M Navasa

Università degli Studi di Modena e Reggio Emilia, Modène, Emilia-Romagna, Italy

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Publications (245)1200.25 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: The value of transient elastography (TE) to assess clinical outcomes in hepatitis C recurrence after liver transplantation (LT) has not been explored so far. We studied 144 hepatitis C-infected and 48 non-hepatitis C virus (HCV)-infected LT recipients and evaluated the prognostic value of TE 1 year after transplantation to predict clinical decompensations and graft and patient survival. In HCV patients, cumulative probabilities of liver decompensation 5 years after LT were 8% for patients with liver stiffness measurement (LSM) <8.7 kilopascals (kPa) versus 47% for patients with LSM ≥ 8.7 kPa (p < 0.001). Five-year graft and patient cumulative survival were 90% and 92% in patients with LSM < 8.7 kPa (p < 0.001) and 63% and 64% in patients with LSM ≥ 8.7 kPa, respectively (p < 0.001). Patients with low LSM 1 year after LT had excellent outcomes independently from receiving antiviral treatment or achieving sustained virological response (SVR). In contrast, graft survival significantly improved in patients with LSM ≥ 8.7 kPa who achieved SVR. No association between outcomes and LSM at 12 months was observed in non-HCV patients. In conclusion, LSM 1 year after LT is a valuable tool to predict hepatitis C-related outcomes in recurrent hepatitis C and can be used in clinical practice to identify the best candidates for antiviral therapy.
    American Journal of Transplantation 01/2014; · 6.19 Impact Factor
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    ABSTRACT: BACKGROUND/AIMS: Cirrhosis recurrence is frequent after orthotopic liver transplantation (OLT) for hepatitis C (HCV). Since transplantation causes liver denervation, we hypothesized that the response to propranolol might differ in transplanted than in non-transplanted patients with cirrhosis and portal hypertension. METHODS: Twenty-one patients with cirrhosis recurrence after OLT with portal hypertension were compared to 20 HCV portal hypertensive non-transplanted patients with cirrhosis, matched for sex, age, presence of varices and Child-Pugh score. Patients underwent systemic and hepatic hemodynamic measurements at baseline and 20 minutes after i.v. propranolol (0.15 mg/Kg). RESULTS: At baseline, transplanted cirrhotics had lower HVPG (14.8 ± 2.9 vs.17.3 ± 4.4 mmHg, p=0.035) but higher mean arterial pressure (100.3 ± 12.3 vs. 91.8 ± 11.6 mmHg, p=0.044) and systemic vascular resistance (2253 ± 573 vs. 1883 ± 525 dyn.sec.cm-5, p=0.028) than non-transplanted cirrhotics. There were no differences in cardiac index. Propranolol significantly decreased HVPG, to a similar extent in transplanted and non-transplanted cirrhotics (-14.1 ± 8.0% vs -16.9 ± 9.5%, NS). MAP tended to increase in transplanted cirrhotics while it slightly decreased in non-transplanted (+5.1 ± 14.2% vs -4.8 ± 6.4%, p=0.007), whereas reduction of cardiac index was less marked in transplanted cirrhotics (-18.6 ± 7.6% vs -26.9 ± 9.0%, p=0.005). CONCLUSIONS: Patients with HCV-related cirrhosis and portal hypertension after OLT have lower baseline HVPG but similar HVPG response to propranolol infusion as compared to non-transplanted cirrhotics. Contrary to non-transplanted patients, propranolol increased systemic vascular resistance and arterial pressure in transplanted cirrhotics and attenuated the fall in cardiac index. © 2013 American Association for the Study of Liver Diseases.
    Liver Transplantation 02/2013; · 3.94 Impact Factor
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    ABSTRACT: In this descriptive study, we examined the role of single-operator cholangioscopy (SOC) in the evaluation of biliary complications after liver transplantation (LT). We prospectively included adult recipients of deceased donor LT who were referred for endoscopic retrograde cholangiopancreatography between June 2009 and July 2011. All patients underwent SOC with biopsy of the biliary anastomosis. Sixteen patients were included: 12 with biliary anastomotic strictures (ASs), 2 with common bile duct stones, 1 with a bile leak, and 1 with sphincter of Oddi dysfunction. Patients with ASs displayed 1 of 2 patterns: (A) mild erythema (n = 9) or (B) edema, ulceration, and sloughing (n = 3). Those without ASs displayed a pale mucosa with mild edema at the anastomosis. Patients with ASs and pattern B required a longer period of stenting than patients with pattern A (457 versus 167 days, P = 0.02). In addition, patients with pattern A had a better response and better resolution of their strictures with endoscopic therapy than those with pattern B (66% versus 33%, P = 0.13). Histological examinations of ASs showed nonspecific intraepithelial inflammation in patients with patterns A and B. Biopsy samples from patients without ASs showed normal columnar epithelial bile duct cells. The total cholangioscopy time for all procedures was 26.8 ± 10.1 minutes. In conclusion, SOC in LT recipients is feasible and allows adequate visualization and tissue sampling of ASs and bile ducts. Two distinct visual patterns that are easily identified with SOC may help to predict the outcomes of endoscopic therapy in patients with biliary complications after LT. Liver Transpl 19:199-206, 2013. © 2012 AASLD.
    Liver Transplantation 02/2013; 19(2):199-206. · 3.94 Impact Factor
  • Gut 01/2013; · 10.73 Impact Factor
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    ABSTRACT: Opportunistic pulmonary infections (OPI) represent common life-threatening complications after solid organ transplantation. Our objective was to describe pulmonary infections caused by opportunistic pathogens in solid-organ transplant patients. We analyzed all adult solid organ recipients (liver, heart, kidney, and pancreas) between July 2003 and June 2010, reporting all episodes of pulmonary opportunistic infection. During the study period, 1656 solid organ transplants were performed and 188 opportunistic infections were diagnosed in 163 patients (incidence 10%). In 40 cases, the site of infection was the lung (21%) with 57.5% occurring between the first and sixth month posttransplantation. The most frequently isolated microorganism was Aspergillus spp (n = 25, 63%), followed by Pneumocystis jirovecii (n = 6 cs, 15%). Twenty-five patients with an opportunistic pulmonary infections died during the follow-up including, 16 related to the infection (40%). The causative organism responsible for the highest mortality was Aspergillus spp (n = 12; 48%). Twenty-one patients with an opportunistic nonrespiratory infection died, five of them related to it (4%). Opportunistic pulmonary infection was associated with an increased mortality rate (P < .001). There was a trend toward a higher mortality among patients who developed OPI during the first 6 months after transplantation. Opportunistic pulmonary infections after solid organ transplantation are not infrequent. The period of risk for developing this infectious complications goes beyond the first 6 months posttransplantation. Mortality due to these infections was high in comparison to that of opportunistic nonrespiratory infections. It is important to keep a high index of suspicion for infectious complications during all posttransplant periods, as this is the first step toward a rapid diagnosis and adequate treatment.
    Transplantation Proceedings 11/2012; 44(9):2673-5. · 0.95 Impact Factor
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    ABSTRACT: Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.
    American Journal of Transplantation 09/2012; · 6.19 Impact Factor
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    ABSTRACT: Anastomotic strictures (ASs) of the biliary duct after liver transplantation (LT) are primarily managed with endoscopic retrograde cholangiopancreatography (ERCP), but in some cases, this fails because of difficulties in passing the strictures. The aim of this case-control study was to examine specific risk factors for initial ERCP failure and the outcomes of percutaneous transhepatic cholangiography (PTC) as a second-line approach in LT recipients with ASs. Between January 2002 and December 2010, we identified LT recipients with ASs who experienced initial ERCP failure (which was defined as the inability to traverse the AS with guidewires in 2 or more consecutive procedures). A period-matched control group (ratio = 1:2) with ASs and initial ERCP success was analyzed. Preoperative, intraoperative, postoperative, and endoscopic variables were evaluated as risk factors. The outcomes of PTC and the need for hepaticojejunostomy (HJ) or retransplantation were evaluated. Seventeen cases who experienced initial ERCP failure were compared with 34 controls. The median times from LT to ERCP were similar (8.7 months for cases and 8.6 months for controls, P = not significant). A multivariate analysis revealed that previous bile leaks [odds ratio (OR) = 6.07, 95% confidence interval (CI) = 1.0-36.5] and more than 4 U of intraoperatively transfused red blood cells (OR = 11.51, 95% CI = 1.9-71.2) were independent risk factors for failure. PTC was an effective second-line treatment in only 3 of 12 cases (25%). The need for HJ was more frequent for the cases (13/17 or 76.5%) versus the controls (7/34 or 20.6%, P < 0.001). One patient in each group underwent retransplantation (P = not significant). In conclusion, previous bile leaks and high packed red blood cell transfusion requirements during surgery are risk factors for initial ERCP failure in LT recipients with ASs. A high proportion of these patients will need surgery as their final therapy.
    Liver Transplantation 04/2012; 18(4):482-9. · 3.94 Impact Factor
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    ABSTRACT: Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end-stage liver disease and cold and reperfusion warm ischemic times were 55 years (49-60), 19 (14-21) and 380 (325-430) and 30 min (26-35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One-year recipient and graft survivals were 82% and 70%, respectively (median follow-up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly.
    American Journal of Transplantation 11/2011; 12(1):162-70. · 6.19 Impact Factor
  • X Forns, M Navasa
    American Journal of Transplantation 08/2011; 11(8):1559-60. · 6.19 Impact Factor
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    ABSTRACT: Complications of the biliary tract after liver transplantation are successfully managed with ERCP; however, the incidence and risk factors for post-ERCP complications remain unknown. To examine the incidence, risk factors, and short-term outcome of post-ERCP complications in liver transplant (LT) recipients. Retrospective evaluation of all ERCPs performed in LT recipients at our institution during a 7-year, 4-month period. Tertiary referral center. A total of 243 ERCPs performed in 121 LT recipients with duct-to-duct anastomosis. Incidence of post-ERCP complications. Predictive factors were determined by univariate and multivariate analyses. Overall complications occurred in 22 procedures (9%) (13 mild, 9 moderate): pancreatitis in 9 patients (3.7%), cholangitis in 8 patients (3.3%), postsphincterotomy bleeding in 4 patients (1.6%), and subcapsular hematoma in 1 patient (0.4%). The mean hospitalization for post-ERCP complications was 4.8 days (range 2-11 days). Logistic regression identified mammalian target of rapamycin inhibitors (odds ratio [OR], 4.65; 95% CI, 1.01-21.81; P = .049), serum creatinine level greater than 2 mg/dL (OR, 4.17; 95% CI, 1.07-16.26; P = .04), biliary sphincterotomy (OR, 3.03; 95% CI, 1.07-8.53; P = .037), and more than 2 pancreatic duct contrast injections (OR, 2.95; 95% CI, 1.10-7.91; P = .032) as independent risk factors for post-ERCP complications, whereas steroid therapy (OR, 0.23; 95% CI, 0.08-0.63; P = .004) was an independent protective factor. Single-center retrospective study. The rate of complications after ERCP in LT recipients seems to be similar to that of non-LT recipients. Complications in this analysis were more common in LT recipients receiving mammalian target of rapamycin inhibitors and those with renal failure, biliary sphincterotomy, and more than 2 pancreatic duct injections, whereas they were less common in those patients on steroid therapy.
    Gastrointestinal endoscopy 06/2011; 74(2):285-94. · 6.71 Impact Factor
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    ABSTRACT: Information concerning the risk factors and outcome of late infection (LI) after solid organ transplantation (SOT) still remains scarce. We prospectively analyzed all patients undergoing SOT from July 2003 to March 2008, who survived the first 6 months after surgery and with a minimum 1-year follow-up. Risk factors associated with the development of bacterial and cytomegalovirus (CMV) LI and survival were identified. Overall, 942 SOT recipients (491 kidney, 280 liver, 65 heart, and 106 double transplants) were included. During the study period 147 patients (15.6%) developed 276 episodes of LI (incidence rate, 0.43 per 1000 transplantation-days). Bacteria were the most prevalent etiology (88.0%). Primary sources of infection included urinary tract (36.9%), intra-abdominal (16.7%), and sepsis without source (13.4%). Independent risk factors for late bacterial infection were: age (hazard ratio [HR] [per year] 1.0; 95% confidence interval [CI]: 1.0-1,0), female gender (HR 1.7; 95%CI: 1.1-2.6), anti-hepatitis C virus (HCV) positive serostatus (HR 1.8; 95%CI: 1.1-3.0), chronic allograft dysfunction (HR 3.2; 95%CI: 1.7-6.1), early CMV disease (HR 2.2; 95%CI 1.2-4.1), and early bacterial infection (HR 2.5; 95%CI 1.6-3.8). The occurrence of chronic allograft dysfunction was an independent risk factor for late CMV disease (HR 6.5; 95%CI: 1.7-24.6), whereas immunosuppression based on mammalian target of rapamycin inhibitors protected against the development of late CMV disease (HR 0.3; 95%CI: 0.1-1.0). Cox model selected anti-HCV positive serostatus (adjusted HR [aHR] 2.67; 95%CI: 1.27-5.59), age (aHR [per year] 1.06; 95%CI: 1.02-1.10), and the occurrence of LI (aHR 9.12; 95%CI: 3.90-21.33) as independent factors for mortality. LI did not constitute an uncommon complication in our cohort, and patients at risk may benefit from close clinical monitoring.
    Transplant Infectious Disease 04/2011; 13(6):598-607. · 1.98 Impact Factor
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    ABSTRACT: IL28B gene polymorphisms are associated with the response to antiviral therapy in hepatitis C patients. We investigated the influence of IL28B polymorphisms on the response to therapy before and after liver transplantation (LT). Genotyping of SNPs rs8099917 and rs12979860 was performed in 128 HCV-infected liver transplant recipients and in their donors; all patients underwent antiviral treatment after LT. The prevalence of genotypes rs12979860CC and rs8099917TT was higher in donors than in recipients (50% vs.19%, p < 0.001 and 67% vs. 38%, p < 0.001, respectively). Response to antiviral therapy was significantly higher for recipient genotype rs12979860CC as compared to rs12979860CT/TT both before (100% vs. 48% p = 0.013) and after LT (59% vs. 25% p = 0.002). The figures were almost identical for SNP rs8099917. Sustained virological response after LT was particularly high in patients with favorable recipient and donor genotypes (p < 0.01 for both SNPs). In a subgroup of 34 patients treated while awaiting LT, a favorable donor IL28B genotype was associated with an improved virological response after LT. Our results support a major role of recipient IL28B genotype in the response to antiviral treatment for hepatitis C recurrence. Interestingly, donor genotype also seems to influence the response pattern, especially in recipients who have a favorable IL28B genotype.
    American Journal of Transplantation 04/2011; 11(5):1051-7. · 6.19 Impact Factor
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    ABSTRACT: Neutralizing antibody (nAb) activity during the course of natural infection is believed to be crucial to combating virus propagation. The aim of this study was to measure the impact of nAb response on HCV early kinetics and genetic evolution in the liver transplantation (LT) setting. A cohort of 28 patients undergoing LT for HCV-related cirrhosis was included in the study. Viral load, nAb titers and hypervariable region 1 (HVR1) sequences were determined in serum samples obtained before and at different time points after LT. Serum nAb titers were assessed using HCV pseudoparticles (HCVpp). HVR1 sequences were obtained by direct sequencing. Patients were classified according to viral kinetic patterns (plateau or increasing), during the first week after LT. All patients demonstrated high titers of nAbs before LT, although this was not associated with early kinetic patterns or HVR1 evolution during the first week after LT. We found that in patients with plateau HCV early kinetics, the virus required adaptive mutations, while in those with increasing viral loads, the HVR1 region remained largely conserved (p = 0.015). These data suggest that HCV adaptation via selection of the best-fitted variants may account for early viral kinetics following LT.
    American Journal of Transplantation 03/2011; 11(4):767-74. · 6.19 Impact Factor
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    ABSTRACT: Biliary complications occur in 5-25% of patients after liver transplantation and represent a major source of morbidity in this group of individuals. The major risk factor for most of these complications is ischemia of the bile tree usually due to obstruction or vascular insufficiency of the hepatic artery. The most common complications include biliary strictures (anastomostic and nonanastomotic), bile leaks, and biliary filling defects. The initial diagnostic approach starts with a high index of suspicion along with an abdominal ultrasound and Doppler exam. Magnetic resonance imaging is highly sensitive and is usually reserved for confirmation. The vast majority of these complications can be successfully treated with endoscopic retrograde cholangiography, however if this procedure cannot be performed a percutaneous approach or surgery is recommended. Nonanastomotic strictures and living donor recipients present a less favorable response to endoscopic management. This review focuses on the current diagnostic and therapeutic approaches for the management of biliary complications after liver transplantation.
    Gastroenterología y Hepatología 02/2011; 34(2):107-15. · 0.57 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
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    ABSTRACT: The introduction of the genotype 2a isolate JFH1 was a major breakthrough in the field of hepatitis C virus (HCV), allowing researchers to study the complete life cycle of the virus in cell culture. However, fully competent culture systems encompassing the most therapeutically relevant HCV genotypes are still lacking, especially for the highly drug-resistant genotype 1b. For most isolated HCV clones, efficient replication in cultured hepatoma cells requires the introduction of replication-enhancing mutations. However, such mutations may interfere with viral assembly, as occurs in the case of the genotype 1b isolate Con1. In this study, we show that a clinical serum carrying a genotype 1b virus with an exceptionally high viral load was able to infect Huh7.5 cells. Similar to previous reports, inoculation of Huh7.5 cells by natural virus is very inefficient compared to infection by cell culture HCV. A consensus sequence of a new genotype 1b HCV isolate was cloned from the clinical serum (designated Barcelona HCV1), and then subjected to replication studies. This virus replicated poorly in a transient fashion in Huh7.5 cells after electroporation with in vitro transcribed RNA. Nonetheless, approximately 3 weeks post electroporation and thereafter, core protein-positive cells were detected by immunofluorescence. Surprisingly, small amounts of core protein were also measurable in the supernatant of electroporated cells, suggesting that HCV particles might be assembled and released. Our findings not only enhance the current method of cloning in vitro HCV replication-competent isolates, but also offer valuable insights for the realization of fully competent culture systems for HCV.
    PLoS ONE 01/2011; 6(8):e23587. · 3.73 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.

Publication Stats

7k Citations
1,200.25 Total Impact Points

Institutions

  • 2013
    • Università degli Studi di Modena e Reggio Emilia
      Modène, Emilia-Romagna, Italy
  • 1999–2013
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 1993–2012
    • Hospital Clínic de Barcelona
      • • Servicio de Cirugía General y Digestiva
      • • Servicio de Hepatología
      • • Servicio de Reumatología
      Barcino, Catalonia, Spain
  • 1987–2012
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 2011
    • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
      Barcino, Catalonia, Spain
  • 2005
    • Southern Medical Clinic
      San Fernando, City of San Fernando, Trinidad and Tobago
    • University of Toronto
      • Division of Gastroenterology
      Toronto, Ontario, Canada
  • 2003
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
  • 2001
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 1997
    • Hospital Universitari Germans Trias i Pujol
      Badalona, Catalonia, Spain