the molecular and clinical background of OCI and its epidemiological significance. We also identify and discuss the most important methodological pitfalls, which can be a source of inconsistency between studies. Data that have accumulated so far, strongly support the existence of extrahepatic HCV replication in individuals negative for serum HCV-RNA by conventional clinical tests. OCI emerges as a condition where the immune system is unable to fully resolve infection but it is continuously stimulated by low levels of HCV antigens, leading to progression of liver pathology and extrahepatic HCV-related complications. Moreover, the development of monitoring strategies or management guidelines for OCI is still hampered by the lack of clear definition and the confusion regarding its clinical significance. Careful study design and the introduction of uniform protocols for the detection of low-level HCV-RNA are crucial for obtaining reliable data on OCI.
Highlights
The therapeutic end-point for directacting antivirals (DAA) therapy is currently recognized as the sustained virological response (SVR) in serum assessed at 12 weeks after the end of treatment using RNA nucleic acid testing (NAT) technologies with a lower limit of detection (LoD) of 15 IU/mL
It was shown that the expression of certain genes involved in lymphoma development increases in B cells of patients after IFN therapy-induced SVR, and this is more pronounced when the residual HCV can be detected in peripheral blood mononuclear cells (PBMCs) [30]
It was shown that HCV-specific CD4+ and CD8+ cellular immune responses exist in PBMC of seropositive patients with occult HCV infection (OCI) and in 52% seronegative and aviremic individuals with HCV-RNA persisting in liver tissue [45,46] (Figure 1)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Beginning from 2004, independent research groups started to find small amounts of HCV-RNA in liver tissue, serum, and in peripheral blood mononuclear cells (PBMCs) of patients, who were never diagnosed with HCV infection or who achieved therapeutically induced SVR [3,4,5]. Occult viral persistence by definition escapes clinical diagnostic schemes and can last for many years after spontaneous or treatment-induced SVR. Several of the most recent articles with research on OCI prevalence were selected to underline methodological differences and inconsistencies in reporting. This data served to determine suggested methodological key points to be considered in research on OCI
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