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Background: The aim of the study was to evaluate the incidence of abnormality of liver tests (LTs) or hepatotoxicity in a large group of inflammatory bowel disease (IBD) patients and, specifically, to assess the incidence of azathioprine (AZA) / mercaptopurine (MP)-induced liver injury in a long-term follow-up study. Methods: All consecutive IBD patients followed for at least 5 years were included in this retrospective study. LTs including alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyl transferase, and bilirubin were periodically monitored. “Abnormality-of-LTs” was defined as LTs between N (upper limit of the normal range) and 2 N, and “liver injury/hepatotoxicity” as LTs >2 N. Results: A total of 786 patients were included, and 138 received AZA/MP; 120 patients (15%) and 39 (5%) presented abnormality of LTs or hepatotoxicity, respectively, during follow-up. The most frequent explanations were AZA/MP treatment and fatty liver disease. Among AZA/MP-treated patients (690 patient-years follow-up) the incidence of abnormal LTs and hepatotoxicity was, respectively, 7.1% and 2.6% per patient-year. Most patients spontaneously normalized LTs despite maintaining AZA/MP. These drugs were withdrawn due to hepatotoxicity (LTs >5 N and lack of decrease despite 50% dose reduction) in 3.6% of the patients and all of them normalized LTs. Conclusions: In IBD patients, AZA or MP treatment induces abnormality of LTs in a relatively high proportion of the cases, but the development of true hepatotoxicity/liver injury is exceptional. Moreover, most of the cases of thiopurine-induced hepatotoxicity in IBD patients are mild, and the abnormalities in LTs spontaneously return to normal values despite AZA/MP being maintained, therapy withdrawal being necessary in only ≈4% of the patients. (Inflamm Bowel Dis)

There are 4 major concepts in vascular development: vasculogenesis (formation of blood vessels from angioblasts), angiogenesis (formation of vascular sprouts from preexisting vessels), arteriogenesis (thickening and development of vessels) and lymphangiogenesis (formation of lymphatic vessels). In the last decade, these concepts, especially angiogenesis and lymphangiogenesis, have acquired major importance due to their role in tumoral growth and metastatic dissemination. Moreover, the activity of various diseases that involve chronic inflammation, such as asthma, psoriasis and rheumatoid arthritis, has been associated with vascular development. Several growth factors and cytokines are involved in this process and consequently investigation into these elements, both in peripheral blood and their expression in affected tissues, could elucidate the role of vascular development in diseases whose pathogenesis involves chronic inflammation, such as inflammatory bowel disease. The presence of distinct molecules involved in vascular development processes, such as vascular endothelial growth factor (VEGF), basic fibroblastic growth factor and placental growth factor, among others, has been studied in both ulcerative colitis and Crohn's disease, although not extensively. It has been suggested that the phenomena of vasculogenesis, angiogenesis and lymphangiogenesis play a critical, although not exclusive, role in the inflammation that characterizes inflammatory bowel disease. In general, the results obtained to date suggest that new vascular formation is involved in the pathogenesis of these diseases.

Objective Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylates (5-ASA). Our aim was to conduct a retrospective study of IBD patients, both with and without 5-ASA treatment, who underwent regular evaluation of renal function over a 4-year period. Methods Serum creatinine was measured before the start of 5-ASA therapy, and thereafter yearly up to 4 years. Creatinine clearance (Cl Cr ) was estimated from serum creatinine (Cockroft & Gault formula). The influence of 5-ASA treatment on renal function was assessed by univariate and multivariate analysis. Results A total of 150 IBD patients (ulcerative colitis in 45%, Crohn's disease in 55%) were included. Sixty-two patients were receiving 5-ASAs (95% coated mesalazine, mean dose 1.9 ± 0.8 g/day). Both serum creatinine levels and Cl Cr were similar in patients with and without 5-ASA treatment, and remained stable throughout the 4-year follow-up in patients taking 5-ASAs. In the multivariate analysis, 5-ASA treatment (or its dose) was not correlated with serum creatinine levels or Cl Cr . No interstitial nephritis was reported during follow-up. Conclusion 5-ASA-related renal disease was not found in our series, suggesting that the occurrence of renal impairment in IBD patients receiving these drugs is exceptional. Our results do not support the recommendation of serum creatinine monitoring in patients receiving 5-ASA treatment.

Background: The purposes of this study were to determine soluble angiogenic factors in Crohn's disease (CD) patients and to compare these factors according to the pathological behavior of the disease in order to establish a possible relationship with its evolution in patients with CD. Methods: Blood samples were collected from 70 patients with CD, grouped according to their phenotypic behavior, and from 30 healthy controls. Vascular endothelial growth factor (VEGF), placental growth factor (PlGF), angiopoietin 1 (Ang1), angiopoietin 2 (Ang2), and their cognate receptors [VEGFR1, VEGFR2, and angiopoietin receptor tyrosine kinase (Tie2)] were assayed by ELISA. Results: Circulating levels of VEGF, PlGF, VEGFR1, Ang2, and Tie2 were significantly higher in CD patients than in healthy controls (489 ± 271 versus 335 ± 118 pg/mL, P < 0.001; 31 ± 9 versus 23 ± 9 pg/mL, P < 0.001; 1.7 ± 0.4 versus 1.0 ± 0.3 ng/mL, P < 0.001; 4.8 ± 2.0 versus 3.9 ± 2.0 ng/mL, P < 0.05; and 36 ± 5 versus 22 ± 7 ng/mL, P < 0.001, respectively). Conversely, CD patients showed significantly lower serum levels of Ang1 than healthy controls (40 ± 12 versus 67 ± 22 ng/mL; P < 0.001). No differences between the groups were found in VEGFR2 serum level. The circulating levels of the angiogenic factors did not differ significantly when the CD patients were classified according to pathological phenotype. Conclusions: In comparison with healthy controls, CD patients were found to have an active angiogenic profile, as detected by significant alterations in levels of angiogenesis soluble markers. These patients did not differ in serum levels of angiogenic factors according to phenotypic disease behavior. (Inflamm Bowel Dis 2007)

There are 4 major concepts in vascular development: vasculogenesis (formation of blood vessels from angioblasts), angiogenesis (formation of vascular sprouts from preexisting vessels), arteriogenesis (thickening and development of vessels) and lymphangiogenesis (formation of lymphatic vessels). In the last decade, these concepts, especially angiogenesis and lymphangiogenesis, have acquired major importance due to their role in tumoral growth and metastatic dissemination. Moreover, the activity of various diseases that involve chronic inflammation, such as asthma, psoriasis and rheumatoid arthritis, has been associated with vascular development. Several growth factors and cytokines are involved in this process and consequently investigation into these elements, both in peripheral blood and their expression in affected tissues, could elucidate the role of vascular development in diseases whose pathogenesis involves chronic inflammation, such as inflammatory bowel disease. The presence of distinct molecules involved in vascular development processes, such as vascular endothelial growth factor (VEGF), basic fibroblastic growth factor and placental growth factor, among others, has been studied in both ulcerative colitis and Crohn's disease, although not extensively. It has been suggested that the phenomena of vasculogenesis, angiogenesis and lymphangiogenesis play a critical, although not exclusive, role in the inflammation that characterizes inflammatory bowel disease. In general, the results obtained to date suggest that new vascular formation is involved in the pathogenesis of these diseases.

Antecedentes y objetivos IFX es un anticuerpo monoclonal quimerico frente a TNFa, eficaz en el tratamiento de la Enfermedad Inflamatoria Intestinal (EII). La eficacia de dicho tratamiento podria estar relacionada con la modificacion de distintas proteinas angiogenicas, como son algunos miembros de la familia genica del factor de crecimiento del endotelio vascular (VEGF y PlGF), las angiopoyetinas (Ang1 y Ang2) y su receptor (Tie2). Diversos estudios revelan un aumento de las concentraciones sericas de VEGF en pacientes con Enfermedad de Crohn (EC) en comparacion con controles sanos, y unicamente existe un trabajo en el que se ha observado un decremento de las concentraciones sericas de VEGF en los pacientes con EC tras la infusion de IFX. Nuestro objetivo fue comparar las concentraciones de estas proteinas angiogenicas en pacientes con EII y en controles sanos y analizar su modificacion durante el tratamiento con IFX. Metodos Estudio prospectivo y caso-control en 30 individuos sanos y 12 pacientes con EII que inician tratamiento con IFX en pauta de induccion+mantenimiento. Se obtuvo una muestra serica de los individuos sanos y 4 de los pacientes con EII coincidiendo con los momentos previos a las 4 primeras dosis de IFX (semana 0, 2, 6, y 14). Las concentraciones de VEGF, PlGF, Ang1, Ang2 y Tie2 se determinaron mediante ELISA. Resultados Edad media de los controles 43±13 anos, 50% varones. De los 12 pacientes con EII, 11 presentaban EC y 1 Colitis Ulcerosa; su edad media fue de 35,4±8 anos, 75% mujeres, 50% fumadores y 50% en tratamiento concomitante con corticoides y azatioprina. En todos los casos hubo respuesta al tratamiento con IFX (CDAI/Truelove-Witts). Los pacientes con EII tuvieron concentraciones significativamente mas altas de Ang-2 (p=0,001) y su receptor Tie-2 (p=0,000) que los controles. No se encontraron diferencias significativas para el resto de proteinas. En los pacientes con EII, se observo una tendencia a presentar valores mas bajos de Ang1 que los controles. Las concentraciones de VEGF, PlGF, Ang1, Ang2 y Tie2, no se modificaron significativamente durante el tratamiento con IFX. VEGF (pg/ml) PlGF(ng/ml) Ang-1 (ng/ml) Ang-2 (ng/ml) Tie-2 (ng/ml) Controles Sanos 335±118 23±9 67±23 4±2 22±7 Pre tratamiento 333±206 21±10 56±17 9±6* 80±46* Semana 2 231±159 19±7 55±19 8±7 73±47 Semana 6 284±206 17±6 49±19 8±5 74±47 Semana 14 321±221 18±6 45±17* 8±4 70±41 * Valores significativos (p