Biomedical subjects

B C Portmann

Publications and source records attributed to B C Portmann.

50 records · Page 3Linked to original sources

PubMed1991

Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis.

Long-term follow-up of 27 patients with hepatitis B virus-related chronic liver disease treated by transplantation showed that 23 had hepatitis B virus recurrence. In 13 patients late changes in the grafts were similar to those described in other series: minor abnormalities in five cases, chronic active hepatitis in five cases and non-hepatitis B virus-related graft dysfunction in three cases. Three patients had incomplete histological follow-up. Analysis of the histological changes and viral antigen expression in six cases revealed a distinct and novel pattern termed fibrosing cholestatic hepatitis. Development of fibrosing cholestatic hepatitis was associated with rapidly progressive graft dysfunction. It is postulated that this pattern of fibrosing cholestatic hepatitis develops because of a high cytoplasmic expression of viral antigens, including HBsAg. The remaining case had some features of fibrosing cholestatic hepatitis. The main histological features of this unique syndrome include thin, perisinusoidal bands of fibrosis extending from portal tracts to surround plates of ductular-type epithelium; prominent cholestasis; ground-glass transformation; and ballooning of hepatocytes with cell loss and mild mixed inflammatory reaction.

Adult↗

PubMed1991

Hepatic interferon-alpha gene transcripts and products in liver specimens from acute and chronic hepatitis B virus infection.

In this study we have examined the localization of interferon-alpha in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-alpha production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-alpha messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who subsequently recovered. In contrast interferon-alpha polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-alpha messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-alpha synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-alpha. These data support previous observations that interferon-alpha production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus.

Acute Disease↗

PubMed1990

Detection of hepatitis B virus antigens in liver tissue. A relation to viral replication and histology in chronic hepatitis B infection.

The expression of hepatitis B virus antigens was studied by double staining liver tissue with appropriate antisera and correlated with serum hepatitis B viral DNA and histology in 28 patients with disease related to chronic hepatitis B virus infection. The cellular localization of hepatitis B core and hepatitis B e antigens generally coincided, but there were important differences at a subcellular level. Thus, hepatitis B e antigen was detected in nuclei and/or cytoplasm but strong cytoplasmic hepatitis B e antigen was associated with a high serum hepatitis B viral DNA (P = 0.0017) but not with active liver disease. Hepatitis B core antigen could also be detected in nuclei and/or cytoplasm, but strong cytoplasmic hepatitis B core antigen expression, exceeding that of hepatitis B e antigen, was associated with active liver disease (P = 0.041) and not with serum hepatitis B virus DNA. The proportion of hepatocytes expressing hepatitis B surface antigen correlated inversely with the serum titer (P = 0.0017), whereas hepatitis B surface and nucleocapsid antigens were usually expressed independently. The data support the hypothesis that cytoplasmic hepatitis B core antigen and not hepatitis B e antigen is the target for immune system-mediated cytolysis of hepatocytes. Cytoplasmic hepatitis B e antigen is not associated with liver damage but is instead associated with high levels of hepatitis B virus replication.

Antibodies, Monoclonal↗

PubMed1989

The relationship between HLA-DR3 and T-cell regulation of immunoglobulin production in primary sclerosing cholangitis.

Immunoglobulin production in vitro, its control by concanavalin A-activated suppressor T-cells, and the relationship between abnormalities in nonantigen-specific suppression and histocompatibility antigens have been studied in 20 patients with primary sclerosing cholangitis (PSC). Suppression of IgG, IgM, and IgA synthesis was impaired in 12 patients with PSC alone, but was normal in 8 with PSC and associated ulcerative colitis (UC). The HLA antigens B8 and DR3 were increased in frequency in both groups of patients, but an association between DR3, and to a lesser extent B8, and defective suppressor T-cell function was only observed in the patients with PSC alone. These results not only provide further evidence of an association between HLA DR3 and impaired nonantigen-specific suppression but also indicate the genetic complexity of this association and its specificity, being found in this study in only one subgroup of patients with PSC.

Adult↗

PubMed1988

Rapid diagnosis of cytomegalovirus infection by in-situ hybridisation in liver grafts.

Cytomegalovirus (CMV) is a major cause of hepatic dysfunction after liver transplantation, but proof of infection and distinguishing CMV hepatitis from other causes of impaired liver function can be difficult. In-situ hybridisation for CMV-DNA in liver biopsy specimens was assessed in 25 liver graft recipients in whom CMV was suspected on clinical grounds. CMV-DNA was detected in all 10 patients with primary CMV infection, in whom a close correlation was found between the number of CMV-DNA-positive cells and both the number of cells containing viral inclusions identified by light microscopy and the clinical severity of disease. In contrast, CMV-DNA was not detected in patients with secondary CMV infection, or in those without evidence of CMV infection. In-situ hybridisation for CMV-DNA provides an accurate and rapid diagnosis of CMV infection, and allows specific antiviral therapy to be used earlier.

Complement Fixation Tests↗

PubMed1988

Interleukin-1 and interleukin-2 activity in chronic hepatitis B virus infection.

Abnormalities of lymphocyte proliferation in chronic hepatitis B virus infection are well documented, although the underlying mechanisms are poorly understood. To determine whether these defects may be secondary to disordered lymphokine production, we have simultaneously assayed interleukin-1 and interleukin-2 production in 31 chronic carriers of the hepatitis B virus. Supernatants from mononuclear cells cultured both in the presence and absence of lipopolysaccharide contained significantly increased quantities of interleukin-1 activity in patients compared with normal controls (p less than 0.01). Lysates of monocytes from patients also contained more interleukin-1 than those of controls (p less than 0.05) in the presence of lipopolysaccharide or silica, or both. These results indicate that interleukin-1 production is markedly elevated in patients with chronic hepatitis B virus infection, whereas in contrast, interleukin-2 production was found to be reduced in these patients (p less than 0.01). As one of the biological properties of interleukin-1 is to stimulate fibroblasts to produce collagen, the relationship between fibrosis in the liver biopsy specimen and interleukin production was examined. There was a highly significant correlation (p less than 0.001) between interleukin-1 production and the severity of fibrosis, suggesting that this lymphokine may be closely related to the development of cirrhosis in such patients.

Adult↗

PubMed1987

Oncocytic liver cell adenoma.

A 46-year-old woman underwent right hepatic lobectomy for the removal of a solitary liver tumour from a non-cirrhotic liver. The macroscopic and light microscopic features were those of a liver cell adenoma but the cells appeared oncocytic. Electron microscopy confirmed the numerous mitochondria characteristic of oncocytes. The difficulty of distinguishing oncocytic liver cell adenoma from fibrolamellar hepatocellular carcinoma is discussed.

Carcinoma, Hepatocellular↗

PubMed1987

Influence of aetiology, clinical and histological features on survival in chronic active hepatitis: an analysis of 204 patients.

To determine which clinical and laboratory features may influence survival in patients with chronic active hepatitis, we undertook a retrospective study of 204 patients seen on this unit over a 15-year period and applied logistic regression analysis. One hundred and six patients had autoimmune chronic active hepatitis, 69 'cryptogenic' chronic active hepatitis (no autoimmune markers or other aetiological factors identified), and 29 were HBsAg-seropositive. Variceal haemorrhage, encephalopathy and ascites were common presenting features in the cryptogenic group while the presence of jaundice and other immunopathic diseases did not differ between the groups. Cirrhosis was more common at presentation in the cryptogenic group. Remission was induced with corticosteroids and azathioprine in 82 per cent of patients with autoimmune chronic active hepatis and in 77 per cent of patients with cryptogenic chronic active hepatitis and the annual relapse rate was similar in the autoimmune and cryptogenic groups. Five-year survival was 87 per cent in the autoimmune group, 65 per cent in the cryptogenic group, and 80 per cent in those with HBsAg-positive disease, and on logistic regression analysis, the presence of cirrhosis at presentation was the only independent factor which adversely affected survival. Overall survival in the cirrhotic patients at five and 12 years was 63 and 48 per cent respectively compared with 95 and 92 per cent in those without cirrhosis.

Adolescent↗

PubMed1986

T and B cell function in alcoholic liver disease.

Increased in vivo synthesis of immunoglobulin in patients with alcoholic liver damage has been attributed to direct activation of B cells, although other defects of lymphocyte function have been identified suggesting a more generalised defect. In the present study we have investigated the role of T cell regulation of immunoglobulin production in alcoholic liver disease analysed according to the presence or absence of alcoholic hepatitis. Spontaneous production of IgG and IgA was elevated and co-culture experiments confirmed hyper-reactivity of B cells, but also suggested impaired T cell function. Suppressor cell activity for IgG and IgA was impaired. Similarly, the response to pokeweed mitogen for IgG and IgA was defective, although this was more marked for secretion than for proliferation suggesting an associated T helper defect. No differences in the immunological abnormalities were identified between those with alcoholic hepatitis and those with other alcoholic liver diseases. This study demonstrates a broad defect of T cells and a hyper-reactivity of B cells in patients with alcoholic liver disease, irrespective of the severity of hepatic inflammation.

Adult↗

PubMed1986

Mesenchymal hamartoma of the liver--report of an unusual case.

An 8 year old girl presented with gross hepatomegaly, anaemia and pyrexia unresponsive to antibiotics. At laparotomy a cystic mass 19 cm in diameter was found arising from the liver. The cyst contained 2.4 litres of changed blood and an abscess cavity filled with thick pus was present in the cyst wall. Histological examination showed the appearances of a mesenchymal hamartoma of the liver, a rare diagnosis at this age. This case is unusual as mesenchymal hamartoma has not been previously reported presenting with pyrexia and anaemia as well as hepatomegaly.

Anemia↗

PubMed1985

Risk factors in development of hepatocellular carcinoma in cirrhosis: prospective study of 613 patients.

In a prospective study of 613 patients with cirrhosis of different aetiological types increasing age, male sex, and non-UK nationality were found to be significant independent risk factors for the progression of cirrhosis to hepatocellular carcinoma. Seropositivity for hepatitis B surface antigen and the duration and aetiology of cirrhosis were not related to the development of the disease. Age and sex were also found to be significant risk factors when UK patients alone were considered. Seropositivity for hepatitis B surface antigen may be associated with hepatocellular carcinoma only because hepatitis B virus infection is a common cause of cirrhosis.

Adult↗

PubMed1984

Hepatocellular carcinoma in primary biliary cirrhosis: detection by alpha-fetoprotein estimation.

Serial estimations of serum alpha-fetoprotein in 130 white patients from the United Kingdom with primary biliary cirrhosis who were followed for periods of 1-52 mo revealed 5 cases of hepatocellular carcinoma; all were subsequently confirmed histologically. At the time alpha-fetoprotein was first noted to be elevated, none had signs or symptoms of tumor development. Of the 52 patients who died during the follow-up period, hepatocellular carcinoma was the cause of death in 3 (33%) of the 9 men, and 2 (5%) of the 43 women. Allowing for the marked predominance of women among patients with primary biliary cirrhosis, hepatocellular carcinoma may be no less frequent in primary biliary cirrhosis than in other types of cirrhosis.

Adult↗

PubMed1984

Hepatocellular carcinoma in the non-cirrhotic liver: a comparison with that complicating cirrhosis.

The clinicopathological features of 50 patients with hepatocellular carcinoma arising in a non-cirrhotic liver are described and compared with those of 100 patients in whom the tumour arose as a complication of cirrhosis. The non-cirrhotic patients were significantly younger, more often female and had a less strong association with serum markers of hepatitis B virus infection. Liver function tests and serum AFP were less often abnormal and survival was significantly better than in the cirrhotic group. The different aetiological factors, clinical features and prognosis of hepatocellular carcinoma arising in the non-cirrhotic liver compared to the more common form of hepatocellular carcinoma which complicates cirrhosis justifies detailed investigation by liver biopsy and other techniques.

Adolescent↗

PubMed1979

Leukocyte migration inhibition in response to biliary antigens in primary biliary cirrhosis, sclerosing cholangitis, and other chronic liver diseases.

The leukocyte migration inhibition test has been used to investigate cellular immune responses to antigens in a protein fraction (BPF) of normal human gallbladder bile in patients with a variety of intra- and extrahepatic diseases. Inhibition of leukocyte migration in the presence of BPF was observed in 30 (81%) of 37 patients with PBC, in 8 (80%) of 10 patients with sclerosing cholangitis, and in 7 (26%) of 27 patients with chronic active hepatitis. Only 1 of 31 patients with other liver diseases or with uncomplicated ulcerative colitis showed a similar response to BPF. The BPF was found to contain three antigens which were distinct from plasma proteins. Immunofluorescence studies revealed that one of these antigens appears to be derived from that part of the hepatocellular membrane which forms the bile canaliculus and that a second appears to be associated with the epithelial cell membranes of interlobular and septal bile ducts. The site of origin of the third antigen could not be established. It is suggested that cellular immune responses to biliary antigens could be involved in the progressive bile duct destruction of chronic biliary disease.

Adult↗