Multidrug-resistant bacterial infections after liver transplantation: Prevalence, impact, and risk factors.

BACKGROUND & AIMS: Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT). METHODS: This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT. RESULTS: We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates. CONCLUSION: MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors. IMPACT AND IMPLICATIONS: Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation.

Reproductive and pregnancy control in Wilson disease patients in Spain.

BACKGROUND AND AIM: Recommendations on pregnancy, lactation, and contraception in women with Wilson disease are briefly stated in international guidelines but are not entirely homogeneous. Data regarding the management of these special events among patients with Wilson disease in Spain are lacking. We used the Wilson Registry platform of the Spanish Association for the Study of the Liver to question patients on their reproductive and gestational lives. METHODS: This was a multicentre ambispective study including adult women with Wilson disease in the Spanish Wilson Registry interviewed about their contraception, childbearing, pregnancy, and lactation experiences. Clinical and analytical data were extracted from the registry. RESULTS: The study included 92 women from 17 centres in Spain. Most (63%) reported having a previous pregnancy history. The rate of spontaneous miscarriages was 21.6%, mainly occurring in the first trimester and up to one third among undiagnosed patients. Most pregnant women received chelator therapy during pregnancy, but dose reduction was recommended in less than 10%. After delivery, artificial lactation predominated (60.3%) and its use was mainly based on physician's recommendations (68%). Up to 40% of the women included reported some concerns about their reproductive lives, mainly related to the potential drug toxicity to their children. Most of the patients considered the information given by specialists to be sufficient. CONCLUSION: Gestational management among women with Wilson disease in Spain was found to be highly heterogeneous and frequently different from what is described in international guidelines. Education on rare liver diseases should be a priority for scientific societies in order to homogenize patient follow-up and recommendations.

Low applicability of the ‘‘six-and-twelve score” in hepatocellular carcinomatreated with drug-eluting bead transarterial chemoembolization

Objective: the effectiveness of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) dependson the selection of suitable patients. The ‘‘six-and-twelve score” distinguishes three groups of ideal patients with different overall survival, based on the sum of the number and size of tumors. This may impact on clinical practice and trial design. The aim of this study was to assess the reproducibility and prognostic value of the model in western patients treated with drug-eluting beads (DEB)-TACE.Methods: an observational, retrospective, unicentric study with consecutive compensated patients treated with DEBTACE from October 2008 to October 2017. Exclusion criteria were Child-Pugh ≥ 8 and DEB-TACE used as a bridge to liver transplantation.Results: a total of 225 consecutive HCC patients were included; BCLC-0/A, n = 131 (single nodules > 5, n = 29) andBCLC-B, n = 94. Median overall survival (OS) was 27 months (95 % CI, 23.8-30.2). OS was different between BCLC-0/A and BCLC-B: 30 vs. 24 months (p = 0.03), Child-Pugh A5 vs. A6-B7: 30 vs. 27 months (p = 0.003). ‘‘Six-and-twelve score” groups discriminated OS: group 1, n = 123, 32 months (95 % CI, 27.5-63.5); group 2, n = 101, 24 months (95% CI, 19.6-28.4); and group 3, n = 1, 27 months (p = 0.024). When comparing the three scores, the ‘‘six-and-twelve score” showed the best discrimination power: C-index, 0.603; Akaike’s informationcriterion (AIC), 1.642; likelihood ratio test (LRT), 16.21.Conclusion: The ‘‘six-and-twelve score” is a prognostic tool for patients with HCC treated with DEB-TACE. However, few patients were included in the third group (score > 12) and no differences were observed with BCLC, therefore applicability is limited. (AU)

Predictive models for hepatocellular carcinoma development after sustained virological response in advanced hepatitis C / Modelos predictivos para el desarrollo de carcinoma hepatocelular tras la respuesta viral sostenida en pacientes con hepatitis C avanzada

Background & aims: Life-long hepatocellular carcinoma (HCC) surveillance is recommended after sustained virological response (SVR) in patients with advanced hepatitis C. Since the identification of patients who could be safely discontinued for surveillance is essential, we aimed to identify subsets of patients with low-risk HCC. Methods: 491 patients with advanced and compensated fibrosis (≥F3) were prospectively followed after achieving SVR with interferon-free therapies. Clinical–biological parameters and liver stiffness measurement (LSM) were performed before starting treatment (ST) and at SVR, and HCC surveillance was carried out. Results: During a median follow-up of 49.8 months, 29 (5.9%) patients developed HCC [incidence rate: 1.6/100 patient-years (PYs)]. Two predictive models based on LSM (Model-A) or FIB-4 score (Model-B) were proposed. Only SVR parameters were included in the models, because they showed a higher accuracy for predicting HCC than ST measurements. Variables independently associated with HCC were LSM (HR, 1.03; 95% CI, 1.01–1.05), age (HR, 1.04; 95% CI, 1.01–1.08) and albumin levels (HR, 0.90; 95% CI, 0.84–0.97) in Model-A, and FIB-4 (HR, 1.22; 95% CI, 1.08–1.37) and albumin (HR, 0.90; 95% CI, 0.84–0.97) in model-B. Both models allow HCC risk stratification, identifying low-risk groups with an HCC incidence rate of 0.16/100 and 0.25/100 PYs, respectively. An overall increased hazard of HCC was observed over time. (AU)

Antecedentes y objetivos: En pacientes con hepatitis C avanzada se recomienda la vigilancia del carcinoma hepatocelular (CHC) de por vida tras la respuesta viral sostenida (RVS). La identificación de pacientes que podrían interrumpir de manera segura el screening es esencial, por ello nuestro objetivo fue identificar subgrupos de pacientes con bajo riesgo de desarrollo de CHC. Métodos: Se realizó un seguimiento prospectivo de 491 pacientes con fibrosis avanzada y compensada (≥F3) tras la RVS obtenida con terapias libres de interferón. Se registraron parámetros clínico-biológicos y se midió la rigidez hepática mediante elastografía de transición (ET) antes del inicio del tratamiento y en la respuesta viral sostenida y se realizó screening para el desarrollo de CHC. Resultados: Durante una mediana de seguimiento de 49,8 meses, 29 (5,9%) pacientes desarrollaron CHC. (Tasa de incidencia: 1,6/100 pacientes-año [PA]). Se propusieron dos modelos predictivos basados en la puntuación de ET (Modelo-A) o FIB-4 (Modelo-B). Se incluyeron los parámetros en RVS en los modelos porque mostraron una mayor precisión para predecir CHC que las mediciones basales. Las variables asociadas de forma independientes con CHC fueron: ET (HR 1,03 IC; IC 95%, 1,01-1,05), edad (HR 1,04; IC 95%, 1,01-1,08) y niveles de albúmina (HR 0,90; IC 95%, 0,84-0,97) en el Modelo-A, y FIB-4 (HR 1,22; IC 95%, 1,08-1,37) y albúmina (HR 0,90; IC 95%, 0,84-0,97) en el Modelo-B. Ambos modelos permiten la estratificación del riesgo de CHC, identificando grupos de bajo riesgo con una tasa de incidencia de CHC de 0,16/100 y 0,25/100 PA, respectivamente. Se observó un aumento general del riesgo de desarrollar CHC con el tiempo. (AU)

Prevalence and progression of chronic kidney disease after liver transplant: a prospective, real-life, observational, two-year multicenter study

Introduction: chronic kidney disease is a frequent complication after liver transplantation. The use of calcineurin inhibitors is one of the causes of this complication. Current immunsuppression regimens that reduce the use of calcineurin inhibitors may be associated with an improved preservation of renal function. Objective: the study aimed to assess the evolution of renal function after liver transplantation in the current routine clinical practice. Methods: an observational, prospective, multicenter study in adult liver transplant recipients was performed. Two hundred and thirty patients with a good renal function before transplantation were assessed six months post-transplantation (baseline) and every six months until month 30. Results: at baseline, 32% of the patients had a reduction in the glomerular filtration rate below < 60 ml/min/1.73 m2. The mean glomerular filtration rate increased from 72.3 to 75.6 ml/min/1.73 m2 at baseline and month 30 respectively (p < 0.01). The mean serum creatinine levels (mg/dl) decreased from 1.13 to 1.09 (p < 0.01). The percentage of patients with stage 3 chronic kidney disease decreased from 31.7% to 26.4%, whereas the percentage of patients with stage 4 remained unchanged (0.4% at baseline and 0.5% at month 30). No patients progressed to end-stage kidney disease that required dialysis or renal transplantation. Conclusion: in the routine clinical practice, a moderate deterioration of renal function is frequent after liver transplantation. However, advanced chronic kidney disease is infrequent in patients with a good pre-transplant renal function

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Modificaciones en las características de los ingresos hospitalarios por cirrosis descompensada en la era de los antivirales de acción directa frente al virus de la hepatitis C / No disponible

INTRODUCCIÓN: el desarrollo de los regímenes libres de interferón, basados en antivirales de acción directa (AADs), ha supuesto una revolución en el tratamiento de la infección por el virus de la hepatitis C (VHC). OBJETIVO: conocer si han existido cambios en las características de los ingresos hospitalarios por cirrosis descompensada desde la introducción de los AADs. MÉTODOS: se recogieron de forma prospectiva todos los ingresos hospitalarios por cirrosis descompensada en dos periodos: octubre/12-octubre/14 (P-I) y julio/16-julio/18 (P-II). Se registraron variables demográficas y clínicas y se utilizaron los métodos estadísticos habituales para su análisis. RESULTADOS: se registraron 746 ingresos (347 en P-I y 399 en P-II). Los pacientes del P-I fueron más jóvenes (59 vs. 63 años; p = 0,034), mientras que la proporción de ingresos por cirrosis-VHC fue inferior en el P-II (15,8 % vs. 21,6 %; p = 0,041). No hubo diferencias significativas en la proporción de ingresos por otras etiologías de la cirrosis entre ambos periodos. Analizando los ingresos por cirrosis-VHC, los pacientes del P-II tuvieron menos frecuentemente infección viral activa (57,1 vs. 97,3 %; p = 0,001) y en ellos coexistía con mayor frecuencia un consumo excesivo de alcohol (55,5 % vs. 30,7 %; p = 0,003), mientras que la coinfección con VIH fue menos frecuente (1,6 % vs. 10,7 %; p = 0,039). CONCLUSIONES: la proporción de ingresos por cirrosis descompensada ocasionada por el VHC ha descendido en torno a un 30 % desde la introducción de los AADs. Además, las características de los pacientes que ingresan por complicaciones de la cirrosis relacionada con el VHC han cambiado desde la aplicación de los regímenes libres de interferón

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Cuantificación del antígeno de superficie del virus de la hepatitis B en la caracterización y seguimiento / Quantification of the hepatitis B surface antigen in the characterization and follow-up

La reciente disponibilidad de técnicas comerciales para la cuantificación del antígeno de superficie del virus de la hepatitis B (HBsAg) ha provocado un renacimiento en el interés por él. En los últimos años se ha evaluado su potencial como biomarcador de la historia natural de la enfermedad y de la respuesta al tratamiento antiviral. Los valores séricos de HBsAg son reflejo de la actividad transcripcional del cccADN y, por lo tanto, su determinación podría constituir un complemento a la del ADN-virus de la hepatitis B (VHB) en la categorización de las distintas fases de la infección crónica por VHB. Durante su historia natural los valores de HBsAg disminuyen progresivamente desde la fase de tolerancia inmune a la de portador inactivo. En pacientes HBeAg negativo, la determinación combinada de ADN-VHB y de HBsAg puede ser útil en la diferenciación entre portador inactivo y hepatitis crónica HBeAg(-), en la estratificación del riesgo de desarrollar hepatocarcinoma y en la predicción del aclaramiento del HBsAg

The recent availability of commercial techniques for the quantification of the hepatitis B surface antigen (HBsAg) has revived interest in this antigen. In recent years, the antigen’s potential as a biomarker of the natural history of the disease and its response to antiviral treatment has been assessed. HBsAg serum values reflect the transcriptional activity of cccDNA; reading these values could therefore complement the reading of hepatitis B virus (HBV) DNA in the categorization of the various phases of chronic HBV infection. During its natural history, HBsAg values progressively decrease from the immune-tolerant phase to the inactive carrier phase. For patients who are HBeAg-negative, the combined reading of HBV DNA and HBsAg can be useful for differentiating inactive carriers from patients with chronic HBeAg-negative hepatitis, for stratifying the risk of developing hepatocarcinoma and for predicting HBsAg clearance

Tratamiento del paciente con hepatitis crónica por el virus de la hepatitis B / Clinical management of patients with chronic hepatitis B virus infection

La hepatitis crónica por virus de la hepatitis B es aún un problema importante de salud pública, agravado por el creciente fenómeno de la inmigración procedente de zonas con elevada prevalencia de infección por este virus. Durante los últimos años se ha producido un avance notable en los métodos diagnósticos, el conocimiento de la historia natural de la enfermedad y las opciones terapéuticas, incluido el trasplante hepático, lo que se ha traducido en una mejoría en la supervivencia de los pacientes. Todo ello ha ido acompañado de un incremento en la complejidad de la toma de decisiones. Actualmente hay 6 tratamientos aprobados para la hepatitis B, incluidas 2 formulaciones de interferón, el estándar y el pegilado, y 4 análogos de nocleótidos/nucleósidos, lamivudina, adefovir, entecavir y telbivudina, y 2 más que se utilizan en pacientes coninfectados con el virus de la inmunodeficiencia humana, tenofovir y emtricitabina. Sin embargo, ninguno de los tratamientos actuales es capaz de erradicar el virus, por lo que con frecuencia es preciso recurrir a tratamientos prolongados, con el consiguiente riesgo de generar variantes del virus resistentes. Por ello y por la heterogeneidad de la historia natural de la enfermedad, aún no se han establecido con claridad las indicaciones de tratamiento y en qué parámetros deben basarse, cuál es el fármaco o la combinación de fármacos ideal o qué criterios deben seguirse para continuar, modificar o interrumpir el tratamiento. Por tanto, a pesar de los enormes progresos realizados, aún persisten numerosas incógnitas que hacen que el tratamiento clínico de estos pacientes constituya un auténtico reto

Chronic hepatitis B is still a major public health problem, aggravated by the growing phenomenon of immigration from areas with a high prevalence of infection with this virus. In the last few years, marked progress has been achieved in diagnostic methods, knowledge of the natural history of the disease and in therapeutic options, including liver transplantation, which has improved survival in these patients. These advances have been accompanied by an increase in the complexity of decision making. Six treatments have currently been approved for hepatitis B, including two interferon formulations ¿ standard and pegylated ¿ and four neucleos(t)ide analogs, lamivudine, adefovir, entecavir and telbivudine, as well as two further drugs that are used in patients coinfected with HIV, tenofovir and emtricitabine. However, none of the current treatments is able to eradicate the virus and consequently prolonged treatments are often required with the consequent risk of generating resistance. For this reason, as well as the heterogeneity of the natural history of the disease, there is a lack of consensus on the indications for treatment and the parameters in which treatment should be based, the most suitable drug or drug combination, and the criteria to be used to continue, modify or suspend treatment. Therefore, despite the enormous progress made, numerous questions remain that make the clinical management of these patients a major challenge

Tratamiento del paciente con hepatitis crónica por el virus de la hepatitis B / Clinical management of patients with chronic hepatitis B virus infection

La hepatitis crónica por virus de la hepatitis B es aún un problema importante de salud pública, agravado por el creciente fenómeno de la inmigración procedente de zonas con elevada prevalencia de infección por este virus. Durante los últimos años se ha producido un avance notable en los métodos diagnósticos, el conocimiento de la historia natural de la enfermedad y las opciones terapéuticas, incluido el trasplante hepático, lo que se ha traducido en una mejoría en la supervivencia de los pacientes. Todo ello ha ido acompañado de un incremento en la complejidad de la toma de decisiones. Actualmente hay 6 tratamientos aprobados para la hepatitis B, incluidas 2 formulaciones de interferón, el estándar y el pegilado, y 4 análogos de nocleótidos/nucleósidos, lamivudina, adefovir, entecavir y telbivudina, y 2 más que se utilizan en pacientes coninfectados con el virus de la inmunodeficiencia humana, tenofovir y emtricitabina. Sin embargo, ninguno de los tratamientos actuales es capaz de erradicar el virus, por lo que con frecuencia es preciso recurrir a tratamientos prolongados, con el consiguiente riesgo de generar variantes del virus resistentes. Por ello y por la heterogeneidad de la historia natural de la enfermedad, aún no se han establecido con claridad las indicaciones de tratamiento y en qué parámetros deben basarse, cuál es el fármaco o la combinación de fármacos ideal o qué criterios deben seguirse para continuar, modificar o interrumpir el tratamiento. Por tanto, a pesar de los enormes progresos realizados, aún persisten numerosas incógnitas que hacen que el tratamiento clínico de estos pacientes constituya un auténtico reto(AU)

Chronic hepatitis B is still a major public health problem, aggravated by the growing phenomenon of immigration from areas with a high prevalence of infection with this virus. In the last few years, marked progress has been achieved in diagnostic methods, knowledge of the natural history of the disease and in therapeutic options, including liver transplantation, which has improved survival in these patients. These advances have been accompanied by an increase in the complexity of decision making. Six treatments have currently been approved for hepatitis B, including two interferon formulations ¿ standard and pegylated ¿ and four neucleos(t)ide analogs, lamivudine, adefovir, entecavir and telbivudine, as well as two further drugs that are used in patients coinfected with HIV, tenofovir and emtricitabine. However, none of the current treatments is able to eradicate the virus and consequently prolonged treatments are often required with the consequent risk of generating resistance. For this reason, as well as the heterogeneity of the natural history of the disease, there is a lack of consensus on the indications for treatment and the parameters in which treatment should be based, the most suitable drug or drug combination, and the criteria to be used to continue, modify or suspend treatment. Therefore, despite the enormous progress made, numerous questions remain that make the clinical management of these patients a major challenge(AU)