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Biomedical subjects

H Bismuth

Publications and source records attributed to H Bismuth.

At least 73 records · Page 4Linked to original sources
PubMed1999

Liver transplantation for hepatocellular carcinoma.

Liver transplantation for hepatocellular carcinoma (HCC) in patients with cirrhosis is a radical treatment of the tumor and associated precancerous state. It is potentially curative in a proportion of patients. The outcomes of early studies of liver transplantation in this indication were initially unfavorable. Selection of transplant candidates at an early stage, in the absence of extrahepatic spread, gives better survival than surgical resection and alternative nonsurgical treatments. Transarterial chemoembolization can be used for preoperative control of the disease. Adjuvant chemotherapy may be indicated in the postoperative period for the prevention of recurrence in patients with histologic features of invasiveness in the surgical specimen. Liver transplantation as the treatment of choice for early HCC in screening programs in cirrhotic patients may become limited by graft availability as the numbers of hepatitis C-related cases increase. Resection may be indicated if the waiting time is likely to be long.

Adolescent↗
PubMed1999

Continuous delivery of venous 5-fluorouracil and arterial 5-fluorodeoxyuridine for hepatic metastases from colorectal cancer: feasibility and tolerance in a randomized phase II trial comparing flat versus chronomodulated infusion.

High-dose chemotherapy combining regional hepatic artery infusion (HAI) of fluorodeoxyuridine (HAI FUDR) and systemic venous infusion of 5-fluorouracil (i.v. 5-FU) was delivered against liver metastases from colorectal cancer. The hypothesis that chronomodulation of delivery rate along the 24 h time scale would improve the tolerable doses of both drugs was tested. Combined HAI FUDR (80 mg/m2/day) and i.v. 5-FU (1200 mg/m2/day) were administered for five consecutive days every 3 weeks, either as a constant rate infusion (schedule A, 27 patients) or as chronotherapy (schedule B, 29 patients). This latter regimen consisted of a sinusoidal modulation of the delivery rate over the 24 h scale with a maximum at 16:00 for FUDR and 4:00 for 5-FU. Intrapatient dose escalation up to the individual maximum tolerated doses (MTD) was planned for both drugs in the absence of any previous grade 3 or 4 toxicity. All patients had metastatic colorectal cancer, with adjuvant or palliative chemotherapy given to six patients (22%) on schedule A and 12 patients on schedule B (41%). Severe stomatitis occurred in 71% of the patients and was dose limiting. No hepatic toxicity was encountered. Dose reductions of 5-FU and/or FUDR were required for 17 of 27 patients on schedule A (63%) as compared to 11 of 29 patients on schedule B (38%), following reaching the individual MTD (p<0.05). Over the first six cycles, patients on schedule B received higher doses (mg/m2/cycle; FUDR: 522 +/- 85 versus 499 +/- 50, p=0.004 and 5-FU: 5393 +/- 962 versus 5136 +/- 963, p=0.009) and higher dose intensities (mg/m2/week; FUDR: 164 +/- 46 versus 151 +/- 52, p=0.018 and 5-FU: 1652 +/- 478 versus 1553 +/- 535, p<0.041) of both drugs than patients on schedule A. As a result the number of courses with doses of 5-FU above 1200 mg/m2/day and/or FUDR above 110 mg/m2/day was larger in group B than in group A (5-FU, A: 67 of 268, 25% versus B: 133 of 321, 41% and FUDR, A: 86 of 268, 32% versus B: 155 of 321, 48%; p<0.001). Objective responses were observed in 13 patients on schedule A (48%) and 11 patients on schedule B (38%). The results support the need for further exploration of chronotherapy of colorectal cancer liver metastases with combined arterial and venous fluoropyrimidine chemotherapy.

Adult↗
PubMed1999

Nonrandom distribution of hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cell subsets.

The existence of an extrahepatic reservoir of hepatitis C virus (HCV) is suggested by differences in quasispecies composition between the liver, peripheral blood mononuclear cells, and serum. We studied HCV RNA compartmentalization in the plasma of nine patients, in CD19(+), CD8(+), and CD4(+) positively selected cells, and also in the negatively selected cell fraction (NF). HCV RNA was detected in all plasma samples, in seven of nine CD19(+), three of eight CD8(+), and one of nine CD4(+) cell samples, and in seven of eight NF cells. Cloning and sequencing of HVR1 in two patients showed a sequence grouping: quasispecies from a given compartment (all studied compartments for one patient and CD8(+) and NF for the other) were statistically more genetically like each other than like quasispecies from any other compartment. The characteristics of amino acid and nucleotide substitutions suggested the same structural constraints on HVR1, even in very divergent strains from the cellular compartments, and homogeneous selection pressure on the different compartments. These findings demonstrate the compartmental distribution of HCV quasispecies within peripheral blood cell subsets and have important implications for the study of extrahepatic HCV replication and interaction with the immune system.

Amino Acid Sequence↗
PubMed1999

[Labor complications of the HELLP syndrome without any predictive factors].

Liver disease is a rare complication of pregnancy which can be serious for both the mother and the infant. In particular, HELLP syndrome (hemolysis, elevated liver enzymes and a low platelet count) is a life threatening complication of severe preeclampsia. Pregnancies complicated by the HELLP syndrome are usually associated with increased maternal and perinatal morbidity and mortality including disseminated intravascular coagulopathy, pulmonary and cerebral oedema, acute renal failure, rupture of the liver hematoma and a variety of hemorrhagic complications. The HELLP syndrome occurs in 4 to 12% of patients with severe preeclampsia and prompt delivery is the only treatment. We report two cases of HELLP syndrome which developed in women during delivery and without any predictive factors during pregnancy.

Adult↗
PubMed1999

Choledochal cystic malignancies.

Cystic diseases of the bile ducts are rare, but relatively more prevalent in females, and more common in Japan and Asia. Most are diagnosed in children under 10 years of age, with varying patterns of symptoms including right upper quadrant pain, jaundice, and fever. Up to 20% of bile duct cysts are diagnosed in adults, including during pregnancy, in whom the diagnosis can be confounded by associated cholelithiasis, or by abnormalities of the pancreatic junction with pancreatitis. The risk of malignant transformation increases with age, and is more common in cysts of Alonso-Lej Types I, IV, and V (Caroli's Disease). Intracystic lithiasis is frequently associated with tumour, and can give similar radiological appearances. Tumours are often first diagnosed at laparotomy, and can already be unresectable. More than half the tumours are intracystic, but malignant change in cyst mucosa without a tumour mass is often not recognised at surgery. In addition, malignant change in bile duct epithelium can occur after cyst excision, sometimes after many years, and in areas of the biliary tree remote from the cyst, including the gall-bladder. Cyst excision should be attempted at all ages, and patients closely monitored thereafter. Malignancy should be suspected in all adults with bile duct cysts. Hepatectomy, partial or total with transplantation, is the treatment of choice in Caroli's disease.

Adolescent↗
PubMed1998

Histological features predictive of recurrence of primary biliary cirrhosis after liver transplantation.

BACKGROUND: Recurrence of primary biliary cirrhosis (PBC) within liver allografts remains a controversial issue. The aims of this study were to evaluate this risk and to determine the presence, if any, of a predictive histological feature. METHODS: We reviewed the most recent and the 1-year protocol liver biopsies of 69 patients who received transplants for PBC and of 53 control patients. Histological features consistent with PBC recurrence included nonsuppurative destructive cholangitis, mixed portal infiltrate, fibrosis, and ductopenia. A complete evaluation was undertaken in each patient with these histological features. RESULTS: These histological features were present in six patients who received transplants for PBC (8.7% vs. 0% in the control group) and occurred between 1 and 8 years after transplant. In five of the six patients, anti-mitochondrial antibody-2 (anti-M2) antibodies remained at high titers. Cholestasis was present in four patients, and clinical symptoms in two patients. All six patients were negative for hepatitis C antibodies and hepatitis C RNA in their serum. None had bile duct obstruction. The presence of plasma cells in the portal infiltrate at 1 year after transplant was predictive of this risk of recurrence. CONCLUSION: The risk of PBC recurrence is real (8.7%). The presence of plasma cells in the portal infiltrate seems to be an early marker of recurrence of PBC in patients transplanted for this indication.

Adult↗
PubMed1998

Incidence of hepatitis C in patients receiving different preparations of hepatitis B immunoglobulins after liver transplantation.

BACKGROUND: Recurrence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection after liver transplantation is a clinical problem. Polyclonal immunoglobulins against hepatitis B surface antigen (HBIGs) prevent the recurrence of HBV infection, but no effective prophylaxis is available for HCV infection. Before screening of blood donors was introduced in France, HBIGs may have contained antibody to HCV (anti-HCV). OBJECTIVE: To determine the influence of HBIG on the occurrence of hepatitis C after liver transplantation before and after 1990. DESIGN: Retrospective cohort study. SETTING: Liver transplantation unit of a university hospital. PATIENTS: 428 consecutive patients who had liver transplantation because of cirrhosis between 1984 and 1994. MEASUREMENTS: Detection of serum HCV RNA before and 1 year after transplantation and findings on liver graft biopsy. RESULTS: Among the 218 patients who had HCV infection before transplantation, the incidence of HCV viremia after transplantation was lower in those receiving HBIG than in those not receiving HBIG (25 of 46 patients [54%] compared with 162 of 172 patients [94%]; P < 0.001). In patients receiving HBIG, the incidence of HCV viremia after transplantation was lower among those who had transplantation before March 1990 than among those who had transplantation after this date (15 of 33 patients [45%] compared with 10 of 13 patients [77%]; P = 0.05). Among the 210 patients without HCV infection before transplantation, acquired infection was significantly less frequent in those receiving HBIG than in those not receiving HBIG (18 of 68 patients [26%] compared with 40 of 86 patients [47%]; P < 0.001). Passively transmitted anti-HCV was transiently detected in patients receiving HBIG before March 1990. Multivariate analysis in patients with HCV infection before transplantation showed that the absence of HBIG and transplantation after March 1990 were independent significant risk factors for chronic hepatitis C after transplantation. CONCLUSIONS: Polyclonal immunoglobulins that are treated for viral decontamination and contain anti-HCV could prevent HCV infection.

Adult↗
PubMed1998

High incidence of antitissue antibodies in patients experiencing chronic liver allograft rejection.

BACKGROUND: The precise immunologic mechanisms responsible for chronic rejection of liver allografts are unknown. We have recently shown in a rodent model that recipients of liver allografts developed non-major histocompatibility complex antitissue antibodies. The aim of the present study was to test this hypothesis in the clinical setting. METHODS: Posttransplant sera of 14 patients undergoing chronic rejection and of 48 control patients (12 liver transplant patients with chronic active hepatitis or liver cirrhosis related to hepatitis C virus [HCV] infection and without chronic rejection, 10 with sclerosing cholangitis, and 26 with normal liver function tests and liver biopsy) were tested for the presence of antitissue antibodies by indirect immunofluorescence. Pretransplant sera of all these patients lacked antitissue antibodies. RESULTS: Antitissue antibodies were detected in 71% of patients who developed chronic rejection (before or at the time of chronic rejection). This incidence was significantly greater than that observed in patients not undergoing rejection (HCV-related chronic active hepatitis, 16%; sclerosing cholangitis, 0%; normal liver biopsy, 7%). All these autoantibodies were directed against the smooth muscle and/or the nucleus. In two patients, anti-smooth muscle antibodies had an antiactin or antivimentin specificity. CONCLUSIONS: These results show a strong association between chronic allograft rejection and the development of antitissue antibodies and suggest that these antibodies could be used to identify patients at high risk of developing chronic rejection after liver transplantation.

Antibody Formation↗
PubMed1998

Development of anti-tissue antibodies in the rat liver transplant model.

BACKGROUND: The aim of this study was to analyze the humoral immune response associated with orthotopic liver transplantation in the rat liver transplant model, and in particular to test the presence of anti-tissue antibodies. METHODS: Rearterialized liver transplantations were performed in the Dark Agouti (DA)-to-Lewis (LEW) and the LEW-to-DA rat strain combinations. Sera of recipients were analyzed by immunofluorescence (on DA and LEW organ sections) and by western blotting (with DA and LEW liver proteins). RESULTS: We have shown that liver (but not heart or skin) recipients develop a humoral response against non-MHC tissue antigens as evidenced (1) by a pattern of staining comparable to that described in human patients harboring anti-smooth muscle antibodies and (2) by the presence of donor liver peptides recognized in the sera of the recipient by Western blotting. CONCLUSIONS: These experiments indicate that orthotopic transplantation of a nonacutely rejected liver allograft is associated with the development of a previously undescribed anti-tissue antibody response that seems to be neither organ nor MHC restricted.

Animals↗
PubMed1998

Occurrence of gammopathies and lymphoproliferative disorders in liver transplant recipients randomized to tacrolimus (FK506)- or cyclosporine-based immunosuppression.

Lymphoproliferative disorders (LPDs) are a serious side effect of immunosuppression after liver transplantation, and the introduction on the market of a new immunosuppressive drug has been associated with an increased risk of these disorders. To compare the effect of cyclosporine A (CSA) and FK506 in a clinical setting, the incidence of monoclonal or oligoclonal gammopathies known to often precede the appearance of LPDs was evaluated. A total of 88 adult patients was analyzed, 46 were prospectively randomized to CSA and 42 to FK506 for immunosuppression. None of these patients had gammopathy before transplantation. All the patients were tested for immunoglobulin abnormalities five to nine times during a period of 1 year and then two to four times per year thereafter from December 1990 until March 1997. The same incidence of serum immunoglobulin (Ig) abnormalities was observed in both groups (13%) with a mean delay of appearance of 11.1 +/- 5.9 versus 7.6 +/- 3.6 months for CSA and FK506, respectively (P > .05). In each group, the gammopathies were transient in 3 patients and persisted in 2. The class of Ig involved was IgG, and a monoclonal component was documented in 2 patients treated with CSA and in 3 patients with FK506. One patient treated with FK506 developed an LPD localized to the lymph nodes 8 months after the occurrence of serum protein abnormalities. The lymphoproliferative lesions subsequently disappeared with the reduction of immunosuppression. In this study, an immunosuppressive regimen of FK506 has not shown an increased incidence of lymphoproliferation compared with CSA in adult liver transplant patients.

Adrenal Cortex Hormones↗
PubMed1998

[Combination therapy in oncology--hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is being diagnosed with increasing frequency in the Western world as a consequence of the hepatitis C epidemia. Multimodal therapy is now the only effective treatment option to offer a chance of complete tumor control in HCC. Liver transplantation and liver resection, including the selection criteria and patient evaluation, are discussed. The benefits and complications of transarterial chemoembolization and cryotherapy are also reviewed. Liver transplantation is now thought to offer the best treatment option in early HCC and should be regarded as the first line of treatment in selected patients.

Carcinoma, Hepatocellular↗
PubMed1998

Effect of ischemic preconditioning on hepatic tolerance to cold ischemia in the rat.

A short warm ischemia before reperfusion has been shown to improve the tolerance of the heart and the liver to a prolonged warm ischaemia. The present experimental study was conducted to evaluate the effect of such preconditioning on hepatic tolerance to an extended cold ischemia. In a model of isolated perfused liver, livers from Wistar rats (250-350 g) were stored for 24 h in UW (4 degrees C) immediately after harvesting and reperfused for 3 h at 37 degrees C. Control livers subjected to a 24-h cold ischemia were compared to livers subjected to preconditioning (defined as a 5- or 10-min clamping of the hepatic pedicle followed by a 10-min reperfusion before liver harvesting) prior to the definitive 24-h cold ischemia. While there was no difference in bile production between the preconditioned groups and the controls, transaminases and LDH release was significantly increased, vascular resistance was enhanced, and preservation injury was more extensive in both preconditioned groups as compared to controls. In contrast to the beneficial effect reported on prolonged warm ischaemia, preconditioning has a deleterious effect on hepatic tolerance to an extended cold ischemia.

Animals↗