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Biomedical subjects

H Bismuth

Publications and source records attributed to H Bismuth.

At least 181 records · Page 10Linked to original sources
PubMed1994

An observational study of 11 French liver transplant recipients infected with human immunodeficiency virus type 1.

We report the clinical and biological course of infection with human immunodeficiency virus (HIV) type 1 in 11 liver transplant recipients who acquired this infection between 1985 and 1987. Eight patients were infected by blood or blood products from graft-related transfusions and one by the graft itself; the remaining two patients were infected after transplantation and had independent risk factors. All patients received a triple-drug immunosuppressive regimen including cyclosporine. The mean duration of follow-up after liver transplantation was 52 months (standard error, +/- 32 months). Chronic graft rejection was documented in four cases. The cumulative incidences of HIV-related complications and HIV-related deaths were 82% and 27%, respectively. Three patients died rapidly of HIV disease. The survival rate 7 years after transplantation was 36% among the 11 HIV-infected patients, whereas it was approximately 70% among HIV-negative liver transplant recipients during the same period. The course of HIV infection in the four survivors did not appear to differ from that in other patients infected by blood transfusion.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Focus on intractable rejection: 6-month results of the European multicentre liver study of FK 506 and cyclosporin A.

The incidence of intractable rejection was evaluated during the course of a multicentre, randomised, parallel-group study comparing the efficacy and safety of FK 506 and conventional cyclosporin A-based immunosuppressive regimens in patients undergoing primary liver transplantation. A diagnosis of intractable rejection was made if there was histological evidence of unchanged or worsening acute rejection, or chronic rejection after two discrete courses of antirejection therapy. Antirejection regimens were specific to each centre. Patients who experienced intractable rejection could be withdrawn from the study. Patients who were withdrawn from the cyclosporin A treatment group could subsequently receive FK 506 therapy and vice-versa. Intractable rejection was diagnosed in 32/540 patients (5.9%): 7/267 patients (2.6%) in the FK 506 treatment group and 25/273 patients (9.2%) receiving cyclosporin A therapy (P < 0.01). Of these 32 patients, 25 were withdrawn from the study: 3 and 22, from the FK 506 and cyclosporin A treatment groups, respectively. All three patients withdrawn from the FK 506 treatment group are alive: two having undergone retransplantation. Of the 22 patients withdrawn from the cyclosporin A group and converted to FK 506 therapy, 6 were retransplanted, 4 of whom subsequently died. A further two patients died without retransplantation. Thus, in 14 of the 16 patients who were still alive at 6 months, the liver graft was saved after conversion to FK 506 treatment. The reduced incidence of intractable rejection in patients receiving treatment with FK 506, together with the successful rescue of patients developing intractable rejection while receiving cyclosporin A, suggests that FK 506 is an effective immunosuppressive agent following orthotopic liver transplantation.

Adolescent↗
PubMed1994

Corticosteroids and concomitant medication in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation.

The steroid-sparing effect and the use of concomitant medication during the treatment of liver transplant patients with the novel immunosuppressant FK 506 were evaluated within the European multicentre, randomized, parallel-group study in liver transplantation. Patients undergoing primary liver transplantation were randomized to treatment with FK 506 (n = 267) or with a cyclosporin-based immunosuppressive regimen (n = 273). The total cumulative steroid usage was significantly reduced in the FK 506 treatment group, which is likely to have resulted from the lower incidence of acute rejection in these patients. The number of patients receiving antidiabetic, diuretic and antihypertensive therapy did not differ between the two treatment groups, even though the incidence of diabetes mellitus and oliguria was significantly higher in the FK 506 group. It can, therefore, be assumed that in a number of such cases the severity of these events was very mild necessitating no specific therapy.

Adrenal Cortex Hormones↗
PubMed1994

Glucose metabolism in liver transplant recipients treated with FK 506 or cyclosporin in the European multicentre study.

From September 1990 to January 1992, 545 liver transplant patients were randomised to treatment with either FK506 and prednisolone or a conventional cyclosporin-based immunosuppressive regimen (CBIR). Eight European centres participated in the study. Adverse events were reported as defined by each centre. Hyperglycaemia was reported as an adverse event in 30.7% of patients receiving FK 506 compared with 20.5% in the CBIR group (P < 0.01). Diabetes mellitus was reported in 17.2% of patients treated with FK 506 and 9.5% of CBIR-treated patients (P < 0.05). Treatment with insulin was required in 12.0% of patients in the DK 506 treatment group and in 5% in the CBIR group at 6 months. Initially, higher doses of FK 506 were used. During the study, the protocol was changed to allow a lower dose of FK 506. When the early and late cohorts of patients were compared, the incidence of diabetes mellitus fell from 23.9% to 10.5% in FK 506-treated patients but remained relatively constant in the CBIR group (10.4% to 8.7%). The median cumulative doses of i.v. and p.o. corticosteroids were significantly greater in the CBIR group. Thus, in the overall series, the incidence of diabetes mellitus was significantly greater in the FK 506 group as compared with the CBIR group. However, when a lower FK 506 dose was used during the second half of the study, the difference in the incidence of diabetes mellitus disappeared.

Adolescent↗
PubMed1994

Renal complications and development of hypertension in the European study of FK 506 and cyclosporin in primary liver transplant recipients.

We examined the occurrence of renal complications and hypertension in 540 primary liver recipients entered into the European liver trial comparing primary FK 506 to a cyclosporin A based immunosuppression regimen (CBIR). No difference in serious renal impairment or mean creatinine levels was observed with similar rates of "kidney failure" (FK 506 9.4% vs. CBIR 7.3%) and dialysis requirements (FK 506 12% vs. CBIR 11%). "Abnormal kidney function", a less serious parameter of renal impairment, was reported in 89 recipients (33%) in the FK 506 group versus 58 (21%) in the CBIR group (P < 0.01). Development of this complication was associated with elevated intravenous FK 506 dosing schedules, with the mean cumulative dose 43% higher than treated patients with unaffected kidney function. In a later cohort of patients where intravenous dosing was lower, no significant difference in renal complications was detectable. The 6-month prevalence rate of systemic arterial hypertension was noted to be lower in the FK 506-treated patients compared to the CBIR group [33 (17.2%) vs. 47 (25.7%)].

Adolescent↗
PubMed1994

Neurological complications in the European multicentre study of FK 506 and cyclosporin in primary liver transplantation.

Neurological complications were examined in a multicentre, randomized, parallel-group study of 545 patients undergoing primary liver transplantation to compare the efficacy and safety of FK 506- and cyclosporin A-based immunosuppressive regimens (CBIR). In an additional analysis, patients were divided into early and late randomized cohorts to detect the influence of protocol amendements that allowed for FK 506 dose reductions. Initial follow-up was for 6 months. Tremor, headache and insomnia were the most frequently reported adverse events involving the neurological system. Whereas these neurological symptoms were observed significantly more often in FK 506-treated patients (P < 0.05 vs. CsA for the overall population), this was no longer the case for the late FK 506 and CBIR cohorts. The risk of FK 506-treated patients developing tremor was related to the initial i.v. dose, the rate of administration of the i.v. dose and the daily dose (P < 0.01). Headache was significantly correlated with the FK 506 dose (P < 0.05), and insomnia was not related to any dosing variable. Major neurological symptoms, including psychosis, convulsion, coma, aphasia and intracranial haemorrhage, were reported with a low frequency (0.4-5.2%), and differences between both treatment groups were neither significant for the overall population nor for the early and late cohorts of FK 506 and CBIR. Data from the late cohorts showed no differences in the overall incidence of neurological adverse events between FK 506- and CBIR-treated patients.

Cyclosporine↗
PubMed1994

Optimal FK 506 dosage in patients under primary immunosuppression following liver transplantation.

In a retrospective study, we analysed the FK 506 dosage used in primary liver graft recipients enrolled in the European FK 506 multicenter trial conducted from September 1990 to January 1992. In addition, a second cohort of patients treated more recently in a single centre was investigated. The impact of different dosing strategies on the clinical course of the patients was analysed with special emphasis on the incidence of rejection episodes and FK 506 side-effects. Among the patients enrolled in the European FK 506 multicenter trial, those patients enrolled during the "early" phase of the study received a higher oral FK 506 dose [mean oral dosage on day 7 = 0.19 mg/kg body weight (bw) per day, n = 134] compared to patients enrolled during the "late" period of the study (mean oral dosage on day 7 = 0.14 mg/kg bw per day, n = 133). This lower dosage was the result of several protocol amendments performed to reduce the incidence of FK 506 side-effects. Lowering of the FK 506 dosage was accompanied by a reduction in the long-term prevalence of side-effects such as diabetes (n. s.) or hypertension (P < 0.05), while patient survival and rejection frequency remained constant. Patients treated in centres with online FK 506 blood level monitoring experienced significantly less hypertension, less episodes of diabetes and less rejection episodes compared to patients treated in centres without. The clinical course of those patients enrolled in the multicentre trial was compared with the course of a cohort of liver-grafted patients treated with FK 506 more recently in a single centre. These patients had a further reduction in the FK 506 dosage (0.10 mg/kg bw per day p.o. or less according to whole blood levels, with no intravenous FK 506 administration). When compared to patients enrolled in the multicentre trial, these patients experienced less side-effects (nephrotoxicity, hypertension, serious early neurotoxicity) while adaequate immunosuppression was maintained.

Administration, Oral↗
PubMed1994

FK 506 primary immunosuppression following emergency liver transplantation for fulminant hepatic failure. European FK 506 Study Liver Group.

The efficacy and safety of an FK 506-compared to a cyclosporin A based immunosuppression regimen was examined in liver recipients who underwent transplantation for fulminant hepatic failure in the European FK 506 liver study. A consistent trend towards improved patient and graft survival noted in the FK 506-treated patients was apparent from the first postoperative week (e. g. patient survival: day 7, 95.5% vs. 82.1% and month 6, 72.7% vs. 60.7%). Acute (in particular intractable) rejection was less frequent in the FK 506 group (e. g. cumulative intractable rejection rate at 6 months, 6.2% vs. 22.6%). In a single centre (Kings College Hospital), 17 patients were studied in more detail. The FK 506 treatment group had improved graft function, lower steroid requirements and episodes of infection. Accompanying these benefits, apache 111 and TISS scores were lower in this group in the early posttransplant period. Intensive care discharge was earlier and both treatment groups experienced similar toxicity.

Adolescent↗
PubMed1994

Liver transplantation for viral hepatitis: the experience of the hepatobiliary center at Hospital Paul Brousse.

The prevalence of HBV recurrence after liver transplantation is higher in patients with viral B cirrhosis than in patients with viral B-D cirrhosis or fulminant hepatitis B and is related to the presence of HBV replication prior to transplantation. Long-term passive anti-HBs immunoprophylaxis is the best current way for prevention of HBV reinfection and improved long-term survival. The rate of recurrence of HCV infection is high, reaching 85%, and the rate of HCV hepatitis in the graft is approximately 75%. In most cases, HCV hepatitis leads to chronic hepatitis. The severity of graft hepatitis is related to the level of viremia at the time of the hepatitis and to the genotype 1b. The methods of prevention of HCV infection after liver transplantation are yet to be found. The treatment of graft HCV infection with interferon should be well evaluated and given cautiously. Other antiviral treatments without an immunostimulating effect are needed. Finally, patients transplanted for hepatitis B without HBV replication, receiving posttransplant long-term anti-HBs immunoprophylaxis, and those transplanted for HCV cirrhosis have a 5-year survival similar to other groups of transplanted patients. Patients belonging to these groups can be considered as candidates for transplantation. Patients with active HBV replication should be included in specific trials for prevention of HBV reinfection.

Actuarial Analysis↗
PubMed1994

[What future for clinical xenograft of the liver?].

In the cyclosporine era liver orthotopic allotransplantation has shown to be very effective in the treatment of many end-stage liver diseases. Currently, the major limitation in clinical transplantation is the shortage of donor organs unlikely solvable by alternative policies or approaches such as living donors and artificial organs. Animals have been considered as an alternative source of organs offering the following advantages: availability of a predictable and ready supply of donor organs, opportunity to practice transplantation as an elective procedure, possibility to match the size of the graft recipient. However, immunologic barriers are thought to make xenotransplantation impractical between widely divergent (discordant) species. Hyperacute xenograft rejection, in fact, consists of an immediate, diffuse intravascular coagulopathy followed by an aggressive cellular reaction. Recipient preformed natural antibodies and complement are involved in the humoral phase of hyperacute rejection. The violence of this reaction depends on the titer of natural antibodies and on the divergency of the species involved. Species more closely related (concordant) exhibit a less aggressive reaction characterized by an acute cellular rejection. Hepatic allografts and xenografts, though, are unusually resistant to humoral injury and undergo a combination of both humoral and cellular rejection. Preliminary studies have demonstrated a prolonged reduction in natural antibodies accomplished by plasmapheresis and cyclophosphamide combined treatment. Furthermore, new therapeutic agents such as FK 506, rapamycin and deoxyspergualin may find widespread application in clinical transplantation. FK 506 has shown to possess a remarkable efficacy in reversing refractory hepatic allograft rejection as well as ability to inhibit humorally mediated immunity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Transjugular intrahepatic portosystemic shunt worsens the hyperdynamic circulatory state of the cirrhotic patient: preliminary report of a prospective study.

The aim of this prospective nonrandomized study was to assess the immediate and short-term sequelae of transjugular intrahepatic portosystemic shunting on the circulatory hyperdynamic state of the cirrhotic patient. Twelve transjugular portosystemic shunting procedures were performed in 12 cirrhotic patients for sclerotherapy failure (10 cases) and/or intractable ascites (4 cases). Self-expandable stents 10 mm in diameter were used in all cases. Portal pressure measurement and right-heart catheterization were performed before and 30 min and 1 mo after the procedure. The portoatrial pressure gradient decreased from 15 +/- 3 to 7 +/- 3 mm Hg 30 min after surgery (p < 0.0001) to 8 +/- 3 mm Hg 1 mo after surgery (p < 0.001, in comparison with basal values). The cardiac index increased from 4.5 +/- 1.3 to 5.7 +/- 1.5 L/min.m2 30 min after surgery (p < 0.001) to 7.4 +/- 1.4 L/min.m2 1 mo after surgery (p < 0.001). Systemic vascular resistance decreased from 808 +/- 323 to 646 +/- 209 dyne.sec.cm-5 30 min after surgery (p < 0.01) to 467 +/- 101 dyne.sec.cm-5 1 mo after surgery (p < 0.05). This study demonstrates that transjugular portosystemic shunting rapidly and significantly worsens the hyperdynamic circulatory state of the cirrhotic patient. Although apparently noninvasive, this procedure should be considered with caution in cirrhotic patients with limited cardiac reserve.

Adult↗
PubMed1993

Liver transplantation in European patients with the hepatitis B surface antigen.

BACKGROUND: The role of liver transplantation in patients positive for the hepatitis B surface antigen (HBsAg) is controversial because of the high rate of recurrent hepatitis B virus (HBV) infection. It has not been determined whether this risk is greater for certain patients and whether the administration of anti-hepatitis B surface antigen (anti-HBs) immune globulin is beneficial. METHODS: We conducted a retrospective study at 17 European centers of 372 consecutive HBsAg-positive patients who underwent liver transplantation between 1977 and 1990. Recurrence of HBV infection was defined as the reappearance of HBsAg in serum. RESULTS: For all 334 patients with follow-up data, the mean (+/- SE) three-year actuarial risk of recurrence of HBV was 50 +/- 3 percent. The risk was 67 +/- 4 percent among 163 patients with HBV-related cirrhosis, 32 +/- 5 percent among 110 patients with cirrhosis related to hepatitis delta virus, 40 +/- 16 percent among 14 patients with fulminant hepatitis delta infection, and 17 +/- 7 percent among 39 patients with fulminant HBV infection (P < 0.001). Among the patients with HBV-related cirrhosis, the risk of HBV recurrence was greatest (83 +/- 6 percent) in those who were seropositive for HBV DNA at the transplantation and lowest (58 +/- 7 percent) in those with neither HBV DNA nor hepatitis B e antigen detectable in serum. With respect to the use of passive prophylaxis with anti-HBs immune globulin, the risk of HBV recurrence was 75 +/- 6 percent among the 67 patients given no immunoprophylaxis, 74 +/- 5 percent among the 83 treated for two months, and 36 +/- 4 percent among the 209 treated for six months or longer (P < 0.001). In a multivariate analysis the predictors of a lower risk of HBV recurrence were the long-term administration of the immune globulin, hepatitis delta virus superinfection, and acute liver disease. For the entire study cohort, survival was 75 percent at one year and 63 percent at three years, but for those in whom HBV infection recurred, survival was 68 percent at one year and 44 percent at three years. CONCLUSIONS: In this retrospective study of HBsAg-positive patients, liver transplantation had better results in those who had fulminant hepatitis or delta virus superinfection. An absence of viral replication at the time of transplantation and long-term immunoprophylaxis were associated with a reduced risk of recurrent HBV infection and reduced mortality.

Actuarial Analysis↗
PubMed1993

Preoperative chemoembolization for hepatocellular carcinoma.

In a group of 396 patients who had chemoembolization for hepatocellular carcinoma (HCC) between 1984 and 1991, 67 underwent surgery (segmentary/subsegmentary resections: 31; or transplantation: 36). Morbidity was limited to hepatic insufficiency (seven), arterial thrombosis (two), vasculitis (five), cholecystitis (two), and hepatic abscess (one). Perioperative mortality was 5.5% for transplantation and 6.7% for resection. Histological examination of resected specimens showed a total or subtotal tumor necrosis in 58% of the cases, and a necrosis between 50% and 80% in another 18%. Data on recurrence and long-term survival are not significant if retrospectively compared with non-chemoembolized surgically treated patients. Chemoembolization is known to be an effective palliative treatment of HCC. Its role in the preoperative setting is sustained by a 58% of total or subtotal histological necrosis. A multicentric prospective trial to evaluate the role of preoperative chemoembolization for long-term survival and recurrence of HCC is advocated.

Adolescent↗
PubMed1993

Patterns and mechanisms of hepatitis B/hepatitis D reinfection after liver transplantation.

Viral recurrence is the limiting factor in orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) related liver disease. In fact, high rates of HBV infection of the transplanted liver are reported, followed by the recurrence of liver disease in a high percentage of cases. The importance of reinfection stimulates the study of its modalities and mechanisms in order to better identify preventive measures and better select patients for OLT. In HBV and HDV positive patients, the outcome of liver transplantation appears significantly better than in patients that are solely HBV positive, in spite of a high rate of HDV reinfection. Long-term analysis (5 years) of HBV and HDV infection, using the PCR technique, in 15 patients transplanted for an HBV/HDV positive liver disease and treated with anti-HBs immunoglobulin (HBIG), revealed that all patients experienced an HDV reinfection, but only about 7 were still harboring the virus after four years of follow-up. HDV reinfection was either associated to HBV reinfection or isolated whereas no cases of HBV isolated reinfection was observed. Isolated HDV reinfection was frequent and transient in all but one case that was superinfected by HBV. Infected peripheral blood mononuclear cells seem to be implicated in HBV superinfection of HDV infected liver. Liver damage was observed only in cases of HBV/HDV co-infection, suggesting that, in vivo, HBV is necessary to produce liver damage although it is not essential for HDV absorption to target cells, HDV penetration of these cells or HDV genomic replication. In addition, in isolated HDV infection, transient HDV viraemia and its low levels suggest that, perhaps in these patients HDV uses a very limited presence of HBV or alternative ways which are not efficient enough for envelope production. These data suggest that, particularly in HDV positive patients, antiHBs Ig administration, which has previously been proven to significantly reduce HBV reinfection in HBsAg-positive patients, may be useful in changing the natural history of repetition of the original viral infection and liver disease after OLT.

Follow-Up Studies↗