Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection

Abstract

Direct-acting antiviral agents (DAAs) that allow for rapid clearance of hepatitis C virus (HCV) may evoke immunological changes. Some cases of rapid de novo hepatocellular carcinoma (HCC) development or early recurrence of HCC after DAA treatment have been reported. During chronic HCV infection, natural killer (NK) cells exhibited a deviant functional phenotype with decreased production of antiviral cytokines and increased cytotoxicity; however, DAA treatment rapidly decreased their cytotoxic function. Effective DAA therapy also suppressed the intrahepatic activation of macrophages/monocytes. This was followed by a decrease in mucosal-associated invariant T (MAIT) cell cytotoxicity without normalization of cytokine production. Rapid changes in the phenotypes of NK and MAIT cells after DAA treatment may attenuate the cytotoxicity of these cells against cancer cells. Moreover, DAA treatment did not normalize the increased frequencies of regulatory T cells even after clearance of HCV infection. Thus, the persistently increased frequency of regulatory T cells may contribute to a local immunosuppressive milieu and hamper the clearance of cancer cells. This review will focus on recent studies describing the changes in innate and adaptive immune responses after DAA treatment in patients with chronic HCV infection in the context of de novo occurrence or recurrence of HCC.

Potential of antiviral drug oseltamivir for the treatment of liver cancer

“…The incidence of primary liver cancer is largely explained by infection with hepatitis B and C viruses, and such infections account for over 80% of liver cancer cases worldwide (6). In fact, numerous studies have demonstrated a strong correlation between chronic viral hepatitis, particularly hepatitis induced by hepatitis B and C viruses and liver cancer development (6)(7)(8)(9).…”

Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma

“…Two identified subgroups are PD-1 + TCF1 + cells, capable of self-regeneration, and terminally exhausted PD-1 + TCF1 − cells. [19][20][21] The response to anti-PD-1 improves when PD-1 + TCF1 + cells are dominant, but not when the terminally exhausted PD-1 + TCF1 − T cells replace their precursors in the TME. [19][20][21] Multiplex immunohistochemistry and gene expression assays of 919 regions of 158 HCC tissues revealed that the immune microenvironment in HCC is heterogeneous and can be classified into three different subtypes: immune-high, -mid, and -low.…”

“…changes the phenotype of infected hepatocytes and intrahepatic monocytes/macrophages while contributing to HCC. 20,104,105 The inflammatory activity of intrahepatic macrophages, which is closely associated with mucosalassociated invariant T (MAIT) cell activity, is markedly attenuated after rapid viral clearance by DAAs. 106 MAIT cells are activated by IL-12, IL-15, and IL-18, which are usually produced by activated macrophages/monocytes.…”

Prevalence of Genotype 3a in Different Regions of Pakistan: A systematic Review and Meta-Analysis

“…The deadly disease leads to individual liver problems, around 350,000 individuals' yearly loss of their lives around the globe [4]. There are various treatments to cure hepatitis, out of which antiviral medicine can treat 95% of the patients successfully [5,6].…”