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Biomedical subjects

D Samuel

Publications and source records attributed to D Samuel.

At least 73 records · Page 4Linked to original sources

Long-term follow-up after liver transplantation for autoimmune hepatitis: evidence of recurrence of primary disease.

BACKGROUND/AIMS: After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown. METHODS: In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8.5 years). RESULTS: The actuarial 5-year patient and graft survival rates were 91% (+/-6%) and 83% (+/-8%). The actuarial 1-year rate of acute rejection was 50% (+/-10.2%), which was comparable to that of patients transplanted for primary biliary cirrhosis and primary sclerosing cholangitis. Autoantibodies persisted in 77% of patients, at a lower titer than before liver transplantation. Ten patients were excluded from the study of autoimmune hepatitis recurrence, one because of an early postoperative death and nine because of hepatitis C virus infection acquired before or after liver transplantation. In the remaining 15 patients, who were free of hepatitis C virus infection, 5-year patient and graft survivals were 100% and 87%, respectively. Despite triple immunosuppressive therapy, three patients (20%) developed chronic hepatitis with histological and serological features of autoimmune hepatitis in the absence of any other identifiable cause. The disease was severe in two patients, leading to graft failure and asymptomatic in another, despite marked histological abnormalities. In one of these three patients, autoimmune hepatitis recurred on the second liver graft as well. CONCLUSIONS: Patients undergoing liver transplantation for autoimmune hepatitis have an excellent survival rate although severe primary disease may recur, suggesting the need for stronger post-operative immunosuppressive therapy.

Adolescent↗

Evaluation of efficacy of liver transplantation in alcoholic cirrhosis using matched and simulated controls: 5-year survival. Multi-centre group.

BACKGROUND/AIMS: Alcoholic cirrhosis is the most common cause of liver transplantation in US males. The limited number of donor livers calls for "prioritisation", favouring those patients who will benefit most. The aim was to assess the efficacy of liver transplantation in patients with alcoholic cirrhosis. METHODS: We compared the survival of 169 transplanted patients with two conservatively treated control groups, one of 169 patients matched for prognostic factors (age, cirrhosis severity, bleeding history) and one of 169 simulated patients. RESULTS: The probability of survival to 5 years in the transplanted group was 66% (95% confidence interval 58-74%) vs. 52% (44-60; p = 0.03) in the matched group and 54% (51-57; p = 0.01) in the simulated controls. Transplantation was associated with survival (relative risk = 1.51; p = 0.02), independently of risk score (risk = 2.07; p<0.001), indication, period of inclusion, centre experience, and alcohol abstinence. Patients with severe disease (Pugh C11-15) benefited most in terms of 5-year survival: 58% (44-72) vs. 31% (17-45; p = 0.008) in the matched and 35% (30-40; p<0.001) in the simulated control groups. For patients at lower risk there was no significant difference. CONCLUSIONS: Liver transplantation increases the 5-year survival of patients with severe alcoholic cirrhosis. In patients at lower risk, efficacy of transplantation should be confirmed by longer follow-up or by randomised trial.

Case-Control Studies↗

Long-term ganciclovir therapy for hepatitis B virus infection after liver transplantation.

BACKGROUND/AIMS: Hepatitis B virus (HBV) disease on a liver graft is associated with florid viral replication and graft failure. The aim of this study performed between 1992 and 1995 was to investigate the safety and efficacy of long-term intravenous ganciclovir for HBV infection in liver transplant recipients. METHODS: Twelve patients with HBV re-infection and four with de novo HBV infection were studied. HBV DNA was positive in all (median titer: 437.5 pg/ml) and HBeAg was positive in seven. Intravenous ganciclovir was started after a median of 14.5 months from HBsAg positivation and continued for a median of 10 months. RESULTS: A complete response with HBV DNA negativation was seen in ten cases, a partial response with a decrease of more than 50% of initial HBV DNA levels in four and no response in two. Overall tolerance was good. Among the ten complete responders, two seroconverted for both HBsAg and HBeAg and one for HBsAg alone. Among these ten patients, three were re-transplanted for liver failure: two of them are alive; three had a viral breakthrough during treatment; and four remained HBV DNA negative: two are alive and two died. Partial responders and nonresponders were treated with other antiviral agents and three were re-transplanted, two of them are alive. Overall 12 out of 16 patients (75%) survived with a median follow up of 46 months. CONCLUSIONS: Long-term intravenous ganciclovir can persistently inhibit HBV DNA replication in liver transplant recipients and is well tolerated. Further evaluation should be encouraged, especially for HBV recurrence after first-line treatments.

Adult↗

Recurrence of hepatitis C virus infection after liver transplantation.

In patients transplanted for HCV cirrhosis, reinfection by the virus is constant. Medium-term survival is good but long-term occurrence of cirrhosis is likely to impair the long-term prognosis of these patients. Patients should be informed before transplantation of the spontaneous risk of HCV recurrence and of its consequences. As for hepatitis B in the last decade, new antiviral therapies and immunosuppressive approaches will certainly change the course of HCV after transplantation.

Genotype↗

Domino liver transplants for metabolic disorders: experience with familial amyloidotic polyneuropathy.

BACKGROUND: Shortage of liver donors means that new methods of liver procurement must be explored. In domino transplantation, organs explanted during transplantation in one patient are transplanted into a second patient. Domino procedures can be performed with livers from patients having transplantation for hepatic metabolic disorders that cause systemic disease without affecting other liver functions. Familial amyloidotic polyneuropathy (FAP) type I is one of these. STUDY DESIGN: We reviewed the Paul Brousse experience with a domino liver transplant program for FAP, hoping to extend the approach to other metabolic disorders. RESULTS: Livers from 10 patients transplanted for FAP type 1 were used for domino transplants to patients with unresectable primary or metastatic liver cancers. There was no perioperative mortality. Neuropathy or cardiomyopathy did not increase the morbidity of the domino liver explant and transplant procedures. Morbidity for the domino recipients did not appear to be increased. Variant transthyretin was detected in the serum in FAP liver recipients, with no immediate clinical consequences. CONCLUSIONS: The domino approach is feasible and requires careful planning of the surgical procedures for liver explantation, particularly for the nature and site of vascular anastomoses. Domino transplantation of metabolically dysfunctional livers creates new categories of potential donors and potential recipients. It raises new ethical, technical, and societal issues. The domino approach could be used in several genetic or biochemical disorders now treated by liver transplantation. It has the potential to increase the number of liver grafts available for transplantation.

Adult↗

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↗

[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↗

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↗

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↗

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↗

Effects of ribavirin on hepatitis C-associated nephrotic syndrome in four liver transplant recipients.

BACKGROUND: Hepatitis C virus infection (HCV) is associated with a variety of extrahepatic disorders such as membranoproliferative glomerulonephritis (MPGN), which is generally due to cryoglobulinemia. After liver transplantation for HCV cirrhosis, alpha-interferon treatment against the recurrence of HCV in the liver graft is poorly effective and may induce intractable graft rejection. METHODS: We describe the cases of four liver transplant recipients treated with ribavirin for HCV-related glomerulopathy and nephrotic syndrome. RESULTS: The nephrotic syndrome was attenuated or disappeared during ribavirin therapy, and patients showed a marked decrease in proteinuria and an increase in albuminemia. The syndrome relapsed in two patients when ribavirin therapy was stopped, and a favorable response was again obtained in both cases when the treatment was resumed. The main adverse effect of ribavirin was anemia in two patients with renal impairment. No graft rejection occurred. CONCLUSIONS: These findings suggest that continuous therapy with low doses of oral ribavirin may improve the proteinuria of hepatitis C-related glomerulonephritis, at least in liver transplant recipients.

Antiviral Agents↗

What should we expect from a bioartificial liver in fulminant hepatic failure?

Fulminant hepatic failure is associated with high mortality. Liver transplantation is an effective therapy that improves survival, and because of donor organ shortage and urgency, a bioartificial liver could act as an effective bridge to liver transplantation in patients with fulminant hepatic failure. We discuss the place of the bioartificial liver in the treatment of other causes of liver failure.

Europe↗

The role of proline in the prevention of aggregation during protein folding in vitro.

Proline effectively inhibits protein aggregation during the refolding of bovine carbonic anhydrase. Other osmolytes used such as glycine and ethylene glycol fail to exhibit the 'aggregation-blockade' role shown by proline. Results of viscosity and ANS fluorescence (1-anilino-8-naphthalene sulphonic acid) experiments suggest that proline at high concentrations forms an ordered supramolecular assembly. Based on these results, it is proposed that proline behaves as a protein folding chaperone due to the formation of an ordered, amphipathic supramolecular assembly. To our knowledge, this is the first report wherein proline is proposed as a protein folding aid.

Anilino Naphthalenesulfonates↗

Successful treatment of severe azathioprine-induced hepatic veno-occlusive disease in a kidney-transplanted patient with transjugular intrahepatic portosystemic shunt.

Azathioprine-induced veno-occlusive disease of the liver mainly described after kidney transplantation is as rare as severe with a high mortality due to acute portal hypertension and liver failure. A kidney-transplanted patient with severe azathioprine-induced veno-occlusive disease of the liver and worsening despite drug discontinuation was treated by emergency transjugular intrahepatic portosystemic shunt. Whereas the veno-occlusive disease was controlled, the patient developed severe intractable portosystemic encephalopathy successfully treated by a stent reducer maintaining a certain degree of portal diversion. Twelve months after transjugular intrahepatic portosystemic shunt, liver function was normalized and the stent was thrombosed with a subnormal liver histology. Thirty-six months after transjugular intrahepatic portosystemic shunt the patient is alive with normal liver function tests and kidney graft function. Transjugular intrahepatic portosystemic shunt for treatment of severe veno-occlusive disease of the liver is an alternative to tide the patient over until recovery of liver function.

Adult↗

[Indications and results of liver transplantation in the treatment of hepatocellular carcinoma in cirrhosis].

Liver transplantation is a treatment for hepatocellular carcinoma in cirrhosis which is both recognized, because potentially radical, and controversial because associated with a high risk of recurrence. This study reports the results of a consecutive series of 125 patients transplanted for hepatocellular carcinoma in cirrhosis over an 11-year period. Liver transplantation was indicated because of the tumour in 92 cases (74%) and the tumour was an incidental finding in 13 cases (10%) or was discovered on histological examination of the hepatectomy specimen in 20 cases (16%). The operative mortality at two months was 4% with a 20% morbidity, due to vascular (6%) or biliary (14%) complications. Tumour recurrence was observed in 26 patients (21%) Recurrence was exceptional in the incidental or histological forms of hepatocellular carcinoma (5%) and more frequent when the tumour constituted the indication for transplantation (27%). The risk of recurrence and the survival were significantly influenced by the maximal tumour diameter (greater than 30 mm), the number of tumour nodules (greater than 3) and the presence of portal invasion. Inclusion of these factors in patient selection during the second phase of the study allowed a reduction of the risk of recurrence from 33 to 11% and improvement of the 3-year post-transplantation survival from 53 to 76%. Tumours less than or equal to 30 mm in diameter, with no more than 3 nodules, and without portal invasion are ideal indications for transplantation. Tumours with more than 3 nodules and larger than 30 mm appear to constitute a contraindication to transplantation, unless tumour reduction can be achieved by chemoembolization. Intermediate forms of hepatocellular carcinoma between these two extreme forms are possible indications for transplantation, depending on the availability of liver transplants.

Adolescent↗