Neurotensin and hepatocellular carcinoma.
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Carcinoma, Hepatocellular↗
Biomedical subjects
B Portmann
Publications and source records attributed to B Portmann.
Recurrence of autoimmune chronic active hepatitis following orthotopic liver grafting.
In a 26-year-old woman who had received an orthotopic liver graft for end-stage autoimmune chronic active hepatitis, signs indicative of the original disease became apparent 18 months after transplantation, at a time when the maintenance dose of prednisolone had been reduced to 3 mg daily. In addition to anorexia, nausea, and weight loss there was a reappearance of spider naevi, serum autoantibodies, and elevated levels of immunoglobulin G. Features typical of chronic active hepatitis were observed on examination of the liver biopsy, and both the clinical and histological pictures were unlike those of other possible causes of liver dysfunction, such as chronic rejection, cyclosporine hepatotoxicity, and non-A non-B chronic hepatitis. Following substitution of azathioprine for cyclosporine and an increased dose of prednisolone (20 mg daily), there was a rapid improvement in the clinical state and both serum transaminases and immunoglobulins returned to normal values. Histological appearances in a repeat biopsy taken six months later were consistent with chronic active hepatitis in remission. This case provides further evidence of the importance of host factors in the pathogenesis of chronic active hepatitis and emphasizes the necessity for selecting appropriate immunosuppressive therapy in such patients after transplantation.
Adult↗
Duration of chronic active hepatitis and the development of cirrhosis.
Chronic hepatitis implies that clinical and biochemical features of hepatitis have been present for at least 6 months; but irreversible liver damage may occur with subclinical disease suggesting that pathological features should also define chronicity. We examined 28 children with hepatitis B negative chronic active hepatitis to determine whether the severity of abnormal biochemical tests of liver function, raised serum immunoglobulin concentrations, and positive serum autoantibodies, which are characteristic features in immunosuppressant responsive disease, varied with the duration of symptoms. The pattern of abnormality in these patients was similar whether the disease had been present for less than three months, from three to 6 months, or for more than 6 months, and apart from lack of hyperbilirubinaemia was similar in patients presenting with complications of cirrhosis without previous symptoms of liver disease. Two children died of liver disease. The remainder showed a clinical, biochemical, and immunological response to prednisolone or azathioprine, or both. These drugs have now been withdrawn in 8 patients without relapse, and disease activity is completely suppressed in 13. Unfortunately, 15 survivors have definite cirrhosis and a further five have possible cirrhosis. Eight of 10 survivors with symptoms of more than 6 months duration before treatment have cirrhosis compared with two of 12 with symptoms of less than 6 months. It is suggested that consideration of this diagnosis at onset of symptoms and immediate immunosuppressant treatment after appropriate confirmatory investigations may reduce the incidence of cirrhosis in hepatitis B negative chronic active hepatitis in children.
Adolescent↗
Antibodies to alcohol altered liver cell determinants in patients with alcoholic liver disease.
Circulating antibodies reacting specifically with hepatocytes isolated from ethanol pretreated rabbits have been demonstrated by two techniques - induced cytotoxicity and immunofluorescence. In the cytotoxicity assay antibodies were found in seven of 19 (39%) of patients with alcoholic fatty liver (with or without fibrosis), six of 13 (46%) of those with alcoholic hepatitis, 15 of 36 (43%) of those with cirrhosis, and seven of 14 patients (50%) of those with hepatitis and cirrhosis. In the immunofluorescence studies, nine of 15 sera induced a granular pattern of fluorescence on the ethanol pretreated hepatocytes; two sera which induced significant cytotoxicity did not induce immunofluorescence. No ethanol related antibodies were found in normal individuals or in patients with other types of acute or chronic liver disease. These results show that antibodies directed against ethanol altered liver cell determinants are present in the serum of 43% of patients with alcoholic liver disease, and suggest a mechanism whereby chronic alcohol consumption may, by inducing antigenic changes in hepatocyte membranes, trigger a cell damaging immune reaction.
Adult↗
Chronic liver disease in children with leukemia in long-term remission.
Liver disease during chemotherapy and after its completion was studied in 103 leukemic children in long-term remission. Seventy developed chronic liver disease during therapy; 22 out of 56 with adequate follow-up showed persisting abnormality or deterioration of liver function after stopping therapy. In 38 studied prospectively, biopsies were obtained at treatment withdrawal. Five showed chronic lobular, 17 chronic persistent, 9 chronic active hepatitis whereas 7 had minimal changes. These children had transiently detectable serum hepatitis-B virus (HBV) markers during (44.4%), at completion of (7.8%) and subsequent to (48.3%) chemotherapy. Serum HBV markers correlated significantly with both severity of histologic changes (P less than 0.05) and persistent biochemical abnormalities for over 6 months after treatment suspension (P less than 0.001). No direct relationship was found between drug administration and liver damage. The data from the study suggest that in leukemic children viral infections contribute to chronic liver damage, which can jeopardize the long-term prognosis of acute leukemia.
Acute Disease↗
Importance of markers of hepatitis B virus in alcoholic liver disease.
To determine the importance of the presence of serological markers of hepatitis B virus infection in patients with alcohol related liver disease we compared cumulative alcohol intake and clinical and histological features in patients with markers of hepatitis B virus infection and in those without. Hepatitis B surface antigen (HBsAg) was detected in five (2%) out of 285 patients studied and antibody to HBsAg (anti-HBs) in 41 (14%); one patient had antibody to hepatitis B core antigen alone. The combined prevalence of markers of hepatitis B virus infection was similar in patients with alcoholic cirrhosis (18%) and precirrhotic liver disease (13%). Two patients positive for HBsAg had histological features of both alcoholic liver disease and chronic active hepatitis, with stainable HBsAg. Patients with anti-HBs were, however, histologically indistinguishable from patients without markers, and the mean cumulative alcohol intake of patients with anti-HBs was similar to or even higher than that of patients with liver disease of comparable severity who had no evidence of previous infection. The presence of markers of hepatitis B virus infection was related to former residence in countries with a high prevalence of the infection and to previous parenteral treatment and blood transfusions. Infection with hepatitis B virus does not enhance the development of chronic liver disease in heavy drinkers, except in the small number who remain positive for HBsAg.
Adult↗
Androgen related primary hepatic tumors in non-Fanconi patients.
Three cases of androgen related primary hepatic tumor in non-Fanconi patients are described in whom detailed information is available concerning histologic changes and clinical course over long periods. Two patients presented with hepatic rupture and hemoperitoneum requiring surgical intervention. In one case histologic assessment showed a hepatic adenoma which has almost completely regressed over four years since androgen withdrawal. In two patients there was a degree of nuclear pleomorphism not seen in 'spontaneous' adenomas and following androgen withdrawal there has been no evidence of progression or of metastases although the tumor has not regressed over a follow-up period of two years.
Adult↗
Delta infection in the U.K.
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Hepatitis B↗
Evidence of non-A, non-B hepatitis in children with acute leukemia and chronic liver disease.
Eleven children with acute lymphoblastic leukemia and chronic liver disease, who had negative reactions for hepatitis B virus markers in the liver, were studied at the time of therapy withdrawal for an antigen-antibody system linked to non-A, non-B (NANB) hepatitis infection. By immunofluorescence, six of the 11 children had a positive reaction for the NANB antigen in the liver, and five of these six children also had a positive reaction for the NANB antibody in serum. Histologic lesions were more severe in patients with the NANB antigen in the liver compared with those with a negative reaction.
Adolescent↗
Non-A, non-B hepatitis in persistent carriers of hepatitis B virus.
There are reports in the literature that infection with hepatitis A virus in hepatitis B carriers can result in resolution of the carrier state. In an attempt to induce clearance of the carrier state of hepatitis B virus in two persistently infected chimpanzees, the chimpanzees were infused with documented non-A, non-B infectious material. Biochemical and histopathological evidence of hepatitis was accompanied by the unique abnormalities of endoplasmic reticulum associated with non-A, non-B hepatitis in the chimpanzees. Elevation of alanine aminotransferase was accompanied by fourfold reduction in one chimpanzee and sixfold reduction in the other in the plasma levels of HBV-associated DNA polymerase activity and simultaneously by twofold reduction in the concentration of hepatitis B surface antigen in both chimpanzees. A mediator may account for these changes in markers of hepatitis B virus infection, and this mechanism may also explain the occurrence of spontaneous regression in some persistently infected carriers. The significance of transient red cell anaemia in non-A, non-B hepatitis, which was observed in one of the chimpanzees, is yet to be established.
Alanine Transaminase↗
Lymphocyte cytotoxicity to autologous hepatocytes in alcoholic liver disease.
Cytotoxicity of peripheral blood lymphocytes for autologous hepatocytes has been studied in 18 patients with different histological types of alcoholic liver disease. Cytotoxicity was significantly increased in five of ten patients with cirrhosis and/or alcoholic hepatitis but in only one of eight with fatty infiltration or minor histological changes. The cytotoxic effect of T-and non-T-effector cells was separately evaluated in 11 cases. Of six patients with alcoholic hepatitis, non-T lymphocyte cytotoxicity was increased in five and T-cell in only one. These preliminary results are consistent with the concept that autoimmune reactions may play a role in the development and progression of alcoholic hepatitis and cirrhosis, although it is likely that direct hepatotoxic effects of ethanol or its metabolites are also important in determining the pattern of liver injury and perhaps in initiating the immune reactions observed in this study.
Autoantibodies↗
The value of clinical, biochemical, ultrasound and liver biopsy data in assessing patients with liver disease.
To determine the value of clinical, biochemical, ultrasound and liver biopsy data in the management of patients with liver disease, eight doctors each assessed 75 case histories. With clinical and biochemical data alone, the predictive accuracy was significantly higher when identifying patients as 'medical' rather than 'surgical' (97 compared with 79%, p less than 0.001). However, when making a specific diagnosis as opposed to classifying into medical and surgical categories, clinical and biochemical information resulted in a much lower predictive accuracy for both medical (67%) and surgical (56%) patients. With ultrasound data the predictive accuracy increased to 91% when identifying patients as 'surgical'; with liver biopsy it increased to 99% when identifying patients as 'medical'. The value of the different data assessed involves more than an evaluation of diagnostic accuracy, and in this study the relative worth of each test was therefore assessed on a five point scale based on the effect of the information on the doctors. This included a willingness to give specific treatment and make a specific diagnosis, as well as classifying patients into medical and surgical categories and the confidence they felt in their diagnoses. After clinical, biochemical and ultrasound information the doctors were only prepared to give specific treatment to 11.9% of the medical and 9.3% of the surgical patients. After liver biopsy data, however, they were willing to give specific treatment to an additional 66.6% of the medical patients and 25% of the surgical patients. Further evidence of the value of liver biopsy information came from an analysis of the changes in the doctors' confidence in a diagnosis. Thus, 96 patients were assigned a correct specific diagnosis with clinical and biochemical data alone but none were considered as 'definitive' by the doctors; when liver biopsy information was provided 59 (61%) were placed in this category.
Biopsy↗
Outcome of liver disease associated with alpha 1 antitrypsin deficiency (PiZ). Implications for genetic counselling and antenatal diagnosis.
We reviewed the hepatic features in 136 children with alpha 1 antitrypsin deficiency (PiZ). Eighty two were studied prospectively, 74 of whom had chronic liver disease. Sixty seven children with liver disease presented in the first four months of life, four were older infants and children with chronic liver disease, 10 (three with liver disease) were identified in studies of the family of these propositi, and one was identified when she had liver disease associated with infectious mononucleosis. By 17 years of age 20 of these 74 children with chronic liver disease had died, 20 had established cirrhosis, 19 had persisting liver disease, and only 15 had made a complete, clinical and biochemical recovery. The outcome of liver disease was similar in a further 39 previously unreported PiZ infants and children with liver disease who were not prospectively studied. Because liver disease affects only a proportion of infants with PiZ phenotype and because the severity of their liver disease is so variable, we have analysed the outcome of liver disease in 27 observed families and in 20 previously reported families with more than one child with PiZ. In 34 families the outcome of liver disease was similar in the two children. From an analysis of the families with a severely affected child, we conclude that if the first PiZ child of PiZ heterozygote parents has unresolved liver disease, there is a 78% chance that a second PiZ child will have similar liver disease. After careful counselling, fetoscopy, fetal blood sampling, and protease inhibitor phenotyping, possible termination of pregnancy should be carefully considered in these families.
Adolescent↗
The prelaparotomy diagnosis of extrahepatic biliary atresia.
The diagnostic accuracy of laboratory investigations in the prelaparotomy differentiation between extrahepatic biliary atresia (EHBA) and intrahepatic disease (IHD) was assessed in 86 consecutive infants presenting with conjugated hyperbilirubinaemia. Forty five infants had EHBA and 41 IHD. The mean serum bilirubin concentration, gamma-glutamyltranspeptidase (GGT) activity, and the GGT/aspartate transaminase (AST) ratio were appreciably higher in infants with EHBA than in those with IHD. In infants with IHD, however, serum bilirubin concentrations were in the EHBA range in 19 (47%), as were GGT values in 29 (71%), and GGT/AST ratios in 33 (80%). In individual patients neither increasing nor decreasing GGT values were of diagnostic importance. Failure of biliary excretion of 99Tcm-p-Butyl-ida occurred in 29 of 30 (97%) patients with EHBA but also in 22 of 23 (67%) with IHD. In all 5 patients with IHD associated with alpha 1 antitrypsin deficiency these 4 investigations gave results in the EHBA range. Liver biopsy specimen interpretation, correct in 38 of 42 infants with EHBA, gave an overall accuracy of diagnosis of 86%: the results of 3 further biopsies were equivocal. In 33 of 40 infants with IHD bile duct obstruction was excluded; the remaining 7, including 4 with alpha 1 antitrypsin deficiency, showed equivocal changes. Faecal excretion of 131I rose bengal faecal excretion was less than 10% in 36 of 37 patients with EHBA and in 9 of 26 with IHD, giving an overall accuracy of diagnosis of 84%. In patients in whom genetic disorders, such as alpha 1 antitrypsin deficiency had been excluded, interpretation of liver biopsy specimens together with 131I rose bengal faecal excretion remain the most accurate means of identifying those who need surgery for EHBA and of avoiding unnecessary laparotomy in infants with IHD.
Aspartate Aminotransferases↗
Wilson's disease and hepatocellular carcinoma: possible protective role of copper.
A male patient with Wilson's disease developed a hepatocellular carcinoma after treatment for nine years with D-penicillamine. Examination at necropsy showed that excess liver copper had been effectively removed. As copper has been shown to protect against chemically induced hepatocellular carcinoma in rats, this may be the reason for the extreme rarity of hepatocellular carcinoma in patients with Wilson's disease and possibly in other liver diseases with hepatic copper overload.
Adult↗
Value of copper-associated protein in diagnostic assessment of liver biopsy.
Of 1361 consecutive liver biopsy specimens, 24% contained orcein-positive granules. The highest incidence of positivity was found in biliary disease (90.9%), long before cirrhosis had developed, whereas in chronic non-primarily biliary disease, positive results were almost exclusively in patients with well established cirrhosis. Orcein-positive granules were never found in acute liver disease. These granules were also demonstrated in tumour cells of primary hepatocellular tumours (benign 4 of 4 cases; malignant 9 of 37 cases), while all the secondary tumour deposits were negative. In our view the additional information obtained by this technique warrants its adoption as a routine procedure.
Carcinoma, Hepatocellular↗
Liver damage with reversible portal hypertension from vitamin A intoxication: demonstration of Ito cells.
A patient with sudden onset of ascites and hepatosplenomegaly made a complete recovery after vitamin A was withdrawn. Fluorescence microscopy on embedded tissue provided a simple method of demonstrating the accumulation of fat storage (Ito) cells in the liver.
Adult↗
Hepatocellular carcinoma complicating chronic granulomatous hepatitis.
The development of hepatocellular carcinoma, is reported in a patient with chronic granulomatous hepatitis after a seven year interval in which clinical and biochemical improvement had occurred on corticosteroid therapy and in whom, the development of cirrhosis was excluded by liver biopsy.
Carcinoma, Hepatocellular↗