Diagnostic Value of Presepsin for Bacterial Infection in Cirrhosis: A Pilot Study.

INTRODUCTION: Presepsin (or sCD14) has been identified as a protein whose levels increase specifically in the blood of patients with bacterial infections. In this study, we evaluated the clinical performance of sCD14 and its usefulness in the early diagnosis of bacterial infection in decompensated cirrhotic patients. MATERIALS: Seventy patients were enrolled in this study. The mean age of patients was 49.5 years, and 21 were women and 49 men. The heparinized whole blood for the PATHFAST test was used in the evaluation of bacterial infection (T0). The test was repeated after 48 hours (T1); at 96 hours (T2); at 144 hours (T3); then at 15 days (T4) to monitor the clinical responses to therapeutic interventions. RESULTS: Forty-nine patients tested positive for sCD14. The mean sCD14 level was 1854 ± 1744 pg/mL. Microbiological findings confirmed the presence of bacterial infections within 84 ± 4.8 h from enrollment in all 49 positive patients. Thirty-eight patients were considered responders to empirical antibiotic therapy with a decrease of presepsin at the different time points, while an increased level of sCD14 was highlighted in 11 patients. When the test was performed, 45% of the patients showed no signs or symptoms of bacterial infection. At 30 days of follow-up 43 patients survived, and 6 patients died from septic shock. CONCLUSIONS: The PATHFAST test highlighted the presence of infection in a very short time (15 minutes), and the presepsin could be considered an early biomarker in patients with cirrhosis. A greater number of patients are necessary to confirm these data.

Evaluation on the Use of Italian High-Speed Rail to Support Transportation Network for Transplantation Activities.

BACKGROUND: One of the main activities connected with transplantation is the rapid and timely transportation of patients, medical teams, and human organs from donation to transplantation centers under the compliance of national guidelines and principles of quality, performance, and safety. High-speed transportation on a railway network is becoming relevant both in terms of performance and extensiveness of the service. METHODS AND OBJECTIVES: Our study explores the feasibility of adopting a high-speed rail network for the transportation of those organs with large cold ischemia time and those less influenced by transportation-related perturbations (ie, temperature, speed, vibrations), assessing savings and relative performance improvement. In this study, only kidneys have been considered; the transplantation database has been integrated with the national high-speed railway network and timetables. A function is implemented that allocates to air transportations those records with 1 of the 2 ends situated on islands, remote regions, and abroad, while rail transportation is preferred where constraints on capacity and compliance with cold ischemia time are met. Road transportation is still feasible for those records involving 2 adjacent regions and for intraregional transportation. RESULTS: The opportunity of integrated road-rail transportation in place of air or all-road transportation allows users to lower generalized costs and reduce driven distance for personnel and vehicles allocated to a regional transplantation center's fleet and staff. Savings in fleet and staff usage can serve to improve the performances at the local level. CONCLUSIONS: The knowledge and analysis of transportation alternatives for human organs with less stringent safety and preservation criteria allow a more efficient allocation of resources both at the local and national level-without compromising quality and reliability of the system.

Mechanism of cell death in acute-on-chronic liver failure: a clinico-pathologic-biomarker study.

BACKGROUND & AIMS: Mortality of patients who develop acute-on-chronic liver failure (ACLF) is unacceptably high but the predominant mode of cell death is unknown. The aim of this study was to evaluate whether plasma levels of caspase-cleaved cytokeratin M30 (marker of apoptosis) and uncleaved cytokeratin M65 (marker of total cell death) are altered in ACLF patients and relate this to liver histology. METHODS: Twenty-seven patients with acute decompensation of liver disease were divided into two groups: no-ACLF (n = 11) or ACLF (n-16). Healthy controls (n = 8) and acute liver failure (ALF) patients (n = 10) were also enrolled. Cell death was assessed in plasma using an ELISA kit (M30 and M65). Simultaneous biopsy samples were analysed for M30 and caspase-3 staining. RESULTS: Plasma M30 value was significantly elevated in ACLF patients compared with healthy volunteers (P = 0.0001), it was also significantly higher in ACLF patients compared with no-ACLF patients (P = 0.002). M65 levels were higher in ALF compared with ACLF patients (P = 0.002) but the apoptotic index defined by M30/M65 ratio was significantly higher in ACLF patients. Patients with extra-hepatic failure had higher M30 levels compared with patients without organ failure (P = 0.03). M30 staining in liver was more marked in the patients with ACLF and was observed in all the patients that died. CONCLUSIONS: The results of this study suggest that hepatocyte apoptosis is the predominant mode of cell death in ACLF, which can be identified in the peripheral blood. Further studies are required to validate our findings and to determine whether M30 can be used as a biomarker of apoptosis or as a target for therapy.

Renal dysfunction in cirrhosis is not just a vasomotor nephropathy.

The short-term mortality of cirrhotic patients who develop renal dysfunction remains unacceptably high, and as such the treatment of this condition is an unmet need. Although features of kidney injury are well recognized in these patients, the pathophysiology is complex and not completely understood. Improved understanding of the pathophysiological mechanisms involved in renal dysfunction occurring on a background of cirrhosis is key to developing effective treatment strategies to improve survival. Renal dysfunction due to hepatorenal syndrome (HRS) is characteristic of cirrhosis. Our current understanding is that HRS is functional in nature and occurs as a consequence of hemodynamic changes associated with portal hypertension. However, there is evidence in the literature suggesting that, histologically, the kidneys are not always normal in the vast majority of patients who present with renal dysfunction on the background of cirrhosis. Furthermore, there is emerging data implicating nonvasomotor mechanisms in the pathophysiology of renal dysfunction in cirrhosis. This mini-review aims to present the evidence suggesting that factors other than hemodynamic dysregulation have an important role in the development of this major complication for patients with progressive cirrhosis.

A case of portal vein arterialization after a liver transplant.

Hepatic artery thrombosis represents a potentially deadly complication after a liver transplant. Portal vein arterialization recently has been proposed as a bridge approach in patients with hepatic artery thrombosis needing a retransplant. We report the case of a 53-year-old man treated with a liver transplant for a cryptogenetic cirrhosis. One month after a liver transplant, a hepatic artery thrombosis was documented, and a portal vein arterialization as bridge therapy for another liver transplant was performed. After surgery, improvement in the patient's liver functioning was seen. No signs of portal hypertension or hepatic abscesses were documented. Unfortunately, 8 months after the liver transplant, the patient experienced a severe urinary infection caused by a multidrug-resistant Klebsiella and died. An increase in the oxygen supply to the liver parenchyma after portal vein arterializations represents rationale use for managing hepatic artery thromboses. Several cases of treating post liver transplant hepatic artery thromboses have been reported in the literature. Portal vein arterializations can be used as bridge therapy in well-selected situations of post-liver transplant hepatic artery thromboses. Strict surveillance should be used to prevent the onset of complications that can exclude a patient from a transplant. The correct timing for retransplant is not fully known, but we think the shorter the time to retransplant, the better is the patient survival.

[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.

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.