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S G Hubscher

Publications and source records attributed to S G Hubscher.

At least 55 records · Page 3Linked to original sources
PubMed1994

The role of dynamic and morphological studies in the assessment of potential liver donors.

In a prospective study, 66 donor livers were evaluated by monoethylglycinexylidide (MEGX) dynamic clearance and semiquantitative scoring of pathological changes in liver biopsies. The median MEGX level in 63 donors was 89 mcg/L (range 16-250 mcg/L); fifteen had MEGX levels < 50 mcg/L, 17 between 50 and 90 mcg/L, and 31 > 90 mcg/L. There were no cases of primary nonfunction, and no deaths were related to poor graft function. There was no statistically significant difference in peak aspartate aminotransferase (AST), day 5 AST, peak bilirubin, or lowest prothrombin time among the 3 groups. Liver biopsies were assessed in 61 donors: 33 (54%) were normal and 17 (28%) showed mild, 8 (13%) showed moderate, and 3 (5%) showed severe steatosis. Postperfusion biopsy assessing the extent of preservation injury was essentially normal or showed minimal change in 16 (26%), mild change in 29 (48%), moderate in 13 (21%) and severe abnormalities in 3 (5%). The latter 3 biopsies all had severe steatosis. There was no significant difference in early graft function or outcome between moderate/severe groups and normal/minimal groups, although the former had a higher peak AST (P < 0.02) and peak bilirubin (P < 0.004). This detailed prospective analysis suggests that MEGX and the morphological studies may assist in the assessment of potential liver donors but they do not provide a basis on which grafts should be discarded.

Adolescent↗
PubMed1994

Endothelial activation and circulating vascular adhesion molecules in alcoholic liver disease.

Alcoholic hepatitis is characterized by hepatocyte necrosis associated with infiltration of the liver parenchyma by neutrophils. The mechanisms responsible for recruiting neutrophils to the liver are unknown. We report high circulating levels and tissue expression of the endothelial adhesion molecule E-selectin in alcoholic hepatitis. Because expression of E-selectin is involved in neutrophil transmigration into inflamed tissue, it may play a crucial role in the recruitment of neutrophils to the liver in alcoholic hepatitis. By contrast, we detected high levels of vascular cell adhesion molecule-1, the endothelial counter-receptor for the lymphocyte adhesion molecule very late antigen-4, in alcoholic cirrhosis, which is associated with a predominantly mononuclear cell infiltrate. Both diseases were associated with high levels of circulating intercellular adhesion molecule-1, which is released by activated lymphocytes, providing further evidence of immune activation in alcoholic liver disease.

Cell Adhesion↗
PubMed1994

Epstein-Barr virus in inflammatory diseases of the liver and liver allografts: an in situ hybridization study.

The Epstein-Barr virus is associated with a broad spectrum of lymphoproliferative diseases in liver allograft recipients. To investigate the effects of primary infection in children following liver transplantation and the possible role of Epstein-Barr virus in the pathogenesis of unexplained chronic hepatitis after transplantation, we used an in situ hybridization technique to detect small virus encoded nuclear RNAs in posttransplant specimens. For comparison, other posttransplant complications and diseases occurring in the nontransplanted liver were studied with the same method. We examined 114 specimens in the following categories: (a) children with primary Epstein-Barr virus infection after transplant (n = 25), (b) chronic hepatitis more than 12 mo after transplant (n = 14), (c) rejection (n = 15), (d) normal/near-normal histology more than 12 mo after transplant (n = 13) (e) end-stage acute liver disease (n = 9) and (f) end-stage cirrhosis (n = 38). Thirty-three of 114 specimens had labeling of occasional portal and parenchymal lymphoid cells. These were present in each of the six main diagnostic categories listed above: 2 of 25, pediatric; 6 of 14, chronic hepatitis; 4 of 15, rejection; 1 of 13, normal; 4 of 9, acute; and 16 of 38, cirrhosis. In none of the patients with Epstein-Barr virus-infected cells did lymphoproliferative disease subsequently develop. In conclusion, we have been unable to show an obvious association between Epstein-Barr virus infection and graft dysfunction after liver transplantation. Our results suggest that immunological response to primary infection in children after liver transplantation may be adequate.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1994

Cytokeratin immunostaining for detection of biliary epithelium: its use in counting bile ducts in cases of liver allograft rejection.

AIMS: To see how useful the application of a bile duct specific cytokeratin antibody (AE1) was in identifying and counting bile ducts in liver allograft biopsy specimens. METHODS: Eighteen liver biopsy specimens showing acute rejection and 17 biopsy specimens plus six hepatectomy specimens showing chronic rejection were studied. Serial sections were cut and stained with haematoxylin and eosin and AE1 antibody. Two pathologists (RFH and KP) examined the sections with respect to a range of histological features. RESULTS: Similar numbers of bile ducts were identified on haematoxylin and eosin sections as on corresponding sections stained by AE1 in cases of acute rejection and end stage chronic rejection. Greater numbers of bile ducts were identified by AE1 during the early stages of chronic rejection, especially when dense portal inflammatory infiltrates were present. These were often incomplete structures or individual cells within portal tracts, and bile ducts subsequently disappeared in all cases. Ductular proliferation was clearly shown by AE1 in acute rejection and the extent seemed to correlate with the severity of rejection present. By contrast, no ductular proliferation was observed in chronic rejection. CONCLUSIONS: Haematoxylin and eosin stained sections are adequate for counting bile ducts in most biopsy specimens from patients with suspected chronic rejection. Immunostaining for biliary cytokeratins using AE1 is of limited use in occasional cases where bile ducts are obscured by inflammatory cells.

Acute Disease↗
PubMed1994

Fibrous and obliterative cholangitis in liver allografts: evidence of recurrent primary sclerosing cholangitis?

Fibroobliterative lesions and fibrous cholangitis are characteristic histological lesions of primary sclerosing cholangitis. To determine whether such lesions can be found in the liver allograft, and whether they represent recurrent disease, we reviewed all consecutive histological material taken at greater than 6 mo after transplantation in a 3-yr period from a series of 207 liver transplantations (22 with primary sclerosing cholangitis, 185 controls without primary sclerosing cholangitis). Because patients with primary sclerosing cholangitis have a biliary system reconstructed by means of a Roux loop, we compared the findings with those from a further control group of patients who had received a Roux loop for reasons other than primary sclerosing cholangitis. Of 22 patients receiving liver transplants for primary sclerosing cholangitis, 7 (32%) patients had biopsy specimens showing features of biliary obstruction, 6 (27%) showed fibrous cholangitis, and 3 (14%) showed classic fibroobliterative lesions. These findings compared with 3 (14%), 1 (5%) and 0 of 22 Roux controls, and 19 (10%), 4 (2%) and 0 of 185 controls without primary sclerosing cholangitis, respectively. The three patients with fibroobliterative lesions either had clinical episodes of cholangitis or had microorganisms in the large bile ducts. However, both biliary obstructive features and fibrous cholangitis were more common in primary sclerosing cholangitis, and fibroobliterative lesions were found only in patients who received transplants for primary sclerosing cholangitis, despite the presence of cholangitis and Roux loops in control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Distribution of pyruvate dehydrogenase dihydrolipoamide acetyltransferase (PDC-E2) and another mitochondrial marker in salivary gland and biliary epithelium from patients with primary biliary cirrhosis.

Previous studies in which quantitative immunofluorescence was used have shown that certain biliary epithelial cells in liver with primary biliary cirrhosis show increased levels of pyruvate dehydrogenase dihydrolipoamide acetyltransferase compared with controls. This study was designed to determine whether the increase in intensity of pyruvate dehydrogenase dihydrolipoamide acetyltransferase in biliary epithelial cells is accounted for by an increase in the number of mitochondria in the same cells. A double-antibody staining technique was used with antibodies specific for pyruvate dehydrogenase dihydrolipoamide acetyltransferase and another mitochondrial inner membrane marker, recognized by the mouse monoclonal antibody MCA151A. Distribution of the antigens was studied in sections of liver and salivary gland, an additional site that is frequently involved in primary biliary cirrhosis. Confocal microscopy was used to quantify the intensity of fluorescence resulting from binding of fluorochrome-labeled antibody. In both liver and salivary glands MCA151A binding was similar in normal and sections with primary biliary cirrhosis and corresponded to the predicted distribution of mitochondria in these tissues. In the liver staining was less intense in biliary epithelial cells than in hepatocytes. In salivary gland binding of both antibodies was predominantly localized to duct cells, with those forming striated ducts, known to be rich in mitochondria, being most intensely stained. There was high coincidence of the two antigens in salivary glands (p < 0.01) and in biliary epithelial cells from normal liver (p = 0.01). However, in liver with primary biliary cirrhosis, despite high coincidence between the antigens on hepatocytes, biliary epithelial cells showed high intensity of pyruvate dehydrogenase dihydrolipoamide acetyltransferase but not MCA151A.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Primary biliary cirrhosis. Histological evidence of disease recurrence after liver transplantation.

Histological evidence of primary biliary cirrhosis (PBC) recurring after orthotopic liver transplantation (OLT) was looked for in a 'blinded' study of 353 biopsies from 188 patients, 12-100 months post-transplant. Biopsies (172) were obtained from 83 patients transplanted for PBC and 181 biopsies from 105 patients with other liver diseases. Sixteen biopsies from 13 PBC patients (16%) had features suggestive of recurrent disease. The main diagnostic findings were: mononuclear portal inflammatory infiltration (n = 16), portal lymphoid aggregates (n = 14), portal epithelioid granulomas (n = 14) and bile duct damage (n = 15). This combination of changes was not seen in any biopsy from the non-PBC group. Additional features supporting a diagnosis of recurrent disease were ductopenia (n = 7), bile ductular proliferation (n = 7), portal fibrosis (n = 6) and copper deposition (n = 5). Thirteen biopsies from 12 patients were classified as stage I or II histologically. The other patient developed progressive damage in three serial biopsies resulting in an early micronodular cirrhosis, 5 years post-transplant. These observations provide further evidence that PBC recurs after OLT. More studies are required to determine the natural history and clinical significance of the predominantly early histological changes documented so far.

Adolescent↗
PubMed1993

Acute liver allograft rejection--is treatment always necessary?

A group of 195 consecutive adult patients who received a primary orthotopic liver allograft were reviewed retrospectively to analyze the incidence of rejection, the response to antirejection therapy, and the impact of acute rejection on the development of ductopenic rejection. The diagnosis of acute rejection (AR) was based on a combination of clinical and histological criteria, and 69.7% of the patients had at least one episode of acute rejection. Only 6.7% of the patients failed to respond to steroids and were treated with OKT3. Four (2.3%) patients developed acute vanishing bile duct syndrome (within 60 days) and 6 (3.5%) patients developed chronic rejection. Eight patients who spontaneously recovered from AR without additional immunosuppression are described in detail. In addition to histological damage, all developed significant hepatic dysfunction. Except for one patient who died from disseminated fungal infection, the 7 remaining patients are alive with excellent graft function 7 to 21 months posttransplant. While severe AR and recurrent AR should be treated without delay, some patients with mild-to-moderate rejection and hepatic dysfunction may resolve without additional immunosuppression.

Acute Disease↗
PubMed1993

Steroid withdrawal from long-term immunosuppression in liver allograft recipients.

Corticosteroids were withdrawn from the immunosuppressive regimen of 168/197 (85%) of liver transplant patients who survived for more than three months. In 14, steroids were restarted for reasons other than rejection. The remaining 154 patients were evaluated for the occurrence of rejection and graft loss. Risk factors for the development of rejection after steroid withdrawal were assessed. There were 13 episodes of rejection in 12 (7.8%) grafts; 7 (4.5%) experienced acute cellular rejection, and 6 (3.9%) developed chronic ductopenic rejection. All cases of acute rejection resolved with high-dose steroids. Graft and patient loss due to chronic rejection was 3 (1.9%) and 2 (1.3%), respectively. Chronic rejection resolved in 1 patient, 1 was successfully retransplanted, and in the other 2 the principal cause of death was recurrent tumor. None of the risk factors examined (primary indication for transplant, severity of previous acute rejection, use of OKT3, retransplantation, ABO blood group donor/recipient match, CMV infection, and CsA mono versus CsA and AZA double therapy) were associated with the development of chronic rejection poststeroid withdrawal. The prevalence of side effects, after steroid withdrawal, was low; 66% of patients never required antihypertensive medication; 14% experienced a significant septic episode, and only 4 died with sepsis as the major factor. There were no fungal sepsis and no new cases of diabetes. Withdrawal of corticosteroids after 3 months can be successfully achieved in the majority of liver allograft recipients and is associated with a low rate of rejection, graft loss, and complications attributable to immunosuppressive medication.

Adolescent↗
PubMed1993

Recurrent hepatitis B in liver allografts: a distinctive form of rapidly developing cirrhosis.

Recurrent hepatitis B virus (HBV) infection in the liver allograft is a significant cause of morbidity and mortality in those transplanted for chronic HBV disease. A detailed histological and immunohistochemical study of recurrent HBV disease in liver allografts was carried out using archival paraffin-embedded tissue. A total of 34 follow-up liver biopsies from 14 patients transplanted for HBV were available for study. In addition to routine stains, sections were stained with antibodies to a range of HBV antigens. Two patients transplanted for acute HBV remained free of re-infection. Five of seven patients transplanted for chronic HBV disease who were followed-up, developed HBV-associated cirrhosis 12-23 months later. Hepatocyte ballooning, high nucleocapsid antigen load, ductular proliferation and immature fibrous tissue characterized this unusual cirrhosis, which developed rapidly from fibrosing cholestatic hepatitis in at least three cases. Death from liver failure supervened quickly in three of the five patients. These findings support the concept that HBV infection in the liver allograft can be a different disease from that occurring in the non-transplant setting, and may be related to high antigen load.

Adult↗
PubMed1993

Vanishing bile duct syndrome: a possible mechanism for intrahepatic cholestasis in Hodgkin's lymphoma.

A syndrome of idiopathic intrahepatic cholestasis occurs in some patients with Hodgkin's lymphoma. The underlying mechanism is poorly understood. In this paper we describe three patients with Hodgkin's lymphoma in whom severe intrahepatic cholestasis of unknown pathogenesis developed. In two cases jaundice was the presenting symptom; all three patients died with intractable liver damage. The three patients were initially thought to have idiopathic Hodgkin's-associated cholestasis, but subsequent review of histological material revealed advanced vanishing bile duct syndrome in addition to severe cholestasis. Ten liver specimens were obtained from 4 to 97 wk after the onset of jaundice (seven needle biopsies, one wedge biopsy, two postmortem livers). In seven liver specimens taken within 30 wk of the onset of jaundice, portal tracts characteristically had a "burned-out" appearance without secondary periportal changes related to chronic cholestasis. Three biopsy specimens obtained from one of the patients more than 1 yr after the onset of jaundice showed evidence of progressive periportal damage in the form of fibrous expansion, marginal ductular proliferation and copper-associated protein deposition. More than 80% of small portal tracts lacked recognizable bile ducts in the final liver specimens obtained from the three patients. These observations suggest that Hodgkin's lymphoma should be included in the list of diseases associated with loss of intrahepatic bile ducts. The possibility of a vanishing bile duct syndrome should be considered in the differential diagnosis of unexplained intrahepatic cholestasis in patients with Hodgkin's disease.

Adult↗
PubMed1993

Chronic rejection of the liver allograft.

Chronic rejection remains one of the major problems in the management of liver transplant recipients. Histologic diagnosis is central to the management of this condition. It remains difficult to predict cases that will progress toward irreversible rejection, because there are no early diagnostic features. Furthermore, the determination that irreversible rejection has occurred and retransplantation is required also is difficult. There remain many unanswered questions about the cause and pathogenesis of this process. The bile duct loss and arteriopathy parallel changes seen in chronic rejection of other organs. The extent to which this process is specific to the liver or is common to the other transplanted organs and mediated by an immune attack on the vascular bed is unknown. The precise position of HLA matching or mismatching as a risk factor for subsequent chronic rejection remains to be answered but in hepatic transplantation does not seem to be a major factor. The relation between the immunologic trigger of a graft and an aggressive arteriosclerosis is a major challenge, and a greater understanding of this process should provide some new therapeutic options in preventing the disease.

Adult↗
PubMed1992

Hepatic reinnervation following orthotopic liver transplantation in man.

We have studied changes in the pattern of intrinsic hepatic innervation in sequential liver biopsies from 16 patients who underwent orthotopic liver transplantation. Seventy-one needle biopsies were used, including specimens obtained at the time of transplantation (time zero) and up to 4 years post-transplantation; five transplant hepatectomy tissue blocks removed 3-32 months after transplantation were also assessed. Paraffin sections were immunostained with anti-PGP 9.5 and anti-S-100 to identify nerve fibres. All 'time zero' biopsies contained portal nerves and all but two showed staining of parenchymal fibres. After 1 week, no subsequent biopsies contained parenchymal fibres. The disappearance of portal fibres was less rapid and showed greater variability between patients, but they had all disappeared by 6 weeks and there was no positive staining between 6 and 60 weeks. Thereafter, a minority of biopsies showed innervation of a few small portal tracts. Samples from the porta hepatis, hepatectomy specimens, and needle biopsies containing large tracts showed persistence of major nerve trunks at all stages. Abnormally large nerve bundles were seen in some of these areas. The pattern of nerve staining showed no obvious relationship to the intensity of rejection changes. Our results suggest that there is a limited, delayed capacity for regeneration of portal, but not parenchymal, fibres in the transplanted human liver. The physiological significance of this long-term parenchymal denervation in transplanted livers remains to be determined.

Humans↗
PubMed1992

Long-term immunosuppression after liver transplantation: are steroids necessary?

Steroid therapy was withdrawn in 85% of 152 orthotopic liver transplant recipients with grafts surviving for more than 3 months, and 87% of these remained steroid-free. Steroid therapy was restarted in 8% for reasons other than rejection. The most common was conversion of immunosuppression because of cyclosporine nephrotoxicity. The incidence of rejection after steroid withdrawal was low: 3.8% for chronic rejection (CR) and 4.5% for acute rejection. Only 3 grafts (1.9%) were lost because of CR. No risk factors have been identified for the development of CR after steroid withdrawal, but a protective role for azathioprine has been suggested.

Adolescent↗