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Biomedical subjects

D Alagille

Publications and source records attributed to D Alagille.

At least 37 records · Page 2Linked to original sources
PubMed1989

High hepatic gamma-glutamyltransferase (gamma-GT) activity with normal serum gamma-GT in children with progressive idiopathic cholestasis.

gamma-Glutamyl transferase (gamma-GT) was assayed in the serum and liver biopsies of children affected with either progressive idiopathic cholestasis (PIC, Byler's disease), or other types of cholestatic (biliary atresia, cholestasis of various origins) and non-cholestatic diseases. The mean liver gamma-GT activity was increased significantly only in PIC and biliary atresia. In contrast, the serum gamma-GT activity, raised in children with evident damage to the main bile ducts or to the interlobular bile ducts, was normal in children with PIC. Although the mechanism for such a discrepancy between high liver and normal serum gamma-GT activities in PIC is still speculative, this peculiarity could prove to be of use in leading to a better understanding of the disease.

Biliary Atresia↗
PubMed1989

Clinical and immunological heterogeneity of anti-liver-kidney microsome antibody-positive autoimmune hepatitis in children.

A group of children with autoimmune hepatitis is characterized by the presence in their sera of anti-liver-kidney microsome antibody (LKMA) as defined by immunofluorescence. Immunoblot analysis of the sera of 21 such children using rat-liver microsome total proteins as antigen allowed separation into three groups--group 1, whose sera recognized a 50 kDa protein; group 2, whose sera recognized a 66 kDa protein; and group 3, whose sera recognized both proteins. Patients with the anti-66-kDa reactivity more often displayed an acute onset of the disease, less signs of portal hypertension, better sensitivity to immunosuppressive therapy, and less tendency to relapse. They also displayed a lower titer of anti-rat-liver microsome antibody in enzyme-linked immunosorbent assay (ELISA) and a serum reactivity with a rat-liver cytosolic protein. These results (a) indicate that the LKMA-positive autoimmune hepatitis of children is heterogeneous from both clinical and immunological view points, (b) suggest that children with anti-66-kDa reactivity could have a less severe disease than children with the 50-kDa reactivity, and (c) indicate that immunoblot analysis should be added to ELISA and immunofluorescence studies to achieve better characterization of these patients.

Adolescent↗
PubMed1988

Budd-Chiari syndrome in children: report of 22 cases.

Clinical, radiologic, and histologic features in 22 children with Budd-Chiari syndrome are reported. Three children had acute refractory ascites; all the others had hepatomegaly, which was detected either fortuitously or because of abdominal pain or distention. Results of liver function tests were normal or only moderately abnormal. In most cases a combination of ultrasonography and needle liver biopsy pointed to the diagnosis of Budd-Chiari syndrome, which was confirmed by angiography. Eighteen children underwent surgery involving various techniques, depending on the degree of patency of the inferior vena cava. Five children died postoperatively. Histologic studies of the liver, carried out in 12 of the surviving children, showed disappearance or regression of centrilobular hemorrhagic infiltration. Half of the surviving surgical patients are now free of complications after a follow-up of 7 months to 7 years; the others have either secondary thrombosis of the inferior vena cava or stenosis of the shunt or have experienced late pulmonary complications. Our results suggest that (1) Budd-Chiari syndrome must be considered a possible diagnosis in children with firm hepatomegaly and normal or near normal liver function, (2) surgery provides good results in many instances, and (3) the possibility of late complications requires careful follow-up.

Budd-Chiari Syndrome↗
PubMed1988

Plasma fatty acid composition and lipid peroxide levels in children with paucity of interlobular bile ducts.

The total and free fatty acid composition of plasma and lipid peroxide concentrations was studied in 32 cholestatic children with syndromatic paucity of interlobular bile ducts (Alagille's syndrome). The mean lipid peroxide value in these patients was 8.80 +/- 3.70 nmol/ml, nearly 4 times higher than the mean control value. Compared to the control group, the patients exhibited significant variations in total fatty acids, and in particular a relative decrease in linoleic acid (from 29.5 +/- 6.1% in the controls to 19.1 +/- 8.03% in the patients) compensated by an increase in saturated and monounsaturated fatty acids. The plasma lipid peroxide levels were inversely correlated with the unsaturated/saturated fatty acids ratio in total fatty acids, and with the vitamin E status (vitamin E/total lipids). Most of the total and free fatty acid variations observed were largest in patients with severe jaundice. Dietary fat malabsorption and the increase in lipid peroxidation partly explain these results. Furthermore, in free fatty acids, we observed a marked increase in arachidonic acid (from 1.43 +/- 0.85% in the controls to 4.27 +/- 2.24% in the patients), suggesting abnormal eicosanoid synthesis.

Adolescent↗
PubMed1988

[Budd-Chiari syndrome with thrombosis of the inferior vena cava. Treatment by mesenterico-innominate shunt].

We report two cases of patients, 12 and 28 years old, suffering from a Budd-Chiari syndrome with a thrombosed inferior vena cava, who were treated by a shunt interposed between the superior mesenteric vein and the left innominate vein. The aim of this shunt was to avoid pericardiotomy in these patients with peroperative ascites, in order to reduce the risk of pericarditis after surgery. A reinforced polytetrafluoroethylene prosthesis (Gore-Tex) was used, associated with an interposition jugular vein graft in the 12-year old child, alone in the other case. The left innominate vein was isolated through a midline sternotomy, and the prosthesis was placed in a retrosternal position. Operation and postoperative course were uneventful. All signs of ascites disappeared. The patients were free of symptoms, 8 and 4 months after surgery respectively. Shunt patency was documented by angiography and magnetic nuclear resonance.

Adult↗
PubMed1987

Glomerular mesangiolipidosis in Alagille syndrome (arteriohepatic dysplasia).

Alagille syndrome is characterized by the association of chronic cholestasis with a paucity of interlobular bile ducts and a distinctive facies together with cardiovascular, skeletal and eye abnormalities. We examined the kidneys of 26 patients with this syndrome; 22 were under 3 years of age and 4 were 4, 6, 12 and 17 years old, respectively. Eighteen showed glomerular lesions of variable severity characterized by a mesangiolipidosis. In the 8 lesser affected patients light microscopy (LM) disclosed a fibrillar appearance of the mesangium, and electron microscopy (EM) showed lipid vacuoles widespread in the mesangial matrix. In the 10 patients who were affected to a greater degree LM and EM showed, in addition to the mesangial matrix changes, the presence of mesangial foam cells. Clinical signs of renal involvement were mild in all patients except for one who died from chronic renal failure at 8 months of age. The extent of mesangiolipidosis was not related to age but to the degree of cholestasis, the most severe lesions being observed in patients aged 3, 6, 8, and 14 months. The glomerular lesions observed in Alagille syndrome are strikingly similar to those observed in adults with lecithin-cholesterol acyl transferase deficiency and other conditions characterized by an increase in plasma lipoproteins rich in free cholesterol and in phospholipids. We conclude that glomerular involvement should be added to the characteristic features of Alagille syndrome. Also we found that the lipid deposition in the glomeruli of patients with Alagille syndrome is related to an abnormal lipid metabolism, which is the consequence of severe cholestasis. The most striking feature of our study is the early detection of the glomerular lesions, contrasting with the lack of overt clinical renal disease. Renal failure may be a major complication for patients with this syndrome in adulthood.

Adolescent↗
PubMed1987

Sclerosing cholangitis with neonatal onset.

Sclerosing cholangitis is characterized by irregular narrowing of extrahepatic or intrahepatic bile ducts, and in adults is defined mainly by radiologic findings. We describe eight children with cholestasis from the first week of life, followed by early cirrhosis and portal hypertension. Histologic examination of the liver showed absence of interlobular bile ducts in the early cholestatic phase in two patients and biliary cirrhosis later in all patients. Radiologic examination by percutaneous cholecystography under ultrasound guidance, carried out at age 8 months to 9 years, disclosed abnormal intrahepatic bile ducts with rarefaction of segmental branches, stenosis, and focal dilation. The extrahepatic ducts were involved in six patients. No intestinal disease has been found in these patients.

Bile Ducts↗
PubMed1987

Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases.

We have observed two types of paucity of interlobular bile ducts (PILBD) in children with chronic cholestasis: the syndromic type, which is more frequent (80 cases), and the nonsyndromic type (31 cases). Study of patients with syndromic PILBD has enabled us to recognize five major features: peculiar facies (95%), chronic cholestasis (91%), posterior embryotoxon (88%), butterfly-like vertebral arch defects (87%), and peripheral pulmonary artery hypoplasia or stenosis, either isolated or associated with complex cardiovascular abnormalities (85%). By observing these major features, it is possible to differentiate the "complete" syndrome, in which all five features are present (26 cases), from the "partial" syndrome, in which only four (42 cases) or three (12 cases) major features are present. Other less frequent features were observed in patients with complete or partial syndrome: growth retardation (50%), mental retardation (16%), renal disturbances, other vascular malformations, bone abnormalities, high-pitched voice, and delayed puberty. Death occurred in 21 (26%) patients with syndromic PILBD. Therapy consisted of supplementation of medium-chain triglycerides and fat-soluble vitamins and administration of cholestyramine or phenobarbital. An autosomal dominant mode of transmission, with variable penetrance, seems likely.

Bile Ducts, Intrahepatic↗
PubMed1987

Bacterial cholangitis after surgery for biliary atresia.

We retrospectively studied the incidence of bacterial cholangitis in 129 infants operated on because of biliary atresia over 5 years. Forty-six of the 101 children who underwent hepatic portoenterostomy had a total of 105 episodes of cholangitis (range one to eight episodes per child). Most episodes occurred within 3 months of the operation. Factors associated with cholangitis included good or partial restoration of bile flow, abnormal intrahepatic bile ducts or cavities at the porta hepatis, and routine postoperative use of antibiotics. External jejunostomy was not effective in preventing cholangitis. In addition to fever and decreased bile flow, increased erythrocyte sedimentation rate and signs of shock were frequently observed. The responsible organisms, most often gram-negative bacteria, were identified in 79 (75%) episodes by blood or liver cultures. Most were susceptible to trimethoprim-sulfamethoxazole and third-generation cephalosporins during the first episode, but only to cephalosporins during later episodes. The incidence of signs of portal hypertension in children with normal serum bilirubin values at age 5 years was not higher in those who had previously experienced one or more episodes of cholangitis.

Biliary Atresia↗
PubMed1987

Plasma lipid peroxides in cholestatic children.

Plasma lipid peroxide levels were studied in 40 children with chronic cholestasis comprising 21 with syndromatic paucity of interlobular bile ducts (PILBD) and 19 with biliary atresia. Compared to the controls, mean lipid peroxide values were twice as high in children with biliary atresia (4.56 +/- 2.28 nmol/ml) and four times as high in those with PILBD (9.62 +/- 3.3 nmol/ml). These differences are highly significant. In patients with biliary atresia, the increase in lipid peroxide levels was clearly related to the bilirubin, cholesterol and phospholipid concentrations. In the PILBD group, however, there was little evidence of such a relationship. Vitamin E treatment seemed to have no effect on these increased lipid peroxide levels during the evolution of chronic cholestasis, and further investigations are necessary to clarify the pathological mechanisms involved.

Adolescent↗
PubMed1986

Liver disease associated with anti-liver-kidney microsome antibody in children.

In the past 10 years we have examined 20 children with inflammatory liver disease associated with high serum titers of anti-liver-kidney microsome antibody (anti-LKM). The first hepatic symptoms were progressive fatigue and jaundice, the fortuitous finding of hepatomegaly or splenomegaly with raised transaminase activity, or an acute hepatitis-like illness. At the time of diagnosis, hepatomegaly was present in 18 children, splenomegaly in 16, jaundice in nine, and ascites in two. Serum alanine transferase activities were elevated in all but two, who had already received steroids. Serum total gammaglobulin values were greater than 2.0 gm/dl in 16 children, prothrombin activity less than or equal to 60% in six, and serum titer of anti-LKM between 1:100 and 1:100,000. All children but one had cirrhosis, and histologic signs of aggressivity were present in 14. In 11 children one or more extrahepatic diseases were present, including type 1 diabetes, vitiligo, glomerulonephritis, autoimmune hemolytic anemia, hypoglycemia with hyperinsulinism, autoimmune thyroiditis, chronic mucocutaneous candidiasis with hypoparathyroidism, and multiple cutaneous and visceral telangiectasias. Treatment with prednisone and azathioprine improved the liver condition in 16 of the 18 patients given treatment. In eight of them discontinuation of treatment resulted in rapid relapse; 14 are still receiving treatment and have stable hepatic function with follow-up from 8 months to 6 1/2 years. Only two are free of treatment. Four children died, two in spite of immunosuppressive therapy, one during a relapse, and one of extrahepatic disease. These results indicate that this autoimmune inflammatory liver disease may have onset early in life, with several clinical patterns; is frequently associated with certain types of extrahepatic manifestations of autoimmune origin; and is a potentially fatal disease for which immunosuppressive treatment must be started early.

Adolescent↗