Quality of life, depression, and cytokine patterns in patients with chronic hepatitis C treated with antiviral therapy.

PURPOSE: To evaluate the effect of chronic hepatitis C and antiviral therapy on health-related quality of life (HRQoL), depression symptoms and cytokine patterns. METHODS: Twenty HCV+ patients treated with peginterferon plus ribavirin were enrolled in this cohort study and invited to complete SF-12 and BDI questionnaires prior to (T0) and at the end of the treatment (T1). HCV-RNA, serum levels of ALT, AST, haemoglobin, ferritin and IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6 and IL-10 were evaluated at T0 and T1. The questionnaire results were correlated to biochemical and cytokine parameters. RESULTS: Two patients (1%) dropped out and 18 HCV patients composed the final sample (11 males (61.1%); mean age 42.5+/-11.9 yr; mean disease duration 9.7+/-6.9 yr). Between T0 and T1 ALT (p=0.02), AST (p=0.052) HCV-RNA (P=0.0002) and haemoglobin levels decreased (p=0.0003), whereas ferritin level increased (P=0.003). Also, at T1 all cytokine levels were augmented. Regarding depression status, at T0 10 patients (55.5%) scored above to the BDI questionnaire (suggesting clinically significant depression), whereas at T1 14 patients scored 10 or above (77.7%). At T1 the mean BDI score increased, but this difference was not significant. Regarding HRQoL, the majority of patients had T0 summary scores < or = 50. At T1 HRQoL changed and scores decreased in 66.7% of the patients. A correlation was observed between the T0 level of ferritin and the amount of change in BDI and SF-12 mental score between T0 and T1 (Spearman rho = -0.56 and +0.61, respectively) and IL-4 level at T0 and the change in BDI and SF-12 mental scores (Spearman rho = -0.49 and +0.45, respectively). CONCLUSION: BDI, SF-12, IL-4 and ferritin are good tools to predict the appearance of depressive symptoms and worsening of the quality of life in the HCV+ population.

Inflammatory cytokines and S-100b protein in patients with hepatitis C infection and cryoglobulinemias.

OBJECTIVE: To investigate a predictive role for the protein S-100b and serum circulating levels of Th1/Th2 cytokines in patients with chronic hepatitis C virus (HCV) infection with and without mixed cryoglobulinemia (MC). METHODS: Sixty chronically HCV-infected patients were divided into two groups: 30 with and 30 without MC. Patients with MC presented detectable mixed cryoglobulins and clinical weakness, purpura and arthralgias. HCV-RNA and genotype, serum levels of cryoglobulins, principal hepatic indexes and levels of IL-6, IL-18 and S-100b protein were evaluated. Twenty uninfected healthy subjects were a control group to evaluate serum levels of S-100b protein. RESULTS: IL-6 and IL-18 serum levels were higher in the MC+ group than the MC- group (8.7 +/- 4.5 pg/mL versus 4.6 +/- 2.3 pg/mL P < 0.0001 and 743.5 +/- 128.2 pg/mL versus 578.5 +/- 296.5 pg/mL P < 0.001 respectively). S-100b serum levels were higher in HCV+ with MC (0.23 +/- 0.07 microg/L) respect to HCV+ patients without MC (0.17 +/- 0.05 microg/L, P < 0.0001) and were statistically higher than in the control group (0.08 +/- 0.03 microg/L, P < 0.0001 and P < 0.0001, respectively). A positive correlation was shown between serum levels of S-100b protein and levels of cryoglobulins in the group of HCV+ patients MC+ (r=0.72 and P < 0.0001). CONCLUSION: HCV patients with MC have a worse inflammatory condition than those without MC. Moreover, S-100b protein seems to be a sensitive marker of endothelial and tissue damage in chronic HCV hepatitis with cryoglobulinemia.

Antidepressant therapy can improve adherence to antiretroviral regimens among HIV-infected and depressed patients.

Several strategies have been introduced to manage nonadherence to highly active antiretroviral therapy (HAART). Treatment with antidepressants may improve self-reported adherence. In this brief report, a small sample of HIV-depressed patients (n = 9) were treated for a 6-month period with antidepressants improving self-reported adherence based on the HAART scale (poor, good, satisfactory, and optimal). Before the antidepressant treatment, adherence was reported as "good" by 3 patients and "satisfactory" by 6 patients. After antidepressant therapy, adherence to antiretroviral regimes was statistically higher in HIV-depressed on treatment than in HIV-depressed patients not treated with antidepressants (P < 0.0001). We used chi2 test with a significance level at P < 0.05. Treating depression in HIV-infected patients may serve to improve adherence to HAART.

Cytokine patterns correlate with liver damage in patients with chronic hepatitis B and C.

T-cell immunoregulatory cytokines influence the persistence of hepatitis C virus (HCV) chronic infection and the extent of liver damage. Th1 cytokines positively correlate with hepatic inflammation in chronic hepatitis B virus (HBV) infection. The pro-inflammatory, cytokines IL-6 and IL-18, are involved in viral clearance and in metabolic and viral hepatic diseases, respectively. The aim of this study was to evaluate the profile of Th1/Th2 cytokines in HCV and HBV hepatitis. HBV-infected patients showed higher plasma IFN-gamma levels than the HCV+ patients or the control group (p <0.0001). Plasma TNF-alpha and IL-2 were higher in HBV+ in comparison to HCV+ patients (p <0.001) or the control group (p <0.005). Plasma IL-6 and IL-18 were higher in both groups of patients compared to the control group (p <0.04). In HCV+ and HBV+ groups, IL-6 was positively correlated with the duration of the illness (p <0.01 and <0.001, respectively) and viral load (p <0.001 and <0.001, respectively), while IL-18 was positively correlated with serum ALT activity (p <0.01 and <0.001, respectively) and serum AST activity (p <0.01 and <0.001, respectively). We found that in HCV+ and HBV+ patients there are higher levels of Th1 cytokines, particularly in the course of chronic hepatitis B, and that IL-18 and IL-6 levels may have important roles as markers of both inflammation and hepatic injury, particularly in the course of hepatitis C.

Associations between hypertriglyceridemia and serum ghrelin, adiponectin, and IL-18 levels in HIV-infected patients.

HIV-related metabolic abnormalities include hypertriglyceridemia, hypercholesterolemia, insulin resistance, and diabetes mellitus. Recent studies suggest a role of ghrelin in promoting the deposition of triglycerides (TG) in the liver and regulating the metabolic action of adiponectin. Visceral fat is a key regulator of inflammation and it secretes proinflammatory cytokines (eg, interleukin-18, IL-18), with potential atherogenic activity. The aim of this study was to assay serum concentrations of ghrelin, adiponectin, and IL-18 in HIV+ patients, with and without hypertriglyceridemia, who were receiving highly active antiretroviral therapy (HAART). The 49 HIV+ patients were divided in 2 groups: 17 patients with serum TG concentration >200 mg/dl (group A) and 32 patients with normal serum TG concentration (group B). All subjects underwent viral and immunological evaluations and determinations of serum cholesterol, glucose, ghrelin, adiponectin, and IL-18. No differences of viral and immunological parameters were observed between the 2 groups. Serum levels of ghrelin were 768 +/- 596 pg/dl in group A and 470 +/- 248 pg/dl in group B (p = 0.01). Group A had lower serum adiponectin levels (8.4 +/- 3.6 microg/dl) than group B (18.2 +/- 10.1 microg/dl; p = 0.0001). Serum IL-18 levels were 455 +/- 199 pg/ml in group A and 258 +/- 233 pg/ml in group B (p = 0.005). The patients with hypertriglyceridemia showed a positive correlation between serum triglyceride and ghrelin levels (r = 0.51, p = 0.03). These findings suggest potential roles of ghrelin, adiponectin, and IL-18 in the pathogenesis of metabolic disorders in HIV-infected patients.

Association between plasma interleukin-18 levels and liver injury in chronic hepatitis C virus infection and non-alcoholic fatty liver disease.

There is significant upregulation of interleukin-18 (IL-18) expression in viral infectious diseases and in some chronic hepatic diseases, especially (i) hepatitis C virus (HCV) infection, (ii) HCV infection with persistently normal ALT levels (PNAL), and (iii) non-alcoholic fatty liver disease (NAFLD). The aim of this study was a better understanding of the implications of plasma IL-18 levels in the above-mentioned liver diseases. Thirty-four patients with HCV infection, 13 with NAFLD, and 10 controls were enrolled. The HCV-RNA and HCV-genotypes and the serum or plasma levels of IL-18, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase, total cholesterol, triglycerides, alpha(1)-fetoprotein, and ferritin were evaluated. Patients with HCV showed higher levels of IL-18 than the NAFLD patients (p <0.01) and the controls (p <0.005). Patients with NAFLD showed higher values of body mass index and liver disease parameters, compared to HCV-infected subjects or controls. These data confirm previous reports of enhanced expression of IL-18 in patients with HCV and NAFLD, compared to healthy subjects, and suggest that IL-18 is important as a marker of liver diseases.