Correlation between hepatopulmonary syndrome and oxygen saturation pulse oximetry in cirrhotic patients

SUMMARY Hepatopulmonary Syndrome (HPS) is a complication of cirrhosis that worsens the disease's prognosis, pre and post liver transplant. The objective of this study is to analyze the prevalence of HPS in cirrhotic patients at our service and to correlate it with oxygen saturation (SatO2) using a pulse oximeter to evaluate if this is useful as a screening test for HPS. A prospective study was conducted in patients with hepatic cirrhosis conventionally selected from 2014 to 2016. All the patients underwent an echocardiogram with microbubbles and oxygen saturation measurement by pulse oximetry. Those with intrapulmonary shunt were submitted to arterial blood gas analysis. The relationship between oxygen saturation and HPS was assessed by the multivariate model of binary logistic regression. We analyzed 77 patients, and 23.3% (18 patients) had all criteria for HPS. The relationship between HPS and SatO2 did not show statistical significance, even after the variables were adjusted for sex, age, and smoking. Oxygen saturation alone was not able to detect HPS in the sample of cirrhotic patients. More accurate methods for screening and diagnosis of the syndrome should be used.

RESUMO A Síndrome Hepatopulmonar (SHP) é uma complicação da cirrose que piora o prognóstico da doença pré e pós-transplante hepático. O objetivo do trabalho é analisar a prevalência de SHP em pacientes cirróticos de nosso serviço e correlacioná-la com a saturação de oxigênio (SatO2) pelo oxímetro de pulso, e avaliar se este seria útil como um exame de triagem no diagnóstico de SHP. Foi realizado um estudo prospectivo em pacientes portadores de cirrose hepática no período de 2014 a 2016. Todos os pacientes foram submetidos a um ecocardiogama com microbolhas e a saturação de oxigênio pela oximetria de pulso. Aqueles com shunt intrapulmonar foram submetidos a gasometria arterial. A relação entre a saturação de oxigênio e SHP foi avaliada pelo modelo multivariado de regressão logística binário. Foram analisados 77 pacientes, destes 23,3% (18 pacientes) apresentaram todos os critérios para SHP. A relação entre a SHP com a SatO2 não obteve significância estatística, mesmo após as variáveis terem sido ajustadas pelo sexo, idade e tabagismo atual ou passado. A saturação de oxigênio, de forma isolada, não foi capaz de distinguir a SHP na amostra de pacientes cirróticos em nosso estudo. Deve-se utilizar métodos mais acurados para a triagem e diagnóstico dessa síndrome.

Capacidade de exercício e sobrevida de pacientes cirróticos com e sem síndrome hepatopulmonar após o transplante hepático / Capacity of exercise and survival in patients with cirrhosis with and without hepatopulmonary syndrome after liver transplantation

ABSTRACT BACKGROUND: Hepatopulmonary syndrome (HPS) is a complication associated with cirrhosis that may contribute to worsening exercise capacity and reduced survival after liver transplantation (LT). OBJECTIVE: To evaluate exercise capacity, complications and survival after LT in patients with cirrhosis and HPS and to compare these results with the results of patients with cirrhosis without HPS. METHODS: A prospective cohort study, consisting initially of 178 patients, of whom 90 underwent LT (42 with HPS and 48 without HPS). A previous evaluation consisted of the six-minute walk test (6MWT), an exercise test and manovacuometry. Those who underwent LT were evaluated for the mechanical ventilation time (MV), noninvasive ventilation (NIV) use, and survival two years after the procedure. In the statistical analysis, we used the Kolmogorov-Smirnov test, Student's t-test, the linear association square test, and the Kaplan-Meier survival curve. The data were analyzed with the SPSS 16.00 program and considered significant at P<0.05. RESULTS: The HPS group demonstrated a lower peak of oxygen consumption (VO2peak) (14.2±2.3 vs 17.6±2.6) P<0.001 and a shorter distance walked on the 6MWT (340.8±50.9 vs 416.5±91.4) P<0.001 before LT compared with the non-HPS group. The transplanted patients with HPS remained longer hours in MV (19.5±4.3 vs 12.5±3.3) P=0.02, required more NIV (12 vs 2) P=0.01, and had lower survival two years after the procedure (P=0.01) compared with the transplanted patients without HPS. CONCLUSION: Patients with HPS had worse exercise capacity before LT, more complications and shorter survival after this procedure than patients without HPS.

RESUMO CONTEXTO: A síndrome hepatopulmonar (SHP) é uma complicação associada à cirrose que pode contribuir para piora da capacidade de exercício e menor sobrevida após o transplante hepático (TxH). OBJETIVO: Avaliar a capacidade de exercício, as complicações e a sobrevida após TxH em cirróticos com SHP e comparar com os resultados de cirróticos sem esse diagnóstico. MÉTODOS: Estudo de coorte prospectivo, composto inicialmente por 178 pacientes, dos quais 90 foram submetidos ao TxH (42 com SHP e 48 sem SHP). Foi realizada uma avaliação prévia composta pelo teste de caminhada dos seis minutos (TC6M), teste ergométrico e manovacuometria. Os submetidos ao TxH tiveram avaliados o tempo de ventilação mecânica (VM), uso de ventilação não invasiva (VNI), e a sobrevida dois anos após o procedimento. Na análise estatística utilizamos os testes de Kolmogorov-Smirnov, o teste t de Student, o teste do quadrado de associação linear, a curva de sobrevida de Kaplan Meier. Os dados foram analisados no programa SPSS 16.00 sendo considerado significativo P<0,05. RESULTADOS: O grupo SHP apresentou menor pico de consumo de oxigênio (VO2pico) (14,2±2,3 vs 17,6±2,6) P<0,001, e menor distância percorrida no TC6M (340,8±50,9 vs 416,5±91,4) P<0,001 antes do TxH. Os pacientes com SHP transplantados permaneceram mais horas em VM (19,5±4,3 vs 12,5±3,3) P=0,02, necessitaram mais de VNI (12 vs 2) P=0,01, e tiveram menor sobrevida dois anos após o procedimento (P=0,01). CONCLUSÃO: Pacientes com SHP apresentaram pior capacidade de exercício antes do TxH, mais complicações e menor sobrevida após a realização desse procedimento.

Prevalencia y severidad del síndrome hepatopulmonar en pacientes con cirrosis hepática del Hospital Nacional Cayetano Heredia, entre enero y diciembre del 2015 / Prevalence and severity of the hepatopulmonar syndrome in patients with liver cirrhosis attended at Cayetano Heredia Hospital, between January and December 2015

Introducción: El sindrome hepatopulmonar (SHP) es una complicación poco frecuente de la cirrosis hepática (CH) que disminuye considerablemente la calidad de vida de las personas que la padecen. Objetivos: Determinar la prevalencia y severidad del SHP en los pacientes con CH atendidos en el Hospital Nacional Cayetano Heredia (HCH) en el periodo comprendido entre enero a diciembre del 2015. Material y métodos: Estudio transversal, con tamaño de muestra necesario para determinar la prevalencia puntual calculado en 297 pacientes. Resultados: La prevalencia del SHP fue de 0,7% y los casos identificados se clasificaron como SHP leve y severo. Conclusión: La prevalencia del SHP es muy baja en la población de pacientes con cirrosis hepática atendidos en el Hospital Nacional Cayetano Heredia

Introduction: The hepatopulmonary syndrome (HPS) is a rare complication of liver cirrhosis (LC) which significantly diminishes the quality of life for people who suffer. Objectives: To determine the prevalence and severity of HPS in patients with CH treated at the Cayetano Heredia (HCH) Hospital in the period from January to December 2015. Materials and methods: Cross-sectional study with sample size needed to determine the point prevalence calculated in 297 patients. Results: The prevalence of HPS in 0.7% and the identified cases were classified as mild and severe SHP. Conclusion: The prevalence of HPS is very low in the population of patients with liver cirrhosis treated at the Cayetano Heredia Hospital

Características clínicas y laboratoriales de pacientes hospitalizados con hipertensión portal y complicaciones vasculares pulmonares en el Instituto Nacional de Salud del Niño / Clinical and laboratory characteristics of patients with pulmonary hypertension and pulmonary vascular complications hospitalized at the Instituto Nacional de Salud del Niño

El síndrome hepatopulmonar (SHP) y la hipertensión portopulmonar (HTPP) son distintas complicaciones vasculares pulmonares de la hipertensión portal (HTP) y se asocian con una mayor morbilidad y mortalidad. Objetivos: Describir las Características Clínicas y Laboratoriales de los pacientes con HTP y complicaciones vasculares pulmonares hospitalizados en el Instituto Nacional de Salud del Niño. Materiales y métodos: se incluyeron los pacientes con HTP hospitalizados desde enero del 2012 hasta junio del 2013 y que durante su evolución cursaron con SHP o HTPP. Para el análisis se les dividió en un primer grupo de pacientes con cirrosis hepática y un segundo grupo con obstrucción extra hepática de vena porta. Resultados: De 22 pacientes con HTP el 45,5% fueron varones y el rango de edad fue entre 1 mes y 17 años. La etiología en el grupo de cirrosis (n=14) fue: hepatitis autoinmune (35,7%), cirrosis criptogénica (35,7%), error innato del metabolismo (14,3%), hepatitis viral crónica por virus C (7,15%) y atresia de vías biliares extra hepática (7,15%). Las complicaciones vasculares pulmonares, se presentaron más frecuentemente en los pacientes con cirrosis hepática (1 caso de síndrome hepatopulmonar y un caso de hipertensión portopulmonar). En ellos se encontró más frecuentemente disnea, astenia, edema, desnutrición, ascitis, hiperesplenismo y hemorragia digestiva por várices esofágicas, además de valores elevados de ALT, fosfatasa alcalina y menores niveles de albúmina sérica. Conclusiones: En niños con HTP, las complicaciones vasculares pulmonares son muy infrecuentes. En la evaluación de estos pacientes debería incluirse la oximetría de pulso para detectar hipoxemia y posteriormente, de ser necesario una ecocardiografía Doppler y de contraste. Ante el hallazgo de hipertensión sistólica pulmonar es necesario realizar un cateterismo cardiaco derecho.

The hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHN) are distinct pulmonary vascular complications of portal hypertension (PHT) and are associated with increased morbidity and mortality. Objectives: To describe the clinical and laboratory characteristics of patients with pulmonary hypertension and pulmonary vascular complications hospitalized at the Instituto Nacional de Salud del Niño. Materials and methods: We included patients with HTP hospitalized from January 2012 to June 2013 and that during its evolution progressed with SHP or HTPP. For analysis, they were divided into a first group of patients with liver cirrhosis and a second group with extrahepatic portal vein obstruction. Results: Of 22 patients with HPT 45.5% were male and the age range was between 1 month and 17 years. The etiology in the group of cirrhosis (n=14) was: autoimmune hepatitis (35.7%), cryptogenic cirrhosis (35.7%), inborn error of metabolism (14.3%), chronic viral hepatitis C (7.15%) virus and atresia extra-hepatic bile ducts (7.15%). Pulmonary vascular complications more frequently occurred in patients with liver cirrhosis (1 case of HPS and a case of PPHTN). They most often dyspnea, asthenia, edema, malnutrition, ascites, hypersplenism and gastrointestinal bleeding from esophageal varices was found. Also, they had elevated ALT values, alkaline phosphatase and serum albumin values decreased. Conclusions: In children with pulmonary hypertension, pulmonary vascular complications are rare. In the evaluation of these patients pulse oximetry should be included to detect hypoxemia and subsequently a Doppler echocardiography and contrast echocardiography necessary. Dueto the finding of systolic pulmonary hypertension it is necessary to perform right heart catheterization.

Hepatopulmonary syndrome: an update / Síndrome hepatopulmonar: atualização

Hepatopulmonary syndrome (HPS) is a clinical threesome composed of liver disease, intrapulmonary vascular dilatation (IPVD) and arterial gas abnormalities. Its occurrence has been described in up to 32 percent of cirrhotic candidates for liver transplantation. It also affects non-cirrhotic patients with portal hypertension. Its pathogenesis is not well defined, but an association of factors such as imbalance in the endothelin receptor response, pulmonary microvascular remodeling and genetic predisposition is thought to lead to IPVD. Diagnosis is based on imaging methods that identify these dilatations, such as contrast echocardiography or perfusion scintigraphy with 99mTc, as well as analysis of arterial gases to identify elevated alveolar-arterial differences in O2 or hypoxemia. There is no effective pharmacological treatment and complete resolution only occurs through liver transplantation. The importance of diagnosing HPS lies in prioritizing transplant candidates, since presence of HPS is associated with worse prognosis. The aim of this paper was to review the pathogenetic theories and current diagnostic criteria regarding HPS, and to critically analyze the prioritization of patients with HPS on the liver transplant waiting list. Searches were carried out in the Medline (Medical Literature Analysis and Retrieval System Online) via PubMed, Cochrane Library and Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases for articles published between January 2002 and December 2007 involving adults and written either in English or in Portuguese, using the term hepatopulmonary syndrome. The studies of greatest relevance were included in the review, along with text books and articles cited in references that were obtained through the review.

A síndrome hepatopulmonar (SHP) é considerada uma tríade clínica composta de doença hepática, dilatações vasculares intrapulmonares (IPVD) e alterações de gases arteriais. Há descrição de sua ocorrência em até 32 por cento dos cirróticos candidatos ao transplante de fígado, acometendo também não cirróticos com hipertensão portal. Sua etiopatogenia não está bem definida, mas se especula que a associação de fatores como o desequilíbrio na resposta dos receptores vasculares de endotelina, o remodelamento microvascular pulmonar e a predisposição genética propiciem as IPVD. O diagnóstico baseia-se em métodos de imagem que identifiquem essas dilatações, como a ecocardiografia com contraste ou a cintilografia de perfusão com 99mTc, além da análise de gases arteriais, para identificar elevação da diferença alvéolo-arterial de O2 ou hipoxemia. Não existe tratamento medicamentoso eficaz e sua resolução completa ocorre apenas com o transplante de fígado. A importância do diagnóstico da SHP está em priorizar os candidatos ao transplante, uma vez que sua presença está associada ao pior prognóstico. O objetivo deste artigo é fazer revisão das teorias de etiopatogenia da SHP, dos seus critérios diagnósticos atuais, além de realizar análise crítica sobre a prioridade dos pacientes com a síndrome na lista de espera pelo transplante de fígado. Buscaram-se na base de dados Medline (Medical Literature Analysis and Retrieval System Online) via PubMed, Cochrane Library e Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), os artigos publicados no período de janeiro de 2002 a dezembro de 2007, envolvendo adultos, escritos nos idiomas inglês ou português, que apresentassem o termo síndrome hepatopulmonar. Os estudos de maior relevância foram incluídos, além de livros-texto e artigos citados nas referências obtidas na revisão.

Síndrome hepatopulmonar e hipertensión portopulmonar: dos entidades a diferenciar / Hepatopulmonary syndrome and portopulmonary hypertension: two distinct entities

The clinical course of patients with portal hypertension or liver disease may be complicated by two low prevalence entities with high morbimortality: the hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHT). Each one is a consequence ofan impaired hepatic clearance of several vascular mediators, triggering vasodilation of the pulmonary vascular territory in HPS and vasoconstriction with vessel remodelation in PPHT. Both disorders have some similar clinical findings, but useful findings for differential diagnosis are the presence of platypnoea and orthodeoxia in HPS, and echocardiographic extracardiac and intrapulmonary shunt in HPS or pulmonary hypertension in PPHT. Currently, liver transplantation is the only effective treatment for both entities provided that indication and timing must be accurately evaluated. We present a review and three cases of both entities.

El curso clínico de los pacientes con cirrosis y/o hipertensión portal puede verse complicado por dos entidades de baja prevalencia pero de elevada morbimortalidad, que corresponden al síndrome hepatopulmonar (SHP) y la hipertensión portopulmonar (HPP). Ambas se presentan a consecuencia de un déficit en la depuración hepática de diversos mediadores vasculares, provocando en el territorio pulmonar una vasodilatación en el SHP y una vasoconstricción con remodelación vascular en la HPP. Si bien estas entidades comparten algunos aspectos clínicos, resulta útil en su diferenciación la presencia de platipnea y ortodeoxia y el hallazgo ecocardiográfico de un shunt extracardíaco e intrapulmonar en el SHP, o de hipertensión pulmonar en HPP. Hasta el momento la única terapia efectiva para ambas entidades es el trasplante hepático, cuya indicación exige una evaluación rigurosa y oportuna. Se presenta una revisión y tres casos clínicos de ambas entidades.

Prevalence of hepatopulmonary syndrome in patients with decompensated chronic liver disease and its impact on short-term survival

BACKGROUND: Hepatopulmonary syndrome is reported to occur in 4 percent to 32 percent of the patients with chronic liver disease and is associated with poor liver function and shortened patient survival before and after liver transplantation. AIMS: To assess the frequency of hepatopulmonary syndrome in Brazilian patients with decompensated chronic liver disease and to investigate its impact on patient survival. METHODS: One hundred and thirty patients (101 males, mean age 61 ± 12 years) with decompensated chronic liver disease were evaluated for the presence of hepatopulmonary syndrome. The diagnosis of hepatopulmonary syndrome was considered in the presence of alveolar arterial oxygen gradient of more than 15 mm Hg and of pulmonary vascular dilatation assessed by contrast enhanced echocardiography. RESULTS: Hepatopulmonary syndrome was observed in 21 (16 percent) patients. The presence of hepatopulmonary syndrome was significantly associated with severity of liver disease assessed by the MELD (Model for End-Stage Liver Disease) score, but not with in hospital mortality after admission due to decompensated chronic liver disease. CONCLUSIONS: Hepatopulmonary syndrome occurs in 16 percent of patients with chronic liver disease and is associated with disease severity according to the MELD score. Short term mortality following decompensation of chronic liver disease was not associated with hepatopulmonary syndrome.

RACIONAL: A síndrome hepatopulmonar ocorre em 4 por cento a 32 por cento dos pacientes com doença crônica parenquimatosa do fígado e está associada à gravidade da doença hepática e menor sobrevida antes e após o transplante hepático. OBJETIVOS: Avaliar a freqüência da síndrome hepatopulmonar em pacientes brasileiros hospitalizados com doença crônica parenquimatosa do fígado descompensada e investigar o seu impacto na sobrevida intra-hospitalar. MÉTODOS: Cento e trinta doentes (101 homens, idade média 61 ± 12 anos) com doença crônica parenquimatosa do fígado descompensada foram avaliados quanto à presença de síndrome hepatopulmonar. O diagnóstico de síndrome hepatopulmonar foi considerado na presença de aumento do gradiente alvéolo arterial de oxigênio maior que 15 mm Hg e de dilatação vascular pulmonar avaliada pelo ecocardiografia com microbolhas. RESULTADOS: Síndrome hepatopulmonar foi observada em 21 (16 por cento) dos doentes. Sua presença foi associada à gravidade da doença hepática avaliada pela pontuação MELD, mas não com mortalidade intra-hospitalar. CONCLUSÕES: A síndrome hepatopulmonar ocorre em 16 por cento dos pacientes hospitalizados com doença crônica parenquimatosa do fígado, estando associada à gravidade da doença hepática. Mortalidade a curto prazo por descompensação da doença crônica parenquimatosa do fígado não foi associada à presença de síndrome hepatopulmonar.

Intrapulmonary arteriovenous shunt in children with chronic liver disease: clinical features, laboratory data and outcome.

OBJECTIVE: To determine the frequency of hepatopulmonary syndrome in children with chronic liver disease, and its clinical and biochemical associations. METHOD: This study included 53 children with chronic liver disease, who underwent contrast echocardiography with agitated saline and measurement of arterial blood gases. RESULTS: Of the 53 patients studied, 18 had intrapulmonary shunting of blood. This shunting was associated with presence of palpable spleen, cyanosis and dyspnea, but not with abnormalities in the biochemical tests of liver function. At 1-year follow-up, there were 5 deaths among 18 patients with intrapulmonary shunt. In a logistic regression model, PaO 2 < 70 mmHg was found to be a predictor of death (p< 0.05). CONCLUSION: Intrapulmonary shunting is a common and important complication in children with chronic liver disease.

Complicaciones pulmonares de la cirrosis hepática: hipertensión portopulmonar y síndrome hepatopulmonar: la paradoja de la vasoconstricción y vasodilatación pulmonar / Pulmonary complications of hepatic cirrhosis: portopulmonary hypertension and hepatopulmonary syndrome: the paradox of pulmonary vasoconstriction and vasodilation

Las complicaciones pulmonares de las enfermedades crónicas del hígado han sido descritas desde hace más de un siglo. Aunque originadas por una lesión común y vías fisiopatológicas similares, sus manifestaciones clínicas y el diagnóstico son divergentes. Su impacto clínico es importante ya que afectan de forma deletérea el pronóstico de los pacientes. Hasta el momento no existe un tratamiento efectivo para el manejo de estas enfermedades y el trasplante hepático debe ser evaluado de forma muy cuidadosa. En esta revisión se analizan los aspectos más importantes de la hipertensión portopulmonar y del síndrome hepatopulmonar, entidades que bajo el entorno de la hipertensión portal se caracterizan respectivamente por procesos de vasoconstricción y vasodilatación pulmonar.

Cardiopulmonar complications in chronic liver diseases were described 100 years ago. Altough both hepatopulmonary sindrome and portopulmonary hypertension originates from liver damage, clinical findings and diagnosis are very different. These complications are important due to the highly deleterous impact on disease evolution and prognosis. Currently, there is not an ideal treatment for these diseases and liver transplantation should be adequately evaluated. In this review we analyze the most important issues on hepatopulmonary sindrome and portopulmonary hypertension. These complications,under the cornerstone of portal hypertension are characterized by pulmonary constriction and dilatation, respectively.

Sindrome hepatopulmonar / Hepatopulmonary syndrome

El síndrome hepatopulmonar constituye una causa conocida de insuficiencia respiratoria en cirrosis hepática. Se define en base a la tríada de enfermedad hepática generalmente con hipertensión portal, hipoxemia arterial y vasodilatación pulmonar capilar y precapilar, que condicionan shunts de derecha a izquierda, alteraciones en la ventilación-perfusión y en la difusión. Su incidencia oscila entre el 15 y 47 por ciento, y aunque se puede presentar en pacientes con hepatopatía aguda, es una complicación característica de pacientes con cirrosis. Clinicamente existe disnea de esfuerzo, platipnea y ortodeoxia, además de cianosis, acropaquia y nevi aracniformes. Su diagnóstico se basa en el estudio de la función pulmonar y el ecocardiograma con contraste de burbujas. La gammagrafía pulmonar de perfusión con albúmina macroagregada marcada con tecnesio-99m permite la estimación de la fracción del shunt. El trasplante hepático es el único tratamiento demostradamente eficaz, excepto en aquellos pacientes con un trastorno ventilatorio más grave, por su mayor morbi-mortalidad.

The Hepatopulmonary syndrome is a know cause of respiratory failure in cirrhosis. It is a clinical triad characterized by liver disease generally with portal hypertension, arterial hypoxaemia and precapillary-capillary intrapulmonary vascular dilatation leading to right and left shunts, ventilation/perfusion defects and diffusion impairment. Its incidence is about 15 to 47 percent in patients with acute liver disease but characteristly in chronic liver disease. Shortness of breath, orthodeoxia and platypnoea, togheter with cyanosis, digital clubbing and spider naevi are common. Its diagnosis on the basis of the pulmonary gas exchange abnormality and contrast-enhanced echocardiography. The perfusion lung scanning using technetium-labelled macro-aggregatesalbumin estimate the shunt fraction. The orthotopic liver transplantation is the only efficacy treatment in patients without several gas exchange abnormality.

Ligadura de ducto biliar como modelo de estudo da síndrome hepatopulmonar e estresse oxidativo / Common bile duct ligation as a model of hepatopulmonary syndrome and oxidative stress

RACIONAL: A síndrome hepatopulmonar é caracterizada por uma disfunção hepática e pela existência de dilatações dos vasos pulmonares, levando a alterações nas trocas gasosas, tendo algumas das suas características observadas de forma experimental no modelo de ligadura de ducto biliar. OBJETIVOS: Avaliar o estresse oxidativo no tecido pulmonar de ratos cirróticos por ligadura de ducto biliar comum. MATERIAIS E MÉTODOS: Foram utilizados 12 ratos machos Wistar, pesando entre 200 e 300 g, divididos em dois grupos: controles (Co = 6) e cirróticos (Ci = 6). Foram realizadas avaliações de transaminases, gasometria arterial, avaliação da lipoperoxidação (substâncias reativas ao ácido tiobarbitúrico e quimiluminescência) e quantificação da atividade enzimática antioxidante através das concentrações da enzima superóxido dismutase. Os tecidos analisados para avaliação da síndrome hepatopulmonar foram o fígado cirrótico e o pulmão. RESULTADOS: Os animais com ligadura de ducto biliar apresentaram alteração nas transaminases: aspartato aminotransferase, Co = 105,3 ± 43/Ci = 500,5 ± 90,3 alanina aminotransferase, Co = 78,75 ± 37,7/Ci = 162,75 ± 35,4 e fosfatase alcalina, Co = 160 ± 20,45/Ci = 373,25 ± 45,44. Em relação à lipoperoxidação e à resposta antioxidante, estas também apresentaram diferenças estatisticamente significativas quando avaliadas no pulmão (substâncias reativas ao ácido tiobarbitúrico) Co = 0,87 ± 0,3/Ci = 2,01 ± 0,9; quimiluminescência Co = 16008,41 ± 1171,45/Ci = 20250,36 ± 827,82; superóxido dismutase Co = 6,66 ± 1,34/Ci = 16,06 ± 2,67. CONCLUSÕES: Os dados obtidos sugerem que no modelo experimental de cirrose por ligadura de ducto biliar há aumento significativo da lipoperoxidação no tecido pulmonar, bem como aumento na atividade da enzima antioxidante superóxido dismutase, sugerindo a presença de dano pulmonar decorrente da cirrose biliar secundária.

Clinical and diagnostic characteristics of hepatopulmonary syndrome among iranian patients with cirrhosis

Hepatopulmonary syndrome [HPS] is one of the pulmonary complications of cirrhosis, which is manifested by reduction in arterial blood oxygen. The present study was conducted to evaluate the frequency, clinical and para clinical features of HPS, and to determine their predictive values in diagnosis in a group of Iranian patients. This case series study was performed on 54 cirrhotic patients referred consecutively to the gastroenterology department of Taleghani Hospital between 2003 and 2004. Patients underwent pulmonary echo-contrast to detect intra-pulmonary and intra-cardiac shunts. Arterial blood oxygen, 0[2] gradient [A-a] and orthodoxy were measured in these patients by ABG. All patients underwent endoscopy for possible esophageal varices. Patients who met the following three diagnostic criteria including hepatic cirrhosis, arterial blood deoxygenation [P0[2]<80mmHg] and rapulmonary arterial dilation were classified as clinical HPS while those manifested solely with intrapulmonary arterial dilation were defined as subclinical HPS. Of 54 patients, 10 [18.5%] fulfilled clinical and 7 [13%] subclinical HPS criteria. Patients aged 71-80 years were more commonly affected. Hepatitis B was the most common etiologic factor. Dyspnea [100%] and cyanosis [90%] were the most prevalent clinical features. Dyspnea and clubbing were the most sensitive and specific clinical features, respectively. Pao[2]<70mmHg and arterial-alveolar gradient had the highest sensitivity for HPS diagnosis. Clubbing with the highest positive predictive value [75%] and dyspnea whit the highest negative predictive value [100%] were the best clinical features to diagnose HPS. PaO[2]<70mmHg and P[A-a]0[2]>30 and their sum, have the highest positive and negative predictive values in HPS diagnosis

Síndrome hepatopulmonar: patogenia, diagnóstico e tratamento / Hepatopulmonary syndrome: pathogenesis, diagnosis and treatment

RACIONAL: A síndrome hepatopulmonar é caracterizada por tríade clínica que consiste em: 1) doença hepática e/ou hipertensão portal, 2) dilatações vasculares intra-pulmonares, e 3) anormalidades da oxigenação arterial (pressão parcial de oxigênio <70 mm Hg ou gradiente alvéolo-arterial de oxigênio >20 mm Hg). Sua freqüência varia de acordo com os métodos diagnósticos utilizados. OBJETIVOS: Fazer revisão da literatura sobre patogenia, diagnóstico e tratamento da síndrome hepatopulmonar. MÉTODOS: Levantamento no MEDLINE das publicações nacionais e internacionais mais relevantes sobre a síndrome hepatopulmonar. RESULTADOS: A prevalência da síndrome hepatopulmonar varia de 4 por cento a 17,5 por cento, a depender dos critérios diagnósticos utilizados. A doença hepática associada mais comum é a cirrose. O gradiente alvéolo-arterial de oxigênio parece ser o melhor parâmetro para avaliação das anormalidades da oxigenação arterial. Em relação à detecção das dilatações vasculares intra-pulmonares, a ecocardiografia com contraste é o método de escolha, pois é de fácil realização e pode diferenciar as comunicações intra-pulmonares das intra-cardíacas. No tratamento da síndrome hepatopulmonar, poucos relatos bem sucedidos puderam ser reproduzidos e confirmados utilizando terapia farmacológica e/ou radiologia intervencionista. Atualmente, o transplante de fígado é considerado a principal opção terapêutica desses pacientes, com resultados animadores. CONCLUSÕES: A síndrome hepatopulmonar é uma enfermidade freqüente. Exames gasométricos são necessários para o seu diagnóstico. O transplante de fígado é o tratamento de escolha para os portadores da síndrome.

Hepatopulmonary Syndrome Induced by Common Bile Duct Ligation in a Rabbit Model: Correlation between Pulmonary Vascular Dilatation on Thin-Section CT and Angiography and Serum Nitrite Concentration or Endothelial Nitric Oxide Synthase (eNOS) 1 Expression

OBJECTIVE: To investigate the correlation between radiologic vascular dilatation and serum nitrite concentration and eNOS expression in the endothelial cell and pneumocyte in a rabbit model of hepatopulmonary syndrome induced by common bile duct ligation (CBDL). MATERIALS AND METHODS: Thin-section CT scans of the lung and pulmonary angiography were obtained 3 weeks after CBDL (n=6), or a sham operation (n=4), and intrapulmonary vasodilatation was assessed. The diameter and tortuosity of peripheral vessels in the right lower lobe by thin-section CT and angiography at the same level of the right lower lobe in all subjects were correlated to serum nitrite concentration and eNOS (endothelial nitric oxide synthase) expression as determined by immunostaining. RESULTS: The diameters of pulmonary vessels on thin-section CT were well correlated with nitrite concentrations in serum (r = 0.92, p < 0.001). Dilated pulmonary vessels were significantly correlated with an increased eNOS expression (r = 0.94, p < 0.0001), and the severity of pulmonary vessel tortuosity was found to be well correlated with serum nitrite concentration (r = 0.90, p < 0.001). CONCLUSION: The peripheral pulmonary vasculature in hepatopulmonary syndrome induced by CBLD was dilated on thin-section CT and on angiographs. Our findings suggest that peripheral pulmonary vascular dilatations are correlated with serum nitrite concentrations and pulmonary eNOS expression.

Prevelência da síndrome hepatopulmonar em candidatos a transplante hepático / Hepatopulmonary syndrome in liver transplantation candidates

Hepatopulmonary syndrome is an important clinical problem associated with chronic liver disease. Liver transplantation can result in complete resolution of the arterial hypoxemia associated with this syndrome, even in its most severe presentation. AIM: To determine the prevalence of hepatopulmonary syndrome in adult liver transplant candidates. PATIENTS AND METHODS: Fifty-four consecutives adult patients (> or = 18 years) with severe liver disease waiting for liver transplant were screened for arterial hypoxemia (PaO2 < 70 mm Hg) while they were seated, at rest, and breathing room air. Patients with arterial hypoxemia underwent contrast-enhanced two-dimensional echocardiography and pulmonary function testing. Hypoxemia (PaO2 < 70 mm Hg) was present in 7 of 54 patients (12.9%), although only 1 of them complained of dyspnea. The Child's classification of the patients were: A = 1, B = 4, and C = 1. All seven hypoxemic patients had positive contrast-enhanced two-dimensional echocardiography, consistent with hepatopulmonary syndrome. CONCLUSION: The prevalence of hepatopulmonary syndrome in adult liver transplant candidates is elevated. The screening for hepatopulmonary syndrome should be part of the routine evaluation of liver transplant candidates even in the absence of pulmonary symptoms

Prevalence and Risk Factors of Significant Intrapulmonary Shunt in Cirrhotic patients awaiting liver transplantation / 대한간학회지

BACKGROUNDS/AIMS: Hepatopulmonary syndrome is a condition of severe hypoxia with intrapulmonary shunt (IPS) in the setting of hepatic dysfunction. Liver transplantation has been suggested as a definite treatment for hepatopulmonary syndrome with reversal of IPS in some patients. Inconsistency of response and inability to predict reversibility, however, are significant problems. We performed this study to evaluate the prevalence of significant IPS in pretransplantation cirrhotic patients and to find any risk factors of IPS. METHODS: Fifty-seven patients (M:F = 38:19, median age 49 years (range 18 - 71)) with liver cirrhosis awaiting liver transplantation were serially included. Their IPS status was evaluated using contrast- enhanced echocardiography. Significant shunt was defined as a shunt of grade >or= 2. RESULTS: Significant IPS was detected in 30 (52.6%) among 57 patients. Significant shunt was found in 24 (63.2%) of 38 Child-Pugh class C patients and in 6 (31.6%) of 19 Child-Pugh class A or B patients (p < 0.05). No significant difference in prevalence of significant shunt was seen according to age, sex, presence or absence of hepatocellular carcinoma, ascites, hepatic encephalopathy, and gastroesophageal varix. CONCLUSION: Significant intrapulmonary shunt is a common finding in cirrhotic patients awaiting liver transplantation. Child-Pugh class C is the risk factor associated with high prevalence of significant shunt.

Pulmão e fígado: uma interação ou uma síndrome / Lung and liver: interaction or syndrome?

A cirrose e suas consequências há muito intrigam o médico sobretudo pelo comprometimento multissistêmico e também porque a ciência médica ainda não desvendou boa parte dos aspectos bioquímicos e do metabolismo celular que são afetados pela disfunção hepática crônica. Embora descrita há mais de 100 anos de forma um tanto epírica, a síndrome hepatopulmonar tem sido objeto de estudo e de interesse progressivamente maiores nas últimas décadas. Suas alterações e seus achados começaram, no entanto, a ser bem definidos somente há alguns anos, embora o mecanismo bioquímico etiopatogênico persista na esfera da especulação...