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Biomedical subjects

S Erlinger

Publications and source records attributed to S Erlinger.

At least 127 records · Page 7Linked to original sources

Hepatitis C virus infection in anti-HIV positive and negative French homosexual men with chronic hepatitis: comparison of second- and third-generation anti-HCV testing.

To determine the prevalence of hepatitis C virus (HCV) infection in homosexuals with chronic hepatitis, we tested for anti-HCV antibodies 113 (47 anti-HIV positive) French non-drug-addicted homosexual men admitted for chronic viral hepatitis. Anti-HCV were detected with second- and third-generation ELISAs (ELISA2 and ELISA3) and RIBAs (RIBA2 and RIBA3). Chronic hepatitis was related to non-A, non-B infection in four, to hepatitis D virus (HDV) infection in five and to hepatitis B virus (HBV) infection in 104 patients. Anti-HCV positivity was found in 50.4% and 12.4% of the 113 patients, with ELISA2 and ELISA3, respectively. Positivity with RIBA2 and RIBA3 was found in only six of the 57 ELISA2 positive patients (all six were ELISA3 positive). The high prevalence of positivity with ELISA2 not confirmed by RIBA2 or RIBA3 suggests false-positive results. ELISA2 positive results were more frequent with frozen serum samples than with fresh serum samples (62% vs 23.5%, p = 0.0003). However, even with fresh serum, ELISA2-positive RIBA-negative results remained frequent in anti-HIV positive patients. ELISA3 seems to give more specific results. We conclude that the prevalence of HCV infection, as assessed with RIBA, was 5.3% among French homosexual men with chronic hepatitis (3.8% after exclusion of transfused patients). This low prevalence suggests that homosexual transmission of HCV is relatively uncommon.

Adult↗

Recombinant alpha interferon for chronic hepatitis B in anti-HIV positive patients receiving zidovudine.

In this pilot study of the effects of interferon alfa in 10 anti-HIV positive, chronic hepatitis B patients treated with zidovudine (AZT), tolerance to interferon was good and similar to that in anti-HIV negative patients. After treatment, the HIV stage and CD4 lymphocyte count were unchanged. In two patients hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg) disappeared and the serum alanine aminotransferase (ALT) returned to normal; loss of hepatitis B surface antigen (HBsAg) with absence of histopathological activity was observed after treatment in one of these patients. These preliminary results need to be confirmed by a larger study.

Adult↗

Persistence of systemic and splanchnic hyperkinetic circulation in liver transplant patients.

Portal pressure and portal-systemic collateral circulation after orthotopic liver transplantation have not been investigated. We studied systemic and splanchnic hemodynamics in 17 patients with cirrhosis before and 205 +/- 146 days after orthotopic liver transplantation. Among the 17 orthotopic liver transplantation patients, 12 had undergone hemodynamic study in the 6 mo before orthotopic liver transplantation. Controls were 50 patients with normal liver architecture. Cardiac index remained elevated in orthotopic liver transplantation patients compared with controls (3.6 +/- 0.9 vs 3.1 +/- 0.4 L/min.m2; p < 0.05). Azygos blood flow, which was elevated before orthotopic liver transplantation (585 +/- 402 ml/min), remained elevated after orthotopic liver transplantation (553 +/- 343 ml/min). In transplant patients, hepatic blood flow was higher than it was in controls (2.26 +/- 0.86 vs. 1.38 +/- 0.57 L/min; p < 0.05). Elevated hepatic blood flow correlated with cardiac index (r = 0.647, p < 0.025). In patients with normal graft function, hepatic venous pressure gradient was normal (2 +/- 1 mm Hg). In a patient with acute rejection, a sharp elevation in the hepatic venous pressure gradient was observed; it returned to normal 45 days after treatment. We conclude that despite normal portal pressure, portal-systemic collateral blood flow remains elevated after orthotopic liver transplantation. Possibly because of persistent collateral circulation, which may keep portal tributary blood flow elevated, hepatic blood flow is increased after orthotopic liver transplantation. Elevated splanchnic blood flow, in turn, contributes to the high cardiac index in liver recipients. Finally, a sharp elevation in portal pressure, which may be observed during acute rejection and subsides after treatment, merits further study.

Adult↗

The intraportal lymphoid nodule and its environment in chronic active hepatitis C: an immunohistochemical study.

Intraportal lymphoid nodules have been observed in liver biopsy specimens from patients with autoimmune liver disease and chronic active hepatitis C. They are characterized by a nodular lymphocyte aggregate with a germinal center. The purpose of this in situ immunophenotyping study was to determine immunohistochemically the phenotype of immunocompetent cells in and around intraportal lymphoid nodules in patients with chronic hepatitis C. For comparison, we also examined lymphoid nodules in patients with autoimmune liver disease. Liver biopsy specimens from 13 unselected patients with CAH and hepatitis C antibodies and from 7 unselected patients with autoimmune liver disease seen during the same period were studied. Sections of snap-frozen specimens were immunostained with monoclonal antibodies directed against different subsets of T cells, B cells, follicular dendritic cells and macrophages. Intraportal lymphoid nodules were observed in 11 of 13 patients with chronic hepatitis C. They appeared as lymphoid follicles with activated B cells in germinal centers surrounded by a follicular dendritic cell network. A mantle zone of B cells was present around the aggregate of activated B cells. A T-cell zone comprising CD4-positive helper T cells, CD8-positive suppressor/cytotoxic T cells and a few CD25-positive activated T cells expressing interleukin-2 receptor was seen at the periphery of the nodules. Human leukocyte antigen DR was expressed by B cells and by T cells, indicating that T cells were activated. The immunocompetent cells observed in piecemeal necrosis were predominantly CD4 helper T cells, whereas those seen in the lobule were predominantly CD8 suppressor/cytotoxic T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Oral dissolvents and extracorporeal lithotripsy: respective role and modalities of application].

Oral dissolution therapy can be proposed to patients with symptomatic gallstones, with stones less than 15 mm diameter, in any number, without calcification, within a functioning gallbladder (i.e. opacified by oral cholecystography). In particular, it may be useful in patients aged over 70, or with a high operative risk, or who refuse surgery or general anesthesia. Extracorporeal shock wave lithotripsy (followed by oral dissolution therapy) is also indicated in symptomatic gallstones, without calcification or slightly calcified in a functioning gallbladder, when stone size is between 8-10 and 30 mm and stone number lower than 3. After successful dissolution, recurrence is observed with an incidence of 5 to 10% per year during the first five years. In case of symptomatic recurrence, retreatment is indicated.

Administration, Oral↗

Demonstration of hepatitis B virus DNA by polymerase chain reaction in the serum and the liver after spontaneous or therapeutically induced HBeAg to anti-HBe or HBsAg to anti-HBs seroconversion in patients with chronic hepatitis B.

The objective was to determine the proportion of patients with chronic hepatitis B in whom hepatitis B virus DNA is demonstrated by polymerase chain reaction after HBeAg to anti-HBe or HBsAg to anti-HBs spontaneous or therapeutically induced seroconversion. Polymerase chain reaction was performed on serum 6 and 12 mo after HBeAg to anti-HBe seroconversion in 12 patients and 2, 6 and 12 mo after HBsAg to anti-HBs seroconversion in 13 patients. Polymerase chain reaction was performed on liver tissue after HBeAg to anti-HBe seroconversion in five patients and after HBsAg to anti-HBs seroconversion in one patient. Serum HBV DNA was demonstrated by polymerase chain reaction in 83% of patients 6 or 12 mo after HBeAg to anti-HBe seroconversion and in 58%, 31% and 15% of patients at 2, 6 and 12 mo, respectively, after HBsAg to anti-HBs seroconversion. Liver HBV DNA was demonstrated by polymerase chain reaction in all patients tested. Our results show that (a) a reduced level of hepatitis B virus replication persists in most of the patients after HBeAg to anti-HBe seroconversion and might be predictive of reactivation, and (b) in contrast, hepatitis B virus replication progressively disappears in most of the patients after HBsAg to anti-HBs seroconversion.

Adult↗

Chronic administration of cyclosporin A induces a decrease in hepatic excretory function in man.

Chronic administration of cyclosporin A may induce cholestasis in a few patients. The purpose of this study was to examine the effect of chronic administration of cyclosporin A on serum bile acid levels, serum bilirubin concentration, and bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted patients with normal serum alanine aminotransferase activity receiving cyclosporine A during a mean duration of 33 months (range 7-54) were compared to 20 matched kidney-transplanted patients with normal serum alanine aminotransferase receiving azathioprine for a mean duration of 34 months (range 6-72). As compared to azathioprine-treated patients, patients treated with cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These results suggest that cyclosporin A induces a decrease in hepatic excretory function in man.

Adolescent↗

Fibrin ring granulomas in hepatitis A.

Fibrin ring granuloma is characterized by a fibrinous ring surrounding a central fat vacuole. It has been found in the liver and bone marrow of patients with Q fever, and occasionally with visceral leishmaniasis, cytomegalovirus, Epstein-Barr virus, Staphylococcus epidermidis infections, Hodgkin's lymphoma, and hypersensitivity to allopurinol. We describe a case of serologically confirmed viral hepatitis A with this lesion in the liver biopsy. A false positive anti-hepatitis A virus IgM result has been excluded. This is, to our knowledge, the second reported case of type A hepatitis with hepatic fibrin ring granulomas. It confirms that hepatitis A should be included in the differential diagnosis of this lesion.

Acute Disease↗

Ursodeoxycholic acid limits liver histologic alterations and portal hypertension induced by bile duct ligation in the rat.

Chronic administration of ursodeoxycholic acid (UDCA) has recently been suggested as a potential treatment for cholestatic liver disease. The purpose of this study was to examine the effects of chronic oral administration of UDCA on the histological, biochemical, and hemodynamic abnormalities induced by bile duct ligation in the rat. Fifty-one rats with ligation-section of the common bile duct were randomly and blindly assigned to receive UDCA (25 mg/kg each day) or placebo by gavage for 4 weeks. At the end of the treatment period, morphometric analysis showed that in rats treated with UDCA, hepatocyte and sinusoidal volume fractions were significantly higher than in rats receiving placebo [41.9 +/- 3.2% vs. 28.1 +/- 1.8%, (mean +/- SE) and 7.4 +/- 0.1% vs. 4.3 +/- 0.3%, respectively], whereas bile duct volume fraction (reflecting bile ductular proliferation) and connective tissue fraction were significantly lower in rats treated with UDCA than in rats receiving placebo (14.2 +/- 1.5% vs. 20.0 +/- 1.0% and 35.4 +/- 2.4% vs. 47.6 +/- 1.7%, respectively). Serum aminotransferase and alkaline phosphatase activities, and total serum bile acids and individual bile acid concentrations were not significantly different between the two groups. Portal pressure (12.7 +/- 0.5 mm Hg vs. 17.1 +/- 0.5 mm Hg), portal tributary blood flow (5.7 +/- 0.4 vs. 9.3 +/- 0.4 mL.min-1.100 g-1 body weight), and cardiac index (41.1 +/- 1.8 vs. 50.6 +/- 1.4 mL.min-1.100 g-1 body weight) were significantly lower in UDCA-treated rats than in placebo-treated animals. In portal vein stenosed rats, chronic administration of UDCA had no hemodynamic effects, a finding that suggests UDCA has no direct vasoactive effect on splanchnic circulation. It is concluded that in rats with bile duct ligation UDCA limits the severity of liver disease and consequently of portal hypertension and hyperkinetic circulation.

Animals↗

Detection of serum HBV-DNA by polymerase chain reaction (PCR) in patients before reactivation of chronic hepatitis B.

Reactivation of chronic hepatitis B is characterized by the reappearance of HBV-DNA in serum. The purpose of the study was to determine whether, before reactivation, HBV-DNA would be detectable in serum, using a sensitive procedure of detection, namely polymerase chain reaction (PCR). We studied 17 patients with chronic hepatitis B who experienced an episode of reactivation, defined by the reappearance of HBV-DNA in serum. None of these 17 sera had HBV-DNA demonstrable by dot-blot hybridization nor liquid hybridization in sera collected before reactivation. Using PCR, HBV-DNA was detected, before reactivation, in 13 of the 17 episodes of reactivation tested with Southern-blot and hybridization. HBV-DNA was not detectable with PCR in the serum of four patients who subsequently experienced an episode of reactivation. In conclusion, our results show low level HBV replication before reactivation in most, but not all, HBs-positive, HBV-DNA-negative patients. This suggests that reactivation may occur even in patients with no HBV-DNA demonstrable in serum with PCR prior to reactivation.

Adult↗

Recombinant interferon-alpha for chronic hepatitis C in patients positive for antibody to human immunodeficiency virus. Comité des Anti-Viraux.

To assess the response to and tolerance of recombinant interferon-alpha administration in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection, 12 patients with chronic hepatitis C and HIV infection were given interferon-alpha, 1, 3, or 5 million units thrice weekly, for 4 or 6 months. Four patients had a complete response (normal serum alanine aminotransferase activity [ALT]), 3 had a near-complete response (serum ALT less than one-and-one-half times the upper limit of normal), and 5 had no response at the end of administration. Histologic examination of liver showed an improvement in 1 patient with complete response and no improvement in another patient with no response. In patients with chronic hepatitis C with HIV infection, the response to and tolerance of recombinant interferon-alpha were not different from those usually observed in patients with chronic hepatitis C infection without HIV infection.

Adult↗

Cystic fibrosis: bile secretion.

Bile is an isotonic aqueous solution of bile acids, cholesterol, phospholipids, bile pigments and inorganic electrolytes. It is secreted by the hepatocytes into the bile canaliculi and modified in the bile ductules or ducts. The three main processes identified in the generation of bile flow are: 1. Active transport of bile acids from blood into bile canaliculi. This is responsible of the bile acid-dependent canalicular bile flow. Coupling between water flow and bile acid secretion is probably effected mainly through an osmotic mechanism. There is evidence that water flows (at least in part) through the interhepatocytic junctions. The bile acid-dependent flow accounts for 30 to 60% of spontaneous basal bile flow. 2. A canalicular, bile acid-independent secretion, probably due to transport into bile of organic solutes (glutathione) and inorganic electrolytes. This fraction of bile flow is stimulated by phenobarbital. It represents 30 to 60% of basal bile flow. Normal canalicular bile flow also depends on the integrity of intracellular cytoskeletal organelles, mostly microfilaments. 3. Reabsorption and secretion of fluid and inorganic electrolytes by the ductules and ducts. Secretion chiefly occurs in response to secretin and represents 30% of basal bile flow. Although several ion transport systems have been identified on the biliary epithelial cells (in particular a Na+/H+ exchange, a Na+:HCO3- symport and a CI-/HCO3- exchange), the cellular mechanism of secretion is not known. Abnormalities of bile duct function may account for the liver disease of cystic fibrosis, but these abnormalities have not been characterized.

Bile↗

Antineutrophil cytoplasmic antibodies (ANCA) directed against cathepsin G in ulcerative colitis, Crohn's disease and primary sclerosing cholangitis.

Autoantibodies directed against polymorphonuclear neutrophils (PMN) have been observed in serum from patients with ulcerative colitis (UC), Crohn's disease (CD) and primary sclerosing cholangitis (PSC) using indirect immunofluorescence and fixed granulocyte ELISA. Our study demonstrates the presence in the serum of these patients of autoantibodies which bind to an azurophilic granule component distinct from proteinase 3, elastase and myeloperoxidase. These autoantibodies thus belong to the ANCA family, but their antigen specificity differs from the already characterized ANCA antigens. We have found that the same ANCA antigen target, named UC-antigen, was recognized by serum IgG from patients with UC, CD and PSC. It was purified by Matrex Gel Orange A dye affinity chromatography and subsequent immunoabsorption of contaminant proteinase 3 with immobilized anti-proteinase 3 MoAb. The identity between this UC antigen and cathepsin G was demonstrated by their coelution from Matrex Gel Orange A column and the parallel titration of cathepsin G-specific enzymatic activity and UC-ANCA binding, both in partially purified UC antigen and in highly pure cathepsin G. Furthermore, the use of cathepsin G ELISA confirmed that UC, CD and PSC patients' IgG did indeed bind to cathepsin G. Comparison of the results obtained with azurophilic granule- and cathepsin G-ELISA as well as inhibition of ANCA binding by anti-cathepsin G polyclonal antibodies, revealed that in some patients cathepsin G is the main azurophilic granule target of ANCA while others have other ANCA specificities. The fact that UC, CD and PSC are frequently associated with cathepsin G ANCA, while rarely occurring in other types of vasculitis, is intriguing but suggests that these diseases may have a common pathogenetic mechanism.

Autoantibodies↗

Immunoperoxidase localization of ursodeoxycholic acid in rat biliary epithelial cells. Evidence for a cholehepatic circulation.

To explain the hypercholeretic effect of ursodeoxycholic acid, a cholehepatic shunt circulation has been postulated. This pathway includes secretion by the hepatocyte into bile and absorption by the biliary epithelial cells. To test this possibility, we have attempted to localize ursodeoxycholic acid in hepatocytes and portal bile duct cells by an indirect immunoperoxidase technique using specific polyclonal antibodies against ursodeoxycholic acid and cholic acid conjugates. Rat livers were fixed with paraformaldehyde, incubated with antibodies directed against bile acids and examined by electron microscopy. After infusion of ursodeoxycholic acid and incubation with antibodies against this bile acid, an electron-dense staining was observed on the apical (luminal) membrane of the portal bile ductal cells. In contrast, no staining was observed when no ursodeoxycholic acid was infused, or after infusion with taurocholate and incubation with antibodies against cholic acid conjugates. These observations are consistent with absorption of ursodeoxycholic acid by the portal bile ducts and a cholehepatic circulation of this bile acid.

Animals↗