Evaluation of a new point-of-care oral anti-HCV test for screening of hepatitis C virus infection.

BACKGROUND: Hepatitis C virus (HCV) infection is a public health issue for which an effective universal screening method is urgently needed. An oral anti-HCV test could provide a noninvasive and rapid screening strategy for HCV infection. This study evaluated the performance of a new point-of-care oral assay developed by Well for the detection of HCV antibody. METHODS: Individuals from three centers with and without HCV infection were enrolled. All participants were tested for oral HCV antibody using the Well assay and for serum HCV antibody using established tests (ARCHITECT i2000 anti-HCV assay and InTec serum anti-HCV assay). For participants who obtained positive results, HCV RNA was tested for verification. Some patients underwent the OraQuick HCV test at the same time, and some self-tested with the Well assay during the same period. RESULTS: A total of 1179 participants, including 486 patients with chronic HCV infection, 108 patients with other liver diseases, and 585 individuals who underwent physical examination, were enrolled. The Well anti-HCV test had a sensitivity of 91.88% (95% confidence interval [CI]: 88.97-94.09%) and a specificity of 98.00% (96.58-98.86%) for oral HCV antibody detection. The consistency between the Well and InTec assays was 97.02% (1138/1179). The consistency between the Well and OraQuick assays was 98.50% (197/200). Furthermore, the results of self-testing were highly consistent with those of researcher-administered tests (Kappa = 0.979). In addition, the HCV RNA results also showed that HCV RNA could only be detected on 1 of the 39 false-negative samples, and for 172 positive HCV RNA results, 171 could be detected by the Well oral anti-HCV assay. CONCLUSIONS: The Well oral anti-HCV test offers high sensitivity and specificity and performed comparably to both the OraQuick assay and InTec assay for HCV diagnosis. Thus, the Well test represents a new tool for universal HCV screening to identify infected patients, particularly in regions with limited medical resources.

Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance.

Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein. Selected T cell epitopes were then used to evaluate T cell responses in another 22 chronically HCV-1b infected patients on DAA therapy. Results showed that SPR had better HCV-specific T cell responses than CHC, as manifested by higher response rate, greater magnitude and broader epitope coverage. In addition, SPR recognized novel epitopes in Core, E1, E2, NS4B, NS5A regions that were not present in the CHC. Furthermore, during the first 24 weeks of DAA therapy, there was no functional immune reconstitution of HCV-specific T cells. These results indicate that T cell responses may be a correlate of protection. Therefore, effective preventative vaccines should elicit a robust T cell response. Although various DAA regimens efficiently cleared viruses from the blood of HCV-infected patients, there was no contemporaneous early T cell immune reconstitution, suggesting that early treatment is needed for preserving the functions of HCV-specific T cells.

Enhancing the antihepatitis B virus immune response by adefovir dipivoxil and entecavir therapies.

Chronicity of hepatitis B (CHB) infection is characterized by a weak immune response to the virus. Entecavir (ETV) and adefovir dipivoxil (ADV) are effective in suppressing hepatitis B virus (HBV) replication. However, the underlying immune mechanism in the antiviral response of patients treated with nucleoside or nucleotide analogs is not clearly understood. In this study, regulatory T cells (Tregs) and intracellular cytokines, including IL-2, interferon (IFN)-γ, tumor-necrosis factor (TNF)-α and IL-4, were measured prior to and at 12, 24, 36 and 48 weeks after treatment with ETV or ADV. The cytokines were increased from 24 to 48 weeks after treatment. Higher levels of Th1 cytokines were observed with ETV (n=29) versus ADV (n=28) treatment. By contrast, the numbers of Tregs in both groups were decreased. The altered cytokine profile and cellular component was accompanied by a decrease in HBV DNA levels in both groups, which may contribute to their therapeutic effect in CHB infection. Our findings suggest that the antiviral effect of the drugs may be attributed not only to their direct effect on virus suppression but also to their immunoregulatory capabilities.