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Biomedical subjects

S Hillaire

Publications and source records attributed to S Hillaire.

At least 19 recordsLinked to original sources
PubMed2002

Idiopathic non-cirrhotic intrahepatic portal hypertension in the West: a re-evaluation in 28 patients.

BACKGROUND: Non-cirrhotic portal hypertension of unknown cause is a poorly understood condition attributed to obstructive portal venopathy. AIM: To reassess the manifestations, course, and causes, with special attention to thrombosis. METHODS: Analysis of a cohort of 28 patients. RESULTS: Gastrointestinal bleeding occurred in 11 patients. Liver failure developed at the time of concurrent disease in eight patients, including all four patients who died. Portal vein thrombosis developed in 13 patients. A prothrombotic disorder was found in 12 of 23 fully investigated patients. Hepatoportal sclerosis was observed in 11 patients (with associated perisinusoidal fibrosis and/or nodular regenerative hyperplasia in six); periportal fibrosis, perisinusoidal fibrosis, nodular regenerative hyperplasia, or a combination thereof were observed in other patients. A morphometric evaluation showed an increased number of portal vessels in patients with hepatoportal sclerosis. There was no relation between pathological results and haemodynamic findings or prothrombotic disorders. CONCLUSIONS: Outcome was related to associated conditions. Overlap in pathological, haemodynamic, and causal features suggests a single entity, with prothrombotic disorders as major causal factors, and injury to sinusoids as well as to portal venules as the primary mechanism. Activated coagulation could mediate vascular injury in the absence of thrombosis. Anticoagulation should be considered.

Adult↗
PubMed2001

Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy.

BACKGROUND & AIMS: The outcome of portal vein thrombosis in relation to associated prothrombotic states has not been evaluated. We assessed current outcome and predictors of bleeding and thrombotic events in a cohort of 136 adults with nonmalignant, noncirrhotic portal vein thrombosis, of whom 84 received anticoagulant therapy. METHODS: Multivariate Cox model analysis for event-free survival and analysis taking into account multiple events were used. RESULTS: Median follow-up was 46 months. The incidence rate of gastrointestinal bleeding was 12.5 (95% confidence interval [CI], 10-15) per 100 patient-years. Large varices were an independent predictor for bleeding. Anticoagulant therapy did not increase the risk or the severity of bleeding. The incidence rate of thrombotic events was 5.5 (95% CI, 3.8-7.2) per 100 patient-years. Underlying prothrombotic state and absence of anticoagulant therapy were independent predictors for thrombosis. In patients with underlying prothrombotic state, the incidence rates of splanchnic venous infarction were 0.82 and 5.2 per 100 patient-years in periods with and without anticoagulant therapy, respectively (P = 0.01). Two nonanticoagulated patients died of bleeding and thrombosis, respectively. CONCLUSIONS: In patients with portal vein thrombosis, the risk of thrombosis is currently as clinically significant as the risk of bleeding. The benefit-risk ratio favors anticoagulant therapy.

Adolescent↗
PubMed2001

Hemodynamic, metabolic and hormonal responses to oral glibenclamide in patients with cirrhosis receiving glucose.

BACKGROUND: In patients with cirrhosis, glucose may induce splanchnic and renal vasodilation. Since the antidiabetic sulfonylurea glibenclamide is known to induce splanchnic and renal vasoconstriction in portal hypertensive animals, this drug may inhibit glucose-induced hemodynamic responses in patients with cirrhosis. The aim of the present study was to investigate, in patients with cirrhosis, the short-term effects of glibenclamide on hemodynamic and humoral responses to glucose. METHODS: Patients were randomly assigned to receive either glibenclamide (5-mg tablet) or a placebo. All patients received an infusion of 10% glucose (62.5 ml/h for 12 h) that was started at the same time as glibenclamide or placebo administration. Studies were performed prior to and 90 min after glibenclamide or placebo. RESULTS: Glibenclamide (i.e. glibenclamide plus glucose) significantly increased plasma insulin concentrations and glycemia while placebo (i.e. glucose alone) significantly increased glycemia but did not change plasma insulin levels. Glibenclamide did not significantly change the hepatic venous pressure gradient while this value was significantly increased following glucose alone. Glibenclamide did not significantly change renal blood flow and glomerular filtration rate while glucose alone significantly increased renal blood flow without affecting the glomerular filtration rate. Glibenclamide significantly decreased cardiac index while glucose alone did not change this value. CONCLUSIONS: In patients with cirrhosis receiving glucose, glibenclamide blunted glucose-induced splanchnic and renal vasodilation. In addition, glibenclamide per se induced a decrease in cardiac index. These findings should be taken into account when glibenclamide is administered to patients with cirrhosis and type 2 diabetes.

Administration, Oral↗
PubMed2001

Hepatic manifestations of hemophagocytic syndrome: a study of 30 cases.

OBJECTIVE: Hemophagocytic syndrome has been defined as the combination of a proliferation of cytologically benign, actively phagocytic macrophages in bone marrow, spleen, or lymph nodes in association with fever, cytopenia, splenomegaly, and hypertriglyceridemia. Hepatic dysfunction is often present but the nature of the hepatic lesions and related manifestations have not been fully characterized. The aim of this study was to ascertain the features of hepatic involvement in hemophagocytic syndrome. METHODS: Thirty patients with hemophagocytic syndrome were retrospectively studied. Inclusion criteria included: 1) bone marrow with hemophagocytic histiocytosis, 2) clinical or biological signs of hepatic involvement, and 3) available liver specimen. RESULTS: The association of fever, jaundice, and hepatomegaly or splenomegaly was present in 50% of the patients. Median value for serum alanine transaminase activity was five times the upper limit of normal values (range, 0.3-125), for serum alkaline phosphatase activity 2.7 upper limit of normal values (range, 0.2-47.7), for total bilirubin 136 micromol/L (range, 4-681 micromol/L), and for factor V 70% (range, 19-145%). Sinusoidal dilatation with hemophagocytic histiocytosis were found in the biopsy specimen in all patients. An underlying condition potentially responsible for altered immune function (lymphoma, leukemia, liver transplantation) was identified in 29 patients. Liver biopsy was diagnostic for the underlying condition in 15 patients (including eight cases with nonspecific bone marrow biopsy findings). High serum bilirubin, elevated serum alkaline phosphatase activity, low factor V level, and lack of treatment for the underlying disease were associated with a poor prognosis. CONCLUSIONS: Hemophagocytic syndrome should be suspected in immunodeficient patients with fever, jaundice, and hepatosplenomegaly. Hepatic lesions are characterized by nonspecific sinusoidal dilatation with hemophagocytic histiocytosis and in 50% of the patients by alterations specific to the underlying condition. Liver biopsy is a useful diagnostic procedure in patients with this clinical presentation.

Adolescent↗
PubMed2001

Factor V Leiden related Budd-Chiari syndrome.

BACKGROUND: The role of factor V Leiden as a cause of Budd-Chiari syndrome has only recently been described. AIMS: To assess the specific features of factor V Leiden related Budd-Chiari syndrome. PATIENTS: Sixty three consecutive patients with hepatic vein or terminal inferior vena cava thrombosis. METHODS: Standardised chart review. RESULTS: Factor V Leiden was found in 20 patients (31% (95% CI 20-43)). In the subgroup of patients with, compared with the subgroup without, factor V Leiden, a combination of prothrombotic states was more common (70% (95% CI 50-90) v 14% (95% CI 3-24)); inferior vena cava thrombosis was more frequent (40% (95% CI 19-61) v 7% (95% CI 0-14)); and distribution of initial alanine aminotransferase values was bimodal (almost normal or extremely increased) versus unimodal (p=0.003). Factor V Leiden accounted for four of five cases of massive ischaemic necrosis (transaminases >50-fold the upper limit of normal values) (p=0.014), and also for all three cases developing during pregnancy. Patients with and without factor V Leiden did not differ with regard to mortality, portosytemic shunting, or listing for liver transplantation. Hepatocellular carcinoma developed in two patients; both had factor V Leiden and indolent obstruction of the inferior vena cava. CONCLUSIONS: In patients with Budd-Chiari syndrome, factor V Leiden (a) is common; (b) precipitates thrombosis mostly when combined with another risk factor; (c) is associated with one of two contrasting clinical pictures: indolent thrombosis-particularly of the inferior vena cava-or massive ischaemic necrosis; and (d) is a major cofactor of Budd-Chiari syndrome developing during pregnancy.

Adult↗
PubMed2000

Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors.

According to a recent hypothesis, venous thrombosis results from the concurrence of several factors. This hypothesis was assessed in patients with portal or hepatic venous thrombosis by simultaneously investigating most of the currently identified prothrombotic disorders, local precipitating factors, and other risk factors such as oral contraceptive use. Patients with a tumorous obstruction and patients with cirrhosis with portal vein thrombosis were excluded. The prothrombotic disorders that were investigated included classical and occult myeloproliferative disorders; antiphospholipid syndrome; protein C; protein S and antithrombin deficiency; factor V Leiden; factor II; and methylene-tetrahydrofolate-reductase gene mutations. We found 1 or several prothrombotic disorders and a local precipitating factor in 26 and 10 of the 36 patients with portal vein thrombosis, respectively; and in 28 and none of the 32 patients with hepatic vein thrombosis, respectively. We found a combination of prothrombotic disorders in 5 and 9 patients with portal and hepatic vein thrombosis, respectively, whereas such a combination is expected in less than 1% of asymptomatic subjects. Of the 10 patients with a local precipitating factor, 8 had a prothrombotic disorder. Of the 13 patients who use oral contraceptives, 10 had a prothrombotic disorder. We conclude that portal or hepatic venous thrombosis should be regarded as an index for 1 or several prothrombotic disorders, whether or not local precipitating factors or oral contraceptive use are found. Concurrence of prothrombotic disorders is more common than expected. Extensive investigation of prothrombotic disorders and anticoagulation should be considered in patients with portal or hepatic venous thrombosis.

Budd-Chiari Syndrome↗
PubMed2000

[Mechanisms of cytokine-induced cholestasis].

INTRODUCTION: Cholestasis is a clinical, biological and histological syndrome that is secondary to the decrease in or disruption of biliary secretion. Clinical or biological cholestasis is common in the course of either infections (parainfectious cholestasis), various cancers (paraneoplastic cholestasis), granulomatosis or in the syndrome accompanying macrophage activation. Cytokine (IL-1, IL-6 and tumor necrosis factor-alpha [TNF-alpha]) synthesis by Kupffer's cells (intrahepatic macrophages) in response to the release of endotoxins occurs in the course of the various clinical syndromes, particularly in the course of sepsis. EXEGESIS: Recently, it has been demonstrated that proinflammatory cytokines and endotoxins lead to cholestasis through modulation of the activity of bile acid transporters and other organic anions. CONCLUSION: Cholestasis observed in various clinical syndromes in response to either proinflammatory cytokines or endotoxins might be related to a decrease in the flow which is secondary to a decrease in the activity of organic anion transporters.

Bile Acids and Salts↗
PubMed2000

Recent portal or mesenteric venous thrombosis: increased recognition and frequent recanalization on anticoagulant therapy.

Characteristics and outcomes of recent portal or mesenteric venous thrombosis are ill-known. We intended to compare these features with those of patients with portal cavernoma, and also to assess the incidence of recanalization of recent thrombosis on anticoagulation therapy. All patients seen between 1983 and 1999 were enrolled into this retrospective study if recent portal or mesenteric venous thrombosis or portal cavernoma had been documented, and if cancer of the liver, pancreas, or bile duct, intrahepatic block including cirrhosis, and obstruction of the hepatic veins had been ruled out. The proportion of recent thrombosis was 7% in patients seen before 1990 and 56% after 1994 (P <.05). Patients with recent thrombosis (n = 33) or cavernoma (n = 108) did not differ with regard to age, sex ratio, or prevalence of prothrombotic states and of previous thrombotic events. In patients with recent thrombosis, septic pylephlebitis was more common and the incidence of gastrointestinal bleeding was lower (2.4 vs. 12.7/100 patient-years). Recanalization occurred in 25 of 27 patients given anticoagulation and 0 of 2 patients not given anticoagulation. The probability of recanalization was related to the extent of thrombosis (P =.003). In conclusion, mesenteric or portal venous thrombosis is increasingly recognized at an early stage. The features differentiating recent thrombosis and cavernoma are related to silent onset precluding early recognition and therapy in the latter. Frequent association with prothrombotic states and frequent recanalization on anticoagulation support the recommendation of early anticoagulation therapy in all patients with recent portal vein thrombosis.

Adult↗
PubMed1999

[Cirrhosis].

Cirrhosis, a condition whose diagnosis is dependent on histology, is characterized by a combination of two main lesions, namely fibrosis and regeneration nodules. Alcohol abuse and viral infections are the two most common causes of cirrhosis. Symptoms and laboratory test abnormalities appear when hepatic failure and portal hypertension occur as a result of the cirrhosis. Ascites, gastrointestinal bleeding, encephalopathy, and bacterial infections are the main clinical manifestations. Hepatocellular carcinoma is a common and dreaded complication of cirrhosis. Serum albumin, serum bilirubin, and the prothrombin time are the most useful laboratory parameters. In combination with clinical criteria they allow determination of the Child-Pugh stage, which is largely used to evaluate the severity of cirrhosis, and evaluation of the prognosis. Recently, the early detection of cirrhosis has been shown to benefit from assays of serum markers for fibrosis, most notably hyaluronate. Quantitative tests evaluating the functional liver mass are helpful for monitoring cirrhosis and for selecting patients for liver transplantation, which is the only available treatment for end-stage cirrhosis.

Alcoholism↗
PubMed1997

Circulating albumin messenger RNA in hepatocellular carcinoma: results of a multicenter prospective study.

The presence of circulating tumor cells might be an indicator of hematogenous spread of tumor cells leading to extrahepatic metastasis. Messenger RNA (mRNA) expression of human albumin, as a liver specific cell marker, has been proposed for this purpose in hepatocellular carcinoma. We conducted a multicenter prospective study in 101 patients with biopsy-proven hepatocellular carcinoma followed-up every 3 months for 1 year or until death. At entry into the study, albumin mRNA was detected in the blood by reverse transcription-polymerase chain reaction (RT-PCR). At entry into the study, 45% of the patients had a positive albumin mRNA test, 53% a single tumor, 16% a portal or venous hepatic thrombosis, and 16% had proven metastasis. After 1 year, there was no significant difference in survival of patients with positive or negative albumin mRNA at entry (P = .16, log-rank test). When patients with metastasis at entry were excluded, again survival did not differ between the two groups (P = .20). Independent prognostic factors of survival were radical therapeutic procedures, metastasis, number of tumors, Child-Pugh score, and thrombosis, but not the albumin mRNA test. Taking the presence of metastasis as a reference, the specificity of the test was 56%, its sensitivity 50%, and its negative predictive value 85%. The present study shows that circulating albumin mRNA detected by means of RT-PCR fails to provide significant information in the diagnosis and prognosis of hepatocellular carcinoma. Further studies are needed to determine whether the use of specific tumor markers could have clinical relevance in this setting.

Adult↗
PubMed1997

Noncirrhotic portal hypertension.

This article reviews the different conditions leading to noncirrhotic intrahepatic portal hypertension, describes the related vascular lesions, and provides a review of the clinical characteristics, diagnosis, and treatment options available. Diseases associated with noncirrhotic portal hypertension are also specifically discussed.

Female↗
PubMed1995

Effects of ursodeoxycholic acid and chenodeoxycholic acid on human hepatocytes in primary culture.

Hepatic bile acid concentrations are elevated in chronic cholestasis because of reduced canalicular excretion and active ileal absorption of the fraction eliminated in the gut. Ursodeoxycholic acid (UDCA) reduces the intestinal absorption of endogenous bile acids, thereby diminishing the concentrations to which liver cells are exposed. In the isolated perfused liver (in which vectorial bile acid transport is maintained), UDCA reduces the cytotoxic and cholestatic effects of endogenous bile acids. As a result, it has been suggested that UDCA or one of its conjugates could have a direct protective effect on hepatocyte structure and function. We therefore studied the effects of chenodeoxycholic acid (CDCA) and tauroursodeoxycholic acid (TUDCA) alone and in combination on the viability and certain functions of human hepatocytes in primary culture. TUDCA did not affect intracellular concentrations of CDCA when added concomitantly. In other experiments, CDCA (100 to 500 mumol/L) induced concentration-dependent increases in lactate dehydrogenase (LDH) leakage and decreases in cellular protein synthesis and albumin secretion. Neither TUDCA nor UDCA had similar effects at the same concentrations, nor did they have a protective effect when added concomitantly with CDCA at equimolar or twice-equimolar concentrations. These results suggest that UDCA has no direct cytoprotective effect when the bile acid concentrations to which human hepatocytes are exposed are unchanged. They also suggest that the hepatoprotective effect of UDCA in cholestatic human liver diseases and in the isolated perfused liver loaded with hydrophobic bile acids occurs through its effect on intestinal and hepatocyte transport systems.

Bile Acids and Salts↗
PubMed1994

Effects of bile acids and cholestasis on major histocompatibility complex class I in human and rat hepatocytes.

BACKGROUND/AIMS: Major histocompatibility complex (MHC) class I molecules, which are normally poorly expressed on the surface of hepatocytes, are overexpressed during cholestasis. The mechanisms responsible for this overexpression were examined. METHODS: The expression of class I molecules, assessed by flow cytofluorimetry, and the class I messenger RNA (mRNA) transcripts, assessed by Northern blot analysis, were measured on normal human hepatocytes in primary culture. RESULTS: Chenodeoxycholic acid induced an overexpression of MHC class I molecules, whereas ursodeoxycholic acid did not. The level of class I mRNA closely reflected that of the membrane protein. Moreover, cholestasis, induced in the rat by ligation-section of the common bile duct, increased the MHC class I mRNA level. Actinomycin D inhibited bile acid-induced class I transcription of rat hepatocytes in primary culture, whereas cycloheximide did not. Finally, class I mRNA expression was induced in hepatocytes by phorbol myristate acetate and by forskolin. This hyperexpression, as well as that observed with chenodeoxycholic acid, was suppressed by an inhibitor of protein kinase C and protein kinase A. CONCLUSIONS: Taken together, these results suggest that chenodeoxycholic acid, as interferon, activates protein kinase C and protein kinase A, resulting in the induction of MHC class I expression.

Adult↗
PubMed1994

Albumin messenger RNA as a marker of circulating hepatocytes in hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most frequent malignancies. Liver transplantation is theoretically the treatment of choice because it eliminates both the hepatocellular carcinoma and the cirrhosis. High frequency of relapse observed after liver transplantation may be explained by the existence of undetectable metastasis before transplantation. The aim of this study was to determine whether albumin messenger RNA (mRNA), a specifically hepatocyte-expressed gene, could be a marker of metastasis in hepatocellular carcinoma. METHODS: Albumin mRNA from circulating malignant hepatocytes was detected in the blood by reverse transcription followed by enzymatic amplification. RESULTS: Albumin mRNA was found in the blood of 3 patients with histologically proven metastatic hepatocellular carcinoma and in 9 of 21 patients with hepatocellular carcinoma and undetectable metastases, giving a percentage rate of 43, similar to the relapse rate following liver transplantation for hepatocellular carcinoma. None of the 8 patients with secondary liver cancer had detectable albumin mRNA. CONCLUSIONS: These results suggest that patients with hepatocellular carcinoma and no detectable albumin mRNA in the blood may be a subgroup with a low risk of relapse following liver transplantation.

Base Sequence↗
PubMed1993

Peritoneovenous shunting of intractable ascites in patients with cirrhosis: improving results and predictive factors of failure.

BACKGROUND: The clinical results of peritoneovenous shunting have not been entirely satisfactory in spite of dramatic improvement of renal function and decrease of ascites. The purpose of this study is to determine whether certain modifications improved our results. METHODS: A modified LeVeen shunt was electively inserted in 56 patients who had cirrhosis with intractable ascites. In 24 patients (42.9%) the Child-Pugh's score was less than 9, and in 32 patients the score was 9 or above. Fourteen patients (25%) had previous variceal bleeding, and 15 patients (26.8%) had previous spontaneous bacterial peritonitis (SBP). LeVeen shunt was modified by the addition of a titanium venous catheter tip. Prophylactic antibiotic therapy was administered to all patients. RESULTS: No operative deaths occurred, and one patient had severe postshunt coagulopathy. Five patients (8.9%) experienced recurrent ascites resulting from blockage from the shunt. The cumulative rate of shunt blockage was 5.6% at 1 year and 12% at 2 years. Seventeen patients (30.3%) have recently had variceal bleeding. The cumulative risk of variceal bleeding was significantly higher in patients with a previous hemorrhage than in those patients without (p < 0.05). Eight patients (14.3%) had SBP after operation. The cumulative risk of SBP was higher in patients with a history of SBP than in those patients without, although the difference was not significant. Fifty-five percent of late deaths were related to variceal bleeding or to SBP. Overall cumulative 1- and 2-year survival rates were 67.2% and 55.2%, respectively. It was 82% and 71% in patients without previous variceal bleeding or SBP. CONCLUSIONS: These data suggest that peritoneovenous shunting might be beneficial only in selected patients. Previous variceal bleeding and/or SBP indicate liver transplantation in suitable patients.

Adult↗
PubMed1990

Comparison of rat liver preservation with Eurocollins and a modified University of Wisconsin solution: transplantation and isolation of hepatocytes for culture.

The efficiency of Eurocollins or modified University of Wisconsin (UW) solution (MUW) in preserving rat livers was compared. After cold storage with one of the solutions, the livers were transplanted or perfused by collagenase for isolation of hepatocytes. Five of the 6 rats receiving a graft preserved with MUW versus none of the 6 rat receiving a graft preserved with Eurocollins solution survived 24 h or more. A significantly greater number of hepatocytes were isolated from livers preserved with MUW than from livers preserved with Eurocollins solution. This suggests a better reperfusion of MUW-preserved livers by collagenase resulting from less endothelial injury. LDH release by cultured hepatocytes, ketone body production and stimulation by glucagon were not significantly different between the two groups. These results confirm the superiority of MUW solution over Eurocollins in preserving liver grafts. They suggest that the advantage of MUW solution results from better protection of vascular endothelium rather than of hepatocytes.

Adenosine↗