[Multimodal treatment for acute antibody-mediated renal transplant rejection: successful rescue therapy with combined plasmapheresis, photopheresis and intravenous immunoglobulin]. / Trattamento multimodale per il rigetto acuto anticorpo-mediato nel trapianto di rene: terapia di salvataggio con plasmaferesi, fotoaferesi e immunoglobuline endovenose.

The fundamental role of antibodies in the development of acute graft rejection has been established recently. Antibody-mediated acute rejection may develop at any time during the post-transplant period. Several therapeutic approaches have been proposed in the last decades. However, there is no standardized therapy. The aim of this study is to report the Sapienza University experience of combined plasma treatment and high-dose intravenous immunoglobulin ± extracorporeal photopheresis. From January 2006 to September 2009, 6 patients were treated at Sapienza University. In 5 cases (83%) complete regression of the acute rejection was observed, followed by stable renal function (median creatinine value at 1-year follow-up: 1.5 mg/dL). No adverse events were reported. Our approach seems to give good results in terms of graft survival and procedure safety. Further studies on a larger number of patients will be needed to confirm the validity of these findings. Moreover, comparison between our protocol and other treatments is necessary.

[Adacolumn apheresis for hepatitis C virus in patients waiting for kidney transplant. Preliminary study]. / Trattamento con Adacolumn leucocitaferesi per la rimozione del virus C nei pazienti in lista per trapianto di rene. Studio preliminare.

Hepatitis C virus (HCV) infection occurs much more frequently in the hemodialysis population than in the general population. Patients with chronic kidney disease with persistent HCV infection may develop serious and progressive chronic liver disease, with associated long-term morbidity and mortality related to cirrhosis and hepatocellular carcinoma. Monocytes and macrophages are known to produce extrahepatic breeding sites and spread the disease. Our aim was to lower the levels of macrophages, granulocytes, monocytes, proinflammatory cells and viremia using an extracorporeal device: the Adacolumn ® leukocyte apheresis system (Otsuka). The Adacolumn is a direct hemoperfusion-type leukapheresis device. The column is a single-use (disposable) polycarbonate column with a capacity of about 335 mL, filled with 220-g cellulose acetate beads of 2 mm in diameter bathed in physiological saline. The carriers adsorb ''activated'' granulocytes and monocytes/macrophages that bear Fc and complement receptors. The patients underwent five 1-hour sessions for five consecutive days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. A reduction of viremia was observed in all patients in association with a decrease in cytokine levels and a proportional decrease in immune cells. Although this study investigated responses in a small number of patients, it was shown that the Adacolumn changed the cellular immunity and promoted early viral response.

Nutritional status: its influence on the outcome of patients undergoing liver transplantation.

BACKGROUND: Malnutrition is frequently present in case of end-stage liver diseases, and in cirrhotic patients, a poor nutritional status is considered to be one of the predictive factors for increased morbidity and mortality rates after surgery. The impact of the recipients' malnutrition on the outcome of liver transplantation (LT) is still under debate and recent studies have shown controversial results. PATIENTS AND METHODS: We prospectively analysed the nutritional status of 38 consecutive patients undergoing LT in our University Hospital. Subjective global nutritional assessments (SGA) and anthropometry were used for the evaluation of the nutritional status. Energy expenditure, dietary intake and energy balance were also evaluated. After LT, multiple short-term outcomes that could be influenced by the nutritional status, such as number of episodes of infections (bacterial, viral and fungal) until discharge from hospital, length of stay in intensive care unit (ICU), length of hospital stay and in-hospital graft and patient's survival, were recorded. RESULTS: Malnutrition was identified in 53% of cases according to the SGA. Pretransplant nutritional status, haemoglobin levels and disease severity were independently associated with the number of infection episodes during the hospital stay. The presence of malnutrition was the only independent risk factor for the length of stay in the ICU and the total number of days spent in hospital. CONCLUSION: The present data suggest that recipients' malnutrition should be taken into account as a factor that increases complications and costs after LT.

Predictive criteria for the outcome of patients with acute liver failure treated with the albumin dialysis molecular adsorbent recirculating system.

The aim of this study was to evaluate the improvement of prognostic parameters after treatment with the molecular adsorbent recirculating system (MARS) in patients with fulminant hepatitis (FH). The parameters conducive to a positive prognosis include: Glasgow Coma Scale (GCS) score >/=11, intracranial pressure (ICP) <15 mm Hg or an improvement of the systolic peak flow of 25-32 cm/s via Doppler ultrasound in the middle cerebral artery, lactate level <3 mmol/L, tumor necrosis factor-alpha <20 pg/mL, interleukin (IL)-6 <30 pg/mL, and a change in hemodynamic instability from hyperkinetic to normal kinetic conditions, and so define the timing (and indeed the necessity) of a liver transplant (LTx). From 1999 to 2008 we treated 45 patients with FH with MARS in the intensive care unit of our institution. We analyzed all the parameters that were statistically significant using univariate analysis and considered the patients to be candidates for inclusion in a multivariate logistic regression analysis. Thirty-six patients survived: 21 were bridged to liver transplant (the BLT group) and 15 continued the extracorporeal method until native liver recovery (the NLR group) with a positive resolution of the clinical condition. Nine patients died before transplantation due to multi-organ failure. We stratified the entire population into three different groups according to six risk factors (the percentage reduction of lactate, IL-6 and ICP, systemic vascular resistance index values, GCS <9, and the number of MARS treatments): group A (0-2 risk factors), group B (3-4 risk factors), and group C (5-6 risk factors). Analyzing the prevalence of these parameters, we noted that group A perfectly corresponded to the NLR group, group B corresponded to the BLT group, and group C was composed of patients from the non-survival group; thus, we were able to select the patients who could undergo a LTx using the predictive criteria. For patients with an improvement of neurological status, cytokines, lactate, and hemodynamic parameters, LTx was no longer necessary and their treatment continued with MARS and standard medical therapy.

Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver.

The organization of the hepatic microvascular network has been widely studied in recent years, especially with regard to cirrhosis. This research has enabled us to recognize the distinctive vascular patterns in the cirrhotic liver, compared with the normal liver, which may explain the cause of liver dysfunction and failure. The aim of this study was to compare normal and cirrhotic rat livers by means of a quantitative mathematical approach based on fractal and Fourier analyses performed on photomicrographs and therefore on discriminant analysis. Vascular corrosion casts of livers belonging to the following three experimental groups were studied by scanning electron microscopy: normal rats, CCl(4)-induced cirrhotic rats and cirrhotic rats after ligation of the bile duct. Photomicrographs were taken at a standard magnification; these images were used for the mathematical analysis. Our experimental design found that use of these different analyses reaches an efficiency of over 94%. Our analyses demonstrated a higher complexity of the normal hepatic sinusoidal network in comparison with the cirrhotic network. In particular, the morphological changes were more marked in the animals with bile duct-ligation cirrhosis compared with animals with CCl(4)-induced cirrhosis. The present findings based on fractal and Fourier analysis could increase our understanding of the pathophysiological alterations of the liver, and may have a diagnostic value in future clinical research.

A 3-year experience with Molecular Adsorbent Recirculating System (MARS): our results on 63 patients with hepatic failure and color Doppler US evaluation of cerebral perfusion.

In our 3-year experience, we treated 63 patients with Molecular Adsorbent Recirculating System (MARS). The patients were divided as follows: 10 primary non-function (PNF) 16%, 10 delayed non-function (DNF) 16%, 16 Fulminant hepatitis (FH) 24%, 23 acute decompensation of chronic liver disease (ACLF) 38%, and 4 hepatic resection 6%. All patients who underwent MARS treatment had bilirubin >15 mg/dL, Glasgow Coma Score between 9 and 11, ammonium >160 microg/dL and non-coagulability. The determining factors taken into consideration for the continuation of MARS treatment were: an improvement in Glasgow Coma Score, and a decrease in ammonium and bilirubin. We also monitored hemodynamic parameters, acid-base equilibrium, and blood gas analysis before and after each treatment. In order to determine patients' neurological conditions, we not only took into account the Glasgow Coma Score, which does not give mathematically precise results but also took into account the fact that patients with hepatic coma had lower cerebral mean velocity in the cerebral arteries than patients without encephalopathy. For this reason, in the last 22 patients we monitored cerebral perfusion, determined by mean flow velocity (Vmean) in the middle cerebral artery. Our results were expressed as mean +/- SD and we analyzed the differences between mean values for each variable, before and after treatment by means of Student's t-test. At the end of treatment, we obtained significant P-values for bilirubin, ammonium, Glasgow Coma Score and creatinine. In 16/20 patients, we could demonstrate a clear correlation between the improvement in clinical conditions (especially neurological status) and improvement in cerebral perfusion, measured by color Doppler US.

MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure.

As reported in the literature, the mortality rates for patients with Acute Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is not possible. Post-transplant mortality mostly depends on the severity of the neurological condition at the time of the operation (20% in I-II degree coma patients and 44% in III degree coma patients). The primary indications for liver transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis (5%) and other indications (2%). Other causes of AHF are Primary Non-Function (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes necessary to monitor the patients with a Liver Support Device to be able to improve the clinical condition of the patients before liver transplantation (LT). In our experience we used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal of albumin-bound substances accumulating in liver failure by the use of albumin-enriched dialysate. The system is used as a bridging device to orthotopic liver transplantation (OLT) of patients with FHF. We studied 34 patients, including 16 males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years and the average number of applications was 6.4; the median length of application was about eight hours. The parameters that we monitored, before and after each treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score), haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also monitored hepatic and renal function. In addition, the clinical conditions of the patients were monitored using kidney and liver ultrasound/ultrasonography (US). Inclusion criteria were bilirubin > 15 mg/dL, ammonia > 160 micro g/dL and a Glasgow Coma Score between 6 and 11. The reduction of bilirubin and ammonia were very significant (P < 0.01), whereas the changes of International Normalized Ratio (INR) were not significant. Also the modifications of albumin, total protein, sodium, potassium and calcium were not significant. In conclusion, four out of nine patients with PNF are alive without a second transplantation and were discharged after about 48 days; four out of nine underwent OLT, while one out of nine died; five out of six patients with DF are alive without a second transplantation, and they were discharged after an average time of 55.5 days, one out of six died; six out of nine patients with fulminant hepatitis underwent OLT and four of these are alive, while two died due to sepsis; three patients are alive without OLT. Four patients with AOCHF underwent OLT and are alive, three patients are alive and on a waiting list, two died while on a waiting list and one patient who experienced reactivation of HBV infection during chemotherapy for non-Hodgkin's lymphoma is alive. In spite of the limited number of cases of our study, we believe that MARS can be applied with high tolerance for a very long period of time. In addition, its repeatability allows it to be used in patients with DNF and FH as a bridge to transplant. In patients with DNF, it is used while waiting for complete recovery of the transplanted organ.