Prevalencia de deficiencia de vitamina K y factores asociados en pacientes con fibrosis quística sin aporte suplementario / Prevalence of vitamin K deficiency and associated factors in non-supplemented cystic fibrosis patients

Introducción. La deficiencia de vitamina K es prevalente en pacientes con fibrosis quística (FQ) aun con aporte suplementario. Se desconocen factores de riesgo fiables para determinar su ocurrencia. Nuestro objetivo fue evaluar la prevalencia de deficiencia de vitamina K y factores asociados en los pacientes con FQ que no recibían aporte suplementario. Métodos. Se determinaron protrombina inducida por ausencia de vitamina K (PIVKA-II) y osteocalcina infracarboxilada (OCic). Se evaluó el estado clínico y su relación con la deficiencia de vitamina K. El análisis estadístico incluyó prueba de Mann-Whitney, ANOVA o Kruskal-Wallis, prueba χ² o prueba de Fisher-Freeman-Halton y regresión logística múltiple lineal y escalonada hacia adelante. Resultados. Se incluyeron 79 pacientes con FQ de entre 0,4-25,3 años. Se observaron valores anómalos de PIVKA-II y OCic en 56 (70,9%) y 45 (57,0%) pacientes. Los pacientes con PIVKA-II elevada eran significativamente mayores (p = 0,0184) y tenían puntajes Z de peso corporal (p= 0,0297) inferiores a los pacientes que tenían concentraciones normales. No se hallaron diferencias entre los pacientes con OCic normal o patológica. Se notificaron valores anómalos de PIVKA-II y OCic más frecuentemente en pacientes con dos mutaciones graves en el gen CFTR y con un estado nutricional malo/deficiente. Los análisis de regresión múltiple lineal y de regresión múltiple escalonada hacia adelante no revelaron factores predictivos sólidos para determinar la deficiencia de vitamina K. Conclusión. La deficiencia de vitamina K es altamente prevalente durante la evolución natural de la fibrosis quística. No se hallaron determinantes clínicos fiables para precisar su ocurrencia.

Introduction. Vitamin K deficiency is highly prevalent in cystic fibrosis (CF) patients despite supplementation. Moreover, no reliable risk factors for its occurrence are known. The aim was to assess the prevalence of vitamin K deficiency and associated factors in non-supplemented CF patients. Methods. Prothrombin concentration induced by vitamin K absence (PIVKA-II) and the undercarboxylated osteocalcin percentage (u-OC) were determined. In all patients clinical status was assessed and its relation to vitamin K deficiency determined. The following tests were used for statistical analysis: Mann-Whitney test, ANOVA test or the Kruskal Wallis test, the chi-squared test or the Fisher-Freeman-Halton test, and multiple linear and multiple forward stepwise logistic regression analysis. Results. The study group comprised 79 CF patients aged 0.4-25.3 years. PIVKA-II and u-OC were abnormal in 56 (70.9%) and 45 (57.0%) patients. Patients with elevated PIVKA-II were significantly older (p= 0.0184) and had lower Z-score values for body weight (p= 0.0297) than those with normal concentrations. Patients with normal or pathological u-OC percentage did not differ. Abnormal PIVKA-II and u-OC were reported more frequently in subjects with two severe CFTR mutations and with worse/poor nutritional status. Multiple linear and forward stepwise regression analyses did not reveal strong predictive factors of vitamin K deficiency. Conclusion. Vitamin K deficiency is highly prevalent in the natural course of cystic fibrosis. There are no reliable clinical determinants of its occurrence.

Prevalence of vitamin K deficiency and associated factors in non-supplemented cystic fibrosis patients. / Prevalencia de deficiencia de vitamina K y factores asociados en pacientes con fibrosis quística sin aporte suplementario.

INTRODUCTION: Vitamin K deficiency is highly prevalent in cystic fibrosis (CF) patients despite supplementation. Moreover, no reliable risk factors for its occurrence are known. The aim was to assess the prevalence of vitamin K deficiency and associated factors in non-supplemented CF patients. METHODS: Prothrombin concentration induced by vitamin K absence (PIVKA-II) and the undercarboxylated osteocalcin percentage (u-OC) were determined. In all patients clinical status was assessed and its relation to vitamin K deficiency determined. The following tests were used for statistical analysis: Mann-Whitney test, ANOVA test or the Kruskal Wallis test, the chi-squared test or the Fisher-Freeman-Halton test, and multiple linear and multiple forward stepwise logistic regression analysis. RESULTS: The study group comprised 79 CF patients aged 0.4-25.3 years. PIVKA-II and u-OC were abnormal in 56 (70.9%) and 45 (57.0%) patients. Patients with elevated PIVKA-II were significantly older (p= 0.0184) and had lower Z-score values for body weight (p= 0.0297) than those with normal concentrations. Patients with normal or pathological u-OC percentage did not differ. Abnormal PIVKA-II and u-OC were reported more frequently in subjects with two severe CFTR mutations and with worse/poor nutritional status. Multiple linear and forward stepwise regression analyses did not reveal strong predictive factors of vitamin K deficiency. CONCLUSION: Vitamin K deficiency is highly prevalent in the natural course of cystic fibrosis. There are no reliable clinical determinants of its occurrence.

INTRODUCCIÓN: La deficiencia de vitamina K es prevalente en pacientes con fibrosis quística (FQ) aun con aporte suplementario. Se desconocen factores de riesgo fiables para determinar su ocurrencia. Nuestro objetivo fue evaluar la prevalencia de deficiencia de vitamina K y factores asociados en los pacientes con FQ que no recibían aporte suplementario. MÉTODOS: Se determinaron protrombina inducida por ausencia de vitamina K (PIVKA-II) y osteocalcina infracarboxilada (OCic). Se evaluó el estado clínico y su relación con la deficiencia de vitamina K. El análisis estadístico incluyó prueba de Mann-Whitney, ANOVA o Kruskal-Wallis, prueba χ2 o prueba de Fisher-Freeman-Halton y regresión logística múltiple lineal y escalonada hacia adelante. RESULTADOS: Se incluyeron 79 pacientes con FQ de entre 0,4-25,3 años. Se observaron valores anómalos de PIVKA-II y OCic en 56 (70,9%) y 45 (57,0%) pacientes. Los pacientes con PIVKA-II elevada eran significativamente mayores (p = 0,0184) y tenían puntajes Z de peso corporal (p= 0,0297) inferiores a los pacientes que tenían concentraciones normales. No se hallaron diferencias entre los pacientes con OCic normal o patológica. Se notificaron valores anómalos de PIVKA-II y OCic más frecuentemente en pacientes con dos mutaciones graves en el gen CFTR y con un estado nutricional malo/deficiente. Los análisis de regresión múltiple lineal y de regresión múltiple escalonada hacia adelante no revelaron factores predictivos sólidos para determinar la deficiencia de vitamina K. CONCLUSIÓN: La deficiencia de vitamina K es altamente prevalente durante la evolución natural de la fibrosis quística. No se hallaron determinantes clínicos fiables para precisar su ocurrencia.

Vitamin K status in cystic fibrosis patients with liver cirrhosis.

The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency.

Pancreatic Elastase-1 Quick Test for rapid assessment of pancreatic status in cystic fibrosis patients.

BACKGROUND: At present, fecal elastase-1 ELISA determination is the most sensitive and specific tubeless pancreatic function test available. However, the results are not available the same day in routine clinical practice. This prospective study aims at evaluating the sensitivity and specificity of the Elastase-1 Quick™ Test by comparing the results with the ELISA test. METHODS: The study was composed of three groups: the screening-diagnosed cystic fibrosis (CF) patients (n=28), the screened, but non-CF subjects (n=36) and non-screened CF patients (n=62). Pancreatic status (normal vs abnormal) was evaluated using the Pancreas Elastase-1 Quick™ Test. Fecal elastase-1 concentration was determined with a commercially available ELISA kit, used as reference. The cut-off for abnormal results was set at <200µg/g of stool. RESULTS: The Pancreatic Elastase-1 Quick Test™ showed the following sensitivities and specificities in the studied groups: 92.8% and 96.6% in all subjects, 90.5% and 100% in screening samples, and 92.8 and 90.5% in CF patients. CONCLUSION: Pancreatic Elastase-1 Quick Test™ proves to be a rapid and reliable option to qualitatively evaluate pancreatic function for diagnostic purposes in a clinical setting of CF care.

A high frequency of the Cystic Fibrosis 2184insA mutation in Western Ukraine: genotype-phenotype correlations, relevance for newborn screening and genetic testing.

We present the first comprehensive report on the distribution and genotype-phenotype correlations of CF-causing mutations in Western Ukraine (former Galicia). The 2184insA mutation was identified in 17 unrelated CF patients, 2 of whom are homozygotes for this allele. This mutation is associated with the classical form of CF. The high frequency of 2184insA mutation (7.20% of all mutated CF chromosomes) suggests that it is likely of Galician origin, from where it has spread throughout Europe and beyond. The achieved 83.71% mutation detection rate fulfills the minimal pre-requisite for introduction of the "two-tier" (IRT/DNA) newborn screening program.