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  • The majority of HCV unaware individuals for which HCV


    The majority of HCV-unaware individuals, for which HCV RNA was obtainable, had active HCV infection and overall almost one-fifth of them had advanced liver disease according to the FIB-4 score; these persons can be classified as having a late HCV diagnosis and are in immediate need of HCV treatment [14]. Moreover over one-half of HCV-unaware individuals had also an HBV coinfection. In this population, unawareness of HCV infection was dabigatran etexilate more common among individuals who were diagnosed late with HIV infection and had no previous STI diagnosis, and it was significantly associated at multivariable analysis with no previous HIV tests, a factor that has been found to be associated with late HIV presentation [8], [15]. Interestingly, a non-negligible proportion of these who were aware of HCV positivity were tested for HIV after a median of 8.4years; this is consistent with a previous analysis suggesting that diagnosis of HCV is in some instances a missed opportunity for an earlier HIV diagnosis [8]. A limitation of this study is that the population was recruited in a single institution, even if it accounts for 47% of the newly diagnosed HIV infections reported during the study dabigatran etexilate in our region [Regional Infectious Diseases Surveillance Unit, written communication, May 25, 2017]. Moreover, information on previous HCV diagnosis was collected through patient’s interview and this may imply a recall bias; nonetheless, we have previously shown a good concordance among self-reported history of viral hepatitis and serological data in this study [8]. Finally, for staging of liver disease among anti-HCV positive individuals we used the FIB-4 score, a non-invasive test that has been specifically validated in persons co-infected with HIV. The accuracy of this test however may be influenced by a series of factors including HIV-related thrombocytopenia, and it has been shown to be inferior to that of transient elastography [16].
    Author contributions
    Funding This work was supported by the Italian Ministry of Health “Fondi Ricerca Corrente-Linea 2 progetto 4” to INMI L. Spallanzani.
    Competing interests
    Introduction HCV has a positive-sense, single-stranded RNA genome consisting of three segments: the 5′ untranslated region (UTR), the single open reading frame (ORF) encoding the viral polyprotein, and the 3′ UTR (Takamizawa et al., 1991). Immediately after the genomic RNA is released into the host cell cytoplasm, it is translated by the host cell machinery to produce the HCV viral proteins. Otherwise, the HCV genomic RNA would be digested by the host cytoplasmic ribonucleases, such as Xrn1, before its amplification by the HCV RNA-dependent RNA polymerase NS5B (Behrens et al., 1996, Li et al., 2013). Therefore, the initial HCV genomic RNA translation by the host machinery is a fundamental property to achieving the HCV infection of human cells. For general cap-dependent translation initiation in eukaryotes, besides the 40S and 60S ribosomal subunits and Met-tRNAiMet, numerous eukaryotic translation initiation factors (eIFs) play important roles to achieve precise and efficient protein synthesis. First, the 40S subunit binds to eIF1A and the multifactor complex, consisting of eIF1, eIF3, eIF5, and the eIF2⋅GTP⋅Met-tRNAiMet ternary complex (TC), to form the 43S pre-initiation complex. It is noteworthy that the human eIF3, which is the largest eIF, consists of 13 subunits, and its molecular weight is about 650 kDa. Next, eIF4A, eIF4B, eIF4E, and eIF4G recruit the 5′-capped UTR of the mRNA to the 43S complex. The 43S complex then scans the downstream region until it encounters an AUG triplet. After the TC recognizes the AUG triplet, the GDP-bound eIF2 is released, and the GTP-bound eIF5B binds to the complex to promote subunit joining. Finally, the 60S-subunit binds to the complex with the concomitant release of eIF1A and GDP-bound eIF5B, and the ribosome initiates translation (Hinnebusch, 2014, Hinnebusch, 2017).