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Biomedical subjects

Paulette Bioulac-Sage

Publications and source records attributed to Paulette Bioulac-Sage.

At least 19 recordsLinked to original sources
PubMed2004

Expression of fibrillin-1 in focal nodular hyperplasia of the liver: a role in microcirculation adaptability.

INTRODUCTION: It has been suggested that the elastic network plays an important role in the tissue response to mechanical stress. The components of the elastic network have been poorly studied in liver diseases. Therefore, in this work, the expression and distribution of fibrillin-1 and elastin were studied in hepatic focal nodular hyperplasia and compared with surrounding liver and hepatocellular adenoma. METHODS: Immunohistochemical studies for fibrillin-1 and elastin were performed on unfixed cryostat sections of focal nodular hyperplasia (22 cases), hepatocellular adenoma (15 cases) and surrounding liver (34 cases). RESULTS: Surrounding normal liver showed only a continuous, thin and regular immunostaining of fibrillin-1 in the space of Disse, whereas elastin was nearly absent. In focal nodular hyperplasia, fibrillin-1 was more strongly expressed in the perisinusoidal space, compared with surrounding liver; in contrast, in adenomas fibrillin-1 immunostaining was irregular and very low in perisinusoidal space, more intense in peliotic areas. CONCLUSIONS: In focal nodular hyperplasia, the increased microfibrillar network containing fibrillin-1 in the space of Disse could reflect an adaptation of the sinusoidal wall to an increased arterial blood flow in sinusoids. In hepatocellular adenoma, the different patterns of fibrillin-1 could be related to the heterogeneity of the arterial vascularization and to the frequent necrotico-hemorrhagic changes. This study comparing the elastic network in two types of lesions with vascularization abnormalities and in the surrounding liver provides interesting new data for understanding the structural role of fibrillin-1 in the space of Disse.

Journal Article↗
PubMed2004

Innervation of the sinusoidal wall: regulation of the sinusoidal diameter.

In the livers of humans, cats, guinea pigs, and tupaia, nerve endings are distributed all over the hepatic lobules. Nerve endings in the intralobular spaces are localized mainly in the Disse spaces and are oriented toward the hepatic stellate cells (HSCs), sinusoidal endothelial cells, and hepatocytes. They are especially closely related to HSCs. Various neurotransmitters such as substance P exist in the nerve endings. In addition, HSCs possess endothelin (ET) and adrenergic receptors and contract in response to the corresponding agonists. In contrast, nitric oxide (NO) inhibits the contraction of HSCs. HSCs thus appear to be involved in the regulation of hepatic sinusoidal microcirculation by contraction and relaxation. In the cirrhotic liver, intralobular innervation is decreased, but ET, ET receptors, and NO are overexpressed in the HSCs. These findings indicate that HSCs in cirrhotic liver may play an important role in the sinusoidal microcirculation through agents such as ET or NO rather than through intralobular innervation.

Animals↗
PubMed2004

Nomenclature of the finer branches of the biliary tree: canals, ductules, and ductular reactions in human livers.

The work of liver stem cell biologists, largely carried out in rodent models, has now started to manifest in human investigations and applications. We can now recognize complex regenerative processes in tissue specimens that had only been suspected for decades, but we also struggle to describe what we see in human tissues in a way that takes into account the findings from the animal investigations, using a language derived from species not, in fact, so much like our own. This international group of liver pathologists and hepatologists, most of whom are actively engaged in both clinical work and scientific research, seeks to arrive at a consensus on nomenclature for normal human livers and human reactive lesions that can facilitate more rapid advancement of our field.

Biliary Tract↗
PubMed2004

Determination of DNA ploidy by fluorescence in situ hybridization (FISH) in hydatidiform moles: evaluation of FISH on isolated nuclei.

In the past 20 years, the diagnosis of hydatidiform moles has become more difficult because of the widespread use of early uterine evacuation. Differentiating hydropic degeneration, partial, and complete moles is important because of their different prognosis. However, clinical diagnosis is less obvious, and the pathologist has to separate the different entities on the basis of very subtle morphologic criteria. In difficult cases, ploidy may be determined by various methods, including fluorescence in situ hybridization (FISH) on routine histological sections from paraffin-embedded specimens. However, FISH analysis is often difficult because of the presence of numerous truncated nuclei. In this context, we have tested the advantages of FISH on isolated nuclei, a well-known variant of the technique that might be more sensitive. We reviewed 24 cases of products of abortion: hydropic degenerations, complete hydatidiform moles, partial moles, and nonmolar triploidies. After histological review, FISH on isolated nuclei proved conclusive in all cases. The results could be easily interpreted thanks to the reduced number of truncated nuclei. The percentage of cells with 2 signals was always >70% in the diploid cases and >60% in the triploid cases. In conclusion, this sensitive technique seems to be a valuable tool for the diagnosis of moles.

Cell Nucleus↗
PubMed2004

Fibrosis is worse in HIV-HCV patients with low-level immunodepression referred for HCV treatment than in HCV-matched patients.

Hepatitis C virus (HCV) infection is frequent in human immunodeficiency virus (HIV)-infected patients. It is known to have an aggressive course in significantly immunosuppressed patients, and cirrhosis C has become one of the main causes of mortality in HIV-HCV coinfected patients since the improvement of antiretroviral therapy. The reasons for this severe fibrotic evolution are unclear. This prospective study compared chronic HCV lesions, liver immunocompetent cells, fibrosis and liver HCV loads in 2 cohorts of naive patients referred for HCV treatment: 33 HIV-HCV coinfected patients with CD4 >250/microL and 33 HCV-infected patients matched for the main risk factors of fibrosis. Fibrosis, particularly perisinusoidal fibrosis, was more marked in the coinfected patients. This occurred in the absence of a significant difference in disease activity. The number of CD3+ cells in the liver was higher in the HIV-HCV patients than in the HCV patients. Conversely, the number of liver CD4+ cells was lower in HIV-HCV patients than in HCV patients. The numbers of CD8+ and CD68+ cells were similar in the 2 groups. Finally, liver HCV load, assessed by immunostaining and reverse-transcription polymerase chain reaction, was similar in the 2 groups. We conclude that in the population of HIV-HCV coinfected patients with low-level immunosuppression referred for HCV treatment, fibrosis is worse than in HCV patients and the proportion of CD4+ lymphocytes among CD3+ cells is markedly decreased in the liver, whereas intrahepatic viral load is similar. Our data confirm the need to treat such patients against HCV, and suggest that HIV infection could favor fibrosis via the modulation of the intrahepatic immune response.

Antigens, CD↗
PubMed2004

Cellular retinol-binding protein-1 expression in normal and fibrotic/cirrhotic human liver: different patterns of expression in hepatic stellate cells and (myo)fibroblast subpopulations.

BACKGROUND/AIMS: Cellular retinol-binding protein-1 (CRBP-1) which is involved in vitamin A metabolism is highly expressed in liver cells, particularly in hepatic stellate cells (HSCs). In this work, the CRBP-1 expression was studied by immunohistochemistry in the different liver cell populations, including HSCs and portal fibroblasts, of normal liver and of fibrotic and cirrhotic liver. METHODS: Normal liver, fibrotic liver in different stages and cirrhotic liver sections were studied. Immunohistochemistry was performed using antibodies against CRBP-1, alpha-smooth muscle actin (SMA), CD 68 and CD 34. RESULTS: In normal liver, quiescent HSCs expressed CRBP-1, while portal fibroblasts did not. In fibrotic or cirrhotic liver, activated HSCs co-expressed CRBP-1 and alpha-SMA; a variable proportion of portal and septal (myo)fibroblasts, more important in cirrhosis, neo-expressed both CRBP-1 and alpha-SMA. Biliary epithelial cells both in normal and pathological situations expressed CRBP-1. Neither Kupffer cells, nor endothelial cells showed CRBP-1 expression. CONCLUSIONS: Our study demonstrates that CRBP-1 is a good marker to identify HSC in normal human liver. Furthermore, in fibrotic or cirrhotic liver, the different patterns of expression for CRBP-1 and alpha-SMA allow the distinction of different subsets of fibroblastic cells involved in fibrogenesis and septa formation.

Actins↗
PubMed2004

Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomas.

BACKGROUND/AIMS: Combined hepatocellular-cholangiocarcinoma (HCC-CC) show dual hepatocellular and biliary epithelial differentiation. To better understand the relations between cholangiocarcinoma (CC), HCC-CC and hepatocellular carcinoma (HCC), we screened for genetic alterations. METHODS: A series of nine CC, 15 HCC-CC and three separated HCC and CC lesions ('collision tumors') were screened for loss of heterozygosity (LOH) using 400 microsatellite markers and for p53 and beta-catenin mutations. A comparison with a previously characterized series of 137 HCC was performed. RESULTS: In six cases of CC and HCC-CC, we identified TP53 gene mutations. A CTNNB1/beta-catenin was identified in two patients presenting collision tumors, but no mutations were found in CC or in HCC-CC. A high level of chromosome instability in both CC and HCC-CC was found. Recurrent specific LOH were identified at 3p and 14q in more than 50% of the CC and the HCC-CC cases, whereas these chromosomal regions were deleted in less than 10% of the HCC cases (P<10(-5)). Minimal common regions of deletion (MCRD) were defined at 3p24-p14 and 14q24-q32, respectively. CONCLUSIONS: These results suggest that combined HCC-CC are genetically closer to CC than HCC and common carcinogenesis pathways may be altered in HCC-CC and CC.

Aged↗
PubMed2003

FNH-like nodules: Possible precursor lesions in patients with focal nodular hyperplasia (FNH).

BACKGROUND: The typical lesion of focal nodular hyperplasia (FNH) is a benign tumor-like mass characterized by hepatocytic nodules separated by fibrous bands. The solitary central artery with high flow and the absent portal vein give the lesions their characteristic radiological appearance. The great majority of cases seen in daily practice conform to the above description. Additional small nodules (from 1-2 up to 15-20 mm in diameter) detected by imaging techniques or on macroscopic examination may be difficult to identify as representing FNH if they lack the key features of FNH as defined in larger lesions. The aim of this study was to characterize these small nodules, and to compare their characteristics with those of typical lesions of FNH present in the same specimens. RESULTS: Eight patients underwent hepatic resections for the removal of a mass lesion ("nodule") diagnosed as: FNH (1 patient); nodules of unknown nature (5 patients); or nodules thought to be adenoma or hepatocellular carcinoma (2 patients). Six nodules out of 9 discovered by imaging techniques met histopathological criteria for the diagnosis of typical FNH, at least in parts of the nodule; 2 nodules corresponded to a minor form of FNH ("subtle FNH") and one nodule to a steatotic area. Although FNH was thought to be found in a normal or nearly normal liver, this study revealed that, in addition, there were various types of small FNH-like nodules and vascular abnormalities in the liver with typical FNH nodule. The various types of small FNH-like nodules (n = 8, diameter 2 to 20 mm) consisted of the association to various degrees of numerous and/or enlarged arteries in portal tracts or in septa, with hyperplastic foci, slight ductular reaction, and regions of sinusoidal dilatation, accompanied by thin fibrous bands. Vascular abnormalities consisted of unpaired arteries, portal tracts with arteries larger than the associated bile duct, and regions of sinusoidal dilatation. CONCLUSIONS: Although these small nodules can be considered as insufficient type or abortive forms of FNH, or adenoma, they can be precursors of the large mass lesions in which FNH was recognized and defined.

Journal Article↗
PubMed2003

Comparison of 2 regimens that include interferon-alpha-2a plus ribavirin for treatment of chronic hepatitis C in human immunodeficiency virus-coinfected patients.

An open-label, randomized trial was conducted to compare the efficacy and safety of 2 regimens of interferon-alpha-2a (IFN-alpha-2a) plus ribavirin for management of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-coinfected patients. Sixty-eight patients were randomized to receive IFN-alpha-2a at a dosage of either (1) 6 MU given 3 times per week for 24 weeks, followed by 3 MU 3 times per week for an additional 24 weeks (group A; 31 patients); or (2) 9 MU per day for 2 weeks, followed by 3 MU per day for 22 weeks, followed by 3 MU 3 times per week for 24 weeks (group B; 37 patients). Ribavirin was added at week 16 of therapy if HCV RNA remained detectable at week 12. Sustained virological response was achieved in 10 patients (15%; 6 in group A and 4 in group B). HCV genotypes 2 or 3 and a decrease in the HCV load of >or=3 log(10) copies/mL between inclusion and week 4 were associated with virological response. In conclusion, the combination of conventional IFN-alpha-2a and ribavirin has poor virological efficacy in HCV-HIV-coinfected patients.

Adolescent↗
PubMed2003

Association of adenoma and focal nodular hyperplasia: experience of a single French academic center.

BACKGROUND: We report our experience of the simultaneous occurrence of adenoma and focal nodular hyperplasia (FNH). Liver cell adenoma together with FNH was found in five out of 30 cases of "multiple benign hepatocytic nodules" collected in our files of the Department of Pathology of the University Hospital of Bordeaux, during the last 12 years. All five cases were women on oral contraceptives. In all cases, the reason for surgery was the discovery, by imaging techniques, of an adenoma (4 cases) or of an unidentified benign tumor, possibly an adenoma. RESULTS: Four cases of FNH were discovered by imaging techniques, prior to surgery. Additional small nodules were diagnosed either during surgery or during the slicing of the specimen in 3 cases. Adenoma and the FNH cases identified by imaging techniques were confirmed as such by light microscopy. Some small nodules could not be categorized with certainty because they contained biliary structures without ductular reaction. In one case, the non-nodular liver was abnormal around the area in which there were multiple nodules: there was approximation of portal tracts with portal and hepatic venous thromboses, and portal tract remnants with arteries surrounded with a rim of fibrosis. In two cases, some large hepatic veins had thickened walls. CONCLUSIONS: The association of FNH and adenoma could be coincidental or secondary to shared causal mechanisms: a) systemic and local angiogenic abnormalities induced by oral contraceptives; b) tumor-induced growth factors; c) thrombosis and local arterio-venous shunting. A better recognition of the association of adenoma and FNH, particularly in the context of multiple nodules, could be useful in clinical practice.

Journal Article↗
PubMed2003

Multiple telangiectatic focal nodular hyperplasia: vascular abnormalities.

The aim of this study was to look for vascular abnormalities in the liver of patients with multiple telangiectatic focal nodular hyperplasia. Four patients, all women on oral contraceptives, were included in this study. In none of the cases was the diagnosis of multiple telangiectatic focal nodular hyperplasia made preoperatively. In the nodules, the pathological aspect was quite characteristic with dilated sinusoidal areas surrounding compact areas. Compact areas comprised portal tract-like structures with vessels, mainly thickened arteries, usually amidst an inflammatory reaction. A ductular reaction of varied intensity was present in three cases. The non-nodular liver was grossly normal. However, in rare areas, there were obvious or minor vascular abnormalities looking like minimal abnormalities seen inside telangiectatic nodules. These results seem to support the concept that multiple telangiectatic focal nodular hyperplasia is a non-specific reaction to focal ischemia induced by various mechanisms such as hepatic vein thrombosis induced, perhaps, by oral contraceptives.

Adult↗
PubMed2003

Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.

BACKGROUND & AIMS: Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/HNF-1alpha) are associated with maturity-onset diabetes of the young type 3 (MODY3), and somatic biallelic inactivations of the gene are found in hepatocellular adenomas and liver adenomatosis. This study investigated cosegregation of HNF-1alpha germline mutations with diabetes and liver adenomatosis in 2 families. METHODS: Two unrelated patients with liver adenomatosis and harboring HNF-1alpha germline and somatic mutations were studied. Subsequently, we screened 9 relatives in the 2 independent families for diabetes, hepatocellular adenomas, and HNF-1alpha germline mutations. RESULTS: In family A, a father and his son presented with an intraperitoneal hemorrhagic rupture of a liver adenomatosis without diabetes. A heterozygous R229X germline mutation was identified in HNF-1alpha in the father and his son and also in his second 27-year-old son without hepatocellular adenomas. In family B, a diagnosis of liver adenomatosis was made fortuitously in a 14-year-old girl. A heterozygous G55fsX57 germline mutation in HNF-1alpha was identified in this patient, her diabetic father, and her 2 sisters. Systematic exploration showed liver adenomatosis in the 2 sisters. Somatic inactivation of the second HNF-1alpha allele was found in liver tumors in both families. CONCLUSIONS: This study describes familial liver adenomatosis and shows the association with germline HNF-1alpha mutations in adults and children. It also highlights the importance of screening for hepatocellular adenomas, diabetes, and HNF-1alpha germline mutations in relatives of patients with liver adenomatosis. Finally, prevalence of liver adenomatosis remains to be evaluated in MODY3 subjects.

Adenoma↗
PubMed2003

The identification of small nodules in liver adenomatosis.

BACKGROUND/AIMS: Liver adenomatosis is characterized by the presence of multiple adenomas of various sizes in the liver. The aim of this study was to characterize the morphology of small nodules which can be difficult to identify. METHODS: Seven patients included in this study underwent surgery for the removal of one or several nodules. All, but one, were females. Three out of seven presented with acute bleeding. Five had six or more nodules at presentation, and two only one, who developed nodules later on during follow-up. RESULTS: All of the large nodules that were >2 cm, except one, were typical adenomas with or without hemorrhagic areas. Smaller nodules (1-2 cm), some of which discovered on the resected specimen were either typical adenomas or non-typical nodules. These non-typical nodules were characterized by a polylobulated aspect with steatotic zones, and in between, bands of non-steatotic hepatocytes with portal tracts-like structures containing occasional cytokeratin 7 and less often cytokeratin 19 positive biliary cells. Numerous steatotic foci were also seen in four cases. They were isolated or grouped forming microadenomas or non-typical micronodules (<1 cm) containing biliary elements. Our findings lead to the following hypothesis: adenomatosis is characterized by the simultaneous occurrence of multiple adenomas; if several adenomatous foci expand at the same time in the same area, they will form one polylobulated nodule containing non-adenomatous tissue with portal tracts in between areas of adenomatous tissue (non-typical micronodule). Such a small micronodule may in turn expand and join another micronodule to form a bigger one by the same process (non-typical nodule). As nodules grow, their non-adenomatous components including hepatocytic plates and portal tracts constituents will progressively disappear to end up with the classical aspect of an adenoma. CONCLUSIONS: This hypothesis supports the concept that non-typical nodules/micronodules are adenomas precursors. However, they can be difficult to classify since they resemble focal nodular hyperplasia precursor.

Adenoma↗