Desempeño del índice FIB-4 en el despistaje de várices esofágicas en pacientes con el diagnóstico de cirrosis hepática / Performance of the FIB-4 index in esophageal varices screening in patients with the diagnosis of liver cirrhosis

RESUMEN Introducción: El diagnóstico de várices esofágicas en pacientes cirróticos se realiza mediante la endoscopía digestiva alta. Se han estudiado predictores no invasivos para el diagnóstico de estas. Objetivo: El objetivo de este estudio es evaluar el desempeño del índice FIB-4 en el despistaje de várices esofágicas en pacientes con diagnóstico de cirrosis hepática. Materiales y métodos: Se realizó un estudio transversal analítico en cuatro hospitales nacionales utilizando historias clínicas de pacientes cirróticos. Se realizó el análisis univariado y bivariado, cálculo de sensibilidad, especificidad, valor predictivo positivo y negativo, razón de verosimilitud positiva y negativa del índice FIB-4 para el despistaje de várices esofágicas, tamaño de estas y profilaxis. Se construyeron curvas ROC para cada grupo de análisis. Resultados: Se incluyó 289 pacientes con diagnóstico de cirrosis hepática, la mayor parte fueron de sexo masculino (54,33%). 77,85% presentaron várices esofágicas. La distribución del tamaño de várices fue de 19,03%, 35,99% y 22,84% para várices grandes, medianas y pequeñas, respectivamente. En el análisis del índice FIB-4 con la presencia de várices se encontró una sensibilidad de 81,3% y una especificidad de 37,5% (AUC: 0,57). Para el tamaño de várices se encontró una sensibilidad 81,8% y una especificidad de 23,9% (AUC: 0,50). En el análisis de FIB-4 para grupos de profilaxis se encontró una sensibilidad de 81,8% y una especificidad de 28,5% (AUC: 0,54). Conclusiones: El índice FIB-4 no tiene un buen desempeño en el despistaje de la presencia várices esofágicas y su tamaño en pacientes con diagnóstico de cirrosis hepática.

ABSTRACT Introduction: The diagnosis of esophageal varices in cirrhotic patients is made by the upper gastrointestinal endoscopy. Multiple non-invasive predictors have been studied for the diag-nosis of esophageal varices. The objective of this study is to testthe FIB4 index as screening of esophageal varices in patients with liver cirrhosis. Materials and methods: A cross-sectional analytic study was developed in four national hospital using hepatic cirrhosis patient's medi-cal files. We assessed the information using univariate and bivariate analysis, sensitivity, speci-ficity, predictive positive and negative value, the positive and negative likelihood ratio calcu-lation of the esophageal varices screening and its size. We built ROC curve for every analysis group. Results: The study included 289 liver cirrhosis patients. Most of the patients were male (54.33%). 77.85% patients had esophageal varices. The distribution of varices was 19.03%, 35.99% and 22.84% for large, medium and small varices, respectively. In the FIB-4 index analysis for the presence of varices, it was found a sensitivity of 81.3%, specificity of 37.5% (AUC: 0.57). The calculation for variceal size showed a sensitivity of 81.8%, specificity of 23.9% (AUC: 0.50). In the analysis of FIB-4 index for prophylaxis groups was found a sensitivity of 81.8% and a specificity of 28.5% (AUC: 0.54). Conclusions: The FIB-4 index has no good performance in the screening for the presence of esophageal varices and its size in liver cirrhosis patients.

Razão da contagem de plaquetas ao quadrado/diâmetro do baço-aspartato aminotransferase: avaliação de um novo método não-invasivo para a predição de varizes esofágicas / Platelet count squared/spleen diameter-aspartate aminotransferase ratio: non-invasive method to predict esophageal varices

ABSTRACT BACKGROUND - Variceal bleeding has a high mortality among cirrhotics, and screening with endoscopy is indicated at the diagnosis of cirrhosis. Screening with endoscopy implies discomfort, risks and considerable costs. OBJECTIVE - To evaluate platelet count squared/spleen diameter-aspartate aminotransferase ratio (PS/SA), as a non-invasive predictor of esophageal varices in cirrhotics. METHODS - This cross-sectional study evaluated cirrhotics for PS/SA and presence of esophageal varices. Outpatient records of cirrhotic patients were reviewed for the abovementioned data. Sensitivity, specificity, negative and positive predictive values of PS/SA were calculated. After the univariate analysis, variables with P<0.10 were submitted to a logistic regression. RESULTS - The study included 164 cirrhotics, 59.70% male, with a mean age of 56.7 years. Hepatitis C was the most frequent cause of cirrhosis, being present in 90 patients. Patients were classified as Child-Pugh A in 52.44% and as Child-Pugh B or C in 47.56%. Esophageal varices were present in 72.56% of the patients at endoscopy. PS/SA, with a cutoff of 3x108, had a sensitivity of 95.80% (confidence interval of 95% - 95%CI=0.92-0.99), a specificity of 22.70% (95%CI=0.10-0.35), a positive predictive value of 77.20% (95%CI=0.70-0.84) and a negative predictive value of 66.70% (95%CI=0.42-0.91). In the logistic regression, only platelet count and Child-Pugh score were associated to esophageal varices (P<0.05). CONCLUSION - PS/SA has an excellent sensitivity to predict esophageal varices, allowing almost one fourth of patients without esophageal varices to spare endoscopy. Nevertheless, PS/SA is not independently associated to esophageal varices.

RESUMO CONTEXTO - A hemorragia varicosa tem elevada mortalidade entre cirróticos, e o rastreamento endoscópico de varizes está indicado no momento do diagnóstico da cirrose. O rastreamento endoscópico implica desconforto, riscos e custos consideráveis. OBJETIVO - Avaliar a razão da contagem de plaquetas ao quadrado/diâmetro do baço-aspartato aminotransferase (PQ/BA) como preditor não-invasivo de varizes esofágicas em cirróticos. MÉTODOS - Este estudo transversal avaliou cirróticos quanto ao PQ/BA e à presença de varizes esofágicas. Prontuários ambulatoriais de cirróticos foram revisados quanto a tais dados. Sensibilidade, especificidade e valores preditivos negativo e positivo do PQ/BA foram calculados. Após a análise univariada, variáveis com P<0,10 foram submetidas à regressão logística. RESULTADOS - O estudo incluiu 164 cirróticos, 59,70% masculinos, com média de idade de 56,7 anos. Hepatite C foi a mais frequente causa de cirrose, estando presente em 90 pacientes. Os pacientes foram classificados como Child-Pugh A em 52,44% e em Child-Pugh B ou C em 47,56%. As varizes esofágicas estiveram presentes à endoscopia em 72,56% dos pacientes. PQ/BA, com um ponto de corte de 3x108, teve sensibilidade de 95,80% (intervalo de confiança de 95% - IC95%=0,92-0,99), especificidade de 22,70% (IC95%=0,10-0,35), valor preditivo positivo de 77,20% (IC95%=0,70-0,84) e valor preditivo negativo de 66,70% (IC95%=0,42-0,91). Na regressão logística, apenas a contagem de plaquetas e o escore de Child-Pugh associaram-se às varizes esofágicas (P<0,05). CONCLUSÃO - PQ/BA apresentou excelente sensibilidade para predizer varizes esofágicas, permitido que cerca de um quarto dos pacientes sem varizes esofágicas evitasse a endoscopia. Entretanto, PQ/BA não se associou de maneira independente às varizes esofágicas.

Preditores não invasivos de varizes esofágicas em crianças e adolescentes com hepatopatia crônica ou obstrução extra-hepática da veia porta / Non-invasive predictors of esophageous varices in children and adolescents with chronic liver disease or extrahepatic portal venous obstruction

OBJETIVO: Identificar preditores não invasivos de varizes esofágicas em crianças e adolescentes com hepatopatia crônica ou obstrução extra-hepática da veia porta. PACIENTES E MÉTODOS: Estudo transversal que incluiu 53 crianças e adolescentes com hepatopatia crônica ou obstrução extra-hepática da veia porta, sem antecedente de hemorragia digestiva ou tratamento de varizes esofágicas, com até 20 anos de idade. Dois grupos foram formados: grupo I (35 pacientes com hepatopatia crônica) e grupo II (18 com obstrução extra-hepática da veia porta). Foram realizados hemograma, razão normalizada internacional, albumina, bilirrubina total, ultrassonografia de abdome e endoscopia digestiva alta. O índice esplênico foi determinado dividindo a dimensão esplênica pelo valor do limite superior da normalidade. As variáveis foram comparadas quanto à presença ou não de varizes esofágicas através de análise univariada (testes qui-quadrado, exato de Fischer e de Wilcoxon) e multivariada (regressão logística). A acurácia foi determinada a partir da área sob a curva ROC. RESULTADOS: As varizes esofágicas foram observadas em 48,5% dos pacientes do grupo I e em 83,3% do grupo II. Plaquetopenia (p = 0,0015), esplenomegalia (p = 0,0003) e a razão plaquetas/índice esplênico (p = 0,0007) se mostraram indicadores preditivos de varizes esofágicas entre os pacientes do grupo I. Após análise multivariada, a plaquetopenia (odds ratio = 21,7) se manteve como um indicador independente da presença de varizes esofágicas entre os pacientes com hepatopatia crônica. CONCLUSÃO: O número de plaquetas, o índice esplênico e a razão plaquetas/índice esplênico se mostraram preditivos de varizes esofágicas em crianças e adolescentes com hepatopatia crônica. Não foram encontrados preditores de varizes esofágicas entre os pacientes com obstrução extra-hepática da veia porta.

OBJECTIVE: To identify non-invasive predictors of esophageal varices in children and adolescents with chronic liver disease or extrahepatic portal venous obstruction (EHPVO). METHODS: 53 patients younger than 20 years with chronic liver disease or EHPVO and no history of bleeding or prophylactic treatment of esophageal varices (EV) were assessed. They were divided into 2 groups: group I (35 with chronic liver disease) and group II (18 with EHPVO). Their blood count, international normalized ratio (INR), albumin, bilirubin, abdominal ultrasonography and upper endoscopy results were taken. A splenic index was determined by dividing the patients' spleen dimension by its uppermost limit according to their age. The variables were compared to EV presence or not. Univariate (chi-square test, Fischer's exact test and Wilcoxon exact test) and multivariate (logistic regression) analyses were performed. A receiver operating characteristic (ROC) curve was constructed and the area under the ROC curve was calculated. RESULTS: EV were observed in 48.5% of group I patients and in 83.3% of group II patients. Low platelet count (p = 0.0015), splenomegaly (p = 0.0003) and splenic index (p = 0.0007) were statistically significant predictors of EV among group I patients. The multivariate analysis showed low platelet count (odds = 21.7) as an independent predictor of EV in patients with chronic liver disease. CONCLUSION: Platelet count, splenic index and platelet-splenic index ratio were predictors of EV in children and adolescents with chronic liver disease. There were no EV predictors among group II patients.

Platelet count/spleen diameter ratio: analysis of its capacity as a predictor of the existence of esophageal varices / Índice contagem de plaquetas/diâmetro do baço: análise de sua capacidade como preditor da existência de varizes esofágicas

CONTEXT: Upper gastrointestinal bleeding associated to esophageal varices is the most dramatic complication of cirrhosis. It is recommended screening every cirrhotic for esophageal varices with endoscopy. OBJECTIVES: To evaluate the capacity of the platelet count/spleen diameter ratio in non-invasively predicting esophageal varices in a population of cirrhotics originated in an independent center from the one in which it was developed. METHODS: The study included patients from the ambulatory care clinic of cirrhosis of a Brazilian hospital and studied platelet count, spleen diameter and presence of esophageal varices, as well as Child and MELD scores. It used a cutoff value of 909 for the platelet count/spleen diameter ratio, as previously published. A sample of 139 patients was needed to grant results a 95 percent confidence level. RESULTS: The study included 164 cirrhotics, 56.7 percent male, with a mean age of 56.6 ± 11.6 years. In the univariate analysis, platelet count, spleen diameter, presence of ascites, Child and MELD scores and the platelet count/spleen diameter ratio were related to esophageal varices (P<0.05). The platelet count/spleen diameter ratio had sensitivity of 77.5 percent (95 percent CI = 0.700-0.850), specificity of 45.5 percent (95 percent CI = 0.307-0.602), positive predictive value of 79.5 percent (95 percent CI = 0.722-0.868), negative predictive value of 42.6 percent (95 percent CI = 0.284-0.567) and accuracy of 68.9 percent (95 percent CI = 0.618-0.760). In the multivariate analysis, platelet count was the only variable which related to esophageal varices (P<0.05). CONCLUSION: Platelet count/ spleen diameter ratio is not adequate to predict esophageal varices in cirrhotics.

CONTEXTO: Hemorragia digestiva por varizes esofágicas é a complicação mais dramática da cirrose. É recomendada triagem de varizes esofágicas em todo o cirrótico. OBJETIVO: Avaliar o índice de contagem de plaquetas/diâmetro do baço como predição de varizes esofágicas em uma população distinta daquela em que ele foi desenvolvido. MÉTODOS: O estudo incluiu pacientes do ambulatório de cirrose de um hospital brasileiro quanto ao número de plaquetas, diâmetro ecográfico do baço, presença de varizes esofágicas, Child e MELD. O ponto de corte do índice foi de 909. Amostra de 139 pacientes foi estimada para conferir nível de confiança de 95 por cento. RESULTADOS: Incluíram-se 164 cirróticos, 56,7 por cento homens e com média de idade de 56,6 anos. Na análise univariada, número de plaquetas, diâmetro do baço, ascite, Child, MELD e o índice de contagem de plaquetas/diâmetro do baço relacionaram-se às varizes esofágicas (P<0,05). Na multivariada, só a contagem de plaquetas associou-se a elas (P<0,05). O índice de contagem de plaquetas/diâmetro do baço apresentou sensibilidade de 77,5 por cento (IC 95 por cento = 0,700-0,850), especificidade de 45,5 por cento (IC 95 por cento = 0,307-0,602), valor preditivo positivo de 79,5 por cento (IC 95 por cento = 0,722-0,868), valor preditivo negativo de 42,6 por cento (IC95 por cento = 0,284-0,567) e precisão de 68,9 por cento (IC 95 por cento = 0,618-0,760). CONCLUSÃO: O índice de contagem de plaquetas/diâmetro do baço não é adequado para a triagem de varizes esofágicas em cirróticos.

Factors predicting in-hospital mortality in patients with cirrhosis hospitalized with gastro-esophageal variceal hemorrhage.

AIM : To identify factors at the time of admission that predict in-hospital mortality in patients with gastro-esophageal variceal hemorrhage. METHODS : Case records of patients admitted with gastro-esophageal variceal hemorrhage between January 1998 and October 2003 were retrospectively analyzed. Relevant clinical and laboratory parameters and their relationship to mortality, were studied. Clinical parameters assessed included Child-Pugh class, ascites, portosystemic encephalopathy (PSE) and occurrence of rebleed within 24 hours of esophago-gastroduodenoscopy. The laboratory parameters assessed were: hemoglobin, prothrombin time, serum bilirubin, creatinine and albumin. RESULTS : Of the 343 patients admitted during the study period, 30 (8.7%) died in hospital. Serum bilirubin (2.4 versus 1.6 mg/dL) and serum creatinine (2.1 vs 1.1 mg/dL) levels were higher among non-survivors than among survivors. Non-survivors were also more likely to suffer from PSE (53%) than survivors (17%), while re-bleeding within 24 hours of endoscopy occurred in 40% and 5% of these groups, respectively. On multivariate analysis, serum creatinine > 1.5 mg/dL at the time of admission (p < 0.001), serum bilirubin > 3 mg/dL (p < 0.001), presence of PSE (p = 0.003) and rebleed within 24 hours of endoscopy (p < 0.001) were significant predictors of mortality. CONCLUSION : Serum creatinine and bilirubin levels, presence of PSE and re-bleeding within 24 hours of initial endoscopy are independent predictors of mortality in patients with gastro-esophageal variceal bleeding.

Correlação entre a contagem de plaquetas no sangue e o gradiente de pressão venosa hepática em pacientes cirróticos / Correlation between platelet blood levels and the hepatic venous pressure gradient among patients with cirrhosis

RACIONAL: A medida do gradiente de pressão venosa hepática é o método mais utilizado para a avaliação da pressão portal. Mais recentemente, a contagem de plaquetas no sangue tem sido apontada como um marcador não-invasivo da presença de hipertensão portal. OBJETIVO: Correlacionar a contagem de plaquetas com os valores do gradiente de pressão venosa hepática em uma população de pacientes cirróticos. PACIENTES E MÉTODOS: Foram estudados 83 pacientes com hepatopatia crônica que realizaram estudo hemodinâmico hepático, em período de 6 anos. Os pacientes foram divididos em grupos conforme a classificação de Child-Pugh e todos realizaram endoscopia digestiva alta para constatar a presença de varizes de esôfago, assim como tiveram a contagem sérica de plaquetas determinada. RESULTADOS: O número de plaquetas variou entre 45.000/mm³ e 389.000/mm³, com média 104.099 e desvio-padrão 58.776. O gradiente de pressão venosa apresentou média igual a 15,2 mm Hg e desvio-padrão igual a 6,4 mm Hg, variando de 1 a 29 mm Hg. Realizou-se regressão linear simples para verificar a correlação entre o gradiente de pressão venosa e o número de plaquetas, o que permitiu constatar fraca correlação entre ambos. Embora se tenha observado menor número de plaquetas, à medida que o calibre das varizes aumentava e nos pacientes com maior grau de disfunção hepatocelular - medida pela classificação de Child-Pugh - não se encontrou significância estatística. CONCLUSÃO: A despeito de não haver demonstrado correlação estatística entre o número de plaquetas com o gradiente de pressão venosa hepática e o grau de disfunção hepatocelular, pelas tendências observadas, acredita-se que ambos os fatores podem estar implicados na patogenia da plaquetopenia em pacientes cirróticos.

Fibrinolytic Activities and Their Relations to Esophageal Variceal Bleeding in Patients with Liver Cirrhosis / 대한소화기학회지

BACKGROUND/AIMS: Esophageal variceal bleeding in liver cirrhosis is a major complication and has high mortality rate. We tried to find fibrinolytic parameters, which correlated with variceal bleeding in cirrhotic patients. METHODS: We divided the cirrhotic patients into two groups: bleeding group (group A, n=15) and non-bleeding group (Group B, n=17). Fibrinolytic parameters (fibrinogen, D-dimer, plasminogen, tissue plasminogen activator [t-PA], fibrin degradation product [FDP], and plasminogen activator inhibitor type-1 [PAI-1]) were compared between two groups. In the group A, serial samplings were taken at the initial period, 3 days, 8 days, 15 days and 6 weeks after the bleeding onset. RESULTS: Plasma levels of FDP and D-dimer in the group A were significantly higher than the group B (1.7 +/- 1.16 vs. 0.95 +/- 1.27 mg/L and 10.96 +/- 6.58 vs. 4.99 +/- 3.50 micro gram/mL, respectively, p value<0.05). The clinical, biochemical, and coagulation parameters didn't show significant differences in both groups. The fibrinolytic parameters were improved along with the hemodynamic stabilization in group A. CONCLUSIONS: Cirrhotic patients with increased fibrinolytic activity were at higher risk of bleeding. Thus, the measurement of these parameters would be useful to identify patients at higher risk of esophageal variceal bleeding.

Estado actual del tratamiento quirúrgico de la hipertensión portal en el sangrado por várices esofágicas: experiencia en el Hospital Vargas de Caracas desde Enero de 1996 hasta Mayo de 1997 / Present state of surgical treatment for portal hipertension in variceal bleeding: experience in the Hospital Vargas sine January of 1996 until May of 1997

Con el objetivo de evaluar el estado actual del tratamiento de la hipertensión portal en la hemorragia digestiva superior por várices esofágicas evaluamos retrospectivamente en el Hospital Vargas de Caracas a 19 pacientes que requirieron de cirugía para la hipertensión portal. El período evaluado estuvo comprendido entre Enero de 1996 y Mayo de 1997. El 57,89 por ciento correspondió al sexo masculino, la edad media del grupo estaba en 47,6 años. En 16 pacientes (84,21 por ciento) se realizó transección esofágica y en el resto una derivación porto sistémica. La cirrosis hepática fue responsable de más del 90 por ciento de los casos con hipertensión portal y la mortalidad global del tratamiento quirúrgico fue de 63,16 por ciento que al correlacionarla con la clasificación de Child-Pugh correspondió con el tipo B en 5 pacienttes (41,66 ppor ciento) y para el tipo C en 6 pacientes (50 por ciento). La sobrevida fue de 37,5 por ciento en los que recibieron transección esofágica. La causa de muerte postoperatoria más frecuente fue la insuficiencia hepática. En vista de nuestros resultados creemos que existe una posibilidad quirúrgica para el tratamiento del sangrado por várices esofágicas que no responden o no son susceptibles de tratamiento médico y/o endoscópico

Portal and systemic fibrinolysis in cirrhotic patients and their relation to oesophageal variceal bleeding

Disturbed hemostasis is well documented among patients with hepatic cirrhosis. In this work, plasma fibrinolytic activity was evaluated in both portal [variceal] and systemic [venous] blood in patients with cirrhosis, in a trial to investigate its possible relation to bleeding esophageal varices, as well as to the degree of liver cell failure, to find out whether it is locally enhanced in the varices or not. Sixty- three cirrhotic patients were the subjects of this work. Sixteen healthy individuals served as normal controls. BT, platelet count, PT, PTT and fibrinogen level were studied in all systemic blood samples. Plasminogen, t-PA, PAI-1, PAP, FDPs and D-dimers were evaluated in systemic and variceal samples. All parameters were considerably altered in diseased groups. With the exception of PAI-1 the impairment of hemostatic parameters tended to parallel the degree of liver cell failure. Unexpectedly, the hemostatic disturbance was more marked in patients with non bleeding esophageal varices than in those with bleeding varices. Furthermore, all fibrinolytic parameters studied showed insignificant differences between systemic and variceal samples, i.e. There is no evidence of locally enhanced fibrinolysis in the varices

Esclerosis de várices esofágicas en niños con hipertensión portal / Esophageal sclerotherapy in children with portal hypertension

102 pacientes con diagnóstico de Hipertensión Portal(HTP) fueron evaluados en el hospital desde 1987 hasta 1995. A 57 se les realizó 2 o más sesiones de escleroterapia, 38 (66,6 por ciento) fueron del sexo masculino. La edad promedio al momento del diagnóstico fue 3.96 años (rango 2 meses-15 años). 33/57 (57,9 por ciento presentaban antecedentes neonatales (característico de la vena umbilical 31, sepsis 2). La hemorragia digestiva superior fue la forma de presentación más frecuente 63.2 por ciento seguida por esplenomegalía 35 por ciento y anemia 1.75 por ciento. El número de episodios de sangramientos fue 208, media de 3.6 y rango de 0-22. Se hicieron 279 sesiones de escleroterapia, media de 4.9 y rango de 2-18. Al comparar sangramiento y riesgo sangramiento paciente/mes, en el período post-tratamiento con pre y durante tratamiento se observó una diferencia altamente significativa. Se logró la obliteración de las várices esofágicas en 25 pacientes (44 por ciento) y una disminución significativa del calibre en 24 (42 por ciento) permaneciendo 8 sin variación

Decreased antithrombin III: is it a cause or a result of oesophageal varices bleeding in endemic hepatic schistosomiasis

Chronic liver disease is often associated with many hemostatic abnormalities including decreased level of antithrombin 3 [AT3]. However, the involvement of AT3, in esophageal varices bleeding has not been demonstrated before. The aim of this study is to demonstrate the hemostatic abnormalities especially the disturbance in AT3 level in patients with bleeding esophageal varices. Forty subjects were studied including 10 normal control cases, 15 cases with bleeding esophageal varices [group 1] and 15 cases with silent varices [group 2]. All cases were subjected to the following hemostatic tests: Prothrombin time [PT], partial thromboplastin time [PTT], antithrombin 3 level, fibrinogen [F] and fibrin degradation products [FDP]. All these tests were done to patients of group 1, the first during the bleeding episode [la] and the second after control of bleeding by two weeks [lb]. There was significant deterioration in all the hemostatic parameters studied in both groups 1 and 2 compared to control. Further significant impairment in some of these parameters namely PT, AT3, FDP and platelet count occurred in patients of group 1 during active bleeding [la] compared to silent varices patients [group 2]. Most of these test differences disappeared after control of bleeding by two weeks with the exception of AT3, which was still significantly lower in group 1b compared with group 2 [p <0.005]. It was concluded that AT3 might be of great value to predict hepatic patients prone to bleed through their esophageal varices. Further prospective studies are needed