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Biomedical subjects

B Portmann

Publications and source records attributed to B Portmann.

At least 217 records · Page 12Linked to original sources

Hepatocellular carcinoma in Great Britain: influence of age, sex, HBsAg status, and aetiology of underlying cirrhosis.

An analysis of 294 patients who died with cirrhosis showed that 24% had developed hepatocellular carcinoma. Haemochromatosis and HBsAg positive chronic active hepatitis were high risk groups (36% and 42% respectively) and the frequency was lowest in primary biliary cirrhosis and HBsAg negative chronic active hepatitis (3% and 11% respectively). Those with hepatocellular carcinoma showed a striking male preponderance (11:1) and further analysis has shown that the proportion developing this tumour in each group was closely related to the proportion of males in that group (r=0.97). Age was the only other significant factor, malignant change occurring more commonly in those over the age of 50 years than those below (30% and 7% respectively, P less than 0.005). The indluence of HBsAg was largely accounted for by the known predisposition of males to carry HBsAg. The group of patients who had developed this tumour without cirrhosis were younger (mean age 39 years) and had a lower male to female ratio of 1.1:1 and the place of contraceptive-related tumour within this group is dicussed.

Adult↗

Lymphocyte cytotoxicity in chronic active hepatitis: effect of therapy and correlations with clinical and histological changes.

A study of lymphocyte cytotoxicity for rabbit hepatocyte cultures in 15 patients with untreated chronic active hepatitis showed positive results in all cases, both HBsAg positive and negative. After immunosuppressive therapy cytotoxicity became negative and remained negative, in four of nine patients followed serially. In 51 patients established on therapy for periods from three months to 12 years, cytotoxicity was negative in 19 and all patients are currently alive. However, in the remaining 32 patients in whom cytotoxicity was positive there has been a 34% mortality. Cytotoxicity remained persistently positive in 12 of 15 patients followed serially, and persistently negative in seven of nine. Cytotoxicity showed a significant association with histological disease activity, especially the extent of piecemeal necrosis, but not with biochemical tests of liver function, immunoglobulins, or autoantibodies. The basis of this cytotoxicity test is an antibody dependent cell-mediated autoimmune reaction directed against a liver specific protein, and the results suggest that in some cases immunosuppressive therapy is followed by control of this reaction. It may be possible to stop therapy in these patients, but in those in whom the reaction continues, as shown by continuing cytotoxicity, the prognosis is not as good and the use of other drug schedules would seem worthy of trial.

Adult↗

Changing pattern of alcoholic liver disease in Great Britain: relation to sex and signs of autoimmunity.

A survey of 293 patients with alcoholic liver disease showed that women, particularly those aged under 45, had a significantly higher incidence of alcoholic hepatitis, with or without superimposed cirrhosis, than men. The long-term prognosis for both women who continued to drink and those who stopped drinking was worse than that for men. Autoantibodies were more common in women, which suggested that immune mechanisms may play a part in the pathogenesis and progression of alcoholic liver disease in women.

Adult↗

Observations on preservation, bile drainage and rejection in 64 human orthotopic liver allografts.

The combined Cambridge/King's College Hospital series of 64 orthotopic liver grafts' experience dates back to 1968. Many patients were referred for liver grafting late in the course of their diseases and were operated on when they were too ill or died before suitable livers could be found. Complications of biliary drainage were the most frequent causes of death. In the past two years we have acquired experience of a method of liver preservation which permits up to 8 hours of safe storage without any complicated machines and we have been able to transport 22 livers by air and road from other institutions to our own unit. This has enlarged the pool of potential donors and therefore reduced the average waiting time for a liver transplant. A new method of biliary drainage has been employed in 24 patients using the vascularised gall bladder as a conduit between the donor and recipient common ducts. This has resulted in a marked reduction in early postoperative complications of biliary fistula and obstructed bile drainage. Now that survival has improved, it has become clear that uncontrollable rejection of the allografted liver in man is much less severe than that experienced with kidney transplants. The results of liver grafting in our unit during the past year are better than those obtained with kidneys from cadaver donors.

Common Bile Duct↗

Lymphocyte cytotoxicity for isolated hepatocytes in alcoholic liver disease.

To determine whether an autoimmune reaction to liver-specific proteins occurs in alcoholic liver disease, the cytotoxic effect of lymphocytes on isolated hepatocytes was determined in 27 alcoholic patients. Cytotoxicity was demonstrated in 15 of 17 patients with a histological diagnosis of alcoholic hepatitis, but in none of 10 with other forms of alcoholic liver disease. The ability of a liver-specific membrane lipoprotein to block the reaction suggests that sensitization to this antigen is responsible for the cytotoxicity. The demonstration of cytotoxicity using T cell-depleted, but not B and K cell-depleted, lymphocytes suggests an antibody-dependent cell-mediated reaction. There was a close correlation between cytotoxicity and the presence of alcoholic hyalin, liver cell necrosis, and piecemeal necrosis, but not with other histological features, immunoglobulines, autoantibodies, or standard liver function tests. The persistence of this autoimmune response, induced in some way by alcohol or one of its metabolites, may be important in the progression of acute alcoholic hepatitis to chronic liver disease.

Acute Disease↗

Immune response to HBsAg and the spectrum of liver lesions in HBsAg-positive patients with chronic renal disease.

Evidence of chronic hepatitis was found on histological examination in nine out of 15 patients positive for hepatitis-B surface antigen (HBsAg) who had either chronic renal failure or a functioning renal transplant. Cirrhosis had already developed in three of the patients, who deteriorated rapidly and died. Liver biopsies from the remaining 12 patients showed the features of chronic aggressive hepatitis in two, chronic persistent hepatitis in four, and minor histological lesions in six. The persistence of HBsAg in patients with renal failure or in those receiving immunosuppressive drugs after a transplant must indicate some impairment of the normal immune response to hepatitis-B viral antigens. Nevertheless, cellular or humoral immunity to HBsAg was detected in all eight patients with chronic hepatitis tested compared with only one out of five with minimal liver lesions, which suggests that the severity of the liver damage may be directly related to the degree of immunocompetence.

Adult↗

Detection of HBSAG in fixed liver tissue - use of a modified immunofluorescent technique and comparison with histochemical methods.

A modified immunofluorescent technique was used for the detection of HBSAg in formalin-fixed liver tissue, thereby allowing retrospective examination of paraffin sections and avoiding the need to split the sample at the time of biopsy. Comparison with two other methods, involving either orcein staining or standard haematoxylin and eosin (H and E) preparation for ground glass hepatocytes, showed slightly fewer positive hepatocytes in individual biopsies with the latter stain, but the specificity of both methods was high. In a series of 146 seropositive and 74 seronegative patients with a variety of liver disorders, hepatocytes positive for HBSAg were found in only one of 55 patients with acute hepatitis type B, whereas large numbers of positive cells were seen in all 22 healthy carriers of the surface antigen. In the 69 patients with chronic persistent or chronic aggressive hepatitis, the frequency of positive biopsies was 86% and 85% respectively. The positive cells in these cases were, in comparison with healthy carriers of HBSAg, much fewer in number and were scattered in random fashion throughout the lobule rather than occurring in discrete clumps or sheets. This variation in the intrahepatic expression of HBSAg may reflect differences in the immune response to hepatitis B viral antigens.

Acute Disease↗

Focal nodular hyperplasia of the liver: a rational approach to treatment.

Focal nodular hyperplasia of the liver in a 3 year old child has been successfully treated by ligation of the hepatic artery branches supplying the lesion. The prominence of the abnormal vasculature in the lesion and its possible aetiological involvement is stressed. Because of the risks of partial hepatectomy, hepatic artery ligation is suggested as the treatment of choice for focal nodular hyperplasia.

Child, Preschool↗

Paracetamol metabolism in the rat: relationship to covalent binding and hepatic damage.

1. The degree of liver damage observed 48 h after administration of 14C ring-labelled paracetamol (3-23 mmol/kg) to rats was proportional to the amount of a highly reactive metabolite retained in the liver, bound covalently to hepatocellular proteins. 2. With increasing doses of paracetamol, urinary excretion of the glucuronide and sulphate conjugates reached a plateau, whereas the output of cysteine and mercapturic acid conjugates increased markedly. 3. The degree of covalent binding at 48 h was proportional to the rate of urinary elimination of these two latter conjugates in the first 24 h after dosing.

Acetaminophen↗

Histological sexing of a reticulum cell sarcoma arising after liver transplantation.

Nuclear sex determination, based on both X and Y chromatin counts in a reticulum cell sarcoma which arose in the liver 5 months after orthotopic grafting, clearly showed that the tumor was of host origin. The Kupffer cells of the graft were also found to be of host origin, demonstrating that their replacement may occur within 6 months of operation.

Female↗

Cellular immune responses to salivary antigens in autoimmune liver disease with sicca syndrome.

Twenty-six patients with primary biliary cirrhosis (PBC) and twenty-two with active chronic hepatitis (ACH) were examined for evidence of the sicca syndrome (keratoconjunctivitis sicca, xerostomia). Measurements of tear flow and total saliva flow showed that at least one sicca feature was present in twenty (77%) of the patients with PBC and ten (45%) of those with ACH. Examination of cellular immune responses to a protein fraction of normal human saliva using the leucocyte migration test showed sensitization to the saliva protein in twenty-three of the thirty cases with sicca syndrome but in only two of the eighteen in whom sicca features were not detected. Antisera raised in guinea-pigs against the saliva protein gave specific immunofluorescent staining of bile duct epithelial cells in sections of normal human liver. These findings suggest that damage to structures in the liver may lead to sensitization to various self-antigens which cross-react with other tissues in which a similar disease process may be consequently be initiated.

Antigens↗

Histological evidence of carcinoma in a hepatic tumour associated with oral contraceptives.

A primary hepatic tumour occurred in a 21-year-old woman who had been taking oral contraceptives for two years; she was treated by partial hepatectomy. Part of the neoplasm showed features suggestive of focal nodular hyperplasia, while the remainder had the histological characteristics of a well-differentiated hepatocellular carcinoma. This is the first report of malignant transformation of a tumour in a patient taking oral contraceptives.

Adult↗

Chronic liver disease developing after outbreak of HBsAG-negative hepatitis in haemodialysis unit.

Chronic liver disease developing after acute hepatitis type B is well documented, but is not thought to occur after acute hepatitis due to other viruses. However, follow-up of 29 patients in a haemodialysis unit who contracted HBsAg-negative acute hepatitis during 1968-70 revealed 8 cases with raised serum-aminotransferase levels dating from that time. Liver biopsy in 7 of these disclosed chronic aggressive hepatitis in 3, of whom 2 had already progressed to advanced cirrhosis. Chronic persistent hepatitis was present in 2 others, and the remaining 2 had non-specific hepatitis in association with massive iron overload. Immunological studies demonstrated a higher frequency of cellular immunity to HBsAg in those who had previously had acute hepatitis than in those who had not, although the prevalence of humoral antibody was similar in the two groups. One possible explanation for these findings is the presence of immunological cross-reaction at a cellular level between the hepatitis B virus and that responsible for the initial outbreak.

Adult↗

Histopathological changes in the liver following a paracetamol overdose: correlation with clinical and biochemical parameters.

The histological appearances of the liver damage occurring after a paracetamol overdose are described in liver biopsies from 104 patients, of whom 38 developed fulminant hepatic failure. Confluent centrilobular necrosis of varying extent was followed by rapid disappearance of necrotic cells, leaving areas of reticulin collapse and a usually mild inflammatory reaction. The histological recovery in even the most severe cases was remarkable, and only one of the 17 survivors whose initial biopsy showed the pattern of interlobular bridging necrosis had appreciable residual fibrosis in a follow-up biopsy taken after 1 yr. A quantitative estimate was made of the amount of surviving liver parenchyma using a morphometric technique and the hepatocyte volume fraction (HVF) in biopsies performed within 10 days of the overdose correlated well with the clinical course and both the maximal prolongation of the prothrombin time and the peak plasma bilirubin concentration in the first 10 days. An HVF value (normal 85 +/- 5 per cent.) of less than 40 per cent. in a biopsy taken within 10 days of the overdose was found only in patients who died. However, HVF measurements on biopsies from three survivors taken later than 10 days after the overdose shows that survival is possible below this critical level.

Acetaminophen↗