Christoph Antoni

Circulating fibronectin isoforms predict the degree of fibrosis in chronic hepatitis C.

Abstract Objective. Hepatic stellate cells only produce fibronectin isoforms in disease states. The isoform-defining domains can be detected in the blood circulation. This study examines whether circulating levels of fibronectin isoforms show a relationship with liver fibrosis on histology in patients with chronic hepatitis C. Material and methods. In a prospective study, 50 patients with chronic hepatitis C who underwent a liver biopsy were compared to 50 matched controls and 35 patients with other liver conditions. Results. Circulating levels of the fibronectin isoforms were significantly higher in patients with chronic hepatitis C compared to healthy controls [oncofetal fibronectin (oFN) 2.45 ± 0.17 versus 1.76 ± 0.16 mg/l, P < 0.005; extra domain-A (EDA) 1.05 ± 0.06 versus 0.86 ± 0.06 mg/l, P < 0.05; and extra domain-B (EDB) 14.55 ± 0.74 versus 9.31 ± 0.58 mg/l, P < 0.001], even though total fibronectin was lower (198.9 ± 3.5 versus 343.6 ± 14.5 mg/l, P < 0.001). A correlation with the fibrosis score was found for both oFN (r = 0.46, P < 0.005) and EDA (r = 0.51, P < 0.001). The combination of an elevation in both markers (oFN and EDA) in the upper quartile was associated with a specificity of > 99% for predicting significant fibrosis (stages 2–4) and 95% for predicting advanced fibrosis (stages 3–4). A combination of decreased values in the lowest tertile for both markers had a specificity of 94% for excluding significant fibrosis. Based on these findings, 30% of the patients scheduled for a liver biopsy could be correctly classified as having or not having significant fibrosis. The remainder would have to proceed with a biopsy. Conclusion. Circulating fibronectin isoforms produced by activated stellate cells represent a viable marker for the presence of significant fibrosis or a lack thereof.

Discriminatory potential of C-reactive protein, cytokines, and fecal markers in infectious gastroenteritis in adults.

This study evaluates potential markers in blood and stools for their ability to distinguish bacterial from viral gastroenteritis. A total of 108 patients were prospectively recruited, of which 27 showed bacterial, 30 viral, and 51 no detectable pathogen, respectively. Cytokines, C-reactive protein (CRP), and white blood cells as well as the 2 fecal markers lactoferrin and calprotectin were determined. Statistics comprised Kruskal-Wallis test and U test in addition to an assessment of receiver operating characteristic. Interferon γ (IFNγ) levels were significantly increased in the viral group compared to the bacterial and nonspecific group. For the bacterial group, both fecal markers lactoferrin and calprotectin as well as CRP were significantly higher in comparison to the other 2 groups. To differentiate between bacterial and viral gastroenteritis, CRP, serum IFNγ, and the fecal proteins lactoferrin and calprotectin may be useful. A corresponding algorithm should be evaluated prospectively.

Prospective noninvasive analysis of hepatic fibrosis in patients with Crohn's disease: correlation of transient elastography and laboratory-based markers.

Background and aims Hepatobiliary disorders, associated either with extraintestinal manifestations or with consequences of treatment, are prevalent among patients with inflammatory bowel disease (IBD). This study aimed to prospectively assess the potential of noninvasive markers for the evaluation of liver fibrosis in patients with Crohn’s disease. Methods A total of 114 patients were recruited. Established markers of fibrosis, namely, aspartate transaminase-to-platelet ratio index (APRI), fibrotest, Forns, sonography, and transient elastography were performed and correlated with disease parameters. In addition to descriptive statistical analysis, Pearson’s correlation coefficients were determined. The t-test and the Mann–Whitney U-test were applied and univariate and multivariate data analyses were performed. Results Ultrasound indicated hepatic steatosis in 33 patients, hepatomegaly in 10, and cirrhosis in two. Liver stiffness as quantified by transient elastography was determined to be 5.06±2.33 kPa (2.6–21.5). Results of noninvasive liver fibrosis markers were as follows: fibrotest,−1.65±0.94; APRI, 0.33±0.22; and Forns, 3.11±2.00. Correlation coefficients were found to be fibrotest/transient elastography: r=0.35291; APRI/transient elastography: r=0.38442; Forns/transient elastography: r=0.33949; fibrotest/APRI: r=0.52937; fibrotest/Forns: r=0.42413; and APRI/Forns: r=0.56491. Correlation of inflammatory markers and noninvasive liver fibrosis tests, respectively, was generally negative, whereas correlation of parameters indicating liver damage and liver fibrosis tests, respectively, was generally positive. Conclusion In a center-based, unselected cohort of patients with Crohn’s disease, the positive correlations between laboratory-based markers of fibrosis and transient elastography were highly significant. A study correlating noninvasive and invasive tools for the assessment of liver fibrosis in IBD is reasonable.

Prevalence of inflammatory bowel disease in alcoholic, non-alcoholic and autoimmune pancreatitis: Inflammatory bowel disease in pancreatitis

OBJECTIVES Patients with inflammatory bowel disease (IBD) frequently reveal features of pancreatic inflammation. However, the prevalence of IBD in patients with alcoholic pancreatitis (AP) and nonalcoholic pancreatitis (NAP) has not yet been determined, and the prevalence of IBD in patients with autoimmune pancreatitis (AiP) from Germany is unknown. AIMS Thus, we aimed, first, to determine the prevalence of IBD in AP, NAP, and AiP from a tertiary center in Germany and, second, to characterize patients with AiP and IBD. METHODS We performed a retrospective cross-sectional study to determine the prevalence of IBD in patients with different forms of pancreatitis presenting to our clinic. RESULTS Compared to the general population and to a control group with viral hepatitis from our clinic, we observed the most significant increase of IBD in patients with AiP (n = 3/28; p < 0.0001 vs. general population, binomial proportion test; p = 0.0112 vs. hepatitis group, Fishers exact test), followed by a significant increase in subjects with NAP (n = 11/278; p < 0.0001 vs. general population, binomial proportion test; p = 0.0338 vs. hepatitis group, Fishers exact test). A review of previous studies on the prevalence of IBD among patients with AiP revealed a combined prevalence of 12 % (n = 43/355). Type 2 AiP is significantly more often associated with IBD than type 1 AiP (n = 28/48, 58 % vs. n = 7/129, 5 %; combined patient cohort, p < 10E - 12; Fishers exact test). CONCLUSIONS Immune-mediated mechanisms related to IBD may participate in the development of AiP, especially AiP type 2, and may also increase the risk for the development of other forms of pancreatic inflammation.