Studies of portal hemodynamics and hepatic oxygen consumption during acute liver allograft rejection.

Hemodynamics and oxygen variables, plasma cytokines, and histological features of a liver tissue sample obtained by transvenous biopsy were evaluated during 65 episodes of acute rejection. The hepatic venous pressure gradient was significantly higher in patients with acute rejection than in those without (5.1+/-0.3 vs. 3.1+/-0.2 mmHg, P<0.01). The increase in pressure gradient was related to the severity of rejection lesions. Hepatic blood flow was significantly lower in patients with than in those without acute graft rejection (1.28+/-0.11 vs. 1.75+/-0.13 L/min, P<0.05). Plasma interleukin-6 levels were significantly increased in patients with acute rejection and positively correlated with pressure gradient values. In patients with acute rejection, a significant decrease in hepatic venous oxygen content (-16%) was associated with a significant increase in hepatic oxygen consumption (+24%), whereas hepatic oxygen transport did not change significantly. In treated patients with a favorable response, the pressure gradient decreased significantly by 46%, but it remained elevated in patients who later developed chronic graft rejection. In conclusion, this study confirms that acute graft rejection may induce an increase in portal pressure, which is related to the severity of rejection lesions. It also shows that acute rejection decreases hepatic blood flow and increases hepatic oxygen consumption. In addition, it suggests that the hepatic venous pressure gradient might be useful to determine the outcome of rejection.

Hemodynamics after orthotopic liver transplantation: study of associated factors and long-term effects.

Among 68 liver transplant recipients, 190 hemodynamic studies were performed to evaluate the role of sepsis, anemia, acute graft rejection, and persistent portosystemic shunts. The hemodynamic outcome after orthotopic liver transplantation (OLT) in stable patients was also determined. Patients with sepsis showed a significant increase in cardiac index (5.1 +/- 0.9 vs. 3.4 +/- 0.7 L/min m2) and hepatic venous pressure gradient (6.3 +/- 2.9 vs. 3.3 +/- 2.1 mm Hg), compared with patients without sepsis. Cardiac index was higher in patients with, than in patients without, anemia (4.1 +/- 0.6 vs. 3.0 +/- 0.6 L/min m2). The hepatic venous pressure gradient was higher in patients with than in patients without acute graft rejection (5.1 +/- 2.9 vs. 2.6 +/- 1.2 mm Hg). Among patients with acute rejection, the hepatic venous pressure gradient was higher in patients with severe rejection than in those with moderate or mild rejection (7.2 +/- 3.3 vs. 4.6 +/- 2.4 and 2.8 +/- 0.9 mm Hg). In the postoperative period, in patients undergoing transplantation for acute liver failure, the hepatic blood flow was normal and significantly lower than in patients receiving transplant for cirrhosis (1.15 +/- 0.37 vs. 1.96 +/- 0.71 L/min). In patients undergoing transplantation for cirrhosis, cardiac index, azygos, and hepatic blood flows significantly decreased after 1 year compared with the first 6 postoperative months. Multivariate analysis showed that sepsis, anemia, and time after OLT were independent variables influencing cardiac index. Sepsis, time after OLT, and the existence of portosystemic shunts were independent variables influencing hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

[Histologic and immunohistochemical profiles of benign granular cell tumors. Report of 41 cases]. / Profils histologique et immunohistochimique des tumeurs bénignes à cellules granuleuses. A propos de 41 cas.

Since the descriptions of << myoblastomas >>, later denominated granular cell tumours, many immunohistological and ultrastructural studies have been undertaken with the aim of establishing their histogenesis. Now the hypothesis of a neurogenic origin appears clear. From the large number of cases (53) diagnosed in Geneva over a period of 10 years, we decided to do a retrospective study of these tumours with regard to their immunohistological phenotypes, using the following markers: S100 protein (S100), Neuron specific enolase (NSE), Vimentin, Chromogranin, Glial fibrillary acidic protein (GFAP), Keratin, Epithelial membrane antigen (EMA), Desmin, Smooth muscle alpha actin. 100% of tumours were positive for S100, and 90% for NSE, which confirms the neurogenic origin. 70% were Vimentin positive, with however a variable intensity. All the other markers were negative. Immunohistological staining for S100 and NSE may be useful tool in the diagnosis of these tumours.

[Prevention of viral recurrence following liver transplantation for post-hepatitis B and B-delta cirrhosis]. / Prévention de la récidive virale après transplantation hépatique pour cirrhose post-hépatitique B et B-delta.

The incidence of recurrence of hepatitis B virus (HBV) following orthotopic liver transplantation (OLT) is as high as 80% when no attempt at prevention has been considered. HBV reinfection is associated with the reappearance of hepatitis B surface antigen (HBsAg) and HBV DNA in serum and, in most cases, with rapid severe graft damage. Immunoprophylaxis using polyclonal anti-HBs immunoglobulins reduces the risk of recurrence but this long-term therapy remains highly expensive. In this report, we use fresh frozen plasma (FFP) with high titers of anti-HBs immunoglobulins in an attempt to reduce HBV recurrence. From July 1987 to September 1993, 11 patients underwent OLT for HBV-related liver disease (18% of our OLT patients). FFP were administered to 6 patients continually for 7 to 46 months. Only one patient, under long-term immunosuppressive treatment before OLT, was reinfected 7 months after OLT. Rapid development of graft failure was observed with histologic manifestations of a fibrosing cholestatic hepatitis, leading to patient death after 12.5 months with concomitant bacterial infection. In this protocol, the rate of reappearance of HBsAg was 17%, a figure which can be favorably compared with other reports. All patients were subsequently tested for HCV and HIV and remained negative. In conclusion, FFP with high titers of anti-HBs immunoglobulins is at least as effective as polyclonal anti-HBs immunoglobulins in reducing the rate of HBV recurrence following OLT. The estimated cost of this new immunoprophylaxis method is less than 10% of the classical prophylaxis based on purified human polyclonal anti-HBs immunoglobulins.

[Positron emission tomography (PET) in the preoperative evaluation of cervical lymph node metastasis of ORL cancer]. / La tomographie par émission de positrons (PET) dans l'évaluation préopératoire des métastases ganglionnaires cervicales des cancers ORL.

The distribution of specific radiolabeled biological compounds in tumor tissues can be imaged by positron emission tomography (PET). The substance used is fluorodeoxyglucose, labeled with the positron emitter fluorine-18. This substance is partly trapped in tumor cells with increased glucose metabolism. This noninvasive imaging technique allows to assess quantitatively and in three dimensions the extent of metastatic disease in ENT cancer. The case presented illustrates the important value we foresee for this new imaging modality in the presurgical staging of cervical metastatic disease of ENT tumors. Sensitivity and specificity of the PET-FDG imaging technique for the loco-regional staging of ENT cancer are, according to preliminary results of an ongoing, prospective clinical study, very high.

Hepatitis C: a possible etiology for cryoglobulinaemia type II.

Out of 15 successive patients with mixed essential cryoglobulinaemia type II (monoclonal IgM kappa/IgG), 13 had serological evidence for hepatitis C infection as shown by specific enzyme immunoassays and immunoblot. RNA was purified from the serum of seven patients and hepatitis C sequences were identified in five following reverse transcription and DNA amplification. The liver histology showed chronic active hepatitis with or without cirrhosis in the 12 patients with hepatitis C who had a liver biopsy. The two patients without serological evidence of hepatitis C suffered from haematological malignancies. Hepatitis C may be a major etiological agent of cryoglobulinaemia type II.

[Liver transplantation for primary biliary cirrhosis]. / Transplantation hépatique pour cirrhose biliaire primitive.

Primary biliary cirrhosis (PBC) is regarded as one of the optimal indications for orthotopic liver transplantation (OLT) in adults. Between July 1987 and August 1991, 7 patients had PBC as the indication for OLT. 6 were transplanted and one patient is still on the waiting list. The patients' mean age was 47 years (range: 39 to 59) and the time from diagnosis to indication for OLT was 4, 7, 8, 10, 12, 15 and 17 years. Variceal hemorrhage episodes treated by sclerotherapy (plus porta-caval shunt in one patient) occurred in 3 patients before OLT. All suffered from jaundice (mean bilirubin 232 mumol/l, range 116 to 536), weakness, anorexia and pruritus. There were no deaths in this series during a mean follow-up time of 26 months (range 6 to 43). With the exception of osteopenia, all complications of chronic liver disease were reversed by OLT. Despite numerous postoperative problems (e.g. reoperations, intense rejection episodes, cytomegalovirus infections and lumbar column fractures), the quality of life is excellent for these 6 patients. Mean bilirubin at time of last follow-up was 18 mumol/l (range 8 to 26). No evidence of PBC recurrence was found. Based on international experience confirmed by this series, we support the notion that no patient suffering from advanced PBC should be denied OLT whenever possible.

[Acute Budd-Chiari's syndrome after surgical treatment of polycystic liver disease]. / Syndrome aigu de Budd-Chiari après traitement chirurgical d'une polykystose hépatique.

A case of acute Budd-Chiari syndrome after surgical treatment of polycystic liver disease is described. This complication, presently unreported in the literature, was secondary to the operative interruption of two hepatic veins, while the third was already obstructed by pericystic fibrosis. Preoperative radiologic vascular mapping should be performed in case of voluminous polycystic liver disease when associated liver resection appears likely.

[Liver transplantation. Preliminary results in the district University Hospital of Geneva]. / La transplantation hépatique. Expérience préliminaire de l'Hôpital cantonal universitaire de Genève.

Between July 1987 and May 1989, 11 liver transplants were performed on 10 patients at the University Hospital of Geneva. Of 15 patients evaluated for elective transplantation, 10 were accepted and put on the waiting list. 5 patients were rejected because of a contraindication or because another treatment seemed preferable. 8 transplantations were eventually performed. Emergency transplantation was considered for 6 patients, but could be performed in only 3. Indications for transplantation were as follows: one hepatocellular carcinoma in a non-cirrhotic patient, 2 post-hepatitis cirrhoses (one B and one non-A-, non-B), 3 primary biliary cirrhoses, one autoimmune cirrhosis, one primary sclerosing cholangitis, one cirrhosis on alpha-1-antitrypsin deficiency, and one fulminant B-Delta hepatitis. Most of these patients had advanced liver disease and a limited life expectancy. 8 of the 10 patients transplanted are nevertheless alive and none is hospitalized at the present time. More than mere survival, however, quality of life regained after transplantation prompts us to consider transplantation early in the progress of the disease. Earlier evaluation of patients would make transplantation feasible soon after the first complication of the disease. This attitude would probably prevent patients from dying while on a waiting list and decrease operative as well as early postoperative risks. Better information and coordination regarding potential donors is necessary in Switzerland to obtain better results in organ transplantation.

Recurrent febrile panniculitis and hepatitis in two patients with acquired complement deficiency and paraproteinemia.

Repeated episodes of febrile panniculitis and hepatitis were the main clinical features in two patients with an IgG1 kappa paraproteinemia and severe depletion of the early components of the classical pathway of complement (acquired C1 inhibitor deficiency). They did not have episodes of cutaneous angioedema or evidence of immune complex disease. In the more severely affected patient, the episodes responded to steroids. These features have not been described with acquired C1 inhibitor deficiency and may be related to complement activation.

[The role of ultrasonography in the diagnosis of diffuse liver disease]. / L'apport de l'ultrasonographie dans le diagnostic des hépatopathies diffuses.

131 patients thought to have diffuse liver disease underwent ultrasonography and percutaneous liver biopsy. The ultrasonographic criteria examined were hepatic echogenicity compared to that of the renal cortex, homogeneity of hepatic parenchyma, and regularity of hepatic outline. On the basis of histologic examination of liver biopsies, several groups of pathologic lesions (not diagnostic entities) were established. Evaluation of ultrasound and histology was double blind. When the lobular architecture of the liver was respected histologically (normal liver, granulomatosis, siderosis, hepatitis), the ultrasound was normal in 86% of cases. The sensitivity of ultrasound was 0.9 for detection of fatty liver and 0.6 for cirrhosis. An abnormal ultrasound predicted structural modifications or a fatty liver in 93% of cases. Ultrasound proved incapable of differentiating between fatty liver and cirrhosis.

Liver glycerokinase deficiency in man with hyperglycerolaemia and hypertriglyceridaemia.

Hyperglycerolaemia and glyceroluria is described in a patient who presented transient dietary-induced hypertriglyceridaemia. The increased glycerol in blood and urine was related to glycerokinase deficiency as evidenced by a hepatic tissue glycerokinase activity of one tenth (4.8 X 10(-5) mmol g-1 min-1) of that of normoglycerolaemic subjects (5.9 X 10(-4) ). As triglycerides are routinely determined by an enzymatic method after hydrolysis to glycerol, the differential diagnosis between true hypertriglyceridaemia and hyperglycerolaemia may prove difficult. Persisting "hypertriglyceridaemia' despite adequate dietary and drug treatment should suggest the existence of undiagnosed hyperglycerolaemia .

Increased frequency of DR3 antigen in alcoholic hepatitis and cirrhosis.

HLA-A, B and DR antigens were determined in 33 patients suffering from confirmed alcoholic hepatitis, with or without cirrhosis. Past alcohol consumption and plasma immunoglobulins were also determined in 21 cases. An increased frequency of the DR-3 antigen was found in patients as compared with the control group (a sample of the Geneva population (31% v. 11%, p less than 0.05)). Although past alcohol consumption tended to be less in DR-3 positive patients in comparison with the other patients, the difference was not significant. No other differentiating clinical, immunological or histological features were observed among DR-3 positive patients. Our findings that there appears to be an increased frequency of DR-3 antigens in patients with alcoholic hepatitis, together with the previous work showing an increased frequency of HLA-B8 in the same condition, is particularly interesting in the light of the known association of both these antigens with autoimmune disease. These results would suggest that liver damage in chronic alcoholism is genetically predisposed, and that autoimmune mechanisms could be involved in the pathogenesis of alcoholic liver disease.

[Long-term tumor-free surviving patients with anaplastic small cell bronchial cancer]. / Langfristig tumorfrei überlegende Patienten mit anaplastischem kleinzelligen Bronchuskarzinom.

Report on 12 patients with small cell lung cancer who achieved disease-free survival for over 24 months after initial therapy. All the cases were classified as limited disease. Median age was 62 years and median performance status 0. Only 2 patients had weight loss of more than 5% in the six months prior to the diagnosis. Four patients were treated by local therapy alone (surgery in 3, radiotherapy in 1). Eight patients received systemic treatment (chemotherapy in 4, chemotherapy plus radiotherapy in 4). Median duration of cytostatic treatment was 17 months, with 3 of 8 patients receiving chemotherapy for less than 6 months. Three patients relapsed 27, 34 and 54 months after initial treatment. Median survival is 52 + months. It is concluded that long term disease-free survival can be achieved in patients with limited disease small cell lung cancer, even where initial treatment is relatively short.