الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus (HCV) is the main cause of chronic liver disease all over the world. HCV affects about 200 million people worldwide. About 350000 deaths per year are due to HCV infection. HCV is classified as a member of Flaviviridae family and Hepacivirus genus. Up to 30% of infected people resolve their acute infection spontaneously, while about 70% turn to chronic HCV infection. chronic HCV infection is detected by the persistence of HCV ribonucleic acid (RNA) in the blood for 6 months or more after the onset of acute infection.
In the last few years, the combination of pegylated interferon (PEG-IFN) and ribavirin (RBV) was the only available treatment option for HCV genotype 4 (HCV-4) infection. But later on, other treatment options are available such as direct acting antivirals (DAAs) which can be used with or without addition of PEG-IFN/RBV. Now, combinations of DAAs are commonly used for the treatment of HCV-4 infection due to higher cure rates, shorter treatment period, and minimal adverse events. One of the most effective and commonly used combinations of (DAAs) for the treatment of HCV-4 is the combination of sofosbuvir (SOF) and daclatasvir (DCV) for 3 months.
Occult HCV infection (OCI) is identified by the presence of HCV RNA in the liver cells or peripheral blood mononuclear cells (PBMCs) of the patients whose serum samples test negative for HCV RNA by polymerase chain reaction (PCR) assays, with or without presence of HCV antibodies. OCI can lead to liver cirrhosis and hepatocellular carcinoma. HCV RNA can be detected in PBMCs instead of liver biopsy in about 70% of patients with an OCI. HCV genotypes 1 and 4 are the most genotypes involved in the OCI.
OCI has been defined in two different forms: cryptogenic and secondary. Cryptogenic OCI: if the patient has no anti-HCV antibodies but has elevated liver enzymes. Secondary OCI: if the patient has anti-HCV antibodies, has normal liver enzymes and had cleared his HCV infection either spontaneously or after anti HCV therapy.
Our study is a cross-sectional study aimed to assess the rate of occurrence of secondary occult hepatitis C virus (HCV) infection in patients treated with the combination of sofosbuvir and daclatasvir.
We included 40 patients whose serum turned negative for HCV RNA, via real time PCR (RT-PCR) after 3 months of the treatment. Blood samples on EDTA were collected from the patients after 3 months of the treatment (at the end of the treatment) to detect HCV RNA in PBMCs. The 40 patients have been classified according to RT-PCR positivity of HCV RNA in PBMCs into two groups: group A (HCV RNA PBMCs negative patients) and group B (HCV RNA PBMCs positive patients).
We have found that HCV RNA was detected in PBMCs in 10 out of 40 (25%) via RT-PCR. Our data revealed the occurrence of secondary occult HCV infection in about 25% of HCV patients treated with the combination of sofosbuvir and daclatasvir.
Previous studies showed that the age (22–66 years) is the common age of OCI. Our study agreed with that, although we detected OCI in older patients above 66 years. This, together with the fact that male sex is predominant in OCI than female sex which is accordant with previous studies by L´opez-Alcorocho and Castillo et al.
In our study, we found that there were statistical significant differences between the two groups regarding liver enzymes as AST, ALT and serum alkaline phosphatase, Other previous studies revealed an insignificant difference in the prevalence of occult HCV infection between patients with normal or high liver enzymes results. Also, we found that there were statistical significant differences between the two groups regarding direct bilirubin and total bilirubin, while there were no statistical significant differences between the two groups regarding indirect bilirubin.
In conclusion, HCV infection is widely spread infection worldwide, But the prevalence is higher in Egypt. RT-PCR is one of the most sensitive and specific tests for diagnosis of OCI by detecting HCV RNA in PBMCs. This study is the first Egyptian study to investigate the prevalence of secondary OCI in chronic HCV patients who had cleared their HCV infection after anti HCV therapy with the combination of sofosbuvir and daclatasvir for 3 months. Our data revealed the prevelance of secondary occult HCV infection in about 25% of HCV patients treated with the combination of sofosbuvir and daclatasvir. This noted that although the combination of sofosbuvir and daclatasvir is highly effective in clearing the HCV infection from the serum, It is less effective in clearing the OCI.