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ABSTRACT: Awareness of previous hepatic encephalopathy (HE) and compliance with treatment can probably reduce HE recurrence. The aim of this study was to assess the degree of awareness of previous HE and its treatment in a group of cirrhotic patients and their caregivers. Thirty-five cirrhotic patients with a history of HE and their caregivers (n = 31) were enrolled. Patients underwent evaluation of HE (clinical, psychometry and electroencephalography), quality of life (SF36 questionnaire), and awareness of HE/treatment on an ad hoc questionnaire (QAE). Caregivers underwent the QAE plus the Caregiver Burden Inventory. On the day of study, 7 patients were unimpaired, 8 had minimal and 20 low-grade overt HE. Of the patients, 37 % were aware of previous HE, 6 % of being on treatment and 6 % understood treatment effects. Of the caregivers, 48 % were aware of previous HE, 6 % of their relative being on treatment and 6 % understood treatment effects. Significant correlations were observed between neuropsychiatric status/linear HE indices and both the patients' quality of life and the caregivers' burden. In conclusion, HE awareness was poor in both patients and caregivers, most likely in relation to insufficient/inadequate provision of information.
Metabolic Brain Disease 07/2012; · 2.20 Impact Factor
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ABSTRACT: Muir Torre syndrome is a rare autosomal dominant cancer-predisposing syndrome characterized by the occurrence of sebaceous gland neoplasms and/or keratoacanthomas associated with visceral malignancies that belong to the spectrum of hereditary non polyposis colorectal cancer (HNPCC), i.e., tumors of gastrointestinal and genitourinary tracts. Hepatobiliary malignancy in association with Muir Torre syndrome has rarely been reported. Here, we describe a case of Muir Torre syndrome associated with an hepatocellular-carcinoma in a patient with a non-cirrhotic liver and an HNPCC-family with multiple cases of hepatocellular carcinoma.
Familial Cancer 05/2011; 11(1):7-12. · 1.30 Impact Factor
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A Vitale,
R Ramirez Morales,
E dalla Bona,
M Scopelliti,
G Zanus,
D Neri,
F d'Amico,
E Gringeri,
F Russo,
P Burra, P Angeli,
U Cillo
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ABSTRACT: The product between donor (D) age and recipient (R) Model for End-Stage Liver Disease (MELD) score at the moment of liver transplantation (LT) has been proposed as a potential D-R matching tool to reduce the risk of "futile" LT from using the MELD score as the main allocation tool. The aim of this study was to evaluate the prognostic ability of D-MELD among a cohort of Italian patients already selected for LT on the basis of a D-R matching philosophy.
We studied 303 consecutive adult patients undergoing first LT for chronic liver diseases with available D-MELD at the moment of LT from 2003 to 2009. Optimal donors were assigned to more severe cirrhotic patients (MELD ≥20); suboptimal organs were allocated to patients with hepatocellular carcinoma (HCC) not responsive to bridging therapies (specific priority score) or other exceptions with MELD <20. A suboptimal donor had age >70 years, severe steatosis by ultrasound, and/or body mass index >30 kg/m(2), partial liver, or hepatitis C (HCV) or B virus positivity.
Characteristics of the study group were a median age of 55 years (range, 27-68 years), HCV positivity in 164 patients (54%), HCC in 134 patients (44%), partial liver use in 25 (8%), MELD 15 (range, 6-40), D-age of 56 years (range, 18-87 years), and median D-MELD score 826 (range, 126-2,988). Overall graft survival was 84%, 79%, and 77% at 1, 3, and 5 years after LT, respectively. Logistic regression did not show a significant correlation between graft failure and D-MELD score in the absence of a significant D-MELD cutoff. Cox regression with D-MELD as the continuous variable showed a hazard ratio (HR) of 0.99 (95% confidence interval [CI], 0.99-1.00; P=NS); and with D-MELD as a dichotomic variable (≥0 to <1,600) an HR of 0.98 (95% CI, 0.63-1.77; P=NS).
The prognostic ability of D-MELD fails in OLT centers that use a more complex D-R matching policy.
Transplantation Proceedings 05/2011; 43(4):974-6. · 1.00 Impact Factor
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G Zanus,
R Boetto,
E Gringeri,
A Vitale,
F D'Amico,
A Carraro,
D Bassi,
P Bonsignore,
G Noaro,
C Mescoli,
M Rugge, P Angeli,
M Senzolo,
P Burra,
P Feltracco,
U Cillo
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ABSTRACT: Surgical resection for malignant hepatic tumors, especially hepatocarcinoma (HCC), has been demonstrated to increase overall survival; however, the majority of patients are not suitable for resection. Radiofrequency ablation (RFA) is the most widely used modality for radical treatment of small HCC (<3 cm). It improves 5-year survival compared with standard chemotherapy and chemical ablation, allowing down-staging of unresectable hepatic masses. Microwave ablation (MWA) has been extensively applied in Asia and was recently introduced in the United States of America and Europe with excellent results, especially with regard to large unresectable HCC. Our single-center experience between May 2009 and October 2010 included application of MWA to 154 patients of median age ± standard deviation of 63.5 ± 8.5 years, 6 males, and 1 female, of mean Model for End-Stage Liver Disease (MELD) score (10.1 ± 3.8). The HCC included, hepatitis C virus (HCV)-related (n=70; 45.5%); alcool (ETOH)-related (n=42; 27%), hepatitis B virus (HBV)-related (n=16; 10.5%); and cryptogenic cases (n=26; 17%). The cases were performed for radical treatment down-staging for multifocal pathology or bridging liver transplantation to orthotopic (OLT) in selected patients with single nodules. A computed tomography (CT) scan was performed at 1 month after the surgical procedure to evalue responses to treatment. Among 6 selected patients who underwent OLT; 5 (83.3%) showed disease-free survival at one-year follow-up. The radical treatment achieved no intraoperative evidence of tumor spread or of pathological signs of active HCC among the explanted liver specimens. In conclusion, a MWA seemed to be a safe novel approach to treat HCC and could serve as a "bridge" to OLT and down-staging for patients with HCC.
Transplantation Proceedings 05/2011; 43(4):1091-4. · 1.00 Impact Factor
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ABSTRACT: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after solid organ transplantation. Reduction of immunosuppression (RI) is accepted as a first step treatment with a long-term complete response rate observed in 23-50% of patients. Chemotherapy for diseases refractory to RI is based on small cohorts treated with different regimens. This paper reports on 10 consecutive cases of PTLD after liver transplantation. The median time from transplantation to PTLD diagnosis was 5 years. PTLD was frequently extranodal involving the transplanted liver. Seven monomorphic PTLD, 2 polymorphic and one Hodgkin disease were observed. Epstein Barr virus was present in tumour tissue only in one case. Initial therapy included RI in all patients. Chemotherapy was used in eight patients. No treatment-related mortality was observed and no patient developed graft rejection during chemotherapy. At a median follow-up period of 25 months, 6 of the 10 patients were alive and without evidence of disease.
Anticancer research 06/2010; 30(6):2383-91. · 1.73 Impact Factor
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A Vitale,
M L Volk,
M Gambato,
G Zanus,
F D'Amico,
A Carraro,
A Pauletto,
P Bonsignore,
M Scopelliti,
M Polacco,
F Russo,
M Senzolo,
P Burra,
A Romano, P Angeli,
U Cillo
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ABSTRACT: Long-term survival rates after orthotopic liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) of any size and number may now be predicted using the Metroticket calculator. The aim of this study was to evaluate the minimum post-OLT survival threshold that would justify the selection of a patient with HCC for OLT.
We used a Markov model, recently developed at the University of Michigan, which assumes that a patient with HCC should undergo OLT if his or her transplant benefit is greater than the cumulative harm to the rest of the waiting list (WL). In the base case, we considered a patient with a low survival perspective without OLT (5-year survival rate, 10%). The data sources to construct and validate the model were as follows: the Organ Procurement and Transplantation Network report, and our prospective database.
Our center was generally characterized by lower WL mortalities, although there were lower transplant probabilities for both HCC and non-HCC patients than the average US center. The proportion of HCC patients on the WL was higher in Padua (25%) than in the United States (10%). The calculated harm to the WL was 434 quality-adjusted days of life in Padua, and 957 in the United States (P < .01). The OLT benefit outweighed the harm to the WL when the 5-year post-OLT survival rate was higher than 30% in Padua, and 61% in the United States.
In a decision model including the concepts of transplantation benefit and harm to the WL, the minimum 5-year post-OLT survival threshold justifying the selection of a patient with HCC for OLT in Padua was 30%.
Transplantation Proceedings 05/2010; 42(4):1194-6. · 1.00 Impact Factor
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Transplantation 01/2010; 90. · 4.00 Impact Factor
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M. Cazzaniga,
C. Pedicino,
F. Salerno,
M. Arghittu,
R. Simonetti,
A. Borroughs,
I. Cacciola,
A. Rossini,
A. Aghemo, P. Angeli,
S. Boccia,
M. Borzio
Digestive and Liver Disease - DIG LIVER DIS. 01/2010; 42.
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Digestive and Liver Disease - DIG LIVER DIS. 01/2010; 42.
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A Vitale,
E Saracino,
F E D'Amico,
F Grigoletto,
P Burra, P Angeli,
P Boccagni,
A Brolese,
G Zanus,
D Neri,
E Gringeri,
F D'Amico,
M Valmasoni,
A Carraro,
M Gambato,
P Feltracco,
A Romano,
M Buggio,
D F D'Amico,
U Cillo
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ABSTRACT: The system that controls the waiting list (WL) and organ allocation for liver transplantation (OLT) seeks to achieve 3 main goals: objectivity, low dropout risks and good post-OLT results. We sought to prospectively validate a priority allocation model that is believed to achieve objectivity without penalizing dropout risk and post-OLT results.
We evaluated a study group of 272 patients enrolled in 2006-2007. WL candidates were divided into 2 categories: cirrhotic patients classified according to Model for End-Stage Liver Disease (MELD) score (MELD list and patients with hepatocellular carcinoma (HCC) organized according to a specific score (non-MELD list). The allocation algorithm for donor-recipient match assigned an optimal graft to the first MELD candidate with a MELD score of >or=20; a suboptimal graft, to the first non-MELD patient. A respective control group of 327 patients transplanted from 2003-2006 was characterized by a unique WL with a free allocation policy. We performed an interim analysis of this prospectively controlled study.
Although the study group showed a lower percentage of OLT (P < .05) than the control group (37% vs 45%), it selected patients for OLT based on a higher MELD score (P < .05), thus obtaining similar dropout, post-OLT survivals, and intention-to-treat (ITT) survival probabilities as the controls. Among MELD patients, we observed a significantly reduced dropout and better ITT survival profiles than those of the control group (P = .02), whereas the similar results were delivered among non-MELD patients (P > .05). Among patients with a MELD score of >or=20, the prevalences of suboptimal grafts (0% vs 48%) and of early graft losses (0% vs 21%) were lower in the study than in the control group (P < .05).
We prospectively validated a priority allocation model based on objective criteria that achieved high ITT survival rates.
Transplantation Proceedings 05/2009; 41(4):1092-5. · 1.00 Impact Factor
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A Vitale,
F D'Amico,
E Gringeri,
M Valmasoni,
A Pauletto,
P Bonsignore,
D Bassi,
F E D'Amico,
M Polacco,
P Burra,
F Russo, P Angeli,
C Poci,
P Feltracco,
A Romano,
U Cillo
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ABSTRACT: The definition of an extended criteria donor for orthotopic liver transplantation (OLT) remains controversial. The donor risk index (DRI) has become the main tool to define the marginality of hepatic grafts in the United States. The aim of this study was to prospectively evaluate the prognostic ability of DRI among a cohort of Italian patients undergoing OLT.
From December 2006 to March 2008, we prospectively calculated DRI in all consecutive cadaveric grafts. Recipient inclusion criteria were: adult patients with chronic liver disease enlisted for primary OLT. The primary end point was the incidence of primary graft dysfunction (PDF), namely, aspartate aminotransferase (AST) >2000 U/mL and prothrombin time <40% on postoperative days 2-7.
We enrolled 74 donor-recipient pairs fulfilling the inclusion criteria. Donor characteristics included DRI 1.7 (range, 0.9-3.0); age 57 years (range, 18-81); ultrasound signs of steatosis in 22 donors (30%); and ischemia time was 536 minutes (range, 290-690). Recipient characteristics are: age 55 years (range, 27-68); hepatocellular carcinoma in 36 subjects (49%); MELD was 16 (range, 7-39); and Child-Pugh score was 8 (range, 6-14). In terms of the primary end points, the DRI did not provide a significant PDF predictor (P = .84). Among all evaluated donor and recipient variables, the following were related to the incidence of graft PDF: donor age (P = .07), ultrasound signs of steatosis (P = .02), donor AST (P = .05), cell saver infusion (P = .07), and warm (P = .04) and cold ischemia (P = .07) times.
The preliminary data of this study showed a poor correlation between DRI and PDF incidence after OLT.
Transplantation Proceedings 05/2009; 41(4):1096-8. · 1.00 Impact Factor
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ABSTRACT: To compare electroencephalographic spectral analysis obtained by periodogram (calculated by means of Fast Fourier Transform) and autoregressive (AR) modelling for the assessment of hepatic encephalopathy.
The mean dominant frequency (MDF) and the relative power of delta, theta, alpha, and beta bands were computed by both techniques from the electroencephalograms (EEG) of 201 cirrhotics and were evaluated in the clinical and prognostic assessment of the patients.
The values of all the five indexes computed by periodogram and AR modelling matched each other, but the latter provided stable values after the analysis of fewer epochs. Independently of the technique, the relative power of theta and alpha bands fitted the clinical data and had prognostic value. The relative power of beta and delta bands computed by AR modelling fitted more closely with clinical data fitted the clinical data more closely.
The electroencephalographic spectral indexes obtained by periodogram and AR modelling were found to be, on average, undistinguishable, but the latter appeared less sensitive to noise and provided a more reliable assessment of low-power bands.
Neurophysiologie Clinique/Clinical Neurophysiology 05/2009; 39(2):107-15. · 1.98 Impact Factor
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Digestive and Liver Disease - DIG LIVER DIS. 01/2009; 41(3).
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ABSTRACT: It is well recognized that acute and/or chronic renal failure is a frequent complication after orthotopic liver transplantation (OLT). The multifactorial nature of the etiology of early as well as late renal failure in patients affected by HBV-related cirrhosis is not adequately appreciated by the transplant community, since renal dysfunction has mainly attributed to calcineurin inhibitor toxicity, alone or in combination with potentially nephrotoxic drugs. In the meanwhile the potential nephrotoxicity of some intravenous immunoglobulin (IVIg) preparations that more than other could affect the renal function was completely unattended. The use of polyvalent immunoglobulins has been associated in the past with several unresolved issues, including potential nephrotoxicity. Pathologic examination of the kidneys generally reveals changes typical of the osmotic nephrosis. The hypothesis of osmotic nephrosis is further supported by the fact that in most cases, acute renal failure has been associated, in the past, with the sucrose-containing IVIg products. In patients who underwent OLT for hepatitis B virus(HBV)-related liver disease the use of anti HBV immunoglobulins (HBIg) to avoid HBV-recurrence is highly effective and has really changed the outcome of this transplantation procedure. Nevertheless, the inappropriate use of HBIg could increase the risk of renal dysfunction, particularly in combination with nephrotoxic drugs.
Minerva gastroenterologica e dietologica 10/2008; 54(3):259-75.
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ABSTRACT: The number of orthotopic liver transplantation performed each year is increasing due to increased safety and logistic facilities. Therefore, the importance of reducing adverse events is progressively growing.
To review present knowledge on the neurological complications of orthotopic liver transplantation.
The epidemiology, the clinical features and the pathophysiology of the neurological complications of orthotopic liver transplants, resulting from a systematic review of the literature in the last 25 years, are summarized.
The review highlights that a relevant variety of neurological adverse events can occur in patients undergoing orthotopic liver transplantation. The knowledge of neurological complications of orthotopic liver transplantation is important for transplantation teams to reduce their prevalence and improve their management. In addition, the likelihood of neurological adverse effects provides evidence for the need of a careful cognitive and neurological work up of patients in the orthotopic liver transplantation waiting list, in order to recognize and interpret neurological dysfunction occurring after orthotopic liver transplantation.
Digestive and Liver Disease 09/2007; 39(8):740-7. · 3.05 Impact Factor
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U Cillo,
A Vitale,
F Grigoletto,
E Gringeri,
F D'Amico,
M Valmasoni,
A Brolese,
G Zanus,
N Srsen,
A Carraro,
P Burra,
F Farinati, P Angeli,
D F D'Amico
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ABSTRACT: This prospective study analyzed the dropout probability and intention-to-treat survival rates of patients with hepatocellular carcinoma (HCC) selected and treated according to our policy before liver transplantation (LT), with particular attention to those exceeding the Milan criteria. Exclusion criteria for LT were macroscopic vascular invasion, metastases, and poorly differentiated disease at percutaneous biopsy. A specific multi-modal adjuvant algorithm was used to treat HCC before LT. A total of 100 HCC patients were listed for LT: 40 exceeded the Milan criteria in terms of nodule size and number (MILAN OUT) either at listing or in list, while 60 patients continued to meet the criteria (MILAN IN). The Milan criteria did not prove to be a significant predictor of dropout probability or survival rates using Cox's analysis. Cumulative dropout probability at 6 and 12 months was 0% and 4% for MILAN OUT, and 6% and 11% for MILAN IN. The intention-to-treat survival rates at 1 and 3 years were 95% and 85% in MILAN OUT, and 84% and 69% in MILAN IN. None of the 68 transplanted patients had recurrent HCC after a median 16-month follow-up (0-69 months). In conclusion, LT may be effective for selected, aggressively-treated HCC patients exceeding the Milan criteria.
American Journal of Transplantation 04/2007; 7(4):972-81. · 6.39 Impact Factor
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P Angeli,
S Guarda,
S Fasolato,
E Miola,
R Craighero,
F Piccolo,
C Antona,
L Brollo,
M Franchin,
U Cillo,
C Merkel,
A Gatta
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ABSTRACT: Intravenous administration of a third-generation cephalosporin is optimal antibiotic treatment for spontaneous bacterial peritonitis.
To compare an intravenous-oral step-down schedule with ciprofloxacin (switch therapy) to intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis, and to evaluate the impact of terlipressin and albumin in the treatment of type 1 hepatorenal syndrome on mortality.
A total of 116 cirrhotic patients with spontaneous bacterial peritonitis, were randomly given switch therapy with ciprofloxacin (61 patients) or intravenous ceftazidime (55 patients). All patients who developed type 1 hepatorenal syndrome were treated with terlipressin (2-12 mg/day) and albumin (20-40 g/day).
Resolution of infection was achieved in 46/55 patients treated with ceftazidime (84%) and in 49/61 patients treated with ciprofloxacin (80%, P = N.S.). An intravenous-oral step-down schedule was possible in 50/61 patients (82%) who received ciprofloxacin; 45/61 patients (74%) were discharged before the end of antibiotic treatment and completed it at home. The mean saving per patient due to the reduction of hospital stay in the ciprofloxacin group was 1150 . Type 1 hepatorenal syndrome was treated successfully in 12/19 patients (63%). As a consequence, the in-hospital mortality rate due to infection was 10%.
Switch therapy with cephalosporin is more cost-effective than intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in cirrhotic patients who are not on prophylaxis with quinolones.
Alimentary Pharmacology & Therapeutics 02/2006; 23(1):75-84. · 3.77 Impact Factor
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Minerva anestesiologica 01/2006; 71(12 Suppl 1):17-26. · 2.66 Impact Factor
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ABSTRACT: Haeme oxygenase could play a role in the pathogenesis of arterial vasodilation in cirrhosis. The aim of this study was to verify the role of haeme oxygenase in the hyporesponsiveness to phenylephrine of small mesenteric arteries in rats with CCl(4) induced cirrhosis, with and without ascites.
Pressurised small resistance mesenteric arteries were challenged with increasing doses of phenylephrine. Dose-response curves were evaluated under basal conditions, after inhibition of haeme oxygenase with chromium-mesoporphyrin, after inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine-methyl-ester (L-NAME), and then after inhibition of both NOS and haeme oxygenase. Haeme oxygenase protein expression was also analysed.
Twenty six control rats and 35 rats with cirrhosis (17 with and 18 without ascites) were studied. Response to phenylephrine was lower in non-ascitic and ascitic cirrhosis than in controls. Chromium-mesoporphyrin increased the response to phenylephrine only in ascitic cirrhosis (p<0.001). L-NAME increased the response to phenylephrine in controls (p<0.001) and in ascitic and non-ascitic cirrhosis (p = 0.002, p<0.001, respectively) but the final response in non-ascitic cirrhosis was similar to that of control rats while it remained impaired in ascitic cirrhosis. Addition of chromium-mesoporphyrin to L-NAME improved the response to phenylephrine in ascitic cirrhosis (p<0.01), with final values not different from those of the other two groups. Protein expression of the inducible isoform of haeme oxygenase was increased in the mesenteric vessels of cirrhotic rats.
Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of experimental cirrhosis with ascites. NOS plays a major role only in the first stage of the disease.
Gut 12/2005; 54(11):1630-6. · 10.11 Impact Factor
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ABSTRACT: No gold standard exists to detect minimal hepatic encephalopathy. Event-related evoked potentials (P300 latency) were proposed as the best tool to assess this condition. EEG spectral analysis and psychometric evaluation are also used to assess minimal hepatic encephalopathy.
The present study aims at comparing these three techniques.
Eighty-six cirrhotic patients without overt hepatic encephalopathy were studied.
Patients underwent EEG spectral analysis, psychometric evaluation and P300. P300 latency was age-adjusted; psychometric tests were age- and education-adjusted. Values >2Z were considered to be altered. The alteration of at least two psychometric tests was considered for cognitive impairment.
At least one of the three indexes was altered in 61% (CI95% = 49-71) patients; EEG spectral analysis was altered in 41% (CI95% = 30-52%) patients, psychometric performance in 34% (CI95% = 24-45%) and P300 latency in 13% (CI95% = 7-22%). P300 latency was altered only in the patients having EEG spectral analysis or psychometric alterations, but for two cases. Psychometric performance and EEG spectral analysis, but not P300 latency, were correlated with indexes of liver function.
P300 latency provided little additional information and was less related to liver function than EEG spectral analysis and psychometrical investigation.
Digestive and Liver Disease 11/2005; 37(11):861-8. · 3.05 Impact Factor
