Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study.

BACKGROUND & AIMS: Hepatitis D virus (HDV) has decreased in Europe, but recent reports indicate a rising trend. We report the epidemiological changes, clinical progress, and effect of treatment on the natural course of HDV infection in Greece during the last 13 years. METHODS: Prospective data were extracted from the HepNet.Greece Cohort-Study. RESULTS: Since 1997, 4673 chronic HBV (CHB) cases (4527 adults, 146 children) have been followed prospectively. Two thousand one hundred thirty-seven patients were tested for anti-HDV [101 (4.7%) positive]. Anti-HDV testing in Greece decreased significantly (57.0% before 2003, 35.3% thereafter; p<0.001). Anti-HDV prevalence among HBsAg-positives was 4.2%; lower in native Greeks (2.8%) than in immigrants (7.5%) or in children (15.3%; p<0.001). Within 2.3 years of follow-up, HDV occurred in 11/2047 HBsAg-positive patients (2.2 new delta-infected adults and 8.7 children per 1000 HBsAg-positive annually). HDV-positive compared to CHB adults were younger (p=0.035) and had more active and advanced disease at baseline, as indicated by laboratory indices and the higher prevalence of cirrhosis at younger age. During a 4.2-year median observation, significantly more anti-HDV-positive than CHB adults developed a liver-related first event (20.0% vs. 8.5%, p Log-rank=0.014).Treatment was received by 46/90 (51.1%) patients, 40 of them interferon-based. In multivariable analysis, interferon significantly decreased disease progression in HDV-positive patients [HR=0.14 (95% CI: 0.02-0.86; p=0.033)]. CONCLUSIONS: In Greece, HDV serology is currently tested in only one-third of HBsAg-positive patients. HDV prevalence is lower in native Greeks compared to immigrants, who may contribute >50% of the HDV infection burden in Greece. Data show that HDV infection is a rapidly progressive disease, but interferon-based treatment may alter its course.

Foxp3 expression in liver correlates with the degree but not the cause of inflammation.

Patients with chronic viral hepatitis display increased expression of Foxp3 in liver, suggesting that Tregs expansion contributes to persistent infection. The purpose of this study was to elucidate whether the expression of Foxp3 relates not to the viral infection but to the resulting liver inflammation. Liver biopsies obtained from 69 individuals (26 chronic HBV hepatitis, 14 chronic HCV hepatitis, 11 nonalcoholic fatty liver disease, 8 autoimmune diseases, 2 methotrexate-related toxicity, and 8 controls) were examined, by qRT-PCR, for the mRNA expression of Foxp3, IL-10, TGF-ß1, Fas, FasL, TRAIL, caspase-3, TNF-α, IFN-γ, and IL-1ß. Significant increase of Foxp3 was observed in all disease groups compared to controls, which was positively correlated with the intensity of inflammation. The expression of the apoptosis mediators Fas, FasL, and TRAIL, but not of IL-10 and TGF-ß1, was also significantly elevated. Our findings indicate that, independently of the initial inducer, liver inflammation is correlated with elevated expression of apoptosis mediators and is followed by local Treg accumulation. Further research towards the elucidation of the underlying casual relationships is required, in order to clarify whether our results signify the existence of a uniform Treg-mediated regulatory mechanism of apoptosis-induced inflammation.

Thrombophilic abnormalities of natural anticoagulants in patients with ulcerative colitis.

BACKGROUND/AIMS: Ulcerative colitis patients have increased risk for thromboembolic events. Factors predisposing to thrombosis in ulcerative colitis are poorly defined. The aim of this study was to evaluate possible thrombophilic abnormalities in patients with ulcerative colitis. METHODOLOGY: Fifty-one patients with ulcerative colitis and 51 healthy controls were studied. Disease activity, clinical and endoscopic, was assessed by standard criteria. Plasma levels of antithrombin, protein C, free protein S and activated protein C resistance were determined in both study groups. Genetic test for factor V Leiden was performed in cases with abnormal activated protein C resistance. Parameters of inflammation and fibrinogen were additionally measured in ulcerative colitis patients. RESULTS: Mean values of free protein S were significantly lower in ulcerative colitis patients (84.01 +/- 21.57) compared to healthy controls (100.17 +/- 24.7) (p < 0.001). Mean values of protein C were higher in ulcerative colitis patients (124.6 +/- 39.03) than healthy controls (100.19 +/- 19.86) (p < 0.001). No other significant differences were observed, but there was a trend towards higher prevalence of low values for antithrombin (9.8% vs. 0%, p = 0.056) and free protein S (19.6% vs. 5.9%, p = 0.072) in ulcerative colitis patients. Three ulcerative colitis patients and three healthy controls had low activated protein C resistance ratio. All these subjects were heterozygous for factor V Leiden. No correlation was observed between abnormalities in thrombophilic parameters and clinical, endoscopic or inflammatory parameters in ulcerative colitis group. CONCLUSIONS: Abnormalities in natural anticoagulants are more common in ulcerative colitis patients compared to healthy controls, irrespective of disease activity. Low activated protein C resistance ratio due to factor V Leiden is not more common in ulcerative colitis patients than in healthy controls.

Hyperhomocysteinemia in ulcerative colitis is related to folate levels.

AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (UC). METHODS: Fasting homocysteine (Hcys), folate, and vitamin B(12) serum levels were measured in 40 UC patients and 50 healthy controls. Clinical data regarding UC were gathered. RESULTS: Median serum Hcys levels in UC patients were similar to controls (12.26 micromol/L vs 12.32 micromol/L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P = 0.028). UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125; 95%CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B(12) deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r(2) = 0.4; P<0.001). CONCLUSION: HHcys is common in UC patients and it is related to folate and vitamin B(12) deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.

Elevated plasma von Willebrand factor levels in patients with active ulcerative colitis reflect endothelial perturbation due to systemic inflammation.

AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity, systemic inflammation and coagulation activation. METHODS: In 46 patients with ulcerative colitis (active in 34 patients), clinical data were gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at baseline and after 12 wk of treatment. Plasma vWF levels were also determined in 52 healthy controls (HC). The relationship of plasma vWF levels with disease activity, disease extent, response to therapy, acute-phase reactants (APRs) and coagulation markers (COAGs) was assessed. RESULTS: The mean plasma vWF concentrations were significantly higher in active UC patients (143.38+/-63.73%) than in HC (100.75+/-29.65%, P = 0.001) and inactive UC patients (98.92+/-43.6%, P = 0.031). ESR, CRP and fibrinogen mean levels were significantly higher in active UC patients than in inactive UC patients, whereas there were no significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients with raised APRs had significantly higher mean plasma vWF levels than those with normal APRs (144.3% vs 96.2%, P = 0.019), regardless of disease activity. Although the mean plasma vWF levels were higher in UC patients with raised COAGs than in those with normal COAGs, irrespective of disease activity, the difference was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted between plasma vWF levels and disease extent. After 12 wk of treatment, significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were noted only in UC patients with clinical and endoscopic improvement. CONCLUSION: Our data indicate that increased plasma vWF levels correlate with active ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels in ulcerative colitis possibly reflect an acute-phase response of the perturbed endothelium due to inflammation. In UC patients, plasma vWF levels may be another useful marker of disease activity or response to therapy.