Long-term humoral immunity and its protective role in liver transplant patients has not been eluc... more Long-term humoral immunity and its protective role in liver transplant patients has not been elucidated. We performed a prospective multicenter study to assess the persistence of IgG antibodies in liver transplant recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 liver transplant recipients were matched with 65 non-transplanted patients by a propensity score including variables with recognized impact on COVID-19. Liver transplant recipients showed a lower prevalence of anti-nucleocapsid (27.7% vs. 49.2%, P = 0.02) and anti-spike IgG antibodies (88.2% vs. 100.0%, P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplant patients one year after COVID-19 (0.49 [IQR 0.15-1.40] vs. 1.36 [IQR 0.53-2.91], P < 0.001). Vaccinated liver transplant recipients showed higher antibody levels compared to unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in non-transplanted individuals (P = 0.70). In liver transplant patients, a longer interval since transplantation (OR=1.10, 95% CI 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies one-year postinfection. In conclusion, compared with non-transplanted patients, liver transplant recipients show a lower long-term persistence of anti-SARS-CoV-2 antibodies. However, SARS-CoV-2 vaccination after COVID-19 in liver transplant patients achieves a significant increase in antibody levels, comparable to that of non-transplanted patients.
Introduction Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decre... more Introduction Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay, improve outcomes and reduce costs. We used this concept to design a comprehensive fast-track pathway (OR-to-discharge) before starting our liver transplant activity and then applied this protocol prospectively to every patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our first six years results. Patients and methods Prospective cohort study of all the liver transplants performed at our institution for the first six years. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and temporary portocaval shunt were strategies common to all cases. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian...
Introduccion: Para el control de la erradicacion de H. pylori post-tratamiento, esta ampliamente ... more Introduccion: Para el control de la erradicacion de H. pylori post-tratamiento, esta ampliamente aceptada la utilizacion de pruebas no invasivas. El HpSA ha sido valorado en varios trabajos con resultados muy variables. En algunos de ellos se ha detectado una disminucion en la especificidad y en la exactitud del test. Objetivo: El objetivo del estudio es comprobar la validez del HpSA para detectar la erradicacion del H. pylori en una poblacion de pacientes con HDA de origen peptico, 3 meses despues de finalizar el tratamiento (OCA). Material y metodos: Se incluyeron en el estudio 29 pacientes (23 hombres y 6 mujeres). Tras finalizar el tratamiento erradicador se hizo un control a los 3 meses realizandose a todos una determinacion de HpSA y comparandolo frente al test de aliento. Resultados: La edad media fue de 64 anos (31-84). Presentaron infeccion por H. pylori 8 pacientes (27,6%). Los resultados obtenidos fueron: sensibilidad: 87,5%, especificidad 42,8%, VPP 36,8%,VPN 90%. Conclu...
Liver international : official journal of the International Association for the Study of the Liver, Jan 26, 2018
The use of non-selective beta-blockers has been associated with lower rates of infection and redu... more The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA. Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients. The detection rate of bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence...
Transplant international : official journal of the European Society for Organ Transplantation, Jan 13, 2017
Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in t... more Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC-based regimens in a large real-world cohort. A total of 331 patients received DCV-based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary endpoint was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention-to-treat (ITT) and per-protocol SVR were 93.05% and 96.9%. ITT-SVR was lower in cirrhosis (n=163) (96.4% vs. 89.6% p=0.017); the SVR in genotype 3 (n=91) was similar, even in advanced fibrosis (96.7% vs. 88%, p=0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died ...
Liver international : official journal of the International Association for the Study of the Liver, Dec 8, 2017
Hepatitis C (HCV) therapy with Sofosbuvir(SOF)/ Simeprevir(SMV) in clinical trials and real-world... more Hepatitis C (HCV) therapy with Sofosbuvir(SOF)/ Simeprevir(SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype(GT)-1 and 4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin(RBV) in a large cohort of cirrhotic patients. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. Overall SVR was 92.3%; the majority of patients were treated with RBV(62%) for 12weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100x10...
Patients with decompensated cirrhosis show a marked innate immune response that shows a wide vari... more Patients with decompensated cirrhosis show a marked innate immune response that shows a wide variability. The reasons for this fact have not been previously evaluated. This investigation was undertaken to study factors influencing the immune response intensity in both serum and ascitic fluid in patients with cirrhosis and ascites with presence of bactDNA. 77 patients with cirrhosis and presence of bactDNA fragments in blood and ascitic fluid were included. Identification of bactDNA was evaluated by 16SrRNA gene PCR followed by nucleotide sequencing and by species-specific PCR. Concentration of amplified bacterial-DNA, bacteria identification, LPS, TNF-alpha, IFN-gamma, Interleukin 12 and nitric oxide in serum and ascitic fluid were evaluated as factors related to intensity of the immune response. Serum and AF levels of bactDNA, TNF-α, IFN-γ and nitric oxide concentration were higher in patients with presence of bactDNA from gram negative bacteria. Serum TNF-α levels showed a significant correlation with concentrations of bactDNA (r=0.88; p=0.001) and LPS (r=0.28; p=0.016). Serum nitric oxide levels were also significantly correlated with concentrations of bactDNA (r=0.761; p=0.001) but not with LPS levels. Levels of INF-γ and IL-12 were not significantly correlated with either bactDNA nor LPS levels. Plasmatic concentration of bactDNA was the most accurately correlated factor with the inflammatory response (ANCOVA model included only levels of bactDNA (r(2) = 0.87, p= 0.047 for TNF-α; r(2) = 0.45, p= 0.03 for NOx). Bacterial-DNA concentration is the most influencing variable associated with serum TNF-α and nitric oxide response. This article is protected by copyright. All rights reserved.
Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis and its c... more Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis and its current situation in Spain is not well known. Therefore, a national registry was created to assess the characteristics of patients with de novo HCC. Between 1/10/2008 and 31/1/2009, 62 centers reported the baseline demographic, clinical and tumor characteristics, the first choice of treatment and eligibility for transplantation (OLT) of HCC diagnosed during this time. There were 705 new cases of HCC, 78% men, mean age 65 years, 89% cirrhosis (58% Child-Pugh class A, 42% HCV, 30% alcohol). Only 334 cases (47%) were diagnosed by screening. The size of the main nodule and BCLC stage were significantly lower in the screening group than in the rest (p<0.001). The applicability of radical therapies (resection and percutaneous ablation) was significantly higher (47.5% versus 24.6%, p<0.001) as well as the evaluation for OLT (31% versus 12%,…
TO THE EDITOR: We have read with interest the article by Jeffrieset al. (1) and the editorial by ... more TO THE EDITOR: We have read with interest the article by Jeffrieset al. (1) and the editorial by Blendis and Wong (2) about the absence of episodes of spontaneous bacterial peritonitis (SBP) in a large series of large-volume paracentesis performed in patients with cirrhosis and refractory ascites. Overall, 328 ascitic fluid (AF) analyses are reported in the previously mentioned study (1) and in the abstracts from Stern et al. (3) and from Kolleet al. (4). None of these patients showed an AF polymorphonuclear (PMN) count above 250/ ml, which is the required threshold to diagnose an episode of SBP (5). Our experience is similar to that described by the aforementioned authors. Between January 1998 and May 2000, we have performed 177 large-volume therapeutic paracentesis in 19 patients with cirrhosis and refractory ascites. Paracentesis were performed in an outpatient basis in the Liver Unit of the Department of Internal Medicine. Patients diagnosed as having nonliver-related ascites, and those showing hepatic complications, such as overt hepatic encephalopathy or gastrointestinal bleeding were excluded from the study. Paracentesis were performed in sterile conditions (6), being routinely followed by plasma volume expansion, according to previously published criteria (7). A sample of 10 ml from each patient was routinely analyzed for PMN count. Patients with lower than 250 PMN/ ml were discharged after the procedure. In this period we have attended 14 men and 5 women with a mean age of 62 yr (range 34–84). The cause of cirrhosis was alcoholic in 9 patients, viral in 7, and mixed (alcohol and viruses) in the remaining 3 patients. Thirteen of the patients were identified as Child-Pugh C, and 6 as ChildPugh B. None of the patients showed signs or symptoms suggestive of SBP at the time of paracentesis. At the moment of evaluation of data, 9.3 6 7 procedures per patient had been performed, and we have not found a single episode of neutrocytic ascites (i.e., 250/ml) in our series. Three of the patients were receiving norfloxacin 400 mg/d QD PO, as secondary prophylaxis of SBP. AF total protein levels were lower than 1.5 g/dl in 13 patients, and 7 patients showed a total bilirubin .3.2 mg/dl. Patients with refractory ascites usually present with advanced liver disease, and therefore might be predisposed to the development of SBP. It has been shown that patients with low AF protein levels (8, 9) and those with total bilirubin higher than 3.2 mg/dl are at risk of developing a SBP episode (10). As previously stated, most of our patients fulfilled these criteria. We found no apparent reasons for the absence of infectious complications in this subset of patients with advanced liver disease with the exception of patients undergoing secondary prophylaxis of SBP with norfloxacin. According with the suggested hypothesis by Blendis (2), a decrease of portal pressure following large-volume paracentesis could reduce the abnormal intestinal permeability observed in these patients, and also the high rate of bacterial translocation to mesenteric lymph nodes from the intestinal lumen. We have observed an abnormal intestinal permeability in Child-Pugh C patients by means of the lactulose/ mannitol test (11), but to our knowledge, no study has shown variations in intestinal permeability or bacterial translocation after the practice of therapeutic paracentesis. In summary, the reasons to explain why patients with asymptomatic refractory ascites undergoing repeated large-volume paracentesis do not develop SBP episodes are not entirely clear so far, but the observed absence of neutrocytic ascites in patients with asymptomatic refractory ascites in the reported series and ours, suggests that it is not necessary to perform a routine PMN count in these patients.
The number of patients receiving amiodarone will increase in future years. As clinically signific... more The number of patients receiving amiodarone will increase in future years. As clinically significant hepatotoxicity associated with oral amiodarone is infrequent and difficult to predict, a new Bayesian-developed model is proposed to help in the causality assessment of amiodarone-induced liver injury. Incidence of abnormal liver enzymes in patients receiving amiodarone was obtained from placebo controlled clinical trials. Published case reports of amiodarone-induced hepatotoxicity were identified through a literature search. Maximum number of expected hepatotoxicity cases in amiodarone and placebo-treated patients was calculated using Poisson distribution. The calculated odds ratio was used as a Prior Odds (PrO) to subsequent quantification, using a Bayesian-approach, of individual amiodarone-induced hepatotoxicity likelihood. PrO of amiodarone-induced hepatotoxicity was 0.48. Thirty nine amiodarone-associated hepatotoxicity case reports were retrieved. Half of published case reports developed an irreversible damage. The amiodarone Bayesian model combining information about latency period and period of remission, together with analytical parameters properly defines the toxicity profile shown in published case reports. The analytical pattern defined by this model is different from the one expected if liver injury in published cases was caused by other etiologies. A method based on a Bayesian-approach, which links information from clinical trials with clinical hepatotoxicity profile from published case reports can be a useful tool for amiodarone-induced liver injury causality assessment. At present, this method is limited due to scarcity and quality of available data. Further efforts are needed to improve model ability in order to identify amiodarone-induced liver injury.
Long-term humoral immunity and its protective role in liver transplant patients has not been eluc... more Long-term humoral immunity and its protective role in liver transplant patients has not been elucidated. We performed a prospective multicenter study to assess the persistence of IgG antibodies in liver transplant recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 liver transplant recipients were matched with 65 non-transplanted patients by a propensity score including variables with recognized impact on COVID-19. Liver transplant recipients showed a lower prevalence of anti-nucleocapsid (27.7% vs. 49.2%, P = 0.02) and anti-spike IgG antibodies (88.2% vs. 100.0%, P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplant patients one year after COVID-19 (0.49 [IQR 0.15-1.40] vs. 1.36 [IQR 0.53-2.91], P < 0.001). Vaccinated liver transplant recipients showed higher antibody levels compared to unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in non-transplanted individuals (P = 0.70). In liver transplant patients, a longer interval since transplantation (OR=1.10, 95% CI 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies one-year postinfection. In conclusion, compared with non-transplanted patients, liver transplant recipients show a lower long-term persistence of anti-SARS-CoV-2 antibodies. However, SARS-CoV-2 vaccination after COVID-19 in liver transplant patients achieves a significant increase in antibody levels, comparable to that of non-transplanted patients.
Introduction Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decre... more Introduction Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay, improve outcomes and reduce costs. We used this concept to design a comprehensive fast-track pathway (OR-to-discharge) before starting our liver transplant activity and then applied this protocol prospectively to every patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our first six years results. Patients and methods Prospective cohort study of all the liver transplants performed at our institution for the first six years. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and temporary portocaval shunt were strategies common to all cases. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian...
Introduccion: Para el control de la erradicacion de H. pylori post-tratamiento, esta ampliamente ... more Introduccion: Para el control de la erradicacion de H. pylori post-tratamiento, esta ampliamente aceptada la utilizacion de pruebas no invasivas. El HpSA ha sido valorado en varios trabajos con resultados muy variables. En algunos de ellos se ha detectado una disminucion en la especificidad y en la exactitud del test. Objetivo: El objetivo del estudio es comprobar la validez del HpSA para detectar la erradicacion del H. pylori en una poblacion de pacientes con HDA de origen peptico, 3 meses despues de finalizar el tratamiento (OCA). Material y metodos: Se incluyeron en el estudio 29 pacientes (23 hombres y 6 mujeres). Tras finalizar el tratamiento erradicador se hizo un control a los 3 meses realizandose a todos una determinacion de HpSA y comparandolo frente al test de aliento. Resultados: La edad media fue de 64 anos (31-84). Presentaron infeccion por H. pylori 8 pacientes (27,6%). Los resultados obtenidos fueron: sensibilidad: 87,5%, especificidad 42,8%, VPP 36,8%,VPN 90%. Conclu...
Liver international : official journal of the International Association for the Study of the Liver, Jan 26, 2018
The use of non-selective beta-blockers has been associated with lower rates of infection and redu... more The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA. Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients. The detection rate of bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence...
Transplant international : official journal of the European Society for Organ Transplantation, Jan 13, 2017
Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in t... more Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC-based regimens in a large real-world cohort. A total of 331 patients received DCV-based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary endpoint was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Intention-to-treat (ITT) and per-protocol SVR were 93.05% and 96.9%. ITT-SVR was lower in cirrhosis (n=163) (96.4% vs. 89.6% p=0.017); the SVR in genotype 3 (n=91) was similar, even in advanced fibrosis (96.7% vs. 88%, p=0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died ...
Liver international : official journal of the International Association for the Study of the Liver, Dec 8, 2017
Hepatitis C (HCV) therapy with Sofosbuvir(SOF)/ Simeprevir(SMV) in clinical trials and real-world... more Hepatitis C (HCV) therapy with Sofosbuvir(SOF)/ Simeprevir(SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype(GT)-1 and 4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin(RBV) in a large cohort of cirrhotic patients. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. Overall SVR was 92.3%; the majority of patients were treated with RBV(62%) for 12weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100x10...
Patients with decompensated cirrhosis show a marked innate immune response that shows a wide vari... more Patients with decompensated cirrhosis show a marked innate immune response that shows a wide variability. The reasons for this fact have not been previously evaluated. This investigation was undertaken to study factors influencing the immune response intensity in both serum and ascitic fluid in patients with cirrhosis and ascites with presence of bactDNA. 77 patients with cirrhosis and presence of bactDNA fragments in blood and ascitic fluid were included. Identification of bactDNA was evaluated by 16SrRNA gene PCR followed by nucleotide sequencing and by species-specific PCR. Concentration of amplified bacterial-DNA, bacteria identification, LPS, TNF-alpha, IFN-gamma, Interleukin 12 and nitric oxide in serum and ascitic fluid were evaluated as factors related to intensity of the immune response. Serum and AF levels of bactDNA, TNF-α, IFN-γ and nitric oxide concentration were higher in patients with presence of bactDNA from gram negative bacteria. Serum TNF-α levels showed a significant correlation with concentrations of bactDNA (r=0.88; p=0.001) and LPS (r=0.28; p=0.016). Serum nitric oxide levels were also significantly correlated with concentrations of bactDNA (r=0.761; p=0.001) but not with LPS levels. Levels of INF-γ and IL-12 were not significantly correlated with either bactDNA nor LPS levels. Plasmatic concentration of bactDNA was the most accurately correlated factor with the inflammatory response (ANCOVA model included only levels of bactDNA (r(2) = 0.87, p= 0.047 for TNF-α; r(2) = 0.45, p= 0.03 for NOx). Bacterial-DNA concentration is the most influencing variable associated with serum TNF-α and nitric oxide response. This article is protected by copyright. All rights reserved.
Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis and its c... more Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis and its current situation in Spain is not well known. Therefore, a national registry was created to assess the characteristics of patients with de novo HCC. Between 1/10/2008 and 31/1/2009, 62 centers reported the baseline demographic, clinical and tumor characteristics, the first choice of treatment and eligibility for transplantation (OLT) of HCC diagnosed during this time. There were 705 new cases of HCC, 78% men, mean age 65 years, 89% cirrhosis (58% Child-Pugh class A, 42% HCV, 30% alcohol). Only 334 cases (47%) were diagnosed by screening. The size of the main nodule and BCLC stage were significantly lower in the screening group than in the rest (p<0.001). The applicability of radical therapies (resection and percutaneous ablation) was significantly higher (47.5% versus 24.6%, p<0.001) as well as the evaluation for OLT (31% versus 12%,…
TO THE EDITOR: We have read with interest the article by Jeffrieset al. (1) and the editorial by ... more TO THE EDITOR: We have read with interest the article by Jeffrieset al. (1) and the editorial by Blendis and Wong (2) about the absence of episodes of spontaneous bacterial peritonitis (SBP) in a large series of large-volume paracentesis performed in patients with cirrhosis and refractory ascites. Overall, 328 ascitic fluid (AF) analyses are reported in the previously mentioned study (1) and in the abstracts from Stern et al. (3) and from Kolleet al. (4). None of these patients showed an AF polymorphonuclear (PMN) count above 250/ ml, which is the required threshold to diagnose an episode of SBP (5). Our experience is similar to that described by the aforementioned authors. Between January 1998 and May 2000, we have performed 177 large-volume therapeutic paracentesis in 19 patients with cirrhosis and refractory ascites. Paracentesis were performed in an outpatient basis in the Liver Unit of the Department of Internal Medicine. Patients diagnosed as having nonliver-related ascites, and those showing hepatic complications, such as overt hepatic encephalopathy or gastrointestinal bleeding were excluded from the study. Paracentesis were performed in sterile conditions (6), being routinely followed by plasma volume expansion, according to previously published criteria (7). A sample of 10 ml from each patient was routinely analyzed for PMN count. Patients with lower than 250 PMN/ ml were discharged after the procedure. In this period we have attended 14 men and 5 women with a mean age of 62 yr (range 34–84). The cause of cirrhosis was alcoholic in 9 patients, viral in 7, and mixed (alcohol and viruses) in the remaining 3 patients. Thirteen of the patients were identified as Child-Pugh C, and 6 as ChildPugh B. None of the patients showed signs or symptoms suggestive of SBP at the time of paracentesis. At the moment of evaluation of data, 9.3 6 7 procedures per patient had been performed, and we have not found a single episode of neutrocytic ascites (i.e., 250/ml) in our series. Three of the patients were receiving norfloxacin 400 mg/d QD PO, as secondary prophylaxis of SBP. AF total protein levels were lower than 1.5 g/dl in 13 patients, and 7 patients showed a total bilirubin .3.2 mg/dl. Patients with refractory ascites usually present with advanced liver disease, and therefore might be predisposed to the development of SBP. It has been shown that patients with low AF protein levels (8, 9) and those with total bilirubin higher than 3.2 mg/dl are at risk of developing a SBP episode (10). As previously stated, most of our patients fulfilled these criteria. We found no apparent reasons for the absence of infectious complications in this subset of patients with advanced liver disease with the exception of patients undergoing secondary prophylaxis of SBP with norfloxacin. According with the suggested hypothesis by Blendis (2), a decrease of portal pressure following large-volume paracentesis could reduce the abnormal intestinal permeability observed in these patients, and also the high rate of bacterial translocation to mesenteric lymph nodes from the intestinal lumen. We have observed an abnormal intestinal permeability in Child-Pugh C patients by means of the lactulose/ mannitol test (11), but to our knowledge, no study has shown variations in intestinal permeability or bacterial translocation after the practice of therapeutic paracentesis. In summary, the reasons to explain why patients with asymptomatic refractory ascites undergoing repeated large-volume paracentesis do not develop SBP episodes are not entirely clear so far, but the observed absence of neutrocytic ascites in patients with asymptomatic refractory ascites in the reported series and ours, suggests that it is not necessary to perform a routine PMN count in these patients.
The number of patients receiving amiodarone will increase in future years. As clinically signific... more The number of patients receiving amiodarone will increase in future years. As clinically significant hepatotoxicity associated with oral amiodarone is infrequent and difficult to predict, a new Bayesian-developed model is proposed to help in the causality assessment of amiodarone-induced liver injury. Incidence of abnormal liver enzymes in patients receiving amiodarone was obtained from placebo controlled clinical trials. Published case reports of amiodarone-induced hepatotoxicity were identified through a literature search. Maximum number of expected hepatotoxicity cases in amiodarone and placebo-treated patients was calculated using Poisson distribution. The calculated odds ratio was used as a Prior Odds (PrO) to subsequent quantification, using a Bayesian-approach, of individual amiodarone-induced hepatotoxicity likelihood. PrO of amiodarone-induced hepatotoxicity was 0.48. Thirty nine amiodarone-associated hepatotoxicity case reports were retrieved. Half of published case reports developed an irreversible damage. The amiodarone Bayesian model combining information about latency period and period of remission, together with analytical parameters properly defines the toxicity profile shown in published case reports. The analytical pattern defined by this model is different from the one expected if liver injury in published cases was caused by other etiologies. A method based on a Bayesian-approach, which links information from clinical trials with clinical hepatotoxicity profile from published case reports can be a useful tool for amiodarone-induced liver injury causality assessment. At present, this method is limited due to scarcity and quality of available data. Further efforts are needed to improve model ability in order to identify amiodarone-induced liver injury.
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Papers by Sonia Pascual