[Reduction of social coverage for symptomatic slow-acting drugs for osteoarthritis: a disinvestment initiative in Argentina, 2015-2017]. / Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017.

In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the "social subsidy"), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries' out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.

En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud.

Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017 / Reduction of social coverage for symptomatic slow-acting drugs for osteoarthritis: a disinvestment initiative in Argentina, 2015-2017

RESUMEN En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud.

ABSTRACT In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the "social subsidy"), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries' out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.

Effect of a Social Norm Email Feedback Program on the Unnecessary Prescription of Nimodipine in Ambulatory Care of Older Adults: A Randomized Clinical Trial.

Importance: Nimodipine is a highly prescribed drug for the treatment of cognitive impairment and dementia in Argentina. There is little evidence to support the use of nimodipine for cognitive impairment and dementia. Objective: To test the effectiveness of a behavioral intervention based on social norm feedback to reduce prescription of nimodipine for cognitive impairment in Argentina. Design, Setting, and Participants: This pragmatic parallel-group randomized clinical trial included 2 arms with a 1:1 allocation ratio. General practitioner physicians in the national health care system for older adults in Argentina (INSSJP-PAMI) with history of high nimodipine prescription rate were enrolled. The study was conducted from May 2019 to October 2019, and data were analyzed from November 2019 to February 2020. Interventions: The treatment group received 2 emails with evidence-based information about nimodipine plus the individual's level of nimodipine prescription compared with their peers. The control group received 2 emails with general information about the risks of overprescription in older adults. Main Outcomes and Measures: The primary outcome was the cumulative number of nimodipine prescriptions per 1000 prescriptions of all drugs made by the targeted physicians during the 6 months of the study. Secondary outcomes included annual monetary savings attributable to the intervention and physicians' qualitative perceptions of the acceptability of the procedure. Results: Of 1811 physicians enrolled, 906 physicians (354 [39.1%] women; mean [SD] age, 57.10 [10.73] years) were randomized to treatment and 905 participants (331 [36.6%] women; mean [SD] age, 56.49 [10.47] years) to the control group. Physicians in the treatment group wrote a mean of 93.25 (95% CI, 89.27 to 97.24) prescriptions of nimodipine, compared with 98.99 (95% CI, 95.00 to 102.98) prescriptions among practitioners in the control group during the half-year of the intervention (mean difference, -5.73 [95% CI, -11.38 to -0.10] prescriptions; P = .046), which meant a 5.79% reduction. Regression analysis revealed a significant association of the group condition with number of prescriptions per 1000 total prescriptions when controlling for baseline prescriptions (B = -0.312 [95% CI, -0.465 to -0.160]; P < .001). The observed difference corresponds to a 4.48% reduction in nimodipine prescriptions per 1000 prescriptions of all drugs made by physicians in the treated group compared with the control group. Physicians who effectively opened the email in the treatment group (427 physicians [47.1%]) prescribed the drug 11.3% less compared with the control group (426 physicians) (mean difference, -10.78 [95% CI, -18.53 to -3.03] prescriptions; P = .006). Expenditures were 7.18% lower in the treatment group, resulting in an estimated annual net cost benefit of US $234 893.35 (95% CI, $225 565.35 to $237 112.30). Conclusions and Relevance: In this randomized clinical trial, the social norm email feedback program showed an effect on curbing the nonrecommended prescription of nimodipine. It was highly cost-effective and well accepted by participants. Trial Registration: ISRCTN.org identifier: ISRCTN17823729.

What is happening with not recommended drugs for dementia in Argentina? Prescription patterns and direct costs analysis.

OBJECTIVES: The only recommended pharmacological treatments for specific dementias are donepezil, galantamine, rivastigmine, and memantine (recommended drugs, RD). However, other drugs without recommendations (not recommended drugs, NRD) are often used to treat patients with cognitive impairment (CI) in Argentina. The INSSJyP is the largest health insurance in Argentina. The objective of this study is to analyze the prescription pattern, cost, and implications of NRD used for the treatment of CI in the INSSJyP. MATERIALS: This is a retrospective, population-based study of the INSSJyP outpatients' prescriptions database for drugs usually prescribed for CI during 2015. These data were compared with the same database in 2009. The number of "prescriptions" always refers to dispensed packages. RESULTS: A total of 3 255 438 packages of drugs usually indicated for CI were prescribed during 2015: 1 912 476 packages of RD (59%) and 1 342 962 packages of NRD (41%).Comparing the results with those obtained in 2009, there is a 148% gross increase in the prescription of both RD and NRD for CI, although the rates/1000 affiliates/year show a lesser rise for NRD (70.1%) compared to RD (103.9 %).The expenditure on CI drugs prescribed during 2015 was 77 million USD. NRD cost represented approximately 20 million USD. CONCLUSION: Inappropriate drug use increases health costs in developing countries. We found a high number of patients with a probable diagnosis of CI treated with NRD. It is extremely relevant that all the healthcare professionals can update their knowledge and modify behavioral insights about appropriate prescription for specific dementias.

El cáncer como prioridad en la agenda sanitaria / Cancer as a priority on the health agenda

El cáncer concentra el 20% del total de defunciones en el país y representa la segunda causa de muerte. El objetivo de esta investigación operativa fue elaborar un análisis de situación con propuestas de mejora para incorporar al cáncer en la agenda política de los candidatos presidenciales. El estudio incluyó técnicas cualicuantitativas, el uso del Monitoreo de Resultados para un Sistema de Equidad (MoRES, "Monitoring Results for Equity System") para identificar brechas en relación a derechos vulnerados, mapeo de actores, uso de herramientas analíticas epidemiológicas y comunicacionales. Los resultados mostraron dos ejes programáticos para acercar propuestas a los distintos espacios políticos: incremento y optimización del financiamiento y la gestión de la enfermedad, por un lado, y, por el otro, incremento y optimización del financiamiento de los registros oncológicos a nivel provincial que permita mejorar la calidad de los datos. Todos tenemos responsabilidades sobre el monitoreo de las acciones y la implementación de la agenda de salud. Con la información disponible, Argentina está en condiciones de avanzar sobre la reducción en brechas de inequidades, pero hace falta que los portadores de derechos y de obligaciones se movilicen con visión y agenda compartida, un gran desafío que no es imposible de alcanzar. (AU)

Cancer represents the second cause of death, concentrating approximately 20% of the total deaths. The objective of this operational investigation was to elaborate a situation analysis with proposals for improvement to place cancer on the political agenda of presidential candidates. The study included qualitative and quantitative techniques, the use of MoRES ("Monitoring Results for Equity System") to identify inequality gaps in relation to violated rights, stakeholder mapping, the use of epidemiological and communicational analytical tools. The results of two programmatic axes to bring proposals to the different political spaces: improvements in financing and disease management, on the one hand, and, on the other, better financing and management of cancer registries at the provincial level that allowsimproving the quality of the data. We all have responsibilities on health agenda. With the available information, Argentina is in a position to move forward on the reduction of inequity and inequality gaps. An informed society, committed to health and aware of where priorities are, can contribute more and better to the formulation of a based rights health agenda. (AU)

[Psychotropic drugs prescription to elderly people in the national institute of social services for retirees and pensioners of argentina (PAMI)]. / Prescripción de psicofármacos a personas mayores en el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados de Argentina (PAMI).

OBJECTIVE: To analyze the prescribing pattern of psychotropic drugs to affiliates over 60 years of age at the National Institute of Social Services for Retirees and Pensioners of Argentina (PAMI). MATERIALS AND METHODS: We conducted a retrospective study of the at the National Institute of Social Services for Retirees and Pensioners of Argentina (PAMI) database on the population over 60 years of age who received at least one psychotropic drug during 2016. RESULTS: During the year 2016, 30% of the population over 60 years of age received the prescription of at least one psychotropic drug. There was a greater prescription of psychotropic drugs to women than to men (75.3% vs. 24.7%). Of the drugs prescribed, 67% were benzodiazepines, 20% were antidepressants, 9% were antipsychotics and 4% were non-benzodiazepine hypnotics. 54% of the drugs prescribed were clonazepam and alprazolam. 21% of the population received three or more prescriptions during the period studied. There was a relatively greater prescription of psychotropic drugs in the population of 75 years old or older. CONCLUSIONS: Taking into account the risks of adverse effects, interactions and the inclusion of some of these drugs among those that should not be prescribed among older adults, the high prescription rate of some of these drugs is alarming. It is necessary to develop strategies among general practitioners, specialists and also among the general population in order to reduce the prescription of psychotropic drugs.

[Adrenal insufficiency in cirrhotic patients]. / Insuficiencia suprarrenal relativa en pacientes cirróticos.

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

Insuficiencia suprarrenal relativa en pacientes cirróticos / Adrenal insufficiency in cirrhotic patients

La insuficiencia suprarrenal relativa (ISR) es frecuente en pacientes cirróticos con sepsis grave, asociándose a un pobre pronóstico. Se desconoce su importancia en condiciones de enfermedad estable. El objetivo del trabajo ha sido evaluar la prevalencia de la ISR en una serie de pacientes cirróticos estables y su relación con el deterioro de la función hepática. Se determinó el impacto de la ISR en la supervivencia y se correlacionaron los niveles entre el cortisol basal en plasma y saliva en sujetos controles y cirróticos. Fueron incluidos 47 pacientes ambulatorios y 16 controles. La funcionalidad del eje hipotalámico-pituitario-suprarrenal se valoró mediante la prueba de estimulación con 250 μg de ACTH sintética EV, definiendo la ISR como delta cortisol < 9 μg/dl. Respecto al grado de deterioro de la función hepática, 22 tenían un Child-Pugh ≤ 8 y 25 pacientes = 9. La prevalencia de ISR fue de un 22%, siendo significativamente más elevada en aquellos con mayor deterioro de la función hepática (8/32 vs. 3/13, p < 0.05). Se observó correlación entre el cortisol salival y el plasmático basal (r = 0.6, p < 0.0004). Por último, la supervivencia fue más elevada en los pacientes sin ISR al año (97%) y a los tres años (91%) que aquellos que desarrollaron esta complicación (79 % y 51%, p < 0.05, respectivamente). En resumen, la prevalencia de ISR es elevada en los pacientes con cirrosis estable y se relaciona con un deterioro de la función hepática y una mayor mortalidad.

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 μg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh ≤ 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with ≤ 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions / / La ingesta de una comida ocasiona un aumento de la rigidez hepática, lo que sugiere que esta determinación debe ser siempre evaluada en ayuna

Introduction: The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. Aim: We evaluated the effect of food intake on LS in patients with different degrees of liver disease. Patients and methods: We evaluated 24 patients (F≤1, n = 11 and F> 1, n = 13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30 min after ingestion of a standard liquid meal. Results: Food intake increased PBF (51 ± 10%, p < 0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8 ± 3.3 to 10.3 ± 4.1 kPa, p < 0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F > 1). Hemodynamic and LS values returned to baseline pre-meal levels within 2 hours. Conclusion: LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions (AU)

Introducción: El desarrollo de nuevos métodos que permiten la determinación no invasiva de la rigidez hepática ha abierto una nueva era en el manejo de la fibrosis hepática. Objetivo: El objetivo del trabajo fue evaluar el efecto de ingesta de una comida sobre la rigidez hepática en pacientes con diferentes grados de fibrosis. Pacientes y métodos: Se evaluaron 24 pacientes (F ≤ 1, n = 11, y F > 1, n = 13), que fueron estudiados basalmente y 30 min después de la ingesta de una comida estándar (Ensure Plus®). La rigidez hepática se midió por Fibroscan®, y los parámetros hemodinámicos portales, mediante Doppler. La ingesta de una comida ocasionó un aumento del flujo sanguíneo portal (51 ± 10%, p < 0,001). La hiperemia esplácnica fue acompañada por un marcado incremento en la rigidez hepática (7,8 ± 3,3 a 10,3 ± 4,1 kPa, p < 0,001). Este efecto fue similar en pacientes con fibrosis mínima (F ≤ 1) y con fibrosis significativa (F > 1). Los valores de ambos parámetros retornaron a niveles similares a los basales a las 2 h luego de la ingesta. Conclusión: Este estudio demuestra que la respuesta vascular posprandial se acompaña de aumento de la rigidez hepática. Los cambios son independientes del grado de fibrosis. Nuestros resultados sugieren fuertemente que los estudios deben realizarse en condiciones de ayuno (AU)

Fulminant presentation of autoimmune hepatitis: clinical features and early predictors of corticosteroid treatment failure.

BACKGROUND AND AIMS: Classical features of autoimmune hepatitis (AIH) may be altered during the abrupt onset of the disease. Corticosteroid therapy can be life-saving, but its use in the fulminant presentation of AIH (F-AIH) remains controversial. We aimed to assess the clinical features of patients with F-AIH and to describe the role of corticosteroids in this population. PATIENTS AND METHODS: We retrospectively analyzed 154 adult patients with fulminant hepatic failure who were admitted to six liver transplantation (LT) programs. The AIH simplified criteria were used to identify patients with F-AIH. RESULTS: We identified 40 (26%) patients with F-AIH. Compared with other etiologies, patients with F-AIH presented a longer interval from jaundice to encephalopathy (26 vs. 16 days, P=0.02) and a lower Model for End-Stage Liver Disease (MELD) score on admission (29 vs. 33, P=0.002). Overall, 25 (62%) patients with F-AIH underwent LT, eight (20%) patients survived, and seven (18%) died without LT. Seventeen patients received corticosteroids therapy, of whom seven (41%) survived without LT. Among the treated patients, higher MELD score and encephalopathy grade of 3 or more were associated significantly with corticosteroid failure. CONCLUSION: Patients with F-AIH have a more indolent presentation compared with the non-F-AIH population. Altogether, only eight (20%) patients presenting with F-AIH survived without LT. A subset of patients with F-AIH and an initial MELD score less than 27 and low-grade hepatic encephalopathy might benefit from administration of corticosteroids.

Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

INTRODUCTION: The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. AIM: We evaluated the effect of food intake on LS in patients with different degrees of liver disease. PATIENTS AND METHODS: We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. RESULTS: Food intake increased PBF (51±10%, p<0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8±3.3 to 10.3±4.1kPa, p<0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. CONCLUSION: LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions.

[De novo malignant tumors following liver transplantation. A single-center experience in Argentina]. / Tumores malignos de novo en el trasplante hepático. Experiencia de un centro en la Argentina.

The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5% (n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41%. The actuarial probability of survival at 1 and 5 years was 83 and 55%, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis.

Tumores malignos de novo en el trasplante hepático experiencia de un centro en la Argentina

El objetivo del presente trabajo ha sido evaluar la incidencia y las características clínicas de los tumores aparecidos de novo en los pacientes sometidos a trasplante hepático, como así también su supervivencia. Para ello, analizamos en forma retrospectiva los 168 trasplantes hepáticos realizados en 159 pacientes adultos en el período mayo 2006 hasta mayo 2014, encontrando una incidencia de neoplasia de novo de 7.5% (n = 12). La edad media en el momento del diagnóstico fue de 63 ± 7 años. Las neoplasias más frecuentes fueron las de piel no melanoma y adenocarcinomas. El 50% de las neoplasias se desarrollaron en el segundo y tercer año postrasplante. El tipo de inmunosupresión no influyó en el tipo de tumor; sin embargo, debemos destacar que la mayor parte de los pacientes recibieron tacrolimus, micofenolato y/o corticoides. El tiempo medio de seguimiento tras el diagnóstico del tumor fue 25 ± 29 meses (0-76), y la tasa de mortalidad fue de un 41% (5/12 pacientes IC95%,15-72).La supervivencia global luego del trasplante a 1 y 5 años, calculada por análisis de Kaplan-Meier, fue de 83 y 55%, respectivamente. Los tumores de novo son frecuentes luego del trasplante hepático y presentan un patrón evolutivo diferente al de la población general. Teniendo en cuenta esta evolución más agresiva, es fundamental el seguimiento periódico en estos pacientes para realizar un diagnóstico lo más precoz posible.

The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5% (n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41%. The actuarial probability of survival at 1 and 5 years was 83 and 55%, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis.

Tumores malignos de novo en el trasplante hepático experiencia de un centro en la Argentina

El objetivo del presente trabajo ha sido evaluar la incidencia y las características clínicas de los tumores aparecidos de novo en los pacientes sometidos a trasplante hepático, como así también su supervivencia. Para ello, analizamos en forma retrospectiva los 168 trasplantes hepáticos realizados en 159 pacientes adultos en el período mayo 2006 hasta mayo 2014, encontrando una incidencia de neoplasia de novo de 7.5% (n = 12). La edad media en el momento del diagnóstico fue de 63 ± 7 años. Las neoplasias más frecuentes fueron las de piel no melanoma y adenocarcinomas. El 50% de las neoplasias se desarrollaron en el segundo y tercer año postrasplante. El tipo de inmunosupresión no influyó en el tipo de tumor; sin embargo, debemos destacar que la mayor parte de los pacientes recibieron tacrolimus, micofenolato y/o corticoides. El tiempo medio de seguimiento tras el diagnóstico del tumor fue 25 ± 29 meses (0-76), y la tasa de mortalidad fue de un 41% (5/12 pacientes IC95%,15-72).La supervivencia global luego del trasplante a 1 y 5 años, calculada por análisis de Kaplan-Meier, fue de 83 y 55%, respectivamente. Los tumores de novo son frecuentes luego del trasplante hepático y presentan un patrón evolutivo diferente al de la población general. Teniendo en cuenta esta evolución más agresiva, es fundamental el seguimiento periódico en estos pacientes para realizar un diagnóstico lo más precoz posible.(AU)

The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5% (n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41%. The actuarial probability of survival at 1 and 5 years was 83 and 55%, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis.(AU)

Tumores malignos de novo en el trasplante hepático. Experiencia de un centro en la Argentina. / [De novo malignant tumors following liver transplantation. A single-center experience in Argentina].

The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5

(n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41

. The actuarial probability of survival at 1 and 5 years was 83 and 55

, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis.

Fibrosis progression in maintenance liver transplant patients with hepatitis C recurrence: a randomised study of everolimus vs. calcineurin inhibitors.

BACKGROUND & AIMS: Robust clinical data evaluating fibrosis progression in hepatitis C virus (HCV) liver transplant patients receiving an mTOR inhibitor vs. calcineurin inhibitor (CNI) are lacking. To evaluate fibrosis progression in maintenance liver transplant patients receiving everolimus- or CNI-based immunosuppression. METHODS: In a randomised, multicentre, open-label study, 43 maintenance liver transplant patients with recurrent HCV infection were randomised to continue CNI-based immunosuppression or switch to everolimus. RESULTS: For patients with biopsy data at month 12, mean Ishak-Knodell fibrosis score at baseline was 2.6 ± 0.9 (n = 14) with everolimus vs. 1.9 ± 1.1 (n = 18) with CNI (P = 0.043), and 1.9 ± 1.2 vs. 2.2 ± 1.3 at month 12. Ishak-Knodell fibrosis score decreased from baseline to month 12 by a mean of -0.7 ± 1.1 with everolimus, but increased by 0.2 ± 1.2 with CNI (P = 0.046). No acute rejection or graft losses occurred up to month 12. Estimated GFR at month 12 was 65.6 ml/min/1.73 m² with everolimus and 62.2 ml/min/1.73 m² with CNI [mean difference 3.4 ml/min/1.73 m² compared to CNI control group, 95% CI -4.9, 11.8 ml/min/1.73 m², P = 0.411 (analysis of covariance adjusting for baseline GFR)]. Adverse events occurred in 95.5% of everolimus patients and 71.4% of CNI patients (serious adverse events 31.8% and 0.0%, respectively). Adverse events led to everolimus discontinuation in five patients (22.7%). CONCLUSIONS: This exploratory study suggests that conversion from CNI to everolimus reduces progression of liver fibrosis, and preserves renal function without jeopardising efficacy in liver transplant recipients with recurrent HCV, but is associated with a higher incidence of adverse events and serious adverse events. These preliminary findings merit examination in a larger trial.

Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

Changing etiologies and outcomes of acute liver failure: perspectives from 6 transplant centers in Argentina.

There is significant geographic variation in the etiologies and prognoses of acute liver failure (ALF). The aims of the present study were to determine the causes and short-term outcomes of ALF in Argentina, to evaluate the performance of prognostic criteria, and to identify clinical prognostic factors of death. We performed a retrospective analysis of 154 adult patients with ALF who were admitted to 6 liver transplantation (LT) programs between June 2005 and December 2011. The most frequent causes of ALF were viral hepatitis B (46 patients or 30%), autoimmune hepatitis (AIH; 40 patients or 26%), and indeterminate causes (40 patients or 26%). No acetaminophen (ACM) overdose was reported. One hundred and twenty one patients (78%) were included on the waiting list, and LT was performed for 83 patients (54%). Overall survival rate is now corected to 73%. Multivariate logistic regression identified 2 independent variables associated with adverse outcomes on admission: a Model for End-Stage Liver Disease (MELD) score ≥ 29 and an encephalopathy grade ≥ 3. In a direct comparison using a receiving operating characteristic curve analysis, the MELD score [C statistic = 0.830, 95% confidence interval (CI) = 0.73-0.93] had better prognostic accuracy for predicting outcomes than the Clichy criteria (C statistic = 0.719, 95% CI = 0.58-0.85) or the King's College criteria (C statistic = 0.631, 95% CI = 0.49-0.77). In conclusion, hepatitis B and AIH were the most frequent causes of fulminant hepatic failure in our series, and no cases of ACM overdosing were identified. A MELD score ≥ 29 and an encephalopathy grade ≥ 3 at admission were associated with death. The MELD score at admission showed the highest prognostic accuracy.

An unreported case of pancreatic panniculitis in a liver transplant patient.

Pancreatic panniculitis is an uncommon condition that can occur in association with pancreatic disease. Most of the cases reported to date were associated with acute or chronic pancreatitis and pancreas cancer. Recently, development has been described in kidney transplant patients and secondarily to allograft pancreatitis in a pancreas-kidney transplant recipient. Both findings suggest that immunological processes may be involved in the pathogenesis of this entity. We report for the first time a case of acute pancreatitis associated with pancreatic panniculitis in a patient who underwent a liver transplant 10 months before. A 69-year-old man with a history of epigastric pain of a few days of evolution was presented with painful subcutaneous nodules on both legs. Blood chemistry showed raised serum amylase and lipase levels. Ultrasonography and multislice CT scan were suggestive of an acute pancreatitis. A skin biopsy showed typical features of pancreatic panniculitis which included lobular panniculitis with lipocyte degeneration with ghost cells. The administration of octreotide resulted in both a rapid improvement of symptoms and a disappearance of skin lesions. Liver transplant specialists should be aware that the pancreatic panniculitis could be a manifestation ofpancreas disease in patients who have undergone l ver transplantation.

[Efficacy of the association of a single dose of hepatitis B hyperimmune gammaglobulin and entecavir in the prophylaxis of hepatitis B after liver transplantation: experience of a single center in Argentina]. / Eficacia de la asociación de una sola dosis de gamaglobulina hiperinmune anti-hepatitis B más entecavir en la profilaxis de la hepatitis B después del trasplante hepático: experiencia de un centro en la Argentina.

The present study reports the effectiveness of the association of a single dose of hepatitis B immunoglobulin (HBIg) associated to entecavir in the prophylaxis of hepatitis B in patients who have undergone liver transplantation. Six patients that had been transplanted because of hepatitis B liver disease were retrospectively evaluated. Three of them developed non-oncological complications related to liver cirrhosis, two had hepatocellular carcinoma and another one had fulminant HBV hepatitis. The mean follow-up was 22 months (range: 7-52 months). The 6 patients received entecavir as prophylactic treatment before transplantation. The pretransplant viral load was undetectable in all patients. HBsAg seroconversion was observed in four of the six patients. Three patients died during follow-up, two because of recurrent hepatocellular carcinoma, none of them had detectable HBV serum viral load. In a small series of patients we could demonstrate that a regimen with a single dose of gamma globulin entecavir is effective in the post-transplant management of patients with liver disease associated with HBV. Future studies will be able to demonstrate the effectiveness of specific gamma globulin-free regimens.