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S G Hubscher

Publications and source records attributed to S G Hubscher.

At least 73 records · Page 4Linked to original sources
PubMed1992

Sclerosing cholangitis associated with multifocal fibrosis: a case report.

The association of sclerosing cholangitis, retroperitoneal fibrosis, and Riedel's thyroiditis has been reported twice before, and on both occasions the authors successfully used steroids to control the fibrotic process. A further case of fibrosis with this triad of organ involvement in which a combination of surgery and steroid treatment has arrested disease progression is described. This suggests an inappropriate immune response in this type of fibrotic overlap syndrome.

Cholangitis, Sclerosing↗
PubMed1992

Is the intercellular adhesion molecule-1/leukocyte function associated antigen 1 pathway of leukocyte adhesion involved in the tissue damage of alcoholic hepatitis?

Alcoholic hepatitis is characterised histologically by an intense inflammatory cell infiltrate made up predominantly of neutrophils but including other cell types, particularly lymphocytes. Leukocyte cytotoxicity requires cell adhesion, which is mediated via receptors on the leukocyte surface including leukocyte function associated antigen-1 (LFA-1) which binds to the ligand intercellular adhesion molecule-1 (ICAM-1) on the target cell. The distribution of ICAM-1 and LFA-1 expression in liver biopsy specimens from patients with alcoholic liver disease was examined to ascertain whether this pathway of leukocyte adhesion is involved in the tissue damage of alcoholic hepatitis. Specimens were stained for ICAM-1 and LFA-1 by a three step immunoalkaline-phosphatase method using monoclonal antibodies against ICAM-1 and LFA-1. LFA-1 staining on portal tract inflammatory cells and parenchymal inflammatory cells and ICAM-1 staining on liver components were examined. ICAM-1 expression on hepatocytes was significantly greater in alcoholic hepatitis compared with fatty liver (p less than 0.001) and normal controls (p less than 0.01). ICAM-1 expression correlated with the histological degree of hepatocellular damage (tau = 0.79; p = 0.0005) and parenchymal inflammation (tau = 0.65; p less than 0.001, and with LFA-1 expression on parenchymal leukocytes (tau = 0.63; p = 0.01). The ICAM-1/LFA-1 pathway may therefore be involved in leukocyte mediated tissue damage during alcoholic hepatitis.

Antibodies, Monoclonal↗
PubMed1991

Vanishing bile-duct syndrome following liver transplantation--is it reversible?

Loss of bile ducts is a characteristic feature of chronic rejection in the liver allograft (also known as irreversible rejection and vanishing bile-duct syndrome). Typically, this occurs as a progressive lesion resulting in irreversible damage and graft failure requiring retransplantation. In this study, we describe 6 patients who developed a transient loss of bile ducts following liver transplantation. This occurred in a series of 138 patients who underwent the first 160 liver transplant operations in the Birmingham Liver Transplant Programme (incidence = 4.4% of patients, 3.7% of grafts). Forty needle biopsies were obtained from the 6 patients between 6 and 1303 days after transplantation. Thirteen specimens, taken between 8 and 1253 days posttransplant (median 98 days) showed an absence of bile ducts in more than 50% of portal tracts. Other histologic features of chronic rejection, inflammatory bile-duct lesions, perivenular cholestasis, and hepatocyte dropout were also seen in these biopsies, and severe cholestasis was present biochemically (median serum bilirubin level 240 mumol/L). The histologic and biochemical changes were thought to be compatible with a diagnosis of chronic/irreversible rejection, but the decision to carry out retransplantation was deferred on the basis of stable and, subsequently, improving biochemistry. Follow-up biopsies showed recovery of duct loss and other histologic abnormalities. All 6 patients are currently alive and well with good graft function. It is concluded that a transient, reversible bile-duct loss can occur after liver transplantation and that cases with this condition are indistinguishable from those who subsequently develop irreversible graft damage. In view of the risks associated with additional immunosuppression and/or retransplantation, caution is advocated in the interpretation of ductopenia in posttransplant liver biopsies. We suggest that the term "early chronic rejection" might be appropriate to describe cases in which a definite diagnosis of irreversible graft damage cannot be made.

Adolescent↗
PubMed1991

The spectrum of bile duct lesions in end-stage primary sclerosing cholangitis.

Tissue from 15 livers with primary sclerosing cholangitis, obtained at transplantation, was examined histologically with respect to: small and medium sized bile duct lesions; large bile duct lesions; fibrosis/cirrhosis; and parenchymal changes. Lesions affecting small and medium-sized bile ducts were quantified by determining the percentage of 20 portal tracts involved. The two characteristic bile duct lesions of primary sclerosing cholangitis, periductal fibrosis and fibro-obliterative scars, were largely confined to medium-sized portal areas. Although present in each case, the number of such lesions varied considerably. Loss of bile ducts was the most conspicuous feature in small portal tracts where the diagnostic duct lesions of primary sclerosing cholangitis were rarely observed. Inflammation, ulceration and cholangiectases of large intrahepatic ducts were common, and appear to be useful additional diagnostic features.

Adolescent↗
PubMed1991

Increased expression of intercellular adhesion molecule 1 on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis.

It has been suggested that immunological mechanisms involving lymphocyte-mediated damage are important in the characteristic bile-duct damage that occurs in primary biliary cirrhosis and primary sclerosing cholangitis. Because adhesion is necessary for the interaction of lymphocytes with their target structures, we have studied the expression of intercellular adhesion molecule 1, a ligand for the leukocyte adhesion receptor lymphocyte function-associated antigen 1 in the liver of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Strong expression of intercellular adhesion molecule 1 was seen on interlobular bile ducts and proliferating bile ductules in both conditions. In primary biliary cirrhosis, medium-sized ducts, which are spared by the disease, were negative. Minimal bile-duct staining was seen in conditions in which bile-duct damage is not a major feature, such as nonbiliary cirrhosis and acute liver diseases. In patients with cirrhosis from any cause, strong expression of intercellular adhesion molecule 1 was detected on the periseptal hepatocytes adjacent to new connective tissue. The intensity of immunohistochemical staining was recorded using a semiquantitative visual scoring system that was subsequently validated quantitatively by confocal laser scanning microscopy. The expression/induction of intercellular adhesion molecule 1 on bile ducts may be important in the pathogenesis of bile-duct damage in primary biliary cirrhosis and primary sclerosing cholangitis and is further evidence to support an immune pathogenesis in these two conditions. Furthermore, the induction of intercellular adhesion molecule 1 on hepatocytes may be an important factor in the liver-cell damage and fibrosis that occur during the development of cirrhosis.

Bile Ducts↗
PubMed1991

Distribution of dihydrolipoamide acetyltransferase (E2) in the liver and portal lymph nodes of patients with primary biliary cirrhosis: an immunohistochemical study.

The reason for the close association between primary biliary cirrhosis and the appearance of antibodies that recognize the E2 component of pyruvate dehydrogenase complex is not understood. The distribution of the three pyruvate dehydrogenase complex subunits was examined in the liver and lymph nodes of patients with primary biliary cirrhosis, patients with other liver diseases and normal subjects by immunohistochemistry using affinity-purified antibodies. Intensity of staining was assessed semiquantitatively and validated by scanning laser confocal microscopy. In primary biliary cirrhosis tissue, the E2 staining pattern did not parallel the reported distribution of mitochondria. E2 staining in biliary epithelial cells was consistently stronger than in hepatocytes. In primary biliary cirrhotic liver, staining of biliary epithelium was significantly stronger than in normal or other liver disease controls; many bile ducts in primary biliary cirrhotic liver demonstrated very high intensity, diffuse distribution of stain. No differences in staining intensity were seen between perivenular hepatocytes in primary biliary cirrhotic liver and those in controls; periportal hepatocytes in primary biliary cirrhotic liver were, however, more intensely stained than perivenular cells. In primary biliary cirrhotic portal lymph nodes, a subset of macrophages showed high-intensity, diffuse distribution of stain. By contrast, staining with antibodies to E1 and E3 (other components of pyruvate dehydrogenase complex) produced uniform-intensity, mitochondrial distribution both in primary biliary cirrhosis and control tissue. The increased intensity of E2 in primary biliary cirrhotic tissue could be explained in terms of abnormal metabolism of E2 by biliary epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗
PubMed1990

Changes in the expression of major histocompatibility complex class II antigens in liver allograft rejection.

The expression of major histocompatibility complex (MHC) class II antigens was studied in human liver grafts by immunohistochemical staining with monoclonal antibodies to HLA-DR, HLA-DP, and HLA-DQ antigens. Staining was carried out on frozen sections from 13 normal livers, used as controls, and 85 post-transplant specimens in six histological categories: acute rejection (n = 25); chronic rejection (n = 21); massive haemorrhagic necrosis (n = 2); resolving acute rejection (n = 10); non-rejection complications--pure cholestasis, ischaemia, biliary obstruction (n = 23); and stable graft function greater than 1 year post-transplantation (n = 4). Staining was graded semi-quantitatively on a scale of 0-3+ in bile ducts, hepatocytes, and vascular endothelium. Expression of class II antigens was increased in bile ducts, hepatocytes, and vascular endothelium in all of the post-transplant groups compared with controls. The degree of expression of HLA-DR and HLA-DP in bile ducts and vascular endothelium was significantly greater in cases of rejection than in the non-rejection groups. These observations suggest that increased class II antigen expression may be important in the pathogenesis of immune-mediated bile duct and endothelial damage in liver allografts. Immunohistochemical staining for class II antigens in post-transplant biopsies may also be useful as an adjunct to conventional histological diagnosis.

Antibodies, Monoclonal↗
PubMed1989

Intercellular adhesion molecule 1 on liver allografts during rejection.

The expression of intercellular adhesion molecule 1 (ICAM-1), a ligand for the leucocyte adhesion receptor lymphocyte-function-associated antigen 1 (LFA-1), was studied on liver tissue after transplantation. There was greater ICAM-1 expression on bile ducts, endothelium, and perivenular hepatocytes (structures affected by the rejection process) in patients with acute rejection than in donor livers, patients with stable transplants, or patients with non-rejection complications. The expression on bile ducts and hepatocytes was greater in patients in whom there was progression to chronic, irreversible rejection. In patients with resolving rejection ICAM-1 expression was greatly reduced after high-dose corticosteroid treatment. The expression in patients with non-rejection complications and in those with long-term stable grafts was similar to that seen in the donor controls. The induction of ICAM-1 on tissues may be an important step in the development of the inflammatory response of rejection and in determining which cells are the targets of immune damage. The reduction of ICAM-1 expression seen after successful treatment with high-dose corticosteroids suggests that this might be an important mode of action of these drugs.

Acute Disease↗
PubMed1989

Soluble interleukin-2 receptors in serum and bile of liver transplant recipients.

Soluble interleukin-2 receptors (IL2R) were measured as markers of lymphocyte activation in serum and bile of liver transplant recipients. Serum and biliary levels were significantly higher in patients with acute rejection than in those with other complications (serum p less than 0.0025, bile p less than 0.001) or stable grafts (both p less than 0.0001). Levels rose 24 h before rejection could be detected by conventional liver tests. Biliary levels were more specific and sensitive than serum levels for rejection. Local production of IL2R accounted for the high levels in bile; the bile to serum ratio of IL2R was greater than that of albumin in 16 of 18 patients with acute rejection. Serum levels were high early in the course of chronic rejection but fell as it progressed to end-stage. Measurement of soluble IL2R may have a role in the early diagnosis of acute rejection and in identifying patients with chronic rejection in whom further immunosuppression will provide no benefit.

Acute Disease↗
PubMed1989

Hepatic vein webs and resistant ascites. Diagnosis, management and implications.

Webs of hepatic veins have been rarely described. Two patients presented with intractable ascites in whom hepatic venography demonstrated this unusual finding. Liver biopsies from both patients showed variable patterns of perivenular fibrosis. Transvenous balloon dilatation of the web was effective in abolishing the pressure gradient across the obstruction and improving hepatic venous outflow. Both patients showed a dramatic clinical improvement following the procedure, with complete resolution of ascites in one patient and considerable improvement in the other with symptoms not recurring over 18 months of follow-up. The histological features that help to distinguish hepatic venous outflow obstruction from other causes of perivenular fibrosis are described.

Adult↗
PubMed1989

Hepatic endothelial cells. Targets in liver allograft rejection?

Hepatic endothelial cell damage was evaluated in patients following liver transplantation using 2 serum markers: hyaluronic acid (HA), which measures hepatic endothelial cell function, and factor VIII related antigen (VIIIRAg), an indicator of generalized endothelial damage. HA was elevated in rejection (median 22.3 x control) when compared with stable patients (3.7 x control; P less than 0.00001) and those with posttransplant complications not related to rejection (6.8 x control; P less than 0.0005). The highest levels were seen in patients with chronic rejection (28.7 x control). Levels were also elevated in acute rejection (21.3 x control), and the highest levels in this group were seen in patients who subsequently developed chronic rejection (25.2 x control). Serial studies demonstrated that HA increased 24 hr before serum bilirubin in patients developing acute rejection. VIIIRAg was elevated in all posttransplant patients with no significant difference between rejection and other complications. These results show that hepatic endothelial dysfunction occurs during acute and particularly chronic rejection of liver allografts suggesting that VECs may be an important target of the immune response. Measurement of HA may allow for the early diagnosis of acute rejection and the identification of patients at risk of developing chronic rejection.

Adolescent↗