Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features / Colagenose pulmão dominante em pacientes com doença pulmonar intersticial: prevalência, estabilidade funcional e manifestações extratorácicas comuns

OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). METHODS: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD). RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria. .

OBJETIVO: Descrever as características de uma coorte de pacientes com colagenose pulmão dominante (CPD). MÉTODOS: Estudo retrospectivo de pacientes com doença pulmonar intersticial (DPI), anticorpo antinuclear (ANA) positivo (≥ 1/320), com ou sem autoanticorpos específicos, e com a presença de ao menos uma manifestação clínica sugestiva de doença do tecido conjuntivo (DTC). RESULTADOS: Dos 1.998 avaliados, 52 preencheram inicialmente os critérios para o diagnóstico de CPD: 37% eram homens; a média de idade ao diagnóstico era de 56 anos e a mediana do tempo de seguimento era de 48 meses. Durante o seguimento, 8 pacientes preencheram os critérios para um diagnóstico definitivo de DTC. Os 44 pacientes restantes formaram o grupo CPD, no qual as manifestações extratorácicas mais prevalentes foram artralgia, doença do refluxo gastroesofágico e fenômeno de Raynaud. Os autoanticorpos mais prevalentes nesse grupo foram ANA (89%) e anti-SSA (anti-Ro, 27%). A média de CVF no início e na última avaliação foi de 69,5% e 74,0% do predito, respectivamente (p > 0,05). Pneumonia intersticial não específica e pneumonia intersticial usual foram identificadas em 45% e 9% das TCARs, respectivamente; 36% das TCARs eram não classificáveis. Uma prevalência semelhante foi identificada na histologia. Dilatação esofágica difusa foi identificada em 52% das TCARs. Capilaroscopia subungueal foi realizada em 22 pacientes; 17 apresentavam um padrão de esclerodermia. CONCLUSÕES: No grupo CPD, houve predominância feminina, e os pacientes apresentaram alterações espirométricas leves ao diagnóstico, com diferentes padrões de DPI, em sua maioria não classificáveis, tanto em TCAR como na histologia. Estabilidade funcional foi identificada no seguimento. A dilatação esofágica em TCAR e o padrão de esclerodermia na capilaroscopia subungueal foram achados frequentes que poderiam servir como critérios diagnósticos. .

Clinical characteristics associated with hepatic steatosis on ultrasonography in patients with elevated alanine aminotransferase / Características clínicas associadas a esteatose hepática à ultrassonografia em pacientes com alanina aminotransferase elevada

CONTEXT AND OBJECTIVE: The main causes of hepatic steatosis (HS) are alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD). Although liver biopsy is the gold standard for NAFLD diagnosis, the finding of abnormal aminotransferases in abstinent individuals, without known liver disease, suggests the diagnosis of NAFLD in 80-90 percent of the cases. Identification of clinical factors associated with HS on abdominal ultrasound may enable diagnoses of fatty liver non-invasively and cost-effectively. The aim here was to identify clinical variables associated with HS in individuals with elevated alanine aminotransferase (ALT) levels. DESIGN AND SETTING: Cross-sectional study in a single tertiary care center. METHODS: Individuals with elevated ALT, serologically negative for hepatitis B and C, were evaluated by reviewing medical files. Patients who did not undergo abdominal ultrasonography were excluded. RESULTS: Among 94 individuals included, 40 percent presented HS on ultrasonography. Compared with individuals without HS, those with fatty liver were older (P = 0.043), with higher body mass index (BMI) (P = 0.003), diabetes prevalence (P = 0.024), fasting glucose levels (P = 0.001) and triglycerides (P = 0.003). Multivariate analysis showed that BMI (odds ratio, OR = 1.186; 95 percent confidence interval, CI: 1.049-1.341; P = 0.006) and diabetes mellitus (OR = 12.721; 95 percent CI: 1.380-117.247; P = 0.025) were independently associated with HS. CONCLUSIONS: Simple clinical findings such as history of diabetes and high BMI may predict the presence of HS on ultrasonography in individuals with elevated ALT and negative serological tests for hepatitis.

CONTEXTO E OBJETIVO: Doença hepática alcoólica e doença hepática esteatótica não alcoólica (DHENA) são as principais causas de esteatose hepática (EH). Apesar de a biópsia hepática ser o método de escolha para diagnóstico DHENA, o achado de aminotransferases elevadas em indivíduos abstêmios, sem doença hepática conhecida, sugere o diagnóstico de DHENA em 80-90 por cento dos casos. A identificação de variáveis clínicas associadas à EH na ultrassonografia abdominal pode permitir o diagnóstico de DHENA de forma não invasiva e custo-efetiva. O objetivo foi identificar variáveis clínicas associadas à EH em indivíduos com níveis elevados de alanina aminotransferase (ALT). TIPO DE ESTUDO E LOCAL: Estudo transversal em um único centro de atendimento terciário. MÉTODOS: Indivíduos com ALT elevada e sorologias negativas para os vírus de hepatite B e C foram avaliados por meio de revisão de prontuários. Os pacientes não submetidos à ultrassonografia foram excluídos. RESULTADOS: Foram incluídos 94 indivíduos, 40 por cento deles com EH à ultrassonografia. Quando comparados aos indivíduos sem EH, aqueles com EH apresentaram maior prevalência de diabetes (P = 0,024), maiores idade (P = 0,043) e índice de massa corpórea (IMC) (P = 0,003), glicemia de jejum mais elevada (P = 0,001) e triglicerídeos mais elevados (P = 0,003). A análise multivariada evidenciou que o IMC (odds ratio, OR = 1,186, 95 por cento intervalo de confiança, IC 1,049-1,341, P = 0,006) e o diabetes mellitus (OR = 12,721, 95 por cento IC 1,380-117,247, P = 0,025) foram associadas independentemente à EH. CONCLUSÕES: Achados clínicos simples como história de diabetes e o IMC elevado podem predizer a presença de EH à ultrassonografia de indivíduos com ALT elevada e sorologias negativas para hepatite.

Esteatose hepática em uma população escolar de adolescentes com sobrepeso e obesidade / Hepatic steatosis in a school population of overweight and obese adolescents

Objetivo: Avaliar esteatose hepática pelo método de ultrassom como fator de risco concomitante entre adolescentes com sobrepeso. Métodos: Estudo de caso-controle incluindo 83 casos (47 com sobrepeso e 36 obesos) e 89 controles (peso normal), frequência pareada por gênero, ano de nascimento, estágio pubertário (Tanner 4/5) e renda. Casos e controles foram selecionados de 1.420 alunos matriculados em uma escola pública de ensino médio na Vila Mariana, São Paulo. Os critérios de Must et al. foram usados para classificação do estado nutricional. A doença hepática gordurosa não-alcoólica foi diagnosticada por meio de ultrassonografia realizada e analisada por um radiologista. Foram medidas atividades enzimáticas hepáticas (alanina e aspartato transaminases, fosfatase alcalina, gama-glutamil transpeptidase) e bilirrubina direta. Oito co-variáveis foram inseridas em modelos de regressão logística; o critério de inclusão de variáveis foi a associação com sobrepeso nas análises bivariadas (p < 0,20). Um valor de p < 0,05 foi estabelecido como critério de inclusão nos modelos finais de regressão logística. Resultados: A prevalência de esteatose hepática diagnosticada por ultrassonografia foi de 27,7 por cento em alunos com sobrepeso/obesos e de 3,4 por cento em alunos com peso normal. Razões de chances ajustadas (IC95 por cento) para imagens compatíveis com doença hepática gordurosa não-alcoólica e gama-glutamil transpeptidase > 24 U/L foram 10,77 (2,45-47,22) e 4,18 (1,46-11,94), respectivamente. Conclusões: Este é o primeiro estudo populacional mostrando que a esteatose hepática tem forte associação com sobrepeso/obesidade entre adolescentes matriculados em uma escola pública brasileira. A ferramenta de diagnóstico usada nesta investigação é um método não-invasivo que poderia ser aplicado para monitorar adolescentes com sobrepeso e obesos e propor ações para prevenir doenças hepáticas mais graves na fase adulta.

Objective: To assess hepatic steatosis by ultrasound method as a concomitant risk factor among overweight adolescents. Methods: A case-control study including 83 cases (47 overweight and 36 obese) and 89 controls (normal weight), frequency matched by gender, year of birth, pubertal stage (Tanner 4/5), and income. Cases and controls were selected from 1,420 students enrolled in a Vila Mariana public high school, in São Paulo, Brazil. Must et al. criteria were used for nutritional status classification. Nonalcoholic fatty liver disease was diagnosed through hepatic ultrasonography performed and analyzed by one radiologist. Hepatic enzymatic activities (alanine and aspartate transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase) and direct bilirubin were measured. Eight covariables were fitted into logistic regression models; criterion for inclusion of variables was the association with overweight in the bivariate analyses (p < 0.20). A value of p < 0.05 was set as the criterion for inclusion into the final logistic regression models. Results: Prevalence of hepatic steatosis diagnosed through ultrasonography was 27.7 percent in overweight/obese students and 3.4 percent in normal weight students. Adjusted odds ratios (95 percentCI) for images compatible with nonalcoholic fatty liver disease and gamma-glutamyl transpeptidase > 24 U/L were 10.77 (2.45-47.22) and 4.18 (1.46-11.94), respectively. Conclusions: This is the first population-based study showing that hepatic steatosis is strongly associated with overweight/obesity among adolescents attending a Brazilian public school. The diagnostic tool used in this investigation is a non-invasive method that might be applied to monitor overweight and obese adolescents and to propose actions for preventing more severe hepatic diseases in adulthood.

Hepatic cytochrome P450 2E1 activity in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a worldwide phenomenon spanning all the continents. The pathogenesis of NAFLD has not been completely elucidated. One hypothesis is that hepatic cytochrome P450 2E1 (CYP2E1) plays an important role in increasing the lipid peroxidation and oxidative stress in NAFLD. OBJECTIVE: The aim of the present study was to examine hepatic CYP2E1 activity in patients with NAFLD. MATERIAL AND METHOD: Healthy subjects were included. After an overnight fasting, the subjects were orally administered 400 mg chlorzoxazone (CHZ) and serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 8 hours after dosing. For patients with NAFLD, plasma samples were collected at 0 (predose), 1.5, 2, 2.5 and 3 hours after dosing. Plasma CHZ and 6-hydroxychlorzoxazone (6-OH-CHZ) was assayed by reversed-phase high-performance liquid chromatography (HPLC) with UV detector. Hepatic CYP2E1 activity was calculated by using concentration ratio of 6-OH-CHZ / CHZ. RESULTS: High concentration levels of CHZ and 6-OH-CHZ in healthy subjects were found between 1.5 to 3 hours after the dose. At 1.5 to 3 hours, the concentration ratio of 6-OH-CHZ / CHZ of patients with NAFLD seemed to be more than of healthy subjects. The time point which showed most different was 2.5 hours. (0.40 +/- 0.27 vs. 0.25 +/- 0.12 microg/ml, respectively, p = 0.10). CONCLUSION: Although significant difference of the concentration ratio of 6-OH-CHZ / CHZ between the two groups was not exhibited, the data demonstrated the possibility of the increasing hepatic CYP2E1 activity in NAFLD. The concentration ratio of 6-OH-CHZ / CHZ at the point 2.5 hours may be the best index for measuring hepatic CYP2E1 activity in NAFLD.

Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women

CYP2E1 enzyme is related to nonalcoholic steatohepatitis (NASH) due to its ability for reactive oxygen species production, which can be influenced by polymorphisms in the gene. The aim of this study was to investigate hepatic levels, activity, and polymorphisms of the CYP2E1 gene to correlate it with clinical and histological features in 48 female obese NASH patients. Subjects were divided into three groups: (i) normal; (ii) steatosis; and (iii) steatohepatitis. CYP2E1 protein level was assayed in microsomes from liver biopsies, and in vivo chlorzoxazone hydroxylation was determined by HPLC. Genomic DNA was isolated for genotype analysis through PCR. The results showed that liver CYP2E1 content was significantly higher in the steatohepatitis (45 percent; p=0.024) and steatosis (22 percent; p=0.032) group compared with normal group. Chlorzoxazone hydroxylase activity showed significant enhancement in the steatohepatitis group (15 percent, p=0.027) compared with the normal group. c2 rare allele of RsallPstl polymorphisms but no C allele of Dral polymorphism was positively associated with CHZ hydroxylation, which in turn is correlated with liver CYP2E1 content (r=0.59; p=0.026). In conclusion, c2 allele is positively associated with liver injury in NASH. This allele may determine a higher transcriptional activity of the gene, with consequent enhancement in pro-oxidant activity of CYP2E1 thus affording liver toxicity.

Problemas del embarazo relacionados con errores hereditarios de la ß-oxidación mitocondrial fetal / Complications during the pregnancy about disorders for fetal fatty acid mitochondrial ß oxidation

Hace algún tiempo reportado que errores hereditarios en la oxidación de ácidos grasos en el feto, pueden predisponer a complicaciones de la madre durante el embarazo. El campo de los errores innatos del metabolismo crece permanentemente como resultado del reporte continuo de nuevas enfermedades en diferenres vías metabólicas, ayudado por el auge en investigación y tecnologia desarrollado en el área. El presente trabajo, revisa la interrelación entre los errores hereditarios de la ß-oxidación mitocondrial de los ácidos grasos en fetos homocigotos, o heterocigotos compuestos y el embarazo de madres heterocigotas para las mismas deficiencias

Comportamiento del índice de D`Ritis en la esteatosis hepática / Behaviour of D`Ritis index in hepatic steatosis

A partir del diagnóstico endoscópico de esteatosis hepática en 120 pacientes, se realizó un estudio del comportamiento del índice de D`Ritis en dichos enfermos. Se comprobó que los cocientes de D`Ritis menores y mayores que 1 fueron los de mayor frecuencia. Asimismo se comprobó que la esteatosis hepática es más frecuente en el sexo masculino, fundamentalmente a partir de los 45 años de edad. Se muestra la presencia de la hepatitis, el alcoholismo, la diabetes mellitus y la obesidad como factores de riesgo de la esteatosis hepática