Miquel Navasa - Academia.edu (original) (raw)
Papers by Miquel Navasa
Best Practice & Research Clinical Gastroenterology, 2012
Annals of Internal Medicine, 1989
Excerpt To the Editor:Recently, Speich and colleagues (1) reported three patients who developed s... more Excerpt To the Editor:Recently, Speich and colleagues (1) reported three patients who developed severe anaphylactoid reactions after indocyanine-green was administered. The three cases were collect...
Annals of hepatology, 2016
BACKGROUND AND RATIONALE The REPLACE study (NCT01571583) investigated telaprevir-based triple the... more BACKGROUND AND RATIONALE The REPLACE study (NCT01571583) investigated telaprevir-based triple therapy in patients who have recurrent genotype 1 hepatitis C virus (HCV) infection following liver transplantation and are on a stable immunosuppressant regimen of tacrolimus or cyclosporin A. Patients received telaprevir 750 mg 8-hourly with pegylated interferon 180 μg weekly and ribavirin 600 mg daily, followed by a further 36 weeks of pegylated interferon and ribavirin alone and 24 weeks of follow-up. Efficacy (sustained virological response [SVR] 12 weeks after last planned study dose), safety and tolerability of telaprevir throughout the study were assessed. Pharmacokinetics of telaprevir, tacrolimus and cyclosporin A were also examined. RESULTS In total, 74 patients were recruited. Overall, 72% (53/74; 95% CI: 59.9 to 81.5) of patients achieved SVR at 12 weeks following completion of treatment. Anticipated increases in plasma concentrations of tacrolimus and cyclosporin A occurred du...
eLife, 2021
While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C ... more While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C virus (HCV) production, the role of the liver/hepatocytes in clearance of circulating HCV remains unknown. Frequent HCV kinetic data were recorded and mathematically modeled from five liver transplant patients throughout the anhepatic (absence of liver) phase and for 4 hr post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n = 3) or declined (n = 2) with t1/2~1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t1/2 = 5 min) followed by a slower decline (t1/2 = 67 min). Consistent with the majority of patients in the anhepatic phase, when we monitored HCV clearance at 37°C from culture medium in the absence/presence of chronically infected hepatoma cells that were inhibited from secreting HCV, the HCV t1/2 in cell culture was longer in the absence of chronically HCV-infected cells. The resu...
Gastroenterología y Hepatología, 2020
Gastroenterología y Hepatología (English Edition), 2021
Abstract Objective To evaluate the results of isolated liver and combined liver and kidney transp... more Abstract Objective To evaluate the results of isolated liver and combined liver and kidney transplantation in a retrospective series of 32 patients with hepatorenal liver and kidney disease. Patients and methods A retrospective observational study that enrolled patients with polycystic liver disease (PLD) and polycystic liver and kidney disease (PLKD) who were evaluated for transplantation between January 1999 and December 2019 at Hospital Clinic de Barcelona [Clinical Hospital of Barcelona]. Results Of 53 patients enrolled, 32 (60.3%) had an indication for transplantation, 12 received a single liver transplant and 20 received a double liver and kidney transplant. The mean age was 52 years and 83.9% of the recipients were women. The main indication for liver transplantation was disabling symptomatic hepatomegaly (93.5%). Among the postoperative complications, in the combined liver and kidney transplant group, hepatic artery thrombosis and renal artery thrombosis were detected. In both groups there was an inferior vena cava lesion. Three patients presented acute cellular rejection responding to corticosteroids and one presented humoral rejection which was treated with plasmapheresis. During the follow-up period of 80 (27–121) months, the liver transplant survival rate was 100% and the kidney transplant survival rate was 90%. Two patients in the combined liver and kidney transplant group died (one due to cardiovascular causes and the other due to intestinal adenocarcinoma). Conclusions Isolated liver transplantation or combined liver and kidney transplantation in selected patients with polycystic disease yields excellent results, with few complications, very good transplant survival and excellent patient survival (93.8%).
Journal of Clinical Medicine, 2020
Tobacco use is more prevalent among alcohol liver disease (ALD) transplant patients and exerts ha... more Tobacco use is more prevalent among alcohol liver disease (ALD) transplant patients and exerts harmful effects to the patient and to the graft. The aims of this study were to examine the impact of smoking status (nonsmoker, ex-smoker, active smoker) on patient survival and clinical outcomes, and to assess risk factors for active smoking before and after liver transplant (LT). An observational retrospective cohort study with 314 ALD patients undergoing LT from January 2004 to April 2016. Recipients were followed until April 2017 or death. Kaplan–Meier and Cox proportional hazards regression analyses were used to assess risk of mortality according to smoking status before LT. Smokers had a 79% higher risk of dying than those who had never smoked or quit smoking before LT. Ex-smokers had a greater survival probability (96.2%, 93.8%, 86.9%, and 83.1% at 1, 3, 5, and 10 years after LT) than active smokers until LT (96.0%, 85.6%, 80.0%, and 70.4%). Active smokers before LT with poor toxic...
Gastroenterología y Hepatología, 2020
Annals of Hepatology, 2010
The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, also known as DIHS (drug-indu... more The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, also known as DIHS (drug-induced hypersensitivity syndrome), is a severe idiosyncratic reaction to several drugs, mainly antiepileptics and antibiotics, which can occasionally produce acute liver failure. In this article we present two cases of the DRESS syndrome presenting with severe acute hepatitis, including the first case of DRESS associated with levetiracetam. Although both cases finally resolved with good outcomes, DRESS can lead to acute liver failure and has a bad prognosis when liver damage is present. Rapid diagnosis is crucial since withdrawal of the offending drug is the key of treatment, while the potential role of corticosteroids is discussed.
Liver Transplantation, 2019
The selection of liver transplantation (LT) candidates with alcohol‐use disorder (AUD) is influen... more The selection of liver transplantation (LT) candidates with alcohol‐use disorder (AUD) is influenced by the risk of alcohol relapse (AR) after LT. We aimed to investigate the risk factors of AR after LT and its impact on graft and recipient outcomes. A retrospective study was conducted that included all consecutive patients with AUD undergoing LT from January 2004 to April 2016 (n = 309), excluding patients with alcoholic hepatitis. Odds ratios (ORs) and 95% confidence intervals (CIs) for AR were analyzed by multinomial logistic regression. Cox regression with time‐dependent covariates was used to analyze patient survival and graft cirrhosis. There were 70 (23%) patients who presented AR (median follow‐up, 68 months), most of them (n = 44, 63%) presenting heavy AR. The probability of heavy AR was 2.3%, 7.5%, 12%, and 29% at 1, 3, 5, and 10 years after LT, respectively. The independent risk factors for heavy AR included a High‐Risk Alcoholism Relapse (HRAR) score ≥3 (OR, 2.39; 95% CI, 1.02‐5.56; P = 0.04) and the duration of abstinence (months) before LT (OR, 0.81; 95% CI, 0.66‐0.98; P = 0.03). In recipients with <6 months of abstinence before LT, the probability of heavy AR after LT was higher in patients with an HRAR score ≥3 than in those with an HRAR score <3 (20%, 36.7%, and 47% versus 6.8%, 12.4%, and 27% at 1, 3, and 5 years, respectively; log‐rank 0.013). The risk of graft cirrhosis was increased in patients with heavy AR (hazard ratio, 3.44; 95% CI, 1.58‐7.57; P = 0.002) compared with nonrelapsers, with no differences in patient survival. In conclusion, the HRAR score is helpful in identifying the risk of harmful AR after LT in candidates with <6 months of alcohol abstinence without alcoholic hepatitis. These patients could benefit from a longterm integrative patient‐centered approach after LT until lifestyle changes are implemented.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Jan 30, 2018
The development of non-invasive biomarkers that reflect the state of immune suppression remains a... more The development of non-invasive biomarkers that reflect the state of immune suppression remains an unmet need in liver transplantation (LT). Torque Teno Virus (TTV) is a highly prevalent, non-pathogenic DNA virus whose plasma levels may be associated with the immune status of the host. The aim of this study was to assess the role of TTV as a biomarker of immune suppression in LT recipients. TTV DNA in plasma was quantified by real-time PCR at different time-points during the first year after transplant in a prospectively followed cohort of 63 de novo LT recipients, and any correlation between TTV DNA and biopsy-proven acute cellular rejection (ACR) and opportunistic infections was then evaluated. In addition, TTV DNA was studied in 10 long-term LT recipients in monotherapy with tacrolimus, 10 tolerant recipients and 10 healthy controls. TTV was detected in the plasma of all patients. Among the 63 LT recipients, 20 episodes of ACR were diagnosed, and there were 28 opportunistic infec...
Journal of General Virology, 2018
Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence th... more Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence that leads to high graft loss rates early after liver transplantation (LT). To investigate the pathogenic mechanisms of CHC, we analysed HCV quasispecies in CHC patients compared to a control group (mild hepatitis C recurrence) by deep pyrosequencing. At the time of LT, NS5B quasispecies complexity was similar between the two groups but, after LT, it decreased more sharply in CHC patients than in the control group. Interestingly, the major variant before LT propagated efficiently and remained as the dominant sequence after LT in 62 % of CHC patients versus 11 % of controls (P=0.031). Sequence analysis of the complete non-structural region in a limited number of patients revealed a potential 12 aa signature specific to the CHC group. These data suggest that intrinsic molecular determinants in the circulating HCV quasispecies may provide a fitness advantage, contributing to the development of CHC.
Journal of hepatology, Jan 28, 2018
Subclinical inflammatory changes are commonly described in long-term transplant recipients underg... more Subclinical inflammatory changes are commonly described in long-term transplant recipients undergoing protocol liver biopsies. The pathogenesis of these lesions remains unclear. The aim of this study was to identify the key molecular pathways driving progressive subclinical inflammatory liver allograft damage. All liver recipients followed at Hospital Clínic Barcelona who were >10 years post-transplant were screened for participation in the study. Patients with recurrence of underlying liver disease, biliary or vascular complications, chronic rejection, and abnormal liver function tests were excluded. Sixty-seven patients agreed to participate and underwent blood and serological tests, transient elastography and a liver biopsy. Transcriptome profiling was performed on RNA extracted from 49 out of the 67 biopsies employing a whole genome next generation sequencing platform. Patients were followed for a median of 6.8 years following the index liver biopsy. Median time since transpl...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Jan 31, 2018
Cholestatic hepatitis (CH) is an extremely severe form of recurrent hepatitis C (HCV) after liver... more Cholestatic hepatitis (CH) is an extremely severe form of recurrent hepatitis C (HCV) after liver transplantation (LT) that results in graft loss from complications of portal hypertension if HCV is not eliminated. While the new direct antiviral agents are highly effective in treating CH, the impact of viral eradication in graft fibrosis and portal pressure in this particular form of recurrence is unknown. We aimed to describe the histological impact of viral cure one year after sustained virological response (SVR) in a single-center cohort comprising 12 LT recipients with CH who achieved SVR after antiviral therapy between 2001 and 2015. A liver biopsy, HVPG measurement, liver stiffness measurement and ELF score determination were performed before treatment and 12 months after SVR. The follow-up biopsy showed absence of fibrosis in 5 patients (42%), F1 in 4 (33%), F2 in 1 (8%) and cirrhosis in the remaining 2 patients (17%). HVPG decreased from 8 to 4 mmHg 12 months after SVR (p=0.1...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, May 19, 2018
Ischemic type biliary lesions arise most frequently after DCD liver transplantation and result in... more Ischemic type biliary lesions arise most frequently after DCD liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug TPA as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to one hour of cardiac arrest and divided among three groups: no pre-arrest heparinization nor TPA during post-mortem regional perfusion, no pre-arrest heparinization but TPA given during regional perfusion, and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled one hour after cardiac arrest, fibrin deposition was not detected, even when heparin was not given prior to arrest. While it was not useful to prevent microvascular clot formation, pre-...
Hepatology (Baltimore, Md.), Jan 27, 2017
Sustained virological response (SVR) improves survival in post liver transplant (LT) recurrent he... more Sustained virological response (SVR) improves survival in post liver transplant (LT) recurrent hepatitis C. However, the impact of SVR on fibrosis regression is not well defined. In addition, the performance of noninvasive methods to evaluate the presence of fibrosis and portal hypertension after SVR has been scarcely evaluated. We aimed to investigate the degree of fibrosis regression (decrease ≥1 METAVIR stage) after SVR and its associated factors in recurrent hepatitis C, as well as the diagnostic capacity of noninvasive methods in the assessment of liver fibrosis and portal hypertension after viral clearance. We evaluated 112 HCV-infected LT recipients who achieved SVR between 2001 and 2015. A liver biopsy was performed before treatment and 12 months after SVR. HVPG, liver stiffness measurement (LSM) and ELF score were also determined at the same time points. Sixty-seven percent of the cohort presented fibrosis regression: 43% in recipients with cirrhosis and 72-85% in the remai...
United European Gastroenterology Journal, 2017
Background Bile leak after liver transplantation (LT) is commonly treated with endoscopic retrogr... more Background Bile leak after liver transplantation (LT) is commonly treated with endoscopic retrograde cholangiopancreatography (ERCP); however, there are limited data regarding the optimal treatment strategy. Objective We aimed to examine the role of ERCP in LT recipients with bile leaks at two large institutions. Methods We reviewed all ERCPs performed in LT recipients with bile leak and duct-to-duct biliary anastomosis at two high-volume transplant centers. Results Eighty patients were included. Forty-seven (59%) patients underwent ERCP with plastic stent placement (with or without sphincterotomy) and 33 patients (41%) underwent sphincterotomy alone. Complete resolution was obtained in 94% of the stent group vs. 58% of the sphincterotomy group ( p < 0.01). There was no difference in three-month survival among both groups. Percutaneous transhepatic therapy and surgery were required in 4% and 6% in the stent group vs. 12% and 42% in the sphincterotomy group, respectively ( p = 0.2...
Journal of Hepatology, 2017
Best Practice & Research Clinical Gastroenterology, 2012
Annals of Internal Medicine, 1989
Excerpt To the Editor:Recently, Speich and colleagues (1) reported three patients who developed s... more Excerpt To the Editor:Recently, Speich and colleagues (1) reported three patients who developed severe anaphylactoid reactions after indocyanine-green was administered. The three cases were collect...
Annals of hepatology, 2016
BACKGROUND AND RATIONALE The REPLACE study (NCT01571583) investigated telaprevir-based triple the... more BACKGROUND AND RATIONALE The REPLACE study (NCT01571583) investigated telaprevir-based triple therapy in patients who have recurrent genotype 1 hepatitis C virus (HCV) infection following liver transplantation and are on a stable immunosuppressant regimen of tacrolimus or cyclosporin A. Patients received telaprevir 750 mg 8-hourly with pegylated interferon 180 μg weekly and ribavirin 600 mg daily, followed by a further 36 weeks of pegylated interferon and ribavirin alone and 24 weeks of follow-up. Efficacy (sustained virological response [SVR] 12 weeks after last planned study dose), safety and tolerability of telaprevir throughout the study were assessed. Pharmacokinetics of telaprevir, tacrolimus and cyclosporin A were also examined. RESULTS In total, 74 patients were recruited. Overall, 72% (53/74; 95% CI: 59.9 to 81.5) of patients achieved SVR at 12 weeks following completion of treatment. Anticipated increases in plasma concentrations of tacrolimus and cyclosporin A occurred du...
eLife, 2021
While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C ... more While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C virus (HCV) production, the role of the liver/hepatocytes in clearance of circulating HCV remains unknown. Frequent HCV kinetic data were recorded and mathematically modeled from five liver transplant patients throughout the anhepatic (absence of liver) phase and for 4 hr post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n = 3) or declined (n = 2) with t1/2~1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t1/2 = 5 min) followed by a slower decline (t1/2 = 67 min). Consistent with the majority of patients in the anhepatic phase, when we monitored HCV clearance at 37°C from culture medium in the absence/presence of chronically infected hepatoma cells that were inhibited from secreting HCV, the HCV t1/2 in cell culture was longer in the absence of chronically HCV-infected cells. The resu...
Gastroenterología y Hepatología, 2020
Gastroenterología y Hepatología (English Edition), 2021
Abstract Objective To evaluate the results of isolated liver and combined liver and kidney transp... more Abstract Objective To evaluate the results of isolated liver and combined liver and kidney transplantation in a retrospective series of 32 patients with hepatorenal liver and kidney disease. Patients and methods A retrospective observational study that enrolled patients with polycystic liver disease (PLD) and polycystic liver and kidney disease (PLKD) who were evaluated for transplantation between January 1999 and December 2019 at Hospital Clinic de Barcelona [Clinical Hospital of Barcelona]. Results Of 53 patients enrolled, 32 (60.3%) had an indication for transplantation, 12 received a single liver transplant and 20 received a double liver and kidney transplant. The mean age was 52 years and 83.9% of the recipients were women. The main indication for liver transplantation was disabling symptomatic hepatomegaly (93.5%). Among the postoperative complications, in the combined liver and kidney transplant group, hepatic artery thrombosis and renal artery thrombosis were detected. In both groups there was an inferior vena cava lesion. Three patients presented acute cellular rejection responding to corticosteroids and one presented humoral rejection which was treated with plasmapheresis. During the follow-up period of 80 (27–121) months, the liver transplant survival rate was 100% and the kidney transplant survival rate was 90%. Two patients in the combined liver and kidney transplant group died (one due to cardiovascular causes and the other due to intestinal adenocarcinoma). Conclusions Isolated liver transplantation or combined liver and kidney transplantation in selected patients with polycystic disease yields excellent results, with few complications, very good transplant survival and excellent patient survival (93.8%).
Journal of Clinical Medicine, 2020
Tobacco use is more prevalent among alcohol liver disease (ALD) transplant patients and exerts ha... more Tobacco use is more prevalent among alcohol liver disease (ALD) transplant patients and exerts harmful effects to the patient and to the graft. The aims of this study were to examine the impact of smoking status (nonsmoker, ex-smoker, active smoker) on patient survival and clinical outcomes, and to assess risk factors for active smoking before and after liver transplant (LT). An observational retrospective cohort study with 314 ALD patients undergoing LT from January 2004 to April 2016. Recipients were followed until April 2017 or death. Kaplan–Meier and Cox proportional hazards regression analyses were used to assess risk of mortality according to smoking status before LT. Smokers had a 79% higher risk of dying than those who had never smoked or quit smoking before LT. Ex-smokers had a greater survival probability (96.2%, 93.8%, 86.9%, and 83.1% at 1, 3, 5, and 10 years after LT) than active smokers until LT (96.0%, 85.6%, 80.0%, and 70.4%). Active smokers before LT with poor toxic...
Gastroenterología y Hepatología, 2020
Annals of Hepatology, 2010
The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, also known as DIHS (drug-indu... more The DRESS (drug rash, eosinophilia and systemic symptoms) syndrome, also known as DIHS (drug-induced hypersensitivity syndrome), is a severe idiosyncratic reaction to several drugs, mainly antiepileptics and antibiotics, which can occasionally produce acute liver failure. In this article we present two cases of the DRESS syndrome presenting with severe acute hepatitis, including the first case of DRESS associated with levetiracetam. Although both cases finally resolved with good outcomes, DRESS can lead to acute liver failure and has a bad prognosis when liver damage is present. Rapid diagnosis is crucial since withdrawal of the offending drug is the key of treatment, while the potential role of corticosteroids is discussed.
Liver Transplantation, 2019
The selection of liver transplantation (LT) candidates with alcohol‐use disorder (AUD) is influen... more The selection of liver transplantation (LT) candidates with alcohol‐use disorder (AUD) is influenced by the risk of alcohol relapse (AR) after LT. We aimed to investigate the risk factors of AR after LT and its impact on graft and recipient outcomes. A retrospective study was conducted that included all consecutive patients with AUD undergoing LT from January 2004 to April 2016 (n = 309), excluding patients with alcoholic hepatitis. Odds ratios (ORs) and 95% confidence intervals (CIs) for AR were analyzed by multinomial logistic regression. Cox regression with time‐dependent covariates was used to analyze patient survival and graft cirrhosis. There were 70 (23%) patients who presented AR (median follow‐up, 68 months), most of them (n = 44, 63%) presenting heavy AR. The probability of heavy AR was 2.3%, 7.5%, 12%, and 29% at 1, 3, 5, and 10 years after LT, respectively. The independent risk factors for heavy AR included a High‐Risk Alcoholism Relapse (HRAR) score ≥3 (OR, 2.39; 95% CI, 1.02‐5.56; P = 0.04) and the duration of abstinence (months) before LT (OR, 0.81; 95% CI, 0.66‐0.98; P = 0.03). In recipients with <6 months of abstinence before LT, the probability of heavy AR after LT was higher in patients with an HRAR score ≥3 than in those with an HRAR score <3 (20%, 36.7%, and 47% versus 6.8%, 12.4%, and 27% at 1, 3, and 5 years, respectively; log‐rank 0.013). The risk of graft cirrhosis was increased in patients with heavy AR (hazard ratio, 3.44; 95% CI, 1.58‐7.57; P = 0.002) compared with nonrelapsers, with no differences in patient survival. In conclusion, the HRAR score is helpful in identifying the risk of harmful AR after LT in candidates with <6 months of alcohol abstinence without alcoholic hepatitis. These patients could benefit from a longterm integrative patient‐centered approach after LT until lifestyle changes are implemented.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Jan 30, 2018
The development of non-invasive biomarkers that reflect the state of immune suppression remains a... more The development of non-invasive biomarkers that reflect the state of immune suppression remains an unmet need in liver transplantation (LT). Torque Teno Virus (TTV) is a highly prevalent, non-pathogenic DNA virus whose plasma levels may be associated with the immune status of the host. The aim of this study was to assess the role of TTV as a biomarker of immune suppression in LT recipients. TTV DNA in plasma was quantified by real-time PCR at different time-points during the first year after transplant in a prospectively followed cohort of 63 de novo LT recipients, and any correlation between TTV DNA and biopsy-proven acute cellular rejection (ACR) and opportunistic infections was then evaluated. In addition, TTV DNA was studied in 10 long-term LT recipients in monotherapy with tacrolimus, 10 tolerant recipients and 10 healthy controls. TTV was detected in the plasma of all patients. Among the 63 LT recipients, 20 episodes of ACR were diagnosed, and there were 28 opportunistic infec...
Journal of General Virology, 2018
Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence th... more Cholestatic hepatitis C (CHC) is a severe form of hepatitis C virus (HCV) infection recurrence that leads to high graft loss rates early after liver transplantation (LT). To investigate the pathogenic mechanisms of CHC, we analysed HCV quasispecies in CHC patients compared to a control group (mild hepatitis C recurrence) by deep pyrosequencing. At the time of LT, NS5B quasispecies complexity was similar between the two groups but, after LT, it decreased more sharply in CHC patients than in the control group. Interestingly, the major variant before LT propagated efficiently and remained as the dominant sequence after LT in 62 % of CHC patients versus 11 % of controls (P=0.031). Sequence analysis of the complete non-structural region in a limited number of patients revealed a potential 12 aa signature specific to the CHC group. These data suggest that intrinsic molecular determinants in the circulating HCV quasispecies may provide a fitness advantage, contributing to the development of CHC.
Journal of hepatology, Jan 28, 2018
Subclinical inflammatory changes are commonly described in long-term transplant recipients underg... more Subclinical inflammatory changes are commonly described in long-term transplant recipients undergoing protocol liver biopsies. The pathogenesis of these lesions remains unclear. The aim of this study was to identify the key molecular pathways driving progressive subclinical inflammatory liver allograft damage. All liver recipients followed at Hospital Clínic Barcelona who were >10 years post-transplant were screened for participation in the study. Patients with recurrence of underlying liver disease, biliary or vascular complications, chronic rejection, and abnormal liver function tests were excluded. Sixty-seven patients agreed to participate and underwent blood and serological tests, transient elastography and a liver biopsy. Transcriptome profiling was performed on RNA extracted from 49 out of the 67 biopsies employing a whole genome next generation sequencing platform. Patients were followed for a median of 6.8 years following the index liver biopsy. Median time since transpl...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Jan 31, 2018
Cholestatic hepatitis (CH) is an extremely severe form of recurrent hepatitis C (HCV) after liver... more Cholestatic hepatitis (CH) is an extremely severe form of recurrent hepatitis C (HCV) after liver transplantation (LT) that results in graft loss from complications of portal hypertension if HCV is not eliminated. While the new direct antiviral agents are highly effective in treating CH, the impact of viral eradication in graft fibrosis and portal pressure in this particular form of recurrence is unknown. We aimed to describe the histological impact of viral cure one year after sustained virological response (SVR) in a single-center cohort comprising 12 LT recipients with CH who achieved SVR after antiviral therapy between 2001 and 2015. A liver biopsy, HVPG measurement, liver stiffness measurement and ELF score determination were performed before treatment and 12 months after SVR. The follow-up biopsy showed absence of fibrosis in 5 patients (42%), F1 in 4 (33%), F2 in 1 (8%) and cirrhosis in the remaining 2 patients (17%). HVPG decreased from 8 to 4 mmHg 12 months after SVR (p=0.1...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, May 19, 2018
Ischemic type biliary lesions arise most frequently after DCD liver transplantation and result in... more Ischemic type biliary lesions arise most frequently after DCD liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug TPA as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to one hour of cardiac arrest and divided among three groups: no pre-arrest heparinization nor TPA during post-mortem regional perfusion, no pre-arrest heparinization but TPA given during regional perfusion, and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled one hour after cardiac arrest, fibrin deposition was not detected, even when heparin was not given prior to arrest. While it was not useful to prevent microvascular clot formation, pre-...
Hepatology (Baltimore, Md.), Jan 27, 2017
Sustained virological response (SVR) improves survival in post liver transplant (LT) recurrent he... more Sustained virological response (SVR) improves survival in post liver transplant (LT) recurrent hepatitis C. However, the impact of SVR on fibrosis regression is not well defined. In addition, the performance of noninvasive methods to evaluate the presence of fibrosis and portal hypertension after SVR has been scarcely evaluated. We aimed to investigate the degree of fibrosis regression (decrease ≥1 METAVIR stage) after SVR and its associated factors in recurrent hepatitis C, as well as the diagnostic capacity of noninvasive methods in the assessment of liver fibrosis and portal hypertension after viral clearance. We evaluated 112 HCV-infected LT recipients who achieved SVR between 2001 and 2015. A liver biopsy was performed before treatment and 12 months after SVR. HVPG, liver stiffness measurement (LSM) and ELF score were also determined at the same time points. Sixty-seven percent of the cohort presented fibrosis regression: 43% in recipients with cirrhosis and 72-85% in the remai...
United European Gastroenterology Journal, 2017
Background Bile leak after liver transplantation (LT) is commonly treated with endoscopic retrogr... more Background Bile leak after liver transplantation (LT) is commonly treated with endoscopic retrograde cholangiopancreatography (ERCP); however, there are limited data regarding the optimal treatment strategy. Objective We aimed to examine the role of ERCP in LT recipients with bile leaks at two large institutions. Methods We reviewed all ERCPs performed in LT recipients with bile leak and duct-to-duct biliary anastomosis at two high-volume transplant centers. Results Eighty patients were included. Forty-seven (59%) patients underwent ERCP with plastic stent placement (with or without sphincterotomy) and 33 patients (41%) underwent sphincterotomy alone. Complete resolution was obtained in 94% of the stent group vs. 58% of the sphincterotomy group ( p < 0.01). There was no difference in three-month survival among both groups. Percutaneous transhepatic therapy and surgery were required in 4% and 6% in the stent group vs. 12% and 42% in the sphincterotomy group, respectively ( p = 0.2...
Journal of Hepatology, 2017