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PRES (posterior reversible encephalopathy syndrome) is a neurological condition characterised by epileptic seizures, altered consciousness, visual disturbances and/or headache with typical neuroimaging showing reversible subcortical vasogenic oedema mainly in parieto-occipital regions. The pathophysiological mechanism is not fully understood. We present a clinical case in the field of liver transplantation where tacrolimus neurotoxicity may play a relevant role in the development of this syndrome.
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Transplante de Fígado , Síndrome da Leucoencefalopatia Posterior , Humanos , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/etiologia , Transplante de Fígado/efeitos adversos , Imageamento por Ressonância Magnética/métodosRESUMO
Long-term humoral immunity and its protective role in liver transplantation (LT) patients have not been elucidated. We performed a prospective multicenter study to assess the persistence of immunoglobulin G (IgG) antibodies in LT recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 LT recipients were matched with 65 nontransplanted patients by a propensity score including variables with recognized impact on COVID-19. LT recipients showed a lower prevalence of anti-nucleocapsid (27.7% versus 49.2%; P = 0.02) and anti-spike IgG antibodies (88.2% versus 100.0%; P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplantation patients 1 year after COVID-19 (median, 0.49 [interquartile range, 0.15-1.40] versus 1.36 [interquartile range, 0.53-2.91]; P < 0.001). Vaccinated LT recipients showed higher antibody levels compared with unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in nontransplanted individuals (P = 0.70). In LT patients, a longer interval since transplantation (odds ratio, 1.10; 95% confidence interval, 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies 1 year after infection. In conclusion, compared with nontransplanted patients, LT recipients show a lower long-term persistence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, SARS-CoV-2 vaccination after COVID-19 in LT patients achieves a significant increase in antibody levels, comparable to that of nontransplanted patients.
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COVID-19 , Imunidade Humoral , Transplante de Fígado , Anticorpos Antivirais/sangue , COVID-19/imunologia , Vacinas contra COVID-19 , Humanos , Imunoglobulina G/sangue , Estudos Prospectivos , SARS-CoV-2RESUMO
BACKGROUND: Patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. METHODS: Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. RESULTS: A total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9-42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11-24) and 21% (IQR, 15-33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. CONCLUSIONS: Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.
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Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Transplante de Fígado , Adulto , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Estudos de Coortes , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Humanos , Fatores de RiscoRESUMO
BACKGROUND & AIMS: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate. METHODS: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression. RESULTS: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit. CONCLUSIONS: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged. LAY SUMMARY: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients.
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COVID-19/epidemiologia , Transplante de Fígado , Transplantados , Idoso , COVID-19/mortalidade , Inibidores de Calcineurina/uso terapêutico , Feminino , Hospitalização , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Espanha/epidemiologiaRESUMO
The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF-alfa, IL-6, IL-8, and MCP-1) and endothelial activation (E-selectin, ICAM-1, VCAM-1, and MMP-9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non-transplanted HCV-infected patients (LT-/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV-). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV- patients. However, levels of E-selectin, ICAM-1, VCAM-1, and MMP-9 were comparable between LT+/HCV+ and LT-/HCV+ patients before eradication. HCV eradication decreased ICAM-1 (5466.55 pg/ml vs. 3354.88 pg/ml, P < 0.001) and VCAM-1 (10456.52 pg/ml vs. 6658.85 pg/ml, P < 0.001) levels in LT+/HCV+ and LT-/HCV+ patients. Remarkably, HCV eradication restored levels of endothelial activation markers of LT+/HCV+ patients compared with that of LT+/HCV- patients. HCV plays a major role in endothelial dysfunction after LT. Furthermore, HCV eradication restores endothelial activation despite the exposure to immunosuppressive therapy.
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Hepatite C Crônica , Hepatite C , Transplante de Fígado , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , HumanosRESUMO
INTRODUCTION: the presence of donor-specific antibodies (DSA) is thought to affect survival of the allograft and patient after liver transplantation (LT). However, their significance is not well understood. PATIENTS AND METHODS: a prospective study was performed of 32 adult patients who underwent LT in 2011 to analyze the existence of DSA, associated risk factors and medium-term impact. Immunological determinations were performed immediately before LT and at three, six, 12 months and five years after LT. RESULTS: eight patients (24.2 %) presented pre-formed DSA. However, titers were negative in all patients five years after LT and there were no associated events. Eight out of 24 patients (33.3 %) developed de novo DSA. After five years, only two remained positive; both were class II with high mean fluorescence intensity (MFI) values at diagnosis (over 15,000). No association was found between the development of DSA and the risk of rejection, graft loss or death. However, an increase in liver stiffness values was observed in patients with persistent DSA, and focal sinusoidal deposition of C4d and moderate liver fibrosis were reported. CONCLUSION: the incidence of DSA is high after LT. In addition, the persistence of de novo DSA could be associated with silent liver fibrosis with a potential impact on graft outcomes.
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Transplante de Fígado , Adulto , Rejeição de Enxerto/epidemiologia , Antígenos HLA , Humanos , Isoanticorpos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
The prevalence and management of coronary artery disease (CAD) in liver transplantation (LT) candidates are not well characterized. The aims of this study were to evaluate the impact on clinical outcomes of a specifically designed protocol for the management of asymptomatic CAD in LT candidates and to investigate noninvasive risk profiles for obstructive and nonobstructive CAD for 202 LT candidates. Those with high baseline cardiovascular risk (CVR; defined by the presence of classic CVR factors and/or decreased ejection fraction) received coronary angiography and significant arterial stenosis and were treated with percutaneous stents. Patients were followed up after LT until death or coronary event (CE). There were 78 patients who received coronary evaluation (62 direct angiography, 14 computed tomography coronary angiography, and 2 both). Of them, 39 (50%) patients had CAD of any severity, and 6 (7.7%) had significant lesions (5 were amenable to be treated with stents, whereas 1 patient had diffuse lesions which contraindicated the LT). Insulin-dependent diabetes was the only factor related to CAD of any severity (odds ratio, 3.44; 95% confidence interval [CI], 1.00-11.97). A total of 69 patients (46 with coronary evaluation) received LT. The incidence of CEs and overall survival after LT were similar between patients with and without coronary evaluation. Furthermore, no differences occurred between these groups in a multivariate competing risk model (subhazard ratio, 0.84; 95% CI, 0.27-2.61; P = 0.76). In conclusion, the application of an angiographic screening protocol of CAD in a selected high-risk Mediterranean population is safe and effective. The short- and medium-term incidence rates of CEs and death after LT in this population are similar to that observed in low-risk patients.
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Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico , Procedimentos Clínicos , Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Doenças Assintomáticas/epidemiologia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/cirurgia , Estenose Coronária/epidemiologia , Estenose Coronária/etiologia , Estenose Coronária/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Prevalência , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Background: Demographic analyses may reveal current patterns of change in the outcomes of rapidly developing medical procedures because they incorporate the period perspective. Methods: We analyzed the changes in size, age structure, and hospitalizations in the population of liver transplantation (LT) survivors in our center during the last 30 y (nâ =â 1114 patients) and generated projections, including life expectancy (LE), considering cohort and period effects. Life tables were used to project the complete LE (overall 1990-2020 experience), the cohort LE (according to the decade of surgery: 1990-2000, 2000-2010, and 2010-2020), and the period LE (current 2015-2020 experience). Results: The population of LT recipients in follow-up continued to experience progressive growth and aging since 1990 (492 patients [41.9% >65 y] in 2020), and the magnitude of these phenomena may double in the next 30 y. However, the number of admissions and days of admission has been decreasing. The complete LE at LT was 12.4 y, whereas the period LE was 15.8 y. The cohort LE (limited to 10 y) was 5.3, 6.3, and 7.3 y for the 1990-2000, 2000-2010, and 2010-2020 cohorts, respectively. Conclusions: The target population of our medical care after LT is growing and aging. The prevalence of both of these phenomena is expected to increase in the coming years and is associated with a current improvement in LE. However, the hospitalization burden associated with LT survivors is declining. The period effect should be considered for generating up-to-date information on these current trends, which are crucial when designing health policies for LT survivors.
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Introduction: Until now, there has been limited evidence, primarily from US cohorts, focusing on frailty as a patient-oriented outcome after liver transplantation (LT). Our study aimed to explore the relationship between pre- and post-LT frailty in a multicenter European cohort of outpatients with cirrhosis undergoing LT. Methods: We conducted a prospective analysis of data from 180 LT recipients recruited between 2018 and 2020 from 5 Spanish centers. Participants underwent objective and subjective frailty assessments using the Liver Frailty Index (LFI) and the Subjective Clinician Assessment (SCA) pretransplant and at 3- and/or 6-mo posttransplant. Results: The median pretransplant LFI was 3.9, showing minimal change at 3 mo (3.8; Pâ =â 0.331) and improvement at 6-mo post-LT (3.6; Pâ =â 0.001). Conversely, the SCA significantly improved early post-LT: at 3 mo, poor SCA decreased from 11% to 1%, and good SCA increased from 54% to 89% (Pâ <â 0.001), remaining stable between 3- and 6-mo post-LT. Multivariable analysis revealed that each 0.1 increase in pretransplant LFI correlated with a reduced probability of being robust at 3-mo (odds ratio [OR]â =â 0.75; Pâ <â 0.001) and 6-mo post-LT (ORâ =â 0.74; Pâ <â 0.001). There was poor concordance between SCA and LFI, with SCA underestimating frailty both pre- and post-LT (Kappaâ <â 0.20). Conclusion: In our European cohort, incomplete improvement of physical frailty was observed, with <20% achieving robust physical condition within 6-mo post-LT. The pretransplant LFI strongly predicted posttransplant frailty. As the SCA tends to overestimate physical function, we recommend using both subjective and objective tools for frailty assessment in LT candidates and recipients.
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Background & Aims: Frailty is prevalent in liver transplant (LT) candidates. It is considered an independent predictor of adverse outcomes pre- and post-transplant according to data obtained in the United States. We aimed to externally validate the liver frailty index (LFI) in a multicenter cohort of LT candidates. Methods: Outpatients with cirrhosis were prospectively recruited from five Spanish centers (2018-2020). Patients were defined as "frail" by an optimal cut-off of LFI ≥4.5. Patients were followed for at least 6 months to study associations of pre-LT frailty with pre- and post-transplant mortality, length of hospital and intensive care unit (ICU) stays, risk of early (<30 days) and late (30-90 days) post-transplant complications, retransplantation and cardiovascular events. Results: Of 212 patients included, 45 patients (21%) were frail pre-LT, and the median LFI was 3.9 (IQR 3.5-4.4). After a median waiting time of 78 days, 2% died or were delisted for clinical worsening. The LFI at baseline was not predictive of mortality/delisting in LT candidates in univariable or multivariable analyses after adjusting for age and MELD-Na score (hazard ratio 1.48; p = 0.586). In contrast, compared to non-frail patients, frail LT candidates had a significantly higher length of hospital stay (9 vs. 13 days; p = 0.001) and rate of early (<30 days) post-transplant complications (55% vs. 100%; p = 0.021). Conclusions: In the context of a short LT waiting time, frailty does not impact pretransplant mortality and/or delisting. In contrast, LT frailty is predictive of higher post-transplant complication rates and length of hospital stay. Whether strategies aimed at pre- and/or re-habilitation are beneficial in settings with short waiting times needs to be confirmed in prospective studies. Impact and implications: Literature is scarce on the actual impact of physical frailty on adverse outcomes in the liver transplant scenario outside North America. Evidence-based justification to extend the use of objective frailty tools in the decision-making processes in other liver transplant settings is needed. This study is the first to evaluate the predictive value of the liver frailty index in outpatients in the European liver transplant setting, showing that in a low MELD, high access system, frailty does not impact pretransplant mortality and/or delisting but is predictive of higher complication rates and longer post-transplant length of stay. In practical ways, physicians should consider physical frailty as a vital sign to be measured systematically and routinely during clinic visits; researchers are encouraged to initiate prospective studies to evaluate the benefit of applying strategies aimed at pre- and or re-habilitation in liver transplant settings with short waiting times.
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OBJECTIVE: Cirrhosis is characterized by the complex interplay among biological, histological and haemodynamic events. Liver and spleen remodelling occur throughout its natural history, but the prognostic role of these volumetric changes is unclear. We evaluated the relationship between volumetric changes assessed by multidetector computerised tomography (MDCT) and landmark features of cirrhosis. METHODS: We included consecutive cirrhotic patients who underwent liver transplantation (LT) or hepatocellular carcinoma (HCC) resection in whom dynamic MDCT was available. Different volumetric indices were calculated. Fibrosis was evaluated by the collagen proportional area and Laennec sub-stages. Correlation and logistic regression analysis were performed to explore associations of volumetric indexes and fibrosis with key prognostic features across the clinical stages of cirrhosis. RESULTS: 185 patients were included (146 LT; 39 HCC); the predominant aetiology was viral hepatitis (51.35%); 65.9% had decompensated disease and 85.08% clinically significant portal hypertension (CSPH). The standardised liver volume and liver-spleen volume ratio negatively correlated with Model for End-stage Liver Disease (MELD), albumin and hepatic venous pressure gradient (HVPG) and were significantly lower in decompensated patients. The liver segmental volume ratio (segments I-III/segments IV-VIII) best captured the characteristic features of the compensated phase, showing a positive correlation with HVPG and a good discrimination between patients with and without CSPH and varices. Volumetric changes and fibrosis severity were independently associated with key prognostic events, with no association between these two parameters. CONCLUSIONS: Liver and spleen volumetric indices evolve differently along the natural history of cirrhosis and are associated with key prognostic factors in each phase, regardless of fibrosis severity and portal hypertension.
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Carcinoma Hepatocelular , Doença Hepática Terminal , Hipertensão Portal , Neoplasias Hepáticas , Albuminas , Carcinoma Hepatocelular/patologia , Colágeno , Doença Hepática Terminal/complicações , Fibrose , Humanos , Hipertensão Portal/diagnóstico por imagem , Hipertensão Portal/etiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Prognóstico , Índice de Gravidade de Doença , Baço/diagnóstico por imagem , Baço/patologiaRESUMO
Budd-Chiari syndrome (BCS) is characterized by an obstruction of hepatic venous outflow from small hepatic veins to inferior vena cava, caused by acute thrombosis or its fibrous sequellae. An underlying myeloproliferative neoplasm is present in 50% of cases. Clinical manifestations are widely variable, from asymptomatic to fulminant episodes. Long-term complications range from cirrhosis to hepatocellular carcinoma. Behçet's disease (BD) is a rare recurrent inflammatory multisystemic disorder characterized by recurrent skin-mucosa lesions and systemic involvement. Vascular involvement is observed in up to 40% of the patients with BD, and it is one of the major causes of mortality and morbidity. BCS is a rare complication of BD with a frequency of < 5% among patients with vascular involvement. Immunosuppressive treatment is the cornerstone for the management of vascular involvement in BD, while anticoagulant therapy has been an issue of debate. Transjugular intrahepatic portosystemic shunt (TIPS) in severe cases of BCS-of all causes- improves survival. However, there is scarce evidence about the role of TIPS in the setting of BCS in BD. We present a case of a vascular Behçet's disease associated with chronic Budd-Chiari syndrome with progression of thrombosis despite adequate anticoagulant and immunosuppressive treatment, successfully managed with TIPS.
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Síndrome de Behçet , Síndrome de Budd-Chiari , Derivação Portossistêmica Transjugular Intra-Hepática , Síndrome de Behçet/complicações , Síndrome de Budd-Chiari/etiologia , Síndrome de Budd-Chiari/cirurgia , Veias Hepáticas , Humanos , Veia Cava InferiorRESUMO
OBJECTIVES: To assess survival and predictive factors of mortality after an episode of spontaneous bacterial peritonitis (SBP) in cirrhotic patients and to analyze the diagnostic and therapeutic measures used. METHODS: We retrospectively reviewed the medical records of 158 consecutive episodes of SBP treated between January 2003 and December 2005. Survival was studied by Kaplan-Meier curves, compared by the log-rank test. Independent predictive factors of mortality were obtained by a Cox regression model, while independent predictive factors of in-hospital mortality were obtained by logistic regression analysis. RESULTS: A total of 80.4% of the SBP episodes occurred in men and the mean age was 61.23 +/- 12.49 years. The most frequent etiology of cirrhosis was viral (51.3%), followed by alcoholic (39.9%). The distribution of Child-Pugh classification was 5.7% (A), 63.3% (B) and 31% (C). Overall 3-year survival in the sample was 43.3%. Four variables were identified as independent predictive factors of in-hospital and 3-month mortality: renal impairment, hepatic encephalopathy, diagnosis of hepatocellular carcinoma (HCC) and mean arterial pressure (MAP) < 75 mmHg. At the end of the monitoring period, the results of the analysis were as follows: diagnosis of HCC, MAP < 75 mmHg, and age > 65 years. Microbiological detection was achieved in 21% of the episodes. The most frequent microorganisms detected were Escherichia coli in ascitic fluid and Staphylococcus aureus in blood cultures. CONCLUSIONS: SBP has a poor short- and long-term prognosis in cirrhotic patients. Independent predictive factors of short-term survival are renal impairment, hepatic encephalopathy, MAP < 75 mmHg, and the presence of HCC.
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Cirrose Hepática/mortalidade , Peritonite/epidemiologia , Idoso , Carcinoma Hepatocelular/mortalidade , Causas de Morte , Comorbidade , Infecções por Escherichia coli/epidemiologia , Feminino , Hepatite Viral Humana/epidemiologia , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática Alcoólica/mortalidade , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Infecções Estafilocócicas/epidemiologiaRESUMO
AIM: To evaluate the expression of serum fibrosis markers in liver transplantation (LT) recipients on everolimus monotherapy compared to patients on an anti-calcineurin regimen. METHODS: This cross-sectional case-control study included LT patients on everolimus monotherapy (cases) (E) (n = 30) and matched controls on an anti-calcineurin regimen (calcineurin inhibitors, CNI), paired by etiology of liver disease and time since LT (n = 30). Clinical characteristics, blood tests and elastography were collected. Serum levels of transforming growth factor-ß (TGF-ß), angiopoietin-1, tumor necrosis factor (TNF), platelet derived growth factor, amino-terminal propeptide of type III procollagen (PIIINP), hyaluronic acid (HA), VCM-1 (ng/mL), interleukin (IL)-10, interferon-inducible protein 10 (IP-10), vascular endothelial growth factor and hepatocyte growth factor (HGF) (pg/mL) were determined by enzyme-linked immunosorbent assay. Expression of these markers between E and CNI was compared. Stratified analysis was done according to factors that may influence liver fibrosis. Variables are described with medians (interquartillic range) or percentages. RESULTS: A total of 60 patients [age: 59 (49-64), hepatitis C virus (HCV): n = 21 (35%), time from LT: 73 mo (16-105)] were included. Patients had been on everolimus for a median of 15 mo. No differences in inflammatory activity, APRI test or liver elastography were found between the groups. No significant differences were observed between the groups in serum levels of PIIINP, metalloproteinase type = 1, angiopoietin, HGF, IP-10, TNF-α, IL-10 and vascular cell adhesion molecule. Patients on E had a lower expression of TGF-ß [E: 12.7 (3.7-133.6), CNI: 152.5 (14.4-333.2), P = 0.009] and HA [E: 702.89 (329.4-838.2), CNI: 1513.6 (691.9-1951.4), P = 0.001] than those on CNI. This difference was maintained in the stratified analysis when recipient age is more than 50 years (TFG-ß1: P = 0.06; HA: P = 0.005), in patients without active neoplasia (TFG-ß1, P = 0.009; HA: P = 0.01), according to time since LT (> than 5 years, TFG-ß1: P = 0.001; HA: P = 0.002), related to previous history of biliary complications (HA: P = 0.01) and HCV recurrence (HA: P = 0.004). Liver transplant recipients with everolimus monotherapy had less serum expression of TGF-ß y HA than matched patients with anti-calcineurins. This difference remains when classifying patients according to donor age and time since LT. Due to the small sample size, when examining patients with a prior history of biliary complications or recurrent HCV, the difference was non-significant but trends towards the lower expression of TFG-ß1 in the everolimus group. Mammalian target of rapamycin (mTOR) plays a role in the transformation of quiescent hepatocellular stellate cell to their active profibrotic state, and experimental models have demonstrated the potential activity of mTOR inhibition in attenuating fibrogenesis. CONCLUSION: This study supports a possible role of everolimus in liver fibrosis modulation after LT in a clinical setting and suggests that tailoring immunosuppression could avoid fibrosis progression in the allograft.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Antivirais/efeitos adversos , Interações Medicamentosas , Farmacorresistência Viral , Hepacivirus , Humanos , Monitorização Fisiológica , Oligopeptídeos/efeitos adversos , Oligopeptídeos/uso terapêutico , Seleção de Pacientes , Prolina/efeitos adversos , Prolina/análogos & derivados , Prolina/uso terapêutico , Inibidores de Proteases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
Humanos , Masculino , Feminino , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais , Antivirais/imunologia , Antivirais/metabolismo , Pró-Proteína Convertases/uso terapêutico , Sistema Enzimático do Citocromo P-450/efeitos adversos , Anticorpos Antivirais/biossíntese , Antivirais/antagonistas & inibidoresRESUMO
OBJETIVOS: Evaluar la supervivencia y los factores pronósticotras el diagnóstico de un episodio de peritonitis bacterianaespontánea (PBE) en pacientes cirróticos y las medidasdiagnosticadas y terapéuticas utilizadas.MÉTODOS: Se revisaron de manera retrospectiva los datos de158 episodios de PBE consecutivos durante el período deenero de 2003 a diciembre de 2005. Se procedió a un análisisde supervivencia mediante curvas de Kaplan-Meier, su comparaciónmediante el test de rangos logarítmicos, y valoraciónde los factores predictivos independientes mediante regresiónde Cox, y de mortalidad intrahospitalaria medianteregresión logística.RESULTADOS: El 80,4% de los episodios de PBE se produjoen varones, y la edad media fue de 61,23 ± 12,49 años. Laetiología de la cirrosis más prevalente fue viral (51,3%) seguidadel origen etílico (39,9%), y la distribución según laclasificación de Child-Pugh fue del 5,7% (A), 63,3% (B) y31% (C). La supervivencia global de la cohorte a los 3 añosdel seguimiento fue del 43,3%. Se determinaron como factoresindependientes asociados a mortalidad, tanto intrahospitalariacomo a los 3 meses tras la PBE el deterioro de funciónrenal, la presencia de encefalopatía hepática, laexistencia de carcinoma hepatocelular (CHC) y una presiónarterial media (PAM) < 75 mmHg, y a largo plazo la edad> 65 años, la existencia de CHC y la PAM < 75 mmHg. Seconsiguió el aislamiento microbiológico en el 20,3% de losepisodios. El microorganismo más frecuentemente aisladoen el líquido ascítico fue Escherichia coli y en hemocultivosStaphylococcus aureus.CONCLUSIONES: La PBE es un evento pronóstico importanteen la cirrosis hepática, y los factores independientes de mortalidada corto plazo son el deterioro de función renal, lapresencia de encefalopatía hepática, la existencia de CHC yPAM < 75 mmHg
OBJECTIVES: To assess survival and predictive factors ofmortality after an episode of spontaneous bacterial peritonitis(SBP) in cirrhotic patients and to analyze the diagnosticand therapeutic measures used.METHODS: We retrospectively reviewed the medical recordsof 158 consecutive episodes of SBP treated between January2003 and December 2005. Survival was studied by Kaplan-Meier curves, compared by the log-rank test. Independentpredictive factors of mortality were obtained by a Cox regressionmodel, while independent predictive factors of inhospitalmortality were obtained by logistic regressionanalysis.RESULTS: A total of 80.4% of the SBP episodes occurred inmen and the mean age was 61.23 ± 12.49 years. The mostfrequent etiology of cirrhosis was viral (51.3%), followed byalcoholic (39.9%). The distribution of Child-Pugh classificationwas 5.7% (A), 63.3% (B) and 31% (C). Overall 3-yearsurvival in the sample was 43.3%. Four variables were identifiedas independent predictive factors of in-hospital and 3-month mortality: renal impairment, hepatic encephalopathy,diagnosis of hepatocellular carcinoma (HCC) andmean arterial pressure (MAP) < 75 mmHg. At the end of themonitoring period, the results of the analysis were as follows:diagnosis of HCC, MAP < 75 mmHg, and age > 65 years.Microbiological detection was achieved in 21% of theepisodes. The most frequent microorganisms detected wereEscherichia coli in ascitic fluid and Staphylococcus aureus inblood cultures.CONCLUSIONS: SBP has a poor short- and long-term prognosisin cirrhotic patients. Independent predictive factors ofshort-term survival are renal impairment, hepatic encephalopathy,MAP < 75 mmHg, and the presence of HCC (AU)