Bruno gridelli | University of Pittsburgh (original) (raw)
Papers by Bruno gridelli
The American Surgeon, 2005
The aim of this study is to identify the minimum safe amount of effective remnant liver volume (E... more The aim of this study is to identify the minimum safe amount of effective remnant liver volume (ERLV) in patients undergoing a major hepatectomy. Thirty-eight consecutive major hepatectomies (resection of ≥3 Couinaud segments) performed between July 1999 and March 2004 in which a frozen section liver biopsy was obtained were included. No patient had chronic viral hepatitis, cirrhosis, or cholestasis. The total liver volume (TLV) was calculated using the Vauthey formula, and the postsurgical liver volume (PSLV) was derived by subtracting the estimated volume of liver resected from the TLV. The PSLV minus the percentage of macrovesicular steatosis as nonfunctional liver was defined as the effective remnant liver volume (ERLV). Three groups of ERLV/TLV ratios (<30%, between 30% and 60%, and >60%) were correlated with liver resection type, mortality, complications, intraoperative blood transfusions, operative time, length of hospitalization, and mean value of liver function tests ...
World journal of hepatology, Jan 27, 2018
The rapidly growing field of functional, molecular and structural bio-imaging is providing an ext... more The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" forstudy of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and...
BioMed research international, 2017
Diagnosis of de novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) is c... more Diagnosis of de novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) is challenging especially in the absence of hyper-γ-globulinemia. Circulating autoantibodies are not sensitive nor specific in de novo AIH but when positive increase the diagnostic probability. We report the discovery of novel liver microsomal (LM) autoantibodies against CYP-2C19 in a 9-year-old boy with "de novo" AIH developed 7 years after OLT. Graft dysfunction presented with hypertransaminasemia (up to 400 IU/L), while serum γ-globulins remained within the normal range for age. Liver histology and response to high dose prednisone (2 mg/kg/day) with the addition of azathioprine therapy further supported the diagnosis of de novo AIH. Autoantibodies investigation by indirect immunofluorescence (IF) on rodent tissues showed a novel staining pattern involving the pericentral liver zone and sparing the renal tissue. Human but not rat liver proteins immunoblotting allowed us to charac...
Liver Transplantation, 2017
Split‐liver transplantation has been proposed as an alternative to whole liver (WL) transplantati... more Split‐liver transplantation has been proposed as an alternative to whole liver (WL) transplantation to expand the donor pool, but studies comparing adult longterm outcomes between the 2 methods are conflicting and limited. This is the first Italian multicenter study that retrospectively analyzed 119 matched‐pair recipients of whole and extended right grafts (ERGs) for longterm survival outcomes. In the overall population, WL recipients showed higher patient survival at 1 (93% versus 73%), 5 (87% versus 65%), and 10 years (83% versus 60%) after transplantation compared with split‐liver recipients (P < 0.001); graft survivals of WL recipients were also superior at 1 (90% versus 76%), 5 (84% versus 57%), and 10 years (81% versus 52%) posttransplant (P < 0.001). However, among the 81 matched pairs that survived the first posttransplant year, 5‐ and 10‐year patient survivals were 90% and 81% for split recipients and 99% and 96% for whole recipients, respectively (P = 0.34). The 5‐ ...
World Journal of Gastroenterology, 2007
AIM: To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in ci... more AIM: To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS: A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrastenhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m 2 , infused over 30 min using a peristaltic pump, and followed by Lipiodol and Gelfoam embolization. RESULTS: Patients characteristics were: mean age, 62 years; male/female 117/45; Child-Pugh score 6.2 ± 1.1; MELD 8.7 ± 2.3; mean HCC size, 3.6 (range 1.0-12.0) cm. HCC size class was ≤ 2.0 cm, n = 51; 2.1-3.0 cm, n = 35; 3.1-4.0 cm, n = 29; 4.1-5.0 cm, n = 22; 5.1-6.0 cm, n = 11; and > 6.0 cm, n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 ± 1.7). Complete tumor necrosis was obtained in 94 patients (58%), massive (90%-99%) necrosis in 16 patients (10%), partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was:
PLOS ONE, 2015
Background and Aims Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs ... more Background and Aims Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX. Methods and Results Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9-1.3) mg/ dL, and 5.8 (5.4-7.6)] μg/L, respectively), while urinary cGMP was reduced [270 (250-355) vs 581 (437-698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.
The new microbiologica, 2015
Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a positive response... more Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a positive response to pegylated interferon-alpha and ribavirin (pegIFN-alpha/RBV) treatment of HCV-infected patients. This study evaluated the association between SNPs rs12980275, rs12979860 and rs8099917 and treatment outcome of HCV recurrent infection in HCV-positive patients who underwent liver transplant. We aimed to assess to what extent recipient and/or graft donor IL28B polymorphisms contribute to HCV clearance after transplantation influencing the response to the antiviral treatment. We found that the allele frequencies in donors were in agreement with the pattern expected in the European population. The frequency of favourable genotypes was significantly lower in recipients than in donors, reasonably because the recipients represented a group of patients affected by chronic Hepatitis C. Our study demonstrated that the positive outcome of the pegIFN-alpha/RBV treatment of HCV recurrence is associa...
World Journal of Gastroenterology, 2008
World journal of gastrointestinal surgery, Jan 27, 2010
Split-Liver and living-related donor liver transplantation are the newest and both technically an... more Split-Liver and living-related donor liver transplantation are the newest and both technically and ethically most challenging developments in liver transplantation and have contributed to a reduction in donor shortage. We report the technical aspects of surgical procedures performed to achieve a partial graft from a cadaveric and a live donor.
World Journal of Gastroenterology, 2009
World Journal of Gastroenterology, 2013
World Journal of Gastroenterology, 2008
T h e p a p e r s t u d i e s t h e c o m b i n e d ra d i o l o g i c a n d endoscopic approach ... more T h e p a p e r s t u d i e s t h e c o m b i n e d ra d i o l o g i c a n d endoscopic approach (rendez vous technique) to the treatment of the biliary complications following liver transplant. The "rendez-vous" technique was used with an electrokinetic lithotripter, in the treatment of a biliary anastomotic stricture with multiple biliary stones in a patient who underwent orthotopic liver transplant. In this patient, endoscopic or percutaneous transhepatic management of the biliary complication failed. The combined approach, percutaneous transhepatic and endoscopic treatment (rendez-vous technique) with the use of an electrokinetic lithotritor, was used to solve the biliary stenosis and to remove the stones. Technical success, defined as disappearance of the biliary stenosis and stone removal, was obtained in just one session, which definitively solved the complications. The combined approach of percutaneous transhepatic and endoscopic (rendez-vous technique) treatment, in association with an electrokinetic lithotritor, is a safe and feasible alternative treatment, especially after the failure of endoscopic and/or percutaneous trans-hepatic isolated procedures.
Transplantation Proceedings, 2005
To expand the donor pool, clinicians are continually modifying criteria to accept organs, particu... more To expand the donor pool, clinicians are continually modifying criteria to accept organs, particularly those in the so-called expanded or marginal donor pool. The concept and definition of a marginal donors continues to evolve. The impact of their use is the result of a combination of donor and recipient factors. Most clinicians accept steatosis above 30%, donor age over 60 years, prolonged ischemia time, prolonged intensive care unit stay, hypernatremia, previous cardiac arrest, prolonged episodes of hypotension, large use of inotrope drugs, and elevated liver function tests as criteria for designation of a marginal organ. In June 2003, we started to use marginal donors each year tripling the number of transplants per year at our center.
Transplantation, 2000
Solid organ transplant patients undergoing long-term immunosuppression have high risk of developi... more Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.
Surgical Infections, 2006
Liver Transplantation, 2008
This study presents our experience with the use of extended criteria donor (ECD) liver grafts. On... more This study presents our experience with the use of extended criteria donor (ECD) liver grafts. One hundred fifteen liver transplants were divided into 2 groups: standard (S) and nonstandard (NS). Fifty-eight patients in group S received a liver procured from an ideal donor, whereas 57 patients in group NS received an organ from an ECD. On the basis of the number of risk factors, patients were divided into 3 subgroups: the S group with 58 receiving a standard graft, the NS1 group with 44 receiving a graft with 1 or 2 risk factors, and the NS2 group with 13 receiving a graft with 3 to 4 risk factors. Patient survival was not different at 6, 12, and 24 months (P Ͼ 0.05), whereas graft survival was different (P ϭ 0.0079). Both patient survival and graft survival were influenced by the cumulative number of risk factors. The univariate analysis of the donor risk factors detected hemodynamic factors as predictive of graft failure (P ϭ 0.024) and death (P ϭ 0.018). In the multivariate analysis, which was adjusted for recipient age and donor and recipient gender, hemodynamic risk factors and Model for End-Stage Liver. Disease score in the recipient were the only variables independently associated with graft failure (P ϭ 0.006, P ϭ 0.012, negatively). Finally, we observed a reduction of dropout from the list to 9% from 14.1% (P ϭ 0.04) and of mortality on the list to 32.55% from 41.01% (P ϭ 0.11). Critical use of ECD liver grafts allowed recipients in the waiting list to have a greater chance of being transplanted.
Liver Transplantation, 2006
Late graft dysfunction (GD) associated with the development of autoantibodies is a common event a... more Late graft dysfunction (GD) associated with the development of autoantibodies is a common event after pediatric liver transplantation (OLTx) and can present in 2 clinicohistological subsets: de novo autoimmune hepatitis (DNAH) and early chronic rejection (ECR). Sixty out of 247 children developed autoantibodies after OLTx. GD was demonstrated in 22 (37%); based on histology, patients were divided in a DNAH and an ECR group. Portal/periportal inflammatory infiltrate with interface/lobular hepatitis was suggestive for DNAH. Pericentral hepatocytes confluent dropout with a variable degree of central vein endothelitis, but not with ductopenia (loss of Ͼ50% of interlobular bile ducts), was diagnosed as ECR. Nine patients had DNAH and 13 ECR. Five out of 9 in the DNAH group were on cyclosporin (CsA) and 4/9 were on tacrolimus (Tac). In the ECR group, 11 children were treated with CsA and 2 with Tac. All DNAH patients had normal liver function tests on steroids and azathioprine (AZA). Five patients with ECR recovered by increasing calcineurin inhibitors (CNIs) dosage, but in 8/13, including 7 switched from CsA to Tac, AZA and steroids were added to obtain remission of disease. Two patients developed late chronic rejection. DNAH and ECR associated with autoantibodies are forms of late GD after OLTx. DNAH improves after standard treatment of autoimmune hepatitis. ECR has a good response to increased doses of CNIs, although ductopenic chronic rejection may occur. In conclusion, the early differential diagnosis of these conditions and an appropriate treatment seem to allow good overall results reflected by a graft survival of more than 90%.
The Journal of Infectious Diseases, 2000
Epstein-Barr virus (EBV) genome numbers and RNA transcripts from the immediate-early EBV gene BZL... more Epstein-Barr virus (EBV) genome numbers and RNA transcripts from the immediate-early EBV gene BZLF1 were monitored by means of polymerase chain reaction in peripheral blood lymphocytes (PBLs) of 44 children who received liver transplants. The 2 tests were compared, using several parameters to assess their value as predictors of posttransplantation lymphoproliferative disease (PTLD). All patients were infected with EBV. BZLF1 mRNA was positive in 70% of patients, with highest expression in those with largest virus load. Four patients developed PTLD that could not be unequivocally diagnosed by any of the parameters considered alone. Sensitivity of EBV genome number (у40,000 EBV copies/10 5 PBLs) and BZLF1 mRNA (BZLF1 : glyceraldehyde-3-phosphate-dehydrogenase ratio у0.5) was 100%. Specificity of each of the 2 tests alone (98% and 58%, respectively) improved (to 100% and 83%, respectively) when measurement of serum IgG level was included. Because decreased virus load, but not BZLF1 mRNA expression, accurately predicted favorable responses of PTLD to therapy, monitoring of EBV genome numbers alone appears sufficient in children with liver transplants.
Journal of Hepatology, 1990
Human Molecular Genetics, 1996
Lysosomal acid lipase (LAL) gene mutations were identified in three patients with cholesteryl est... more Lysosomal acid lipase (LAL) gene mutations were identified in three patients with cholesteryl ester storage disease (CESD). Direct sequencing of genomic DNA revealed that: patient 1 was a compound heterozygote for a P181L mutation and an A to G 3′ splice site substitution that causes skipping of exon 7, with a loss of 49 amino acids from LAL (∆205-253); patient 2 was a compound heterozygote for a G66V mutation and a 5′ splice site mutation (G to A) that leads to skipping of exon 8 (∆254-277); and patient 3 was a compound heterozygote for a L273S mutation and an unidentified null allele. Furthermore, patients 2 and 3 showed a novel G-2A polymorphism that could be detected by an XbaI restriction fragment length polymorphism. All these mutants and a previously reported H274Y allele were expressed in vitro in HeLa cells using the vaccinia T7 expression system. The resulting recombinant proteins were inactive towards cholesteryl oleate and trioleylglycerol, demonstrating the direct involvement of these mutations in the pathogenesis of CESD. Immunoblotting of normal LAL expressed in HeLa cells revealed four major molecular forms, at least two of high molecular mass (54 and 50-51 kDa) and two of low molecular mass (42 and 43 kDa). L273S and P181L substitutions and ∆254-277 were shown to result in altered LAL molecular forms, some of which suggest that post-translational processing may interfere with the catalytic activity of LAL.
The American Surgeon, 2005
The aim of this study is to identify the minimum safe amount of effective remnant liver volume (E... more The aim of this study is to identify the minimum safe amount of effective remnant liver volume (ERLV) in patients undergoing a major hepatectomy. Thirty-eight consecutive major hepatectomies (resection of ≥3 Couinaud segments) performed between July 1999 and March 2004 in which a frozen section liver biopsy was obtained were included. No patient had chronic viral hepatitis, cirrhosis, or cholestasis. The total liver volume (TLV) was calculated using the Vauthey formula, and the postsurgical liver volume (PSLV) was derived by subtracting the estimated volume of liver resected from the TLV. The PSLV minus the percentage of macrovesicular steatosis as nonfunctional liver was defined as the effective remnant liver volume (ERLV). Three groups of ERLV/TLV ratios (<30%, between 30% and 60%, and >60%) were correlated with liver resection type, mortality, complications, intraoperative blood transfusions, operative time, length of hospitalization, and mean value of liver function tests ...
World journal of hepatology, Jan 27, 2018
The rapidly growing field of functional, molecular and structural bio-imaging is providing an ext... more The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" forstudy of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and...
BioMed research international, 2017
Diagnosis of de novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) is c... more Diagnosis of de novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) is challenging especially in the absence of hyper-γ-globulinemia. Circulating autoantibodies are not sensitive nor specific in de novo AIH but when positive increase the diagnostic probability. We report the discovery of novel liver microsomal (LM) autoantibodies against CYP-2C19 in a 9-year-old boy with "de novo" AIH developed 7 years after OLT. Graft dysfunction presented with hypertransaminasemia (up to 400 IU/L), while serum γ-globulins remained within the normal range for age. Liver histology and response to high dose prednisone (2 mg/kg/day) with the addition of azathioprine therapy further supported the diagnosis of de novo AIH. Autoantibodies investigation by indirect immunofluorescence (IF) on rodent tissues showed a novel staining pattern involving the pericentral liver zone and sparing the renal tissue. Human but not rat liver proteins immunoblotting allowed us to charac...
Liver Transplantation, 2017
Split‐liver transplantation has been proposed as an alternative to whole liver (WL) transplantati... more Split‐liver transplantation has been proposed as an alternative to whole liver (WL) transplantation to expand the donor pool, but studies comparing adult longterm outcomes between the 2 methods are conflicting and limited. This is the first Italian multicenter study that retrospectively analyzed 119 matched‐pair recipients of whole and extended right grafts (ERGs) for longterm survival outcomes. In the overall population, WL recipients showed higher patient survival at 1 (93% versus 73%), 5 (87% versus 65%), and 10 years (83% versus 60%) after transplantation compared with split‐liver recipients (P < 0.001); graft survivals of WL recipients were also superior at 1 (90% versus 76%), 5 (84% versus 57%), and 10 years (81% versus 52%) posttransplant (P < 0.001). However, among the 81 matched pairs that survived the first posttransplant year, 5‐ and 10‐year patient survivals were 90% and 81% for split recipients and 99% and 96% for whole recipients, respectively (P = 0.34). The 5‐ ...
World Journal of Gastroenterology, 2007
AIM: To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in ci... more AIM: To investigate the efficacy of transcatheter embolization/chemoembolization (TAE/TACE) in cirrhotic patients with single hepatocellular carcinoma (HCC) not suitable for surgical resection and percutaneous ablation therapy. METHODS: A cohort of 176 consecutive cirrhotic patients with single HCC undergoing TAE/TACE was reviewed; 162 patients had at least one image examination (helical CT scan or triphasic contrastenhanced MRI) after treatment and were included into the study. TAE was performed with Lipiodol followed by Gelfoam embolization; TACE was performed with Farmorubicin prepared in sterile drip at a dose of 50 mg/m 2 , infused over 30 min using a peristaltic pump, and followed by Lipiodol and Gelfoam embolization. RESULTS: Patients characteristics were: mean age, 62 years; male/female 117/45; Child-Pugh score 6.2 ± 1.1; MELD 8.7 ± 2.3; mean HCC size, 3.6 (range 1.0-12.0) cm. HCC size class was ≤ 2.0 cm, n = 51; 2.1-3.0 cm, n = 35; 3.1-4.0 cm, n = 29; 4.1-5.0 cm, n = 22; 5.1-6.0 cm, n = 11; and > 6.0 cm, n = 14. Patients received a total of 368 TAE/TACE (mean 2.4 ± 1.7). Complete tumor necrosis was obtained in 94 patients (58%), massive (90%-99%) necrosis in 16 patients (10%), partial (50%-89%) necrosis in 18 patients (11%) and poor (< 50%) necrosis in the remaining 34 patients (21%). The rate of complete necrosis according to the HCC size class was:
PLOS ONE, 2015
Background and Aims Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs ... more Background and Aims Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX. Methods and Results Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9-1.3) mg/ dL, and 5.8 (5.4-7.6)] μg/L, respectively), while urinary cGMP was reduced [270 (250-355) vs 581 (437-698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.
The new microbiologica, 2015
Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a positive response... more Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a positive response to pegylated interferon-alpha and ribavirin (pegIFN-alpha/RBV) treatment of HCV-infected patients. This study evaluated the association between SNPs rs12980275, rs12979860 and rs8099917 and treatment outcome of HCV recurrent infection in HCV-positive patients who underwent liver transplant. We aimed to assess to what extent recipient and/or graft donor IL28B polymorphisms contribute to HCV clearance after transplantation influencing the response to the antiviral treatment. We found that the allele frequencies in donors were in agreement with the pattern expected in the European population. The frequency of favourable genotypes was significantly lower in recipients than in donors, reasonably because the recipients represented a group of patients affected by chronic Hepatitis C. Our study demonstrated that the positive outcome of the pegIFN-alpha/RBV treatment of HCV recurrence is associa...
World Journal of Gastroenterology, 2008
World journal of gastrointestinal surgery, Jan 27, 2010
Split-Liver and living-related donor liver transplantation are the newest and both technically an... more Split-Liver and living-related donor liver transplantation are the newest and both technically and ethically most challenging developments in liver transplantation and have contributed to a reduction in donor shortage. We report the technical aspects of surgical procedures performed to achieve a partial graft from a cadaveric and a live donor.
World Journal of Gastroenterology, 2009
World Journal of Gastroenterology, 2013
World Journal of Gastroenterology, 2008
T h e p a p e r s t u d i e s t h e c o m b i n e d ra d i o l o g i c a n d endoscopic approach ... more T h e p a p e r s t u d i e s t h e c o m b i n e d ra d i o l o g i c a n d endoscopic approach (rendez vous technique) to the treatment of the biliary complications following liver transplant. The "rendez-vous" technique was used with an electrokinetic lithotripter, in the treatment of a biliary anastomotic stricture with multiple biliary stones in a patient who underwent orthotopic liver transplant. In this patient, endoscopic or percutaneous transhepatic management of the biliary complication failed. The combined approach, percutaneous transhepatic and endoscopic treatment (rendez-vous technique) with the use of an electrokinetic lithotritor, was used to solve the biliary stenosis and to remove the stones. Technical success, defined as disappearance of the biliary stenosis and stone removal, was obtained in just one session, which definitively solved the complications. The combined approach of percutaneous transhepatic and endoscopic (rendez-vous technique) treatment, in association with an electrokinetic lithotritor, is a safe and feasible alternative treatment, especially after the failure of endoscopic and/or percutaneous trans-hepatic isolated procedures.
Transplantation Proceedings, 2005
To expand the donor pool, clinicians are continually modifying criteria to accept organs, particu... more To expand the donor pool, clinicians are continually modifying criteria to accept organs, particularly those in the so-called expanded or marginal donor pool. The concept and definition of a marginal donors continues to evolve. The impact of their use is the result of a combination of donor and recipient factors. Most clinicians accept steatosis above 30%, donor age over 60 years, prolonged ischemia time, prolonged intensive care unit stay, hypernatremia, previous cardiac arrest, prolonged episodes of hypotension, large use of inotrope drugs, and elevated liver function tests as criteria for designation of a marginal organ. In June 2003, we started to use marginal donors each year tripling the number of transplants per year at our center.
Transplantation, 2000
Solid organ transplant patients undergoing long-term immunosuppression have high risk of developi... more Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.
Surgical Infections, 2006
Liver Transplantation, 2008
This study presents our experience with the use of extended criteria donor (ECD) liver grafts. On... more This study presents our experience with the use of extended criteria donor (ECD) liver grafts. One hundred fifteen liver transplants were divided into 2 groups: standard (S) and nonstandard (NS). Fifty-eight patients in group S received a liver procured from an ideal donor, whereas 57 patients in group NS received an organ from an ECD. On the basis of the number of risk factors, patients were divided into 3 subgroups: the S group with 58 receiving a standard graft, the NS1 group with 44 receiving a graft with 1 or 2 risk factors, and the NS2 group with 13 receiving a graft with 3 to 4 risk factors. Patient survival was not different at 6, 12, and 24 months (P Ͼ 0.05), whereas graft survival was different (P ϭ 0.0079). Both patient survival and graft survival were influenced by the cumulative number of risk factors. The univariate analysis of the donor risk factors detected hemodynamic factors as predictive of graft failure (P ϭ 0.024) and death (P ϭ 0.018). In the multivariate analysis, which was adjusted for recipient age and donor and recipient gender, hemodynamic risk factors and Model for End-Stage Liver. Disease score in the recipient were the only variables independently associated with graft failure (P ϭ 0.006, P ϭ 0.012, negatively). Finally, we observed a reduction of dropout from the list to 9% from 14.1% (P ϭ 0.04) and of mortality on the list to 32.55% from 41.01% (P ϭ 0.11). Critical use of ECD liver grafts allowed recipients in the waiting list to have a greater chance of being transplanted.
Liver Transplantation, 2006
Late graft dysfunction (GD) associated with the development of autoantibodies is a common event a... more Late graft dysfunction (GD) associated with the development of autoantibodies is a common event after pediatric liver transplantation (OLTx) and can present in 2 clinicohistological subsets: de novo autoimmune hepatitis (DNAH) and early chronic rejection (ECR). Sixty out of 247 children developed autoantibodies after OLTx. GD was demonstrated in 22 (37%); based on histology, patients were divided in a DNAH and an ECR group. Portal/periportal inflammatory infiltrate with interface/lobular hepatitis was suggestive for DNAH. Pericentral hepatocytes confluent dropout with a variable degree of central vein endothelitis, but not with ductopenia (loss of Ͼ50% of interlobular bile ducts), was diagnosed as ECR. Nine patients had DNAH and 13 ECR. Five out of 9 in the DNAH group were on cyclosporin (CsA) and 4/9 were on tacrolimus (Tac). In the ECR group, 11 children were treated with CsA and 2 with Tac. All DNAH patients had normal liver function tests on steroids and azathioprine (AZA). Five patients with ECR recovered by increasing calcineurin inhibitors (CNIs) dosage, but in 8/13, including 7 switched from CsA to Tac, AZA and steroids were added to obtain remission of disease. Two patients developed late chronic rejection. DNAH and ECR associated with autoantibodies are forms of late GD after OLTx. DNAH improves after standard treatment of autoimmune hepatitis. ECR has a good response to increased doses of CNIs, although ductopenic chronic rejection may occur. In conclusion, the early differential diagnosis of these conditions and an appropriate treatment seem to allow good overall results reflected by a graft survival of more than 90%.
The Journal of Infectious Diseases, 2000
Epstein-Barr virus (EBV) genome numbers and RNA transcripts from the immediate-early EBV gene BZL... more Epstein-Barr virus (EBV) genome numbers and RNA transcripts from the immediate-early EBV gene BZLF1 were monitored by means of polymerase chain reaction in peripheral blood lymphocytes (PBLs) of 44 children who received liver transplants. The 2 tests were compared, using several parameters to assess their value as predictors of posttransplantation lymphoproliferative disease (PTLD). All patients were infected with EBV. BZLF1 mRNA was positive in 70% of patients, with highest expression in those with largest virus load. Four patients developed PTLD that could not be unequivocally diagnosed by any of the parameters considered alone. Sensitivity of EBV genome number (у40,000 EBV copies/10 5 PBLs) and BZLF1 mRNA (BZLF1 : glyceraldehyde-3-phosphate-dehydrogenase ratio у0.5) was 100%. Specificity of each of the 2 tests alone (98% and 58%, respectively) improved (to 100% and 83%, respectively) when measurement of serum IgG level was included. Because decreased virus load, but not BZLF1 mRNA expression, accurately predicted favorable responses of PTLD to therapy, monitoring of EBV genome numbers alone appears sufficient in children with liver transplants.
Journal of Hepatology, 1990
Human Molecular Genetics, 1996
Lysosomal acid lipase (LAL) gene mutations were identified in three patients with cholesteryl est... more Lysosomal acid lipase (LAL) gene mutations were identified in three patients with cholesteryl ester storage disease (CESD). Direct sequencing of genomic DNA revealed that: patient 1 was a compound heterozygote for a P181L mutation and an A to G 3′ splice site substitution that causes skipping of exon 7, with a loss of 49 amino acids from LAL (∆205-253); patient 2 was a compound heterozygote for a G66V mutation and a 5′ splice site mutation (G to A) that leads to skipping of exon 8 (∆254-277); and patient 3 was a compound heterozygote for a L273S mutation and an unidentified null allele. Furthermore, patients 2 and 3 showed a novel G-2A polymorphism that could be detected by an XbaI restriction fragment length polymorphism. All these mutants and a previously reported H274Y allele were expressed in vitro in HeLa cells using the vaccinia T7 expression system. The resulting recombinant proteins were inactive towards cholesteryl oleate and trioleylglycerol, demonstrating the direct involvement of these mutations in the pathogenesis of CESD. Immunoblotting of normal LAL expressed in HeLa cells revealed four major molecular forms, at least two of high molecular mass (54 and 50-51 kDa) and two of low molecular mass (42 and 43 kDa). L273S and P181L substitutions and ∆254-277 were shown to result in altered LAL molecular forms, some of which suggest that post-translational processing may interfere with the catalytic activity of LAL.