Reversing immune dysfunction and liver damage after direct-acting antiviral treatment for hepatitis C

Abstract

The introduction of small molecules targeting viral functions has caused a paradigm shift in hepatitis C virus (HCV) treatment. Administration of these direct-acting antivirals (DAAs) achieves a complete cure in almost all treated patients with short-duration therapy and minimal side effects. Although this is a major improvement over the previous pegylated interferon plus ribavirin (PEG-IFNα/RBV) standard-of-care treatment for HCV, remaining questions address several aspects of the long-term benefits of DAA therapy. Interferon (IFN)-based treatment with successful outcome was associated with substantial reduction in liver disease–related mortality. However, emerging data suggest a complex picture and several confounding factors that influence the effect of both IFN-based and DAA therapies on immune restoration and limiting liver disease progression. We review current knowledge of restoration of innate and HCV-specific immune responses in DAA-mediated viral elimination in chronic HCV infection, and we identify future research directions to achieve long-term benefits in all cured patients and reduce HCV-related liver disease morbidity and mortality.

Direct acting antiviral therapy rescues neutrophil dysfunction and reduces hemolysis in hepatitis C infection

“…11 The ability of DAA therapy to ameliorate a broad range of extrahepatic manifestations of CHC 27 as well as beneficial effects of DAA therapy on some parts of innate immunity have been described. 13 Data about the effect of DAA on neutrophils is lacking. Neutrophil function in our study rapidly improved during DAA therapy, underpinning the importance of hepatitis C eradication not only to prevent liver disease but also to prevent extrahepatic manifestations caused by CHC.…”

“…12 Currently, interferon-free treatment with second-generation direct acting antivirals (DAAs) are the first-line treatment for CHC patients since several years and have already been shown to have beneficial effects on innate immune mechanisms. 13 However, their influence on neutrophil function has not been studied yet.…”

Management of concomitant hepatocellular carcinoma and chronic hepatitis C: a review

“…In addition to the impact of immunotherapy treatment of HCC on DAA treatment of HCV, we must also consider the opposite, as there is growing research showing the impact of DAAs on immune cells both within the liver and peripherally [74,75] . From this, we might extrapolate that this in turn may impact on the immune surveillance in this population, thus may affect HCC treatment outcomes.…”

“…From this, we might extrapolate that this in turn may impact on the immune surveillance in this population, thus may affect HCC treatment outcomes. Currently the clinical impact of the immune environment and altered immune surveillance is not clear, but insight into these processes in the post-DAA liver is improving, which may be crucial in how we shape our treatment [74] .…”

A prospective study on Foxp3+CD25highCD4+ regulatory T cells in chronic hepatitis C infected patients undergoing direct-acting antiviral combination therapy

“…They are known to act directly without affecting the immune system. However, resetting of the immune response to the pre-infection state and halting the progression of HCV-induced immunopathology after virus elimination is an important determinant of the future course of the disease and long term outcomes of therapy 18 . Since multiple immune functions are modified by Treg cells, it is important to know their dynamics during HCV infection and after viral clearance.…”