A 5‐year prospective study of the late resolution of chronic hepatitis C after antiviral therapy

Abstract

SUMMARY BackgroundPersistence of hepatitis C virus (HCV) in serum is assured after any course of antiviral therapy that failed to obtain a sustained virological response.

Modeling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct‐acting antiviral agents

“…Whether this adds to the evidence in support of the virologic hypothesis or whether sufficient CTL exhaustion had set in by the start of treatment, which was 9 weeks after infection, for the immunologic hypothesis to hold in the patient remains unknown. Similarly, EOT + /SVR has also been reported in some individuals treated with PR 27, 28, 29, 30. Interferon is argued to have a pleiotropic influence on CTLs, enhancing their proliferation and activation in the early stages of infection and rendering them more exhausted during the late stages of infection 47.…”

“…Similarly, EOT + /SVR has also been reported in some individuals treated with PR. [27][28][29][30] Interferon is argued to have a pleiotropic influence on CTLs, enhancing their proliferation and activation in the early stages of infection and rendering them more exhausted during the late stages of infection. 47 Indeed, early initiation of PR treatment has been suggested to improve treatment outcomes.…”

“…Multiple lines of evidence support this hypothesis: Ex vivo studies demonstrate increased exhaustion of CTLs in chronic HCV patients pre‐treatment compared to uninfected individuals and a reduction of this exhaustion accompanied by improved proliferative capacity and functionality of HCV‐specific CTLs during treatment 23, 24, 25. Interferon treatment is unable to induce this reversal,26 explaining the absence of EOT + /SVR with PR treatment, barring a few exceptions 27, 28, 29, 30. When the percentage of hepatocytes infected was reduced below a threshold, exhausted CTLs regained their functionality in a mouse model of HCV infection 31.…”

“…[23][24][25] Interferon treatment is unable to induce this reversal, 26 explaining the absence of EOT + /SVR with PR treatment, barring a few exceptions. [27][28][29][30] When the percentage of hepatocytes infected was reduced below a threshold, exhausted CTLs regained their functionality in a mouse model of HCV infection. 31 Anti-PD-1 therapy, which prevents or reverses CTL exhaustion, has shown some success in HCV-infected primates and humans.…”

Long-term outcomes of chronic hepatitis C patients treated with pegylated interferon 2a plus ribavirin in Iran

“…In other words, patients who obtained SVR to PEG-IFN plus ribavirin, had well long-term outcomes versus non-SVR ones. There are several studies about follow up of chronic hepatitis C patients who were treated with interferon-based therapy (Aronsohn and Reau, 2009;Giannini et al, 2010;Annicchiarico et al, 2007;George et al, 2009;Desmond et al, 2006;Adamek et al, 2007;Dzekova et al, 2009;Arase et al, 2007;Braks et al, 2007;Imazeki et al, 2003;Ciancio et al, 2006;Pradat et al, 2007;Marcellin et al, 1997;Swain and Shiffman, 2004). Each study was conducted with individual forms of interferon-based treatment regimens.…”