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Hepatitis C virus (HCV) is a common cause of chronic hepatitis that may detrimentally progress to liver cirrhosis, liver cell failure and hepatocellular carcinoma (Jazwinski and Muir, 2011). The genome of this RNA virus includes structural and non-structural proteins. The latter proteins are targets of a new generation of antiviral drugs, especially NS3/NS4A, NS5A and NS5B proteins (Asselah and Marcellin, 2011).
DAAs are molecules that target specific nonstructural proteins of the virus and results in disruption of viral replication and infection. There are four classes of DAAs, which are defined by their mechanism of action and therapeutic target. The four classes are nonstructural proteins 3/4A (NS3/4A) protease inhibitors (PIs), NS5B nucleoside polymerase inhibitors (NPIs), NS5B non-nucleoside polymerase inhibitors (NNPIs), and NS5A inhibitors (Poordad and Dieterich, 2012).
Occult HCV infection (OCI) has been reported and was characterized by the presence of HCV RNA in peripheral blood mononuclear cells (PBMNCs) and/or liver tissue among patients who tested negative for both anti-HCV and HCV RNA in serum or plasma (Castillo et al., 2004).
Since its discovery, Occult HCV infection (OCI) was documented in different populations like patients with cryptogenic hepatitis, hemodialysis patients, cryoglobulinemia, HCC and even in asymptomatic normal people (Berasain et al., 2000; Marco et al., 2009; Youssef et al., 2012). Also, there is an increasing amount of data suggests that HCV relapses may represent activation of an occult hepatitis C virus infection (OCI) (Carreño et al., 2012).
This work aimed to study the possibility of persistence of HCV RNA in peripheral blood mononuclear cells(PBMCs) after successful eradication of HCV RNA from serum by direct acting antiviral agents (DAA) and the impact of different factors on occurrence of such condition.
Our study has found that occult hepatitis C virus infection is still a significant problem even after the era of direct antiviral agents; We detected the HCV RNA in the Peripheral blood mononuclear cells in 20 out of 100 (20%) Egyptian patients – with HCV genotype-4 predominance - after achieving sustained virological response-3 (SVR3).
We investigated various factors that may play a role in persistence of HCV in PBMCs; correlating between various factors and PBMC PCR; we found high correlation between liver enzymes (ALT and AST) and PBMC PCR. Also, there were low correlation between PBMC PCR and TLC, PC% and INR. But on multiple regression analysis of these factors, only the AST Enzyme was found significantly higher among the PBMC positive group. Also, using COX proportional hazard model, we found a significant relation between liver cirrhosis and risk of development of OCI.
Neither the pretreatment viral load (the pretreatment PCR), the treatment type, the treatment experience nor the treatment duration showed a statistically significant relationship with the persistence of HCV in PBMC.
In a summary, we found that OCI is still a problem even after the current administration of DAAs, and we investigated the impact of various factors on OCI and found that liver enzymes, and liver cirrhosis carries the major risk on the development of OCI.