Reversal of Immunity After Clearance of Chronic HCV Infection—All Reset?

Abstract

Chronic viral infections cause deterioration of our immune system. However, since persistent infections rarely can be eliminated, the reinvigoration capacity of an exhausted immune system has remained largely elusive. Chronic hepatitis C virus (HCV) infection can since some years be effectively cured with novel direct acting antiviral agents. Thus, it is now possible to study reversal of immunity in patients that are cured from a long-lasting chronic infection. We here highlight recent developments in the analysis of various immune cell populations during and after clearance of HCV infection. Surprisingly, whereas reinvigoration of certain immune traits clearly can be seen, many features of immune exhaustion persist over time after viral elimination. Thus, a long-term chronic insult might result in irreversible damage to our immune system. This will be important to consider in therapeutic vaccination efforts against chronic infection and in the development of immunotherapy based strategies against cancer.

Tracking Down the Epigenetic Footprint of HCV-Induced Hepatocarcinogenesis

“…We specifically highlight the recent accumulated knowledge on the persistence of this epigenetic signature, discuss its implications for hepatocarcinogenesis and whether it is HCV-specific, and underline mechanisms of epigenetic imprinting by HCV infection that identifies potential targets for reversion of the epigenetic signature, which may be considered as a novel approach towards HCC prevention (Figure 1). Other recently suggested mechanisms that contribute to HCC progression following SVR by DAAs, such as the potential involvement of host immunity (Reviewed in [28]), are not discussed in this review. HCV induces epigenetic alterations that persist following cure with DAAs and may be reverted by drugs.…”

Viral Manipulation of the Host Epigenome as a Driver of Virus-Induced Oncogenesis

“…Several lines of evidence demonstrate that specific epigenetic signatures induced by HCV infection result in a "lasting" epigenetic memory, which persists after viral eradication. This permanent "scarring" suggests a novel mechanism for the pathogenesis of HCV even after its eradication with DAAs [55][56][57][58].…”

Viral hepatitis update: Progress and perspectives

“…Currently, treatments are oral with almost no side effects and with SVR rates higher than 97% after 8 to 12 wk. Nowadays, successful treatment leads to regression of clinical symptoms and complications of liver disease even in those patients with other comorbidities, co-infections, or advanced liver disease[ 92 - 94 ]. In this new scenario, as mentioned above, in 2016 the World Health Assembly approved a global strategy to achieve viral hepatitis elimination (C and B), which concerning HCV aims to reduce 90% of new HCV infections (incidence), 65% of deaths (mortality), and treat at least 80% of patients who require treatment[ 95 , 96 ].…”

“…Nevertheless, it does not apply for every patient, and the restoration level was not homogeneous for all individuals. The suppression of HCV replication led to a decrease in expression of T lymphocyte exhaustion markers and an increase in HCV-specific IFN-γ responses after treatment[ 94 , 106 , 107 ]. However, the restoration of exhausted HCV-specific CD8+ T lymphocyte surface phenotype does not result, per se , in a complete functional restoration.…”