New insights into the role of PPARs.

Peroxisome proliferator-activated receptors (PPARs) are fatty acid-activated transcription factors belonging to the nuclear hormone receptor family. While PPARs are best known as regulators of energy homeostasis, evidence also has accumulated recently for their involvement in basic cellular functions. We review novel insights into PPAR functions in skin wound healing and liver, with emphasis on PPARβ/δ and PPARα, respectively. Activation of PPARβ/δ expression in response to injury promotes keratinocyte survival, directional sensing, and migration over the wound bed. In addition, interleukin (IL)-1 produced by the keratinocytes activates PPARβ/δ expression in the underlying fibroblasts, which hinders the mitotic activity of keratinocytes via inhibition of IL-1 signaling. Initially, roles were identified for PPARα in fatty acid catabolism. However, PPARα is also involved in downregulating many genes in female mammals. We have elucidated the mechanism of this repression, which requires sumoylation of PPARα. Physiologically, this control confers protection against estrogen-induced intrahepatic cholestasis.

Early use of TIPS in patients with cirrhosis and variceal bleeding.

Background Patients with cirrhosis in ChildPugh class C or those in class B who have persistent bleeding at endoscopy are at high risk for treatment failure and a poor prognosis, even if they have undergone rescue treatment with a transjugular intrahepatic porto - systemic shunt (TIPS). This study evaluated the earlier use of TIPS in such patients. Methods We randomly assigned, within 24 hours after admission, a total of 63 patients with cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy to treatment with a polytetrafluoroethylene-covered stent within 72 hours after randomization (early-TIPS group, 32 patients) or continuation of vasoactive-drug therapy, followed after 3 to 5 days by treatment with propranolol or nadolol and long-term endoscopic band ligation (EBL), with insertion of a TIPS if needed as rescue therapy (pharmacotherapyEBL group, 31 patients). Results During a median follow-up of 16 months, rebleeding or failure to control bleeding occurred in 14 patients in the pharmacotherapyEBL group as compared with 1 patient in the early-TIPS group (P=0.001). The 1-year actuarial probability of remaining free of this composite end point was 50% in the pharmacotherapyEBL group versus 97% in the early-TIPS group (P<0.001). Sixteen patients died (12 in the pharmacotherapyEBL group and 4 in the early-TIPS group, P=0.01). The 1-year actuarial survival was 61% in the pharmacotherapyEBL group versus 86% in the early-TIPS group (P<0.001). Seven patients in the pharmacotherapyEBL group received TIPS as rescue therapy, but four died. The number of days in the intensive care unit and the percentage of time in the hospital during follow-up were significantly higher in the pharmacotherapyEBL group than in the early-TIPS group. No significant diferences were observed between the two treatment groups with respect to serious adverse events. Conclusions In these patients with cirrhosis who were hospitalized for acute variceal bleeding and at high risk for treatment failure, the early use of TIPS was associated with signif icant reductions in treatment failure and in mortality. (Current Controlled Trials number, ISRCTN58150114.)

Does fructose consumption contribute to non-alcoholic fatty liver disease?

Fructose is mainly consumed with added sugars (sucrose and high fructose corn syrup), and represents up to 10% of total energy intake in the US and in several European countries. This hexose is essentially metabolized in splanchnic tissues, where it is converted into glucose, glycogen, lactate, and, to a minor extent, fatty acids. In animal models, high fructose diets cause the development of obesity, insulin resistance, diabetes mellitus, and dyslipidemia. Ectopic lipid deposition in the liver is an early occurrence upon fructose exposure, and is tightly linked to hepatic insulin resistance. In humans, there is strong evidence, based on several intervention trials, that fructose overfeeding increases fasting and postprandial plasma triglyceride concentrations, which are related to stimulation of hepatic de novo lipogenesis and VLDL-TG secretion, together with decreased VLDL-TG clearance. However, in contrast to animal models, fructose intakes as high as 200 g/day in humans only modestly decreases hepatic insulin sensitivity, and has no effect on no whole body (muscle) insulin sensitivity. A possible explanation may be that insulin resistance and dysglycemia develop mostly in presence of sustained fructose exposures associated with changes in body composition. Such effects are observed with high daily fructose intakes, and there is no solid evidence that fructose, when consumed in moderate amounts, has deleterious effects. There is only limited information regarding the effects of fructose on intrahepatic lipid concentrations. In animal models, high fructose diets clearly stimulate hepatic de novo lipogenesis and cause hepatic steatosis. In addition, some observations suggest that fructose may trigger hepatic inflammation and stimulate the development of hepatic fibrosis. This raises the possibility that fructose may promote the progression of non-alcoholic fatty liver disease to its more severe forms, i.e. non-alcoholic steatohepatitis and cirrhosis. In humans, a short-term fructose overfeeding stimulates de novo lipogenesis and significantly increases intrahepatic fat concentration, without however reaching the proportion encountered in non-alcoholic fatty liver diseases. Whether consumption of lower amounts of fructose over prolonged periods may contribute to the pathogenesis of NAFLD has not been convincingly documented in epidemiological studies and remains to be further assessed.

METABOLIC EFFECTS OF DIETARY PROTEINS

SUMMARY :Non-alcoholic fatty liver disease (NAFLD) is characterized by an elevated intra- hepatocellular lipid (IHCL) concentration (> 5%). The incidence of NAFLD is frequently increased in obese patients, and is considered to be the hepatic component of the metabolic syndrome. The metabolic syndrome, also characterized by visceral obesity, altered glucose homeostasis, insulin resistance, dyslipidemia, and high blood pressure, represents actually a major public health burden. Both dietary factors and low physical activity are involved in the development of the metabolic syndrome. ln animals and healthy humans, high-fat or high-fructose diets lead to the development of several features of the metabolic syndrome including increased intrahepatic lipids and insulin resistance. ln contrast the effects of dietary protein are less well known, but an increase in protein intake has been suggested to exert beneficial effects by promoting weight loss and improving glucose homeostasis in insulin-resistant patients. Increased postprandial thermogenesis and enhanced satiety after protein ingestion may be both involved. The effects of dietary protein on hepatic lipids have been poorly investigated in humans, but preliminary studies in rodents have shown a reduction of hepatic lipids in carbohydrate fed rats and in obese rats. ln this context this work aimed at investigating the metabolic effects of dietary protein intake on hepatic lipid metabolism and glucose homeostasis in humans. The modulation by dietary proteins of exogenous lipid oxidation, net lipid oxidation, hepatic beta-oxidation, triglycerides concentrations, whole-body energy expenditure and glucose tolerance was assessed in the fasting state and in postprandial states. Measurements of IHCL were performed to quantify the amount of triglycerides in the liver. ln an attempt to cover all these metabolic aspects under different point of views, these questions were addressed by three protocols involving various feeding conditions. Study I addressed the effects of a 4-day hypercaloric high-fat high-protein diet on the accumulation of fat in the liver (IHCL) and on insulin sensitivity. Our findings indicated that a high protein intake significantly prevents intrahepatic fat deposition induced by a short- term hypercaloric high-fat diet, adverse effects of which are presumably modulated at the liver level.These encouraging results led us to conduct the second study (Study ll), as we were also interested in a more clinical approach to protein administration and especially if increased protein intakes might be of benefit for obese patients. Therefore the effects of one-month whey protein supplementation on IHCL, insulin sensitivity, lipid metabolism, glucose tolerance and renal function were assessed in obese women. Results showed that whey protein supplementation reduces hepatic steatosis and improves the plasma lipid profile in obese patients, without adverse effects on glucose tolerance or creatinine clearance. However since patients were fed ud-libitum, it remains possible that spontaneous carbohydrate and fat intakes were reduced due to the satiating effects of protein. The third study (Study lll) was designed in an attempt to deepen our comprehension about the mechanisms involved in the modulation of IHCL. We hypothesized that protein improved lipid metabolism and, therefore, we evaluated the effects of a high protein meal on postprandial lipid metabolism and glucose homeostasis after 4-day on a control or a protein diet. Our results did not sustain the hypothesis of an increased postprandial net lipid oxidation, hepatic beta oxidation and exogenous lipid oxidation. Four days on a high-protein diet rather decreased exogenous fat oxidation and enhanced postprandial triglyceride concentrations, by impairing probably chylomicron-TG clearance. Altogether the results of these three studies suggest a beneficial effect of protein intake on the reduction in lHCL, and clearly show that supplementation of proteins do not reduce IHCL by stimulating lipid metabolism, e.g. whole body fat oxidation, hepatic beta oxidation, or exogenous fat oxidation. The question of the effects of high-protein intakes on hepatic lipid metabolism is still open and will need further investigation to be elucidated. The effects of protein on increased postprandial lipemia and lipoproteins kinetics have been little investigated so far and might therefore be an interesting research question, considering the tight relationship between an elevation of plasmatic TG concentrations and the increased incidence of cardiovascular diseases.Résumé :La stéatose hépatique non alcoolique se caractérise par un taux de lipides intra-hépatiques élevé, supérieur à 5%. L'incidence de la stéatose hépatique est fortement augmentée chez les personnes obèses, ce qui mène à la définir comme étant la composante hépatique du syndrome métabolique. Ce syndrome se définit aussi par d'autres critères tels qu'obésité viscérale, altération de l'homéostasie du glucose, résistance à l'insuline, dyslipidémie et pression artérielle élevée. Le syndrome métabolique est actuellement un problème de santé publique majeur.Tant une alimentation trop riche et déséquilibrée, qu'une faible activité physique, semblent être des causes pouvant expliquer le développement de ce syndrome. Chez l'animal et le volontaire sain, des alimentations enrichies en graisses ou en sucres (fructose) favorisent le développement de facteurs associés au syndrome métabolique, notamment en augmentant le taux de lipides intra-hépatiques et en induisant le développement d'une résistance à l'insuline. Par ailleurs, les effets des protéines alimentaires sont nettement moins bien connus, mais il semblerait qu'une augmentation de l'apport en protéines soit bénéfique, favorisant la perte de poids et l'homéostasie du glucose chez des patients insulino-résistants. Une augmentation de la thermogenese postprandiale ainsi que du sentiment de satiété pourraient en être à l'origine.Les effets des protéines sur les lipides intra-hépatiques chez l'homme demeurent inconnus à ce jour, cependant des études préliminaires chez les rongeurs tendent à démontrer une diminution des lipides intra hépatiques chez des rats nourris avec une alimentation riche en sucres ou chez des rats obèses.Dans un tel contexte de recherche, ce travail s'est intéressé à l'étude des effets métaboliques des protéines alimentaires sur le métabolisme lipidique du foie et sur l'homéostasie du glucose. Ce travail propose d'évaluer l'effet des protéines alimentaires sur différentes voies métaboliques impliquant graisses et sucres, en ciblant d'une part les voies de l'oxydation des graisses exogènes, de la beta-oxydation hépatique et de l'oxydation nette des lipides, et d'autre part la dépense énergétique globale et l'évolution des concentrations sanguines des triglycérides, à jeun et en régime postprandial. Des mesures des lipides intra-hépatiques ont aussi été effectuées pour permettre la quantification des graisses déposées dans le foie.Dans le but de couvrir l'ensemble de ces aspects métaboliques sous différents angles de recherche, trois protocoles, impliquant des conditions alimentaires différentes, ont été entrepris pour tenter de répondre à ces questions. La première étude (Etude I) s'est intéressée aux effets d'u.ne suralimentation de 4 jours enrichie en graisses et protéines sur la sensibilité à l'insuline et sur l'accumulation de graisses intra-hépatiques. Les résultats ont démontré que l'apport en protéines prévient l'accumulation de graisses intra-hépatiques induite par une suralimentation riche en graisses de courte durée ainsi que ses effets délétères probablement par le biais de mécanismes agissant au niveau du foie. Ces résultats encourageants nous ont conduits à entreprendre une seconde étude (Etude ll) qui s'intéressait à l'implication clinique et aux bénéfices que pouvait avoir une supplémentation en protéines sur les graisses hépatiques de patients obèses. Ainsi nous avons évalué pendant un mois de supplémentation l'effet de protéines de lactosérum sur le taux de graisses intrahépatiques, la sensibilité à l'insuline, la tolérance au glucose, le métabolisme des graisses et la fonction rénale chez des femmes obèses. Les résultats ont été encourageants; la supplémentation en lactosérum améliore la stéatose hépatique, le profil lipidique des patientes obèses sans pour autant altérer la tolérance au glucose ou la clairance de la créatinine. L'effet satiétogene des protéines pourrait aussi avoir contribué à renforcer ces effets. La troisième étude s'est intéressée aux mécanismes qui sous-tendent les effets bénéfiques des protéines observés dans les 2 études précédentes. Nous avons supposé que les protéines devaient favoriser le métabolisme des graisses. Par conséquent, nous avons cherché a évaluer les effets d'un repas riche en protéines sur la lipémie postprandiale et l'homéostasie glucidique après 4 jours d'alimentation contrôlée soit isocalorique et équilibrée, soit hypercalorique enrichie en protéines. Les résultats obtenus n'ont pas vérifié l'hypothèse initiale ; ni une augmentation de l'oxydation nette des lipides, ni celle d'une augmentation de la béta-oxydation hépatique ou de l'oxydation d'un apport exogène de graisses n'a pu étre observée. A contrario, il semblerait même plutôt que 4 jours d'a]irnentation hyperprotéinée inhibent le métabolisme des graisses et augmente les concentrations sanguines de triglycérides, probablement par le biais d'une clairance de chylornicrons altérée. Globalement, les résultats de ces trois études nous permettent d'attester que les protéines exercent un effet bénéfique en prévenant le dépot de graisses intra-hépatiques et montrent que cet effet ne peut être attribué à une stimulation du métabolisme des lipides via l'augmentation des oxydations des graisses soit totales, hépatiques, ou exogènes. La question demeure en suspens à ce jour et nécessite de diriger la recherche vers d'autres voies d'exploration. Les effets des protéines sur la lipémie postprandiale et sur le cinétique des lipoprotéines n'a que peu été traitée à ce jour. Cette question me paraît néanmoins importante, sachant que des concentrations sanguines élevées de triglycérides sont étroitement corrélées à une incidence augmentée de facteurs de risque cardiovasculaire.

Les complications de la cirrhose hépatique: varices oesophagiennes, ascite et carcinome hépato-cellulaire [Complications of liver cirrhosis: oesophageal varices, ascites and hepato-cellular carcinoma]

The principal treatment for bleeding oesophageal varices is endoscopic ligation. Non-cardioselective beta-blockers are the gold-standard of primary prophylaxis. The principal treatment for ascites is a salt-free diet and diuretics, mainly spironolactone, if necessary associated with a loop diuretic. In refractory ascites, paracentesis or installation of a transjugular intrahepatic portosystemic shunt (TIPS) are two possible treatment options. Cirrhosis patients are at higher risk of developing hepato-cellular carcinoma. Surgery is only possible in a small number of cases. Percutaneous destruction techniques have nearly the same survival rate as that obtained by surgery and should be proposed to patients where surgery is not an option.

Ip-10 Is Associated With Il28b Variation And Predicts The First Phase Decline Of Hcv Rna And Outcome Of Therapy In Chronic Hepatitis C

High systemic levels of IP-10 at onset of combination therapy for chronic hepatitis C mirror intrahepatic mRNA levels and predict a slower first phase decline in HCV RNA as well as poor outcome. Recently several genome wide association studies have revealed that single nucleotide polymorphisms (SNPs) on chromosome19 within proximity of IL28B predict spontaneous clearance of HCV infection and as therapeutic outcome among patients infected with HCV genotype 1, with three such SNPs being highly predictive: rs12979860, rs12980275, and rs8099917. In the present study, we correlated genetic variations in these SNPs from 253 Caucasian patients with pretreatment plasma levels of IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO). The favorable genetic variations in all three SNPs (CC, AA, and TT respectively) was significantly associated with lower baseline IP-10 (CC vs. CT/TT at rs12979860: median 189 vs. 258 pg/mL, P=0.02, AA vs. AG/GG at rs12980275: median 189 vs. 258 pg/mL, P=0.01, TT vs. TG/GG at rs8099917: median 224 vs. 288 pg/mL, P=0.04), were significantly less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P=0.01 respectively) and had significantly higher baseline viral load than carriers of the SNP genotypes (6.3 vs. 5.9 log 10 IU/mL, P=0.0012, 6.3 vs. 6.0 log 10 IU/mL, P=0.026, and 6.3 vs. 5.8 log 10 IU/mL, P=0.0003 respectively). Among HCV genotype 1 infected homozygous or heterogeneous carriers of the favorable C, A, and T genotypes, lower baseline IP-10 was significantly associated with greater decline in HCV-RNA day 0-4, which translated into increased rates of achieving SVR among homozygous patients with baseline IP-10 below 150 pg/mL (85%, 75%, and 75% respectively). In a multivariate analysis among genotype 1 infected patients, both baseline IP-10 and the SNPs were significant independent predictors of SVR. Conclusion: Baseline plasma IP-10 is significantly associated with IL28B variations, and augments the predictiveness of the first phase decline in HCV RNA and final treatment outcome.

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.

Intracerebral alveolar echinococcosis.

There are two species of the genus Echinococcus, Echinococcus multilocularis (also called alveolar hydatid) and Echinococcus granulosus, characterized by distinct growth features in humans. The main endemic regions for human alveolar echinococcosis (AE) caused by E. multilocularis are Central Europe, Russia, Turkey, Japan, China, eastern France and North America. Human echinococcosis is usually caused by an intrahepatic growth of parasitic larvae. Cerebral occurrence of E. multilocularis disease is rare, accounting for only 1% of cases, and is generally considered to be fatal. This report presents two cases of intracerebral E. multilocularis disease which occurred in two infected patients with AE pulmonary metastases. The anatomical and clinical features are discussed. Our retrospective survey would indicate that surgical treatment should be envisaged whenever possible.

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.

TIPS para o controle das complicações da hipertensão portal: eficácia, fatores prognósticos associados e variações técnicas

OBJETIVO: Avaliar a eficácia do TIPS (transjugular intrahepatic portosystemic shunt) para tratar as complicações clínicas em pacientes com hipertensão portal. MATERIAIS E MÉTODOS: Quarenta e quatro pacientes, sendo 30 do sexo masculino e 14 do feminino e com idade média de 52 anos foram analisados. A indicação para realização de TIPS foi hemorragia gastrintestinal em 28 e ascite refratária em 16. Houve 7 pacientes Child-Pugh A, 24 Child-Pugh B e 11 Child-Pugh C. RESULTADOS: O TIPS foi realizado com sucesso em todos os pacientes (100%), verificando-se queda do gradiente pressórico porto-sistêmico médio de 49,69% (de 18,98 mmHg para 9,55 mmHg). Comprovou-se melhora clínica em 35 pacientes (79,55%). A mortalidade pós-operatóriaia foi de 13,64%, sendo mais incidente nos pacientes Child-Pugh C (45,45%). Os fatores mais relevantes de mau prognóstico foram o aumento da bilirrubina e do nível de creatinina. A sobrevida média de pacientes Child-Pugh A foi de 11,5 meses, nos Child-Pugh B foi de 10,97 meses e nos Child-Pugh C foi de apenas 5,9 meses. Foram observadas complicações em nove casos (20,44%). CONCLUSÃO: O TIPS é eficiente para reduzir a pressão portal. As complicações e a morbi-mortalidade relacionadas com o procedimento podem ser consideradas aceitáveis. A mortalidade foi influenciada por alguns fatores clínicos, tais como classe Child-Pugh C e elevação dos níveis séricos de bilirrubina e creatinina.

Arterial Therapies of Non-Colorectal Liver Metastases.

BACKGROUND: The unique situation of the liver with arterial and venous blood supply and the dependency of the tumor on the arterial blood flow make this organ an ideal target for intrahepatic catheter-based therapies. Main forms of treatment are classical bland embolization (TAE) cutting the blood flow to the tumors, chemoembolization (TACE) inducing high chemotherapy concentration in tumors, and radioembolization (TARE) without embolizing effect but very high local radiation. These different forms of therapies are used in different centers with different protocols. This overview summarizes the different forms of treatment, their indications and protocols, possible side effects, and available data in patients with non-colorectal liver tumors. METHODS: A research in PubMed was performed. Mainly clinical controlled trials were reviewed. The search terms were 'embolization liver', 'TAE', 'chemoembolization liver', 'TACE', 'radioembolization liver', and 'TARE' as well as 'chemosaturation' and 'TACP' in the indications 'breast cancer', 'neuroendocrine', and 'melanoma'. All reported studies were analyzed for impact and reported according to their clinical relevance. RESULTS: The main search criteria revealed the following results: 'embolization liver + breast cancer', 122 results, subgroup clinical trials 16; 'chemoembolization liver + breast cancer', 62 results, subgroup clinical trials 11; 'radioembolization liver + breast cancer', 37 results, subgroup clinical trials 3; 'embolization liver + neuroendocrine', 283 results, subgroup clinical trials 20; 'chemoembolization liver + neuroendocrine', 202 results, subgroup clinical trials 9; 'radioembolization liver + neuroendocrine', 64 results, subgroup clinical trials 9; 'embolization liver + melanoma', 79 results, subgroup clinical trials 15; 'chemoembolization liver + melanoma', 60 results, subgroup clinical trials 14; 'radioembolization liver + melanoma', 18 results, subgroup clinical trials 3. The term 'chemosaturation liver' was tested without indication since only few publications exist and provided us with five results and only one clinical trial. CONCLUSION: Despite many years of clinical use and documented efficacy on intra-arterial treatments of the liver, there are still only a few prospective multicenter trials with many different protocols. To guarantee the future use of these efficacious therapies, especially in the light of many systemic or surgical therapies in the treatment of non-colorectal liver metastases, further large randomized trials and transparent guidelines need to be established.

Exclusão vascular do fígado em lesões venosas hepáticas complexas

Injuries to the main hepatic veins carry a very high mortality rate, regardless of the technique used for repair. Isolated reports of survivors have, for the most part, been managed by hepatic vascular exclusion (EVE) techniques, usually with an atriocaval shunt. Herein we report a case of a severe intrahepatic major hepatic vein injury successfully managed with EVE.

Uso de balão intra-hepático para controle temporário da hemorragia em lesão da veia cava retro-hepática

Juxtahepatic veins, retrohepatic vena cava or major hepatic veins injuries carry a very high mortality rate regardless the technique used for its repair. Isolated survivor reports have for the most part been managed by vascular isolation techniques, usually with atriocaval shunt. We report one case with a unique management technique in a patient who sustained gunshot wound to the retrohepatic vena cava. Hemorrhage control had been obtained by intrahepatic balloon tamponade after others maneuvers have failed. The balloon was left in situ for two days as damaged control laparotomy principles and planned reoperation has been chosen.

Utilização da jejunostomia para extração endoscópica de Ascaris lumbricoides da via biliar principal em paciente com doença de Caroli

Grumbach-Auvert disease represents a type of Obstructive Disease of the Intrahepatic Biliary Tree. We presents a case report of a patient with hepatic abscess caused by Ascaris which ascended into hepatic parenquima through hepaticojejunostomy, resolved by endoscopic extraction of it after the jejunostomy of permanent access was opened.

Histopathological diagnosis of intra- and extrahepatic neonatal cholestasis

The histopathology of the liver is fundamental for the differential diagnosis between intra- and extrahepatic causes of neonatal cholestasis. However, histopathological findings may overlap and there is disagreement among authors concerning those which could discriminate between intra- and extrahepatic cholestasis. Forty-six liver biopsies (35 wedge biopsies and 11 percutaneous biopsies) and one specimen from a postmortem examination, all from patients hospitalized for neonatal cholestasis in the Pediatrics Service of Hospital de Clínicas de Porto Alegre, were prospectively studied using a specially designed histopathological protocol. At least 4 of 5 different stains were used, and 46 hepatic histopathological variables related to the differential diagnosis of neonatal cholestasis were studied. The findings were scored for severity on a scale from 0 to 4. Sections which showed less than 3 portal spaces were excluded from the study. Sections were examined by a pathologist who was unaware of the final diagnosis of each case. Bile tract permeability was defined by scintigraphy of the bile ducts and operative cholangiography. The F test and discriminant analysis were used as statistical methods for the study of the hepatic histopathological variables. The chi-square method with Yates correction was used to relate the age of the patients on the date of the histopathological study to the discriminatory variables between intra- and extrahepatic cholestasis selected by the discriminant function test. The most valuable hepatic histopathological variables for the discrimination between intra- and extrahepatic cholestasis, in decreasing order of importance, were periportal ductal proliferation, portal ductal proliferation, portal expansion, cholestasis in neoductules, foci of myeloid metaplasia, and portal-portal bridges. The only variable which pointed to the diagnosis of intrahepatic cholestasis was myeloid metaplasia. Due to the small number of patients who were younger than 60 days on the date of the histopathological study (N = 6), no variable discriminated between intra- and extrahepatic cholestasis before the age of 2 months and all of them, except for the portal expansion, were discriminatory after this age. In infants with cholestasis, foci of myeloid metaplasia, whenever present in the liver biopsy, suggested intrahepatic cholestasis. Periportal ductal proliferation, portal ductal proliferation, portal expansion, cholestasis in neoductules, portal cholestasis and portal-portal bridges suggested extrahepatic obstructive cholestasis.