Decreased IP-10 and Elevated TGFβ1 Levels are Associated with Viral Clearance Following Therapy in Patients with Hepatitis C Virus

Abstract

The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNα) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Rα2), total and active transforming growth factor-beta 1 (TGFβ1), interleukin-18 (IL-18) and interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p = 0.045), but optimal prediction was achieved with an algorithm (“TIPscore”) based on TGFβ1 (total), IP-10, age, sex and HCV genotype (p = 0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p = 0.07), it associates high TGFβ1 and low IP-10 levels with a failure of therapy.

Lack of TGF-β production by hepatitis C virus-specific T cells during HCV acute phase is associated with HCV clearance in HIV coinfection

“…Unfortunately, the lack of available samples did not allow us to study this new parameter. We also did not find any correlation between plasma TGF-b levels and recovery in coinfected patients, contrasting with a previous report based on a score combining TGF-b levels and other factors [21]. The lack of detection of IL-10-producing cells, contrasts with other studies of HCV mono-infection [11].…”

“…While the TGF-b profibrogenic, antiinflammatory and immunosuppressive activities certainly play a key role in HCV pathogenesis, its role in the control of HCV is still controversial. Indeed, high serum TGF-b levels [20] and a TGF-b high-producer genotype have been associated with failure [21] or with sustained virologic response to anti-HCV treatment, respectively [22]. Furthermore, increasing levels of TGF-b in the liver of HCV-infected patients enhanced fibrosis progression [23].…”

Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection

“…In this context, TGF-b is a cytokine with multiple functions that has been associated with the development of hepatic fibrosis [20,21]. However, the role of TGF-b on the outcome of treatment against HCV is unclear and data are scarce and contradictory [22][23][24][25][26][27]. In this regard, high TGF-b levels have been described to diminish response to dual therapy in this population [22].…”

“…However, the role of TGF-b on the outcome of treatment against HCV is unclear and data are scarce and contradictory [22][23][24][25][26][27]. In this regard, high TGF-b levels have been described to diminish response to dual therapy in this population [22]. On the contrary, a study observed a direct relationship between TGF-b levels and response to Peg-IFN in HIV-infected patients with acute hepatitis C [23].…”

Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients

“…During permanent attempts to improve therapeutic strategies, beside the recent approval of two novel direct acting antiviral compounds [2], several predictors of treatment response have been identified [3] with recent studies including gamma-glutamyl-transferase (gGT) [4], cholesterol [5], early viral kinetics [6], interferon-γ-inducible-protein-10 (IP10) [7], ferritin [8] and the interleukin-28B ( IL28B ) polymorphism [9] as further important predictors of sustained viral response (SVR) as well. However, the pursuit of further surrogate factors able to optimize therapeutic regimes remains challenging.…”