Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis

Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease, occurring mainly in patients with advanced cirrhosis and ascites, who have marked circulatory dysfunction,1 as well as in patients with acute liver failure.2 In spite of its functional nature, HRS is associated with a poor prognosis,3 4 and the only effective treatment is liver transplantation. During the 56th Meeting of the American Association for the Study of Liver Diseases, the International Ascites Club held a Focused Study Group (FSG) on HRS for the purpose of reporting the results of an international workshop and to reach a consensus on a new definition, criteria for diagnosis and recommendations on HRS treatment. A similar workshop was held in Chicago in 1994 in which standardised nomenclature and diagnostic criteria for refractory ascites and HRS were established.5 The introduction of innovative treatments and improvements in our understanding of the pathogenesis of HRS during the previous decade led to an increasing need to undertake a new consensus meeting. This paper reports the scientific rationale behind the new definitions and recommendations. The international workshop included four issues debated by four panels of experts (see Acknowledgements). The issues were: (1) evidence-based HRS pathogenesis; (2) treatment of HRS using vasoconstrictors; (3) other HRS treatments using transjugular intrahepatic portosystemic stent-shunt (TIPS) and extracorporeal albumin dialysis (ECAD); and (4) new definitions and diagnostic criteria for HRS and recommendations for its treatment.

Functional renal failure and haemorrhagic gastritis associated with endotoxaemia in cirrhosis

Forty-three patients with cirrhosis and ascites, 21 with normal renal function, 10 with a progressive functional renal failure (FRF), and 12 with a steady FRF, were investigated for the presence of endotoxaemia by the Limulus lysate test. Endotoxaemia was found in nine patients with FRF and in none of the 21 with normal renal function (P less than 0-01). A positive Limulus test was almost exclusively associated with a progressive FRF (eight of 10 patients) and all but one of them died. Renal function improved as endotoxaemia disappeared in the survivor. Endotoxaemia was also associated with haemorrhage due to acute erosions of the gastric mucosa, being present in six of the seven patients who had this complication. Intravascular coagulation was not found in any patient. The Limulus test was positive in the ascitic fluid in 18 of 21 patients tested, although only two of them had peritonitis. These results suggest that endotoxaemia may play a critical role in the development of progressive renal failure and haemorrhagic gastritis in cirrhosis, and emphasise the potential risk of procedures involving reinfusion of ascitic fluid.

Atividade antioxidante in vitro e in vivo de café bebida mole

O objetivo deste trabalho foi determinar a atividade antioxidante do café, bebida mole, in vivo e in vitro, antes e após a torração. Para a análise da atividade antioxidante in vitro, foram utilizados os métodos de sequestro de radicais livres (DPPH) e de atividade quelante de íons Fe2+. Foram utilizados, para o ensaio in vivo, ratos Zucker diabéticos, portadores de síndrome metabólica, e ratos Zucker controle. Os animais receberam doses diárias das bebidas de café, por gavagem, por 30 dias. Após o tratamento, foi realizada a avaliação de peroxidação lipídica. As amostras torradas apresentaram a maior percentagem de sequestro de radicais livres. As concentrações nas amostras de café verde e torrado foram similares às do padrão Trolox. Das amostras torradas, a torração média se destacou com maior atividade quelante de íons Fe2+. Os cafés verdes mostraram maior poder quelante do que os torrados. Compostos presentes no extrato diminuíram a lipoperoxidação hepática e renal que é comum em casos de diabetes e síndrome metabólica. O café apresenta atividade antioxidante e protege o fígado e os rins dos animais contra a lipoperoxidação comumente presente em quadros de diabetes mellitus tipo 2 e síndrome metabólica.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS: Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS: In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS: Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS: Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis.

with specific ANA, in particular of the IgG3 isotype, had significantly more severe biochemical and histological disease compared with those who were seronegative. None of the controls was positive.Conclusions: Disease specific ANA are present in the majority of patients with PBC when investigated at the level of immunoglobulin isotype. PBC specific ANA, in particular of the IgG3 isotype, are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.

Incidence, prevalence and clinical significance of abnormal hematological indices in compensated cirrhosis.

Background & Aims: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prog-nostic significance. Methods: We analyzed a database of 213 subjects with compensated cirrhosis without esopha-geal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglo-bin,<13.5 g/dL for men and 11.5 g/dL for women), leuko-penia (white blood cell counts,<4000/mm 3 ), or thrombo-cytopenia (platelet counts, < 150,000/mm 3 ). The primary end points were death or transplant surgery. Results: Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P .0191) and leukope-nia (P.0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years,a significant difference in death or transplant, mortality,and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at base- line compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r 0.35, P < .0001; white blood cell count, r 0.31, P < .0001). Conclusions: Thrombocy-topenia is the most common and first abnormal HI to occurin patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baselin predicted increased morbidity and mortality.

Management of varices and variceal hemorrhage in cirrhosis.

Variceal hemorrhage is a lethal complication of cirrhosis, particularly in patients in whom clinical decompensation (i.e., ascites, encephalopathy, a previous episode of hemorrhage, or jaundice) has already developed. Practice guidelines for the management of varices and variceal hemorrhage1 in cirrhosis are mostly based on evidence in the literature that has been summarized and prioritized at consensus conferences...

Leiomiossarcoma do intestino grosso: relato de um caso

Os autores relatam um caso de leiomiossarcoma de cólon ascendente acometendo um paciente do sexo masculino, de 49 anos de idade. O paciente iniciou o quadro com anemia e massa abdominal, e a evolução dos sintomas até o diagnóstico final foi de nove meses. Na radiografia simples do abdome havia presença de coleção aérea localizada no hipocôndrio direito, fora da topografia de alças; no clister opaco com duplo contraste foi demonstrado deslocamento inferior da flexura hepática e divertículos. A ultra-sonografia abdominal mostrou lesão expansiva heterogênea, com gás no seu interior, de localização sub-hepática. A tomografia computadorizada do abdome revelou massa escavada com nível líquido, sub-hepática, que não se impregnou pelo meio de contraste. Foi realizada hemicolectomia direita com ileocoloanastomose, e o diagnóstico histopatológico foi de leiomiossarcoma de cólon ascendente.

Pseudomixoma peritoneal: aspectos tomográficos e na ressonância magnética - relato de três casos

O pseudomixoma peritoneal é um tumor incomum, de curso indolente, que se caracteriza pela presença de ascite mucinosa ou implantes na cavidade peritoneal. Origina-se geralmente de lesões no apêndice ou no ovário. O diagnóstico pode ser feito por meio da citologia de aspiração por agulha fina, ultra-sonografia, tomografia computadorizada ou ressonância magnética. Os autores relatam três casos de pseudomixoma peritoneal cujo sítio primário era o ovário, e que foram submetidos a tomografia computadorizada e a ressonância magnética do abdome. Este trabalho enfatiza a importância destes métodos em função de sua capacidade de resolução espacial, imagens multiplanares e diferentes seqüências (na ressonância magnética), permitindo melhor avaliação das lesões. Os exames tomográficos demonstraram massas lobuladas, hipodensas, com limites bem definidos, determinando "lobulações" nas margens hepática e esplênica por compressão extrínseca secundária a implantes peritoneais, sem invasão dos órgãos. A ressonância magnética revelou lesões expansivas com baixo sinal nas imagens ponderadas em T1 e alto sinal em T2, de localização peritoneal, junto às margens do fígado e baço.

Sarcoma embrionário indiferenciado do fígado: relato de caso

O sarcoma embrionário indiferenciado do fígado é uma entidade rara que acomete, principalmente, crianças acima dos cinco anos de idade. O aspecto macroscópico consiste, caracteristicamente, de grande massa hepática com maior componente sólido, porém apresenta algumas áreas císticas. Curiosamente, a tomografia computadorizada superestima o componente cístico da lesão, sendo a ultra-sonografia um método mais fidedigno na demonstração da consistência do tumor. Os estudos por imagem ajudam a afastar enfermidades não-neoplásicas, como abscessos e hematomas hepáticos, e avaliam a extensão das lesões. O diagnóstico de sarcoma embrionário indiferenciado pode ser corretamente presumido quando se consideram os achados de imagem em conjunto com a idade do paciente e o nível de alfa-fetoproteína. Os autores descrevem um caso de sarcoma embrionário indiferenciado no fígado de uma criança do sexo feminino de dez anos de idade, enfatizando seus aspectos imagenológicos e o diagnóstico diferencial.

Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension.

Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information.

Self-expandable metal stents in the treatment of acute esophageal variceal bleeding.

Acute variceal bleeding (AVB) is a life-threatening complication in patients with cirrhosis. Hemostatic therapy of AVB includes early administration of vasoactive drugs that should be combined with endoscopic therapy, preferably banding ligation. However, failure to control bleeding or early rebleed within 5 days still occurs in 15-20% of patients with AVB. In these cases, a second endoscopic therapy may be attempted (mild bleeding in a hemodynamically stable patient) or we can use a balloon tamponade as a bridge to definitive derivative treatment (i.e., a transjugular intrahepatic portosystemic shunt). Esophageal balloon tamponade provides initial control in up to 80% of AVB, but it carries a high risk of major complications, especially in cases of long duration of tamponade (>24 h) and when tubes are inserted by inexperienced staff. Preliminary reports suggest that self-expandable covered esophageal metallic stents effectively control refractory AVB (i.e., ongoing bleeding despite pharmacological and endoscopic therapy or massive bleeding precluding endoscopic therapy) with a low incidence of complications. Thus, covered self-expanding metal stents may represent an alternative to the Sengstaken-Blakemore balloon for the temporary control of bleeding in treatment failures. Further studies are required to determine the role of this new device in AVB.

Uso do contraste oral negativo em exames de colangiografia por ressonância magnética

OBJETIVO: Realizamos estudo prospectivo das vias biliares e pancreáticas através de colangiografia por ressonância magnética, com a utilização de meio de contraste oral negativo. Os nossos objetivos foram verificar se este novo meio de contraste melhora a visualização das vias biliar e pancreática, além de identificar a freqüência de efeitos colaterais ao contraste e sua aceitação pelo paciente. MATERIAL E MÉTODO: Quinze voluntários (oito homens e sete mulheres) com idades variando entre 18 e 54 anos (média de 29 anos), sem queixas ou cirurgias abdominais, foram submetidos a colangiografia por ressonância magnética. Foram realizadas duas seqüências colangiográficas em apnéia, antes e cinco minutos após a ingestão de 300 ml de contraste oral negativo. Os exames foram realizados em equipamento operando a 1,0 T. RESULTADOS: Setenta e três por cento dos voluntários consideraram o gosto ruim ou muito ruim, sugerindo uma aceitação discutível; 27% dos voluntários apresentaram náuseas; 20%, cólicas; 14%, azia ou parestesia labial; e 7%, diarréia. A visualização da via biliar extra-hepática foi considerada melhor após o contraste oral negativo em 9/15 voluntários (60%) e do ducto pancreático principal em todos os cinco em que havia interposição de alças. CONCLUSÃO: O contraste oral negativo melhora a visualização dos ductos hepatocolédoco e pancreático principal em exames de colangiografia por ressonância magnética, apesar da baixa aceitação e dos seus efeitos colaterais.