Immunomodulators, sFas and Fas‐L as potential noninvasive predictors of IFN treatment in patients with HCV genotype‐4

Abstract

Recent studies have indicated that cytokines can be used as markers for disease progression in hepatitis C virus (HCV)-infected patients, therefore this study was conducted to determine the influence of pegylated IFN vs standard IFN on interleukin-2 receptor (IL-2R), IL-6R, IL-8, TNFR-I, TNFR-II, sFas, and sFas-L in Egyptian patients with chronic hepatitis C genotype 4, as no previous studies have been performed on this genotype. We also aim at establishing a possible relationship between these cytokines and the response to INF to determine whether they can be used as noninvasive markers for the response to INF therapy and as monitors for the outcome of treatment. Thirty-eight patients with chronic HCV hepatitis were investigated for the serum levels of the previously mentioned cytokines in a randomized opened controlled trial (22 patients treated with pegylated IFN and 16 patients treated with standard IFN). Cytokine levels were measured by ELISA at 0, 1 and 12 months of IFN therapy. There was marked increase in the serum levels of IL-2R and IL-6R in nonresponders to pegylated interferon, IL-8, TNFR-I and II were significantly higher in nonresponders to standard interferon but were also high in responders of pegylated interferon. sFas and sFas-L showed high levels among responders to pegylated interferon but the standard interferon was again less effective in this regard. Serum levels of TNFR-II, sFas and sFas-L have the potential to be used as serological markers for response to pegylated IFN therapy, and IL-8 is a predictor for nonresponse. Moreover, TNFR-I and II have the potential to be used as markers of response to standard IFN treatment. The persistent correlation between sFas and TNFR-II may elaborate the possible role of pegylated IFN in the induction of apoptosis as a possible new mechanism of viral clearance during treatment with pegylated interferon treatment.

Untitled

“…The differences noticed might be due to the fact that their patients had compensated liver diseases; unlike ours. This figure, however, was in agreement with that in our previous study [26]. …”

“…This was in contrast with the study of Fargion et al [28] in which no significant association with response was found with sex or age. Also our previous study showed that six out of 9 (67%) females treated with standard interferon had sustained viral response, whereas only one of 5 females treated with pegylated interferon showed viral response [26]. …”

Meta-analysis

“…Eighty-four studies were closely evaluated for eligibility[10–16, 18, 26–101]. Fourteen studies did not have extractable treatment outcomes data[26, 29, 36, 47, 50, 58, 61, 64, 74, 86, 87, 92, 100, 101]. Six were redundant[49, 51, 57, 68, 89, 99] and four were not relevant[30, 43, 60, 94].…”

Gene Polymorphism of Proinflammatory Cytokines (Tnf, Il6) and Their Receptors (Tnfrsf1a, Tnfrsf1b, Il6r): Implications for Non-Alcoholic Fatty Liver Disease

“…Например, пока-зано, что у пациентов с циррозом печени хоро-ший прогноз относительно смертности связан с повышенным содержанием в плазме рас-творимых TNFRII-рецепторов [Grunhage et al, 2008]. Содержание растворимых TNFR может быть использовано также как маркер эффек-тивности лечения иммунномодулирующими препаратами пациентов с заболеваниями пе-чени, в частности вирусным гепатитом С [Zekri et al, 2007]. Однако связан ли повышенный уровень этих рецепторов с тяжестью НАЖБП, пока не ясно.…”