Modifications of the Immune Responsiveness in Patients with Hepatitis C Virus Infection following Treatment with IFN-&amp;#945; / Ribavirin

Amati, L.; Caradonna, Luigi; Magrone, Thea; Mastronardi, Maria; Cuppone, R.; Cozzolongo, Raffaele; Manghisi, O. G.; Caccavo, Domenico; Amoroso, Anthony; Jirillo, Emilio

doi:10.2174/1381612024607036

Cited by 26 publications

(22 citation statements)

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“…77 At the end of the treatment (T 6 ), the following differences were noted between responders and non-responders in comparison to findings obtained before therapy (T 0 ). 69,77 Interestingly, in responders to IFN-a/RIB treatment, endotoxemia disappears while an elevated percentage of non-responders are still endotoxemic.…”

Section: The Role Of the Liver In The Response To Lps: Experimental Amentioning

confidence: 78%

Review: The role of the liver in the response to LPS: experimental and clinical findings

Jirillo

Caccavo

Magrone

et al. 2002

Journal of Endotoxin Research

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The liver plays an important physiological role in lipopolysaccharide (LPS) detoxification and, in particular, hepatocytes are involved in the clearance of endotoxin of intestinal derivation. In experimental shock models, tumor necrosis factor (TNF)-a induces hepatocyte apoptosis and lethal effects are due to secreted TNF-a and not to cell-associated TNF-a. An exaggerated production of TNF-a has been reported in murine viral infections, in which mice become sensitized to low amounts of LPS and both interferon (IFN)-g and IFN-a/b are involved in the macrophage-induced release of TNF-a. The prominent role of LPS and TNF-a in liver injury is also supported by studies of ethanol-induced hepatic damage. In humans, evidence of LPS-induced hepatic injury has been reported in cirrhosis, autoimmune hepatitis, and primary biliary cirrhosis and a decreased phagocytic activity of the reticulo-endothelial system has been found in these diseases. The origin of endotoxemia in hepatitis C virus (HCV) infected patients seems to be multifactorial and LPS may be of exogenous or endogenous derivation. In endotoxemic HCV-positive patients responsive to a combined treatment with IFN-a/ribavirin (RIB), endotoxemia was no longer detected at the end of the therapeutic regimen. By contrast, 48% of the non-responders to this treatment were still endotoxemic and their monocytes displayed higher intracellular TNF-a and interleukin (IL)-1b levels than responders. Moreover, in responders, an equilibrium between IFN-g and IL-10 serum levels was attained. In the non-responders, serum levels of IL-10 did not increase following treatment. This may imply that an imbalance between T helper (Th) 1 and Th 2 derived cytokines could be envisaged in the non-responders.

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Section: The Role Of the Liver In The Response To Lps: Experimental Amentioning

confidence: 78%

Review: The role of the liver in the response to LPS: experimental and clinical findings

Jirillo

Caccavo

Magrone

et al. 2002

Journal of Endotoxin Research

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“…Relevant to HCV, HCV-specific IL-10 + CD8 T-cell frequency in the liver correlated inversely to histological activity (16,39). Additionally, changes in serum or Tcell IL-10 levels have been associated with the efficacy of antiviral therapy in some studies (32,34,(40)(41)(42)(43)(44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

Kaplan¹,

Ikeda²,

Li³

et al. 2008

Journal of Hepatology

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“…The same study demonstrated a predominant Th2 pattern with higher circulating levels of IL-6, IL-10 and TNF-α in HCV+ patients compared to HCV-patients, possibly reflecting a more active systemic inflammatory response. On the other hand, modifications in the Th1/Th2 ratio provoked by ribavirin treatment leading to an imbalance towards the Th1 response may be associated with a more favorable outcome regarding HCV therapy (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Effect of hepatitis C serology on C-reactive protein in a cohort of Brazilian hemodialysis patients

Nascimento

Bruchfeld

Suliman

et al. 2005

Braz J Med Biol Res

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Hepatitis C (HCV) is not an uncommon feature in hemodialysis (HD) patients and may be a cause of systemic inflammation. Plasma cytokine interleukin-6 (IL-6) is mainly produced by circulating and peripheral cells and induces the hepatic synthesis of C-reactive protein (CRP), which is the main acute phase reactant. The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP and IL-6, in HD patients. The study included 118 HD patients (47% males, age 47 ± 13 years, 9% diabetics) who had been treated by standard HD for at least 6 months. The patients were divided into two groups depending on the presence (HCV+) or absence (HCV-) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured and the values were compared with those for 22 healthy controls. Median hsCRP and IL-6 values and hsCRP/IL-6 ratio were: 3.5 vs 2.1 mg/l, P < 0.05; 4.3 vs 0.9 pg/ml, P < 0.0001, and 0.8 vs 2.7, P < 0.0001, for patients and controls, respectively. Age, gender, S-Alb, IL-6 and hsCRP did not differ between the HCV+ and HCV-patients. However, HCV+ patients had higher ALT (29 ± 21 vs 21 ± 25 IU/l) and had been on HD for a longer time (6.1 ± 3.0 vs 4.0 ± 2.0 years, P < 0.0001). Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs 0.9, P < 0.05) compared to the HCV-group. The lower hsCRP/IL-6 ratio in HCV+ patients than in HCV-patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP for this population of patients on HD may be required to define inflammation.

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Modifications of the Immune Responsiveness in Patients with Hepatitis C Virus Infection following Treatment with IFN-α / Ribavirin

Cited by 26 publications

References 0 publications

Review: The role of the liver in the response to LPS: experimental and clinical findings

Review: The role of the liver in the response to LPS: experimental and clinical findings

Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis

Effect of hepatitis C serology on C-reactive protein in a cohort of Brazilian hemodialysis patients

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