Vitamin D Deficiency in a Portuguese Cohort of Patients with Inflammatory Bowel Disease: Prevalence and Relation to Disease Activity.

BACKGROUND AND AIMS: Vitamin D deficiency is more common in inflammatory bowel disease (IBD) patients than in the general population. However, there are conflicting data about predictive factors of vitamin D deficiency and its potential association with disease activity. The aims of this study were to determine the prevalence and predictive factors of vitamin D deficiency and to evaluate a possible association with disease activity. METHODS: A prospective observational study was conducted, including patients with IBD from January to July 2016. The Endocrine Society guidelines were considered for defining levels of serum 25-hydroxyvitamin D (25-OH-D) as follows: deficient (< 20 ng/mL, < 10 ng/mL being severe deficiency), insufficient (21-29 ng/mL), and adequate (> 30 ng/mL). RESULTS: A total of 152 patients (52% men; 47.2 ± 17.3 years) were included, of whom 70% had Crohn's disease (CD). Thirty-seven percent of patients were on immunosuppressors and 17% were on biologics. The majority were outpatients (88.2%). Mean 25-OH-D levels were 17.1 ± 8 ng/mL (CD: 16.7 ± 8 ng/mL vs. ulcerative colitis: 17.6 ± 7 ng/mL, p = 0.1). Inadequate levels were present in 90.8% of patients (deficiency: 68.4%; insufficiency: 22.4%). A significant negative correlation between 25-OH-D levels and age (r = -0.2, p = 0.04), C-reactive protein (CRP) levels (r = -0.22, p = 0.004), and Harvey-Bradshaw index (HBi) (r = -0.32, p = 0.001) was found. Patients with severe deficiency showed a higher CRP (0.6 vs. 1.4 mg/dL, p = 0.03), erythrocyte sedimentation rate (ESR) (22 vs. 31 mm/h, p = 0.03), and HBi (2 vs. 5, p < 0.001) and lower hemoglobin (13.6 vs. 12.7 g/dL, p = 0.02). There was no association between vitamin D deficiency and gender, type, extent, and duration of disease, surgery, and other measures of disease activity, such as ESR, hemoglobin (these 2 items except for severe deficiency), fecal calprotectin, or Truelove and Witts classification. CONCLUSIONS: There is a high prevalence of inadequate levels of vitamin D in IBD patients, particularly deficiency (68.4%). There seems to exist an association between lower levels of vitamin D and higher disease activity, especially in CD.

INTRODUÇÃO: A deficiáncia de vitamina D é mais comum na doença inflamatória intestinal (DII) que na população geral. Contudo, existem dados controversos sobre fatores preditivos da deficiáncia de vitamina D e a potencial associação com a atividade da doença. Os objetivos deste estudo foram determinar a prevaláncia e fatores preditivos da deficiáncia de vitamina D e aferir possível associação à atividade da doença. MÉTODOS: Desenhou-se um estudo observacional prospetivo incluindo doentes com DII entre janeiro e julho/2016. Foram consideradas as orientações da The Endocrine Society para definir níveis de 25-hidroxivitamina D (25-OH-D) sérica como: deficientes (< 20 ng/mL, sendo <10 ng/mL deficiáncia grave [DG]), insuficientes (21­29 ng/ mL) e adequados (> 30 ng/mL). RESULTADOS: Foram incluídos 152 doentes (52% homens; 47.2 ± 17.3 anos), dos quais 70% com Doença de Crohn (DC). Do total, 37% estavam medicados com immunossupressores e 17% com biológicos. A maioria (88.2%) estava em ambulatório. O nível sérico de 25-OH-D foi 17.1 ± 8 ng/mL (DC: 16.7 ± 8 ng/mL vs. Colite ulcerosa: 17.6 ± 7 ng/mL, p = 0.1). Verificaram-se níveis inadequados em 90.8% (deficiáncia: 68.4%; insuficiáncia: 22.4%). Registou-se correlação negativa significativa entre níveis de 25-OH-D e idade (r = −0.2, p = 0.04), proteína C-reativa (PCR) (r = −0.22, p = 0.004) e índice Harvey-Bradshaw (iHB) (r = −0.32, p = 0.001). Doentes com DG apresentaram níveis mais elevados de PCR (0.6 vs. 1.4 mg/dL, p = 0.03), velocidade de sedimentação (VS) (22 vs. 31 mm/h, p = 0.03) e iHB (2 vs. 5, p < 0.001), e mais baixos de hemoglobina (13.6 vs. 12.7 g/dL, p = 0.02). Não se verificou associação entre deficiáncia de vitamina D e sexo, tipo, extensão e duração da doença, cirurgia, e outras medidas de atividade da doença como VS, hemoglobina (estas duas exceto para DG), calprotectina fecal ou classificação Truelove e Witts. CONCLUSÕES: Registou-se prevaláncia alta de níveis inadequados de vitamina D na DII, particularmente de deficiáncia (68.4%). Parece existir associação entre níveis mais baixos de vitamina D e maior atividade da doença, nomeadamente na DC.

The impact and evolution of acute-on-chronic liver failure in decompensated cirrhosis: A Portuguese single-center study / Repercusiones y evolución de la insuficiencia hepática crónica agudizada en la cirrosis descompensada: un estudio portugués con un solo centro

Introduction: Acute-on-chronic liver failure (ACLF) is a dynamic syndrome that should be assessed repeatedly. An algorithm for risk stratification in decompensated cirrhosis was recently proposed by the EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) Consortium. Aim: To validate the EASL-CLIF Consortium scores in patients with and without ACLF. Materials and methods: Retrospective single-center cohort study including patients admitted for acute decompensation of cirrhosis between January 2014 and December 2015, and followed-up until December 2016. We separated patients with and without ACLF and compared the various EASL-CLIF Consortium scores to Child-Pugh and MELD for predicting 28-day (M28), 90-day and 12-month mortality. These scores were recalculated at different time points over 28 days. Results: 106 patients were included (age 60.3±10.7 years; 87.7% male), 35.8% of whom met ACLF criteria on admission (50%) or during hospitalization. A CLIF-C AD Score ≥60 on admission was associated with a higher risk of developing ACLF. The onset of ACLF during hospitalization portended a poor prognosis. The prognostic performance of the CLIF-C ACLF Score (AUROC for M28: 0.856±0.071) was globally comparable to that of Child-Pugh and MELD. Overall, ACLF resolved in 54.1% patients, resulting in increased survival. Almost 40% of the patients reached their final ACLF grade after ≥8 days, with 13.9% of ACLF patients experiencing resolution by then. Discussion: We confirmed the accuracy and clinical value of the several proposed scores in our population. Prognosis was better defined by the early clinical course than by the initial evaluation, emphasizing the importance of repeated assessments

Introducción: La insuficiencia hepática crónica agudizada (IHCA) es un síndrome dinámico que se debe evaluar repetidamente. El Consorcio EASL-CLIF (Asociación Europea para el Estudio del Hígado-Insuficiencia Hepática Crónica) ha propuesto recientemente un algoritmo para la estratificación del riesgo en la cirrosis descompensada. Objetivo: Validar las puntuaciones del Consorcio EASL-CLIF en pacientes con y sin IHCA. Materiales y métodos: estudio de cohorte unicéntrico retrospectivo que incluyó a pacientes ingresados por descompensación aguda de cirrosis entre enero de 2014 y diciembre de 2015, a los cuales se les hizo seguimiento hasta diciembre de 2016. Separamos a los pacientes con y sin IHCA, y comparamos las distintas puntuaciones del Consorcio EASL-CLIF con Child-Pugh y MELD en la predicción de mortalidad a los 28 días (M28), a los 90 días y a los 12 meses. Estas puntuaciones se recalcularon en diferentes momentos en el curso de los 28 días. Resultados: se incluyó a 106 pacientes (edad: 60,3±10,7 años; 87,7% varones), el 35,8% de los cuales cumplieron con los criterios de IHCA, en el momento del ingreso (50%) o durante la hospitalización. Una puntuación de CLIF-C AD ≥60 en el momento del ingreso se asoció con mayor riesgo de desarrollar IHCA. El inicio de IHCA durante la hospitalización presagiaba un mal pronóstico. El rendimiento pronóstico de CLIF-C ACLF Score (AUROC de M28: 0,856±0,071) fue globalmente comparable al de Child-Pugh y MELD. En general, el IHCA se resolvió en el 54,1% de los pacientes, lo que produjo un aumento de la supervivencia. Casi el 40% de los pacientes alcanzaron su grado final de IHCA después de ≥8 días y el 13,9% de los pacientes con IHCA experimentaron su resolución para entonces. Discusión: Confirmamos la precisión y el valor clínico de las diversas puntuaciones propuestas en nuestra población. El pronóstico se definió mejor por el curso clínico temprano que por la evaluación inicial, lo que recalca la importancia de las evaluaciones repetidas

The impact and evolution of acute-on-chronic liver failure in decompensated cirrhosis: A Portuguese single-center study.

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is a dynamic syndrome that should be assessed repeatedly. An algorithm for risk stratification in decompensated cirrhosis was recently proposed by the EASL-CLIF (European Association for the Study of the Liver-Chronic Liver Failure) Consortium. AIM: To validate the EASL-CLIF Consortium scores in patients with and without ACLF. MATERIALS AND METHODS: Retrospective single-center cohort study including patients admitted for acute decompensation of cirrhosis between January 2014 and December 2015, and followed-up until December 2016. We separated patients with and without ACLF and compared the various EASL-CLIF Consortium scores to Child-Pugh and MELD for predicting 28-day (M28), 90-day and 12-month mortality. These scores were recalculated at different time points over 28 days. RESULTS: 106 patients were included (age 60.3±10.7 years; 87.7% male), 35.8% of whom met ACLF criteria on admission (50%) or during hospitalization. A CLIF-C AD Score ≥60 on admission was associated with a higher risk of developing ACLF. The onset of ACLF during hospitalization portended a poor prognosis. The prognostic performance of the CLIF-C ACLF Score (AUROC for M28: 0.856±0.071) was globally comparable to that of Child-Pugh and MELD. Overall, ACLF resolved in 54.1% patients, resulting in increased survival. Almost 40% of the patients reached their final ACLF grade after ≥8 days, with 13.9% of ACLF patients experiencing resolution by then. DISCUSSION: We confirmed the accuracy and clinical value of the several proposed scores in our population. Prognosis was better defined by the early clinical course than by the initial evaluation, emphasizing the importance of repeated assessments.

A Complex Case of Cholestasis in a Patient with ABCB4 and ABCB11 Mutations.

The low-phospholipid-associated cholelithiasis (LPAC) syndrome is a form of symptomatic cholelithiasis occurring in young adults, characterized by recurrence of symptoms after cholecystectomy and presence of hepatolithiasis. The case refers to a healthy 39-year-old Caucasian male who presented with abdominal pain and jaundice. His blood tests showed conjugated hyperbilirubinemia and elevated liver enzymes (total bilirubin 6.65 mg/dL, γ-glutamyltransferase 699 IU/L) and abdominal computed tomography revealed dilation of common bile duct and left intrahepatic ducts. Magnetic resonance cholangiopancreatography identified choledocholithiasis, retrieved by endoscopic retrograde cholangiopancreatography, after which there was a worsening of jaundice (total bilirubin 23 mg/dL), which persisted for several weeks, possibly due to ciprofloxacin toxicity. After an extensive workup including liver biopsy, the identification of two foci of hepatolithiasis on reevaluation abdominal ultrasound raised the hypothesis of LPAC syndrome and the patient was started on ursodeoxycholic acid, with remarkable improvement. Genetic testing identified the mutation c.1954A>G (p.Arg652Gly) in ABCB4 gene (homozygous) and c.1331T>C (p.Val444Ala) in ABCB11 gene (heterozygous). In conclusion, we describe the unique case of an adult male with choledocholithiasis, hepatolithiasis, and persistent conjugated hyperbilirubinemia after retrieval of stones, fulfilling the criteria for LPAC syndrome and with possible superimposed drug-induced liver injury, in whom ABCB4 and ABCB11 mutations were found, both of which had not been previously described in association with LPAC.

A síndrome low-phospholipid-associated cholelithiasis (LPAC) é uma forma de coledocolitíase sintomática que ocorre em adultos jovens e que se caracteriza pela recorrência de sintomas após a colecistectomia e pela presença de hepatolitíase. O caso refere-se a um homem caucasiano de 39 anos, saudável, que se apresentou com um quadro de dor abdominal e icterícia. A avaliação laboratorial mostrou hiperbilirrubinémia conjugada e um padrão citocolestático (bilirrubina total 6,65 mg/dL; GGT 699 UI/L) e a tomografia computorizada abdominal revelou dilatação da via biliar principal e vias biliares intra-hepáticas à esquerda. A colangiopancreatografia por ressonância magnética identificou coledocolitíase, extraída por colangiopancreatografia retrógrada endoscópica, tendo-se verificado posterior agravamento da icterícia (bilirrubina total 23 mg/dL) que persistiu por várias semanas, possivelmente por hepatotoxicidade associada à toma de ciprofloxacina. Após uma extensa investigação, incluindo a realização de biópsia hepática, foram identificados dois focos de hepatolitíase em ecografia abdominal de reavaliação, pelo que se colocou a hipótese de LPAC e o doente iniciou terapêutica com ácido ursodesoxicólico, com excelente resposta. O estudo genético identificou a mutação c.1954A>G (p.Arg652Gli) no gene ABCB4 em homozigotia e a mutação c.1331T>C (p.Val444Ala) no gene ABCB11 em heterozigotia. Em suma, descrevemos o caso único de um homem com coledocolitíase, hepatolitíase e hiperbilirribinémia conjugada persistente mesmo após extracção de cálculos, cumprindo critérios de LPAC e possivelmente com sobreposição de lesão hepática induzida por fármacos, tendo-se documentado mutações nos genes ABCB4 e ABCB11, cuja associação com LPAC não havia sido previamente descrita.

Is there a proximal shift in the distribution of colorectal adenomas?

INTRODUCTION: Several studies have shown a proximal shift of colorectal cancer (CRC) during the last decades. However, few have analyzed the changing distribution of adenomas over time. AIM: The aim of this study was to compare the site and the characteristics of colorectal adenomas, in a single center, during two periods. METHODS: We conducted a retrospective, observational study in a single hospital of adenomas removed during a total colonoscopy in two one-year periods: 2003 (period 1) and 2012 (period 2). Patients with inflammatory bowel disease, familial adenomatous polyposis, hereditary non-polyposis colorectal cancer syndrome, or history of CRC were excluded from the study. The χ(2) statistical test was performed. P values less than 0.05 were considered statistically significant. RESULTS: During the two considered periods, a total of 864 adenomas from 2394 complete colonoscopies were analyzed: 333 adenomas from 998 colonoscopies during period 1 and 531 adenomas from 1396 colonoscopies during period 2. There was a significant increase in the proportion of adenomatous polyps in the proximal colon from period 1 to 2 (30.6% to 38.8% (p = 0.015)). Comparing the advanced features of adenomas between the two periods, it was noted that in period 2, the number of adenomas with size ≥1 cm (p = 0.001), high-grade dysplasia (p = 0.001), and villous features (p < 0.0001) had a significant increase compared to period 1. CONCLUSION: Incidence of adenomatous polyps in the proximal colon as well as adenomas with advanced features has increased in the last years. This finding may have important implications regarding methods of CRC screening.