Hepatitis C virus-specific immune responses following direct-acting antivirals administered during recent hepatitis C virus infection.

Individuals who spontaneously clear hepatitis C virus (HCV) infection have demonstrated evidence of partial protective immunity, whereas treatment-induced clearance provides little or no protection against reinfection. We aimed to investigate whether treatment of acute HCV infection with direct-acting antivirals (DAA) prevents establishment of, or reverses, T-cell exhaustion, leading to a virus-specific T-cell immune profile more similar to that seen in spontaneous clearance. The magnitude and breadth of HCV-specific T-cell responses before and after DAA or interferon-based therapy in acute or chronic HCV were compared to those of participants with spontaneous clearance of infection, using Enzyme-linked Immunospot (ELISPOT). PBMCs were available for 55 patients comprising 4 groups: spontaneous clearance (n = 17), acute interferon (n = 14), acute DAA (n = 13) and chronic DAA (n = 11). After controlling for sex, the magnitude of post-treatment HCV-specific responses after acute DAA treatment was greater than after chronic DAA or acute IFN treatment and similar to those found in spontaneous clearers. However, spontaneous clearers responded to more HCV peptide pools indicating greater breadth of response. In conclusion, early treatment with DAAs may prevent or reverse some degree of immune exhaustion and result in stronger HCV-specific responses post-treatment. However, individuals with spontaneous clearance had broader HCV-specific responses.

The 9th Canadian Symposium on Hepatitis C Virus: Advances in HCV research and treatment towards elimination.

Hepatitis C virus (HCV) elimination has evolved into a coordinated global effort. Canada, with more than 250,000 chronically infected individuals, is among the countries leading this effort. The 9th Canadian Symposium on HCV, held in February 2020, thus established and addressed its theme, 'advances in HCV research and treatment towards elimination', by gathering together basic scientists, clinicians, epidemiologists, social scientists, and community members interested in HCV research in Canada. Plenary sessions showcased topical research from prominent international and national researchers, complemented by select abstract presentations. This event was hosted by the Canadian Network on Hepatitis C (CanHepC), with support from the Public Health Agency of Canada and the Canadian Institutes of Health Research and in partnership with the Canadian Liver Meeting. CanHepC has an established record in HCV research by its members and in its advocacy activities to address the care, treatment, diagnosis, and immediate and long-term needs of those affected by HCV infection. Many challenges remain in tackling chronic HCV infection, such as the need for a vaccine; difficult-to-treat populations and unknown aspects of patient subgroups, including pregnant women and children; vulnerable people; and issues distinct to Indigenous peoples. There is also increasing concern about long-term clinical outcomes after successful treatment, with the rise in comorbidities such as diabetes, cardiovascular disease, and fatty liver disease and the remaining risk for hepatocellular carcinoma in cirrhotic individuals. The symposium addressed these topics in highlighting research advances that will collectively play an important role in eliminating HCV and minimizing subsequent health challenges.

Restoration of HCV-Specific Immune Responses with Antiviral Therapy: A Case for DAA Treatment in Acute HCV Infection.

Worldwide, 71 million individuals are chronically infected with Hepatitis C Virus (HCV). Chronic HCV infection can lead to potentially fatal outcomes including liver cirrhosis and hepatocellular carcinoma. HCV-specific immune responses play a major role in viral control and may explain why approximately 20% of infections are spontaneously cleared before the establishment of chronicity. Chronic infection, associated with prolonged antigen exposure, leads to immune exhaustion of HCV-specific T cells. These exhausted T cells are unable to control the viral infection. Before the introduction of direct acting antivirals (DAAs), interferon (IFN)-based therapies demonstrated successful clearance of viral infection in approximately 50% of treated patients. New effective and well-tolerated DAAs lead to a sustained virological response (SVR) in more than 95% of patients regardless of viral genotype. Researchers have investigated whether treatment, and the subsequent elimination of HCV antigen, can reverse this HCV-induced exhausted phenotype. Here we review literature exploring the restoration of HCV-specific immune responses following antiviral therapy, both IFN and DAA-based regimens. IFN treatment during acute HCV infection results in greater immune restoration than IFN treatment of chronically infected patients. Immune restoration data following DAA treatment in chronically HCV infected patients shows varied results but suggests that DAA treatment may lead to partial restoration that could be improved with earlier administration. Future research should investigate immune restoration following DAA therapies administered during acute HCV infection.