Early corticosteroid avoidance in kidney transplant recipients receiving ATG-F induction: 5-year actual results of a prospective and randomized study.

One hundred ninety-seven patients received anti-T-lymphocyte globulins Fresenius, mycophenolate mofetil and delayed cyclosporine, and were randomized to ≥6-month corticosteroids (+CS; n=99) or no CS (-CS; n=98). One- and five-year actual graft survival (censored for death) was 93.2% and 86.4% in the +CS group versus 94.9% and 89.8% in the -CS group (5-year follow-up, p=0.487). Freedom from clinical rejection was 86.9% and 81.8% versus 74.5% and 74.5% (p=0.144), respectively, at 1 and 5 years; 5-year freedom from biopsy-proven rejection was 88.9% versus 83.7% (p=0.227). More late first rejections occurred in the +CS group. Significantly lower 5-year graft survival in patients experiencing rejection was observed for +CS (55.6% vs. 92.0%; p=0.005) with 8/18 versus 2/25 graft losses. Renal function at 5 years was stable and comparable (median serum creatinine, 159 vs. 145 µmol/L; creatinine clearance, 53.5 vs. 56.6 mL/min). More +CS patients developed diabetes, dyslipidemia and malignancies. Rejections in -CS patients occurred early after transplantation and did not impair long-term renal function. In patients receiving CS, rejections occurred later and with a higher risk for subsequent graft failure. A similar and not inferior 5-year efficacy profile and a reduced morbidity were observed in CS-free patients compared to patients who received CS for at least 6 months.

[Herpes simplex hepatitis with macrophage activation syndrome in an immunocompetent patient]. / Hépatite herpétique avec syndrome d'activation macrophagique chez un patient immunocompétent.

INTRODUCTION: Herpes simplex hepatitis is a rare cause of acute hepatitis in immunocompetent patients. The triad of fever, increase in liver enzymes and leucopenia is suggestive of herpes simplex hepatitis. Delayed diagnosis without antiviral therapy contributes significantly to an unfavorable outcome. OBSERVATION: We report a 50-year old immunocompetent male patient, who presented with acute severe hepatitis due to a reactivation of a herpes simplex infection with a complicated course including macrophage activation syndrome and severe coagulopathy. Outcome was finally favorable with early acyclovir therapy. CONCLUSION: Despite its relatively low occurrence rate, diagnosis of herpetic hepatitis should be discussed in immunocompetent patients with acute liver failure. The benefit of an early acyclovir treatment should lead clinicians to consider this uncommon diagnosis in unexplained cases of hepatitis and to test rapidly HSV DNA levels by PCR in plasma.

Number and tumor size are not sufficient criteria to select patients for liver transplantation for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an indication for liver resection or transplantation (LT). In most centers, patients whose HCC meets the Milan criteria are considered for LT. The first objective of this study was to analyze whether there is a correlation between the pathologic characteristics of the tumor, survival and recurrence rate. Second, we focused our attention on vascular invasion (VI). METHODS: From January 1997 to December 2007, a total of 196 patients who had a preoperative diagnosis of HCC were included. The selection criteria for LT satisfied both the Milan and the San Francisco criteria (UCSF). Demographic, clinical, and pathologic information were recorded. RESULTS: HCC was confirmed in 168 patients (85.7%). The median follow-up was 74 months. The pathologic findings showed that 106 patients (54.1%) satisfied the Milan criteria, 134 (68.4%) the UCSF criteria of whom 28 (14.3%) were beyond the Milan criteria but within the UCSF criteria, and 34 (17.3%) beyond the UCSF criteria. VI was detected in 41 patients (24%). The 1-, 3-, and 5-year overall survival rates were 90%, 85%, and 77%, respectively, according to the Milan criteria and 90%, 83%, and 76%, respectively, according to the UCSF criteria (P = NS). In univariate and multivariate analyses, tumor size and VI were significant prognostic factors affecting survival (P < 0.001). Two factors were significantly associated with VI: alfa-fetoprotein level of >400 ng/ml and tumor grade G3. CONCLUSIONS: Tumor size and VI were the only significant prognostic factors affecting survival of HCC patients. Primary liver resection could be a potential selection treatment before LT.

Causes of sirolimus discontinuation in 97 liver transplant recipients.

INTRODUCTION: Sirolimus is a potent immunosuppressant with a mechanism of action different from calcineurin inhibitors (CNIs). It has increasing importance for liver transplant (OLT) patients, in particular if when there is decreased renal function. We evaluated the efficacy and the causes for discontinuation of sirolimus-based immunosuppression among OLT recipients. OBJECTIVE: We retrospectively analyzed 97 liver transplanted patients who were prescribed sirolimus as the principal immunosuppressant. Of these, 61 patients discontinued treatment. Herein we have reported the causes, the timing, and the effects of sirolimus discontinuation. RESULTS: The overall patient survival at 3 years follow-up was 89%. Hepatotoxicity and blood disorders were the most frequent, severe reported side effects. Acute cellular rejection episodes appeared in seven patients and was relieved in 1 to 2 weeks after the sirolimus administration. In 10 patients, the cholestasis associated with chronic rejection was sharply reduced after the introduction of sirolimus. No increase in vascular thrombosis and/or poor wound healing were reported. CONCLUSION: Sirolimus given alone or in combination with CNIs appears to be an effective primary immunosuppressant regimen for OLT patients. However, in the late postoperative period (>3 months) the drug is associated with a relatively high rate of side effects.

[Study of hepatitis C virus leukotropism by characterization of viral quasispecies in the liver transplantation setting]. / Etude du leucotropisme du virus de l'hépatite C par analyse des quasi-espèces virales dans le contexte de la transplantation hépatique.

Besides hepatocytes, representing the main replication site of hepatitis C virus, peripheral blood mononuclear cells also represent a crucial target for viral infection. Hepatitis C virus compartmentalization (i.e., non-random distribution) of viral variants between plasma and peripheral blood mononuclear cells, more frequently observed in liver transplant patients compared to non-transplanted patients, makes liver transplantation an interesting model for the analysis of hepatitis C leukotropism. This article aims to present, firstly, in clinical and biological features arguing favour of hepatitis C virus infection leukotropism and, secondly, to review current knowledge about compartmentalization between plasma and peripheral blood mononuclear cells, especially in the liver transplantation setting.

[Recurrence of hepatitis C virus (HCV) infection after liver transplantation for HCV-related disease: host factors and viral factors implicated in the occurrence and the severity of HCV recurrence]. / Récurrence de l'infection par le virus de l'hépatite C (VHC) après transplantation du foie pour hépatopathie due au VHC: facteurs liés à l'hôte et facteurs viraux impliqués dans la survenue et la gravité de la récurrence de l'hépatite virale C.

Cirrhosis due to chronic infection by hepatitis C virus (HCV), associated or not to a primary hepatocarcinoma, has become the first indication of liver transplantation. Graft reinfection by HCV is considered to be systematic while its prognosis is variable from one patient to another. A better knowledge of factors implicated in the occurrence and severity of hepatitis C recurrence is crucial in order to make optimal patients' monitoring. This article aims to present available data in this field, clarifying the role of viral factors (viral load, genotype, evolution of viral quasispecies) and host-related factors (immune response) which could take part in the development of hepatitis C recurrence.

Is sirolimus responsible for proteinuria?

Sirolimus (SRL) is suspected to induce proteinuria. We retrospectively studied proteinuria in a population of liver (n = 29) and kidney transplant (n = 30) recipients switched to SRL with progressive diminution or withdrawal of calcineurin inhibitors (CNI). We also observed estimated glomerular filtration rate (GFR), modification of treatment with antiproteinuric drugs, and changes in concentration of SRL. Collection of data started 3 months before SRL introduction at a mean follow-up of 21 months. Following SRL introduction, proteinuria was not detected in the 28 liver transplant patients, and was stable in the two others. In the kidney transplant group, proteinuria did not occur in 12 patients, remained stable in three, and was slightly increased in 14 (0.57 +/- 0.93 g/d vs 1.83 +/- 1.26 g/d). For all patients, eGFR remained stable; there was no difference in management of antiproteinuric drugs. As suspected, cyclosporin (CsA) and tacrolimus (FK) serum concentrations were decreased. We observed a significant correlation between the variation of proteinuria and the variation of serum concentration of CsA or FK (respectively, P = .001 and P = .007). On the other hand, we did not find any correlation between variation in proteinuria and concentration of SRL. This retrospective study suggests that in our cohort of liver transplant patients without previous renal damage, SRL did not provoke proteinuria. On the other hand, the slight aggravation of proteinuria in a subgroup of kidney transplant patients seems to be linked to the hemodynamic renal effects due to CNI withdrawal.

[Diffuse sebaceous hyperplasia of the face induced by cyclosporine]. / Hyperplasies sébacées profuses du visage induites par la ciclosporine.

INTRODUCTION: Many cutaneous complications have been reported in patients treated with cyclosporine. Alterations of the pilosebaceous follicle are particularly frequent. Hypertrichosis, follicular keratosis, acne and folliculitis are very common. Nevertheless, the occurrence of sebaceous hyperplasia is exceptional. OBSERVATION: A 27 year-old man consulted in February 2003 for a papulous eruption of the face. He was treated by cyclosporine and prednisone since his renal transplantation in 1993. The lesions flowed together on the cheeks, forehead and temples. The histological analysis confirmed the diagnosis of sebaceous hyperplasia. There was a perceptible improvement of the cutaneous state after one month of isotretinoin treatment. DISCUSSION: Sebaceous hyperplasia appears in about 10 p. 100 of patients treated with cyclosporine. This side effect occurs only in men of a mean age of 40 years. An increase in sebaceous gland size is often described, but profuse forms are uncommon. Our case report is exceptional because of the young age of the patient, and the occurrence of diffuse sebaceous hyperplasia that appeared a long time after the introduction of cyclosporine.

Effects of corticosteroids on HCV infection.

The risk factors for clinical recurrent hepatitis C in liver transplant recipients are not clearly defined. It has been suggested that the corticosteroids included in the treatments of patients undergoing allograft rejection might induce acute hepatitis by increasing HCV replication. In this study we investigated the effects of corticosteroid boluses on HCV viremia in liver allograft recipients treated for acute rejection. Since we had previously developed a model of HCV replication in peripheral blood mononuclear cells (PBMC) in vitro, we also studied the effects of corticosteroids on HCV replication in vitro. A transient peak of HCV viremia was observed in patients treated with corticosteroid boluses for an acute allograft rejection. In the cell cultures, corticosteroids induced an increase of the total amount of viral RNA detectable. Our results demonstrate that corticosteroids induce an increase of hepatitis C virus replication in vivo and in vitro.

[An original case of simultaneous cardiac, pancreatic and renal transplantation. Results over 6 years]. / Observation princeps de transplantation associée cardiaque pancréatique et rénale. Résultat à 6 ans.

Combined transplantation is actually performed on specific and rare indications. We are presenting here the results of a combined heart-kidney and pancreatic graft. It was performed in a patient presenting an idiopathic cardiomyopathy in end-stage failure and a post-diabetic nephropathy on dialysis. Today, organs function is quite satisfactory with a 6 year follow-up. Only one isolated heart rejection episode was observed at the 15th post-operative day. The patient has recovered a full-time professional activity at one year. This successful graft was obtained by an "homogeneous multiorgan approach" during all the pre-peri and postoperative time.

[Imaging of renal graft lymphomas. Apropos of 5 cases]. / Imagerie des lymphomes du rein greffé. A propos de 5 observations.

The occurrence of non-hodgkin's lymphoma is a classical complication after transplantation. The frequent localization near the graft is well established. We report 5 cases of lymphoma, arising from the renal graft, from a series of 648 transplantations (0.77%). The lesions appear as soft tissue masses, iso or hypoechoic with ultrasonography, soft tissue attenuation with CT and low attenuation after contrast medium. With MRI, we note isosignal in T1 and hyposignal in T2 weighted sequences. The involvement of renal parenchyma (n = 3) and the inclusion of the vessels in the masses (n = 2) are frequent. Excretory tract compression leading to obstruction is often associated (n = 3).

[Comparative study of results of hepatic transplantation between 2 groups of patients: alcoholic cirrhosis versus non-alcoholic cirrhosis]. / Etude comparative des résultats de la transplantation hépatique entre deux groupes de malades: cirrhose alcoolique versus cirrhose non alcoolique.

Among the patients treated for alcoholic cirrhosis, only a small group could be candidates for liver transplantation (LT). The aim of this multicentric study was to analyse the results of LT in a group of 75 patients with alcoholic cirrhosis (AC) compared with a group of 61 patients with non-alcoholic cirrhosis (NAC). Results were similar in both groups concerning survival rate and quality of life. However the ability to go back to a normal professional life was less in the AC group. The reported recurrence of alcoholic intoxication, which was around 26%, was much lower for patients who interrupted alcohol consumption during at least 3 months before L.T.

[Problems posed by the inferior vena cava in liver transplantation]. / Problemes posés par la veine cave inférieure en transplantation hépatique.

On the basis of a 200-case series, we report about the problems posed by the inferior vena cava for liver transplantation, and about the means implemented to solve these problems. Before hepatic transplantation, agenesia of the vena cava, which was encountered once, did not prevent grafting. During transplantation, the inferior vena cava posed problems due to its size or to the approach. These were solved using an extracorporeal venovenous shunt, which we advocate to systematically use for liver transplantation. Following transplantation, in addition to hemorrhages, the problems posed by the IVC included supra- or infrahepatic anastomotic stenoses (2 cases) and infrarenal, retrohepatic or suprahepatic thromboses (2 cases). Their repair again resorted to a venovenous shunt, for which we specify the strategy of use.