Lista de espera para transplante hepático: impacto clínico e econômico / Waiting list for liver transplantation: clinical and economic burden

ABSTRACT Background Burden of disease is an indicator that relates to health status. United States and European epidemiological data have shown that the burden of chronic liver disease has increased significantly in recent decades. There are no studies evaluating the impact of complications of chronic liver disease on the waiting list for deceased donor liver transplantation (LTx). Objective: To determine the clinical and economic burden of complications of liver disease in wait-listed patients from the perspective of a transplant center. Methods The study retrospectively analyzed medical records of 104 patients wait-listed for deceased donor LTx from October 2012 to May 2016 and whose treatment was fully provided at the study transplant center. Clinical data were obtained from electronic medical records, while economic data were collected from a hospital management software. To allocate all direct medical costs, two methods were used: full absorption costing and micro-costing. Results: The most common complication was refractory ascites (20.2%), followed by portosystemic encephalopathy (12.5%). The mean number of admissions per patient was 1.37±3.42. Variceal hemorrhage was the complication with longest median length of stay (18 days), followed by hepatorenal syndrome (13.5 days). Hepatorenal syndrome was the costliest complication (mean cost of $3,565), followed by portosystemic encephalopathy ($2,576) and variceal hemorrhage ($1,530). Conclusion: The burden of chronic liver disease includes a great cost for health systems. In addition, it is likely to be even greater as a result of the insidious course of the disease.

RESUMO Contexto O impacto da doença é um indicador relacionado ao estado de saúde. Dados epidemiológicos norte-americanos e europeus mostraram que, nas últimas décadas, o impacto da doença hepática crônica tem aumentado significativamente. Não há estudos que avaliem o impacto das descompensações da doença hepática crônica na lista de espera para transplante hepático (TxH) com doador falecido. Objetivo: Determinar o impacto clínico e econômico das descompensações da doença hepática nos pacientes em lista de espera sob a perspectiva do centro transplantador. Métodos Foram analisados, retrospectivamente, os prontuários de 104 pacientes incluídos em lista de espera para TxH com doador falecido entre outubro de 2012 e maio de 2016 e acompanhados integralmente no centro transplantador. Dados clínicos foram obtidos do prontuário eletrônico, enquanto dados econômicos foram coletados através de software de gestão hospitalar. A apropriação dos custos médicos diretos foi realizada sob duas metodologias: custeio por absorção pleno e microcusteio. Resultados: A descompensação com maior incidência foi a ascite refratária (20,2%) seguida de encefalopatia portossistêmica (12,5%). A média de internações por paciente foi de 1,37±3,42. A hemorragia digestiva alta varicosa foi a descompensação com maior tempo mediano de internação (18 dias), seguida da síndrome hepatorrenal (13,5 dias). A descompensação mais onerosa foi a síndrome hepatorrenal (custo médio de US$ 3.565), seguida encefalopatia portossistêmica (US$ 2.576) e a hemorragia digestiva alta varicosa (US$ 1.530). Conclusão O impacto da doença hepática crônica inclui um custo importante para os sistemas de saúde. Além disso, é provável que seja ainda maior em decorrência do curso insidioso da doença.

Síndrome hepatorrenal en asociación con hepatitis alcohólica y síndrome de Zieve / Hepatorenal syndrome in association with alcoholic hepatitis and Zieve's syndrome

RESUMEN La enfermedad hepática alcohólica tiene un amplio espectro de enfermedades, incluida la hepatitis alcohólica, que en sus formas graves puede conducir al síndrome hepatorrenal. La anemia es común en pacientes alcohólicos, pero una anemia hemolítica asociada con hiperlipidemia e ictericia se reconoce como síndrome de Zieve. Un varón de 42 años con consumo excesivo de alcohol fue admitido por ictericia y dolor abdominal. Durante su evolución presentó azoemia progresiva y anemia hemolítica. Se realizó el diagnóstico de síndrome hepatorrenal asociado a hepatitis alcohólica, así como un síndrome de Zieve. Fue tratado con corticoterapia y la combinación de albúmina y noradrenalina, además del retiro de alcohol, con resultados favorables.

ABSTRACT Alcoholic liver disease has a broad spectrum of diseases, including alcoholic hepatitis, which in its severe forms can lead to hepatorenal syndrome. Anemia is common in alcoholic patients, but a hemolytic anemia in association with hyperlipidemia and jaundice is recognized as Zieve's syndrome. A 42 year old man with heavy alcohol consumption was admitted for jaundice and abdominal pain. During his evolution, he presented progressive azotemia and hemolytic anemia. The diagnosis of hepatorenal syndrome associated with alcoholic hepatitis was made, as well as a Zieve's syndrome. He was treated with corticosteroid therapy and the combination of albumin and norepinephrine, in addition to alcohol withdrawal, with favorable results.

Custo efetividade do uso da terlipressina no tratamento da síndrome hepatorrenal / Cost effectiveness of using terlipressin to treat hepatorenal syndrome

ABSTRACT Background Hepatorenal syndrome (HRS) is the most severe form of acute kidney injury in patients with advanced cirrhosis, and it is associated with high mortality. It is usually diagnosed according to criteria defined by the International Ascites Club. Currently, the most frequently indicated pharmacological therapy for the treatment of HRS is a combination of splanchnic vasoconstrictors (terlipressin or norepinephrine) in combination with albumin. With the progressive increase in healthcare spending, it is important to conduct a cost-effectiveness analysis of pharmacological treatment in patients who are diagnosed with HRS. Objective: To perform a cost-effectiveness assessment for the use of terlipressin in combination with albumin to treat HRS in patients with cirrhosis. Methods: Economic evaluation of cost-effectiveness based on secondary data from studies showed the efficacy of terlipressin therapy compared with norepinephrine combined with albumin or albumin alone. The cost-effectiveness analysis was calculated using an incremental cost-effectiveness ratio (ICER), and a sensitivity analysis was developed by varying the values of therapies and probabilities. The Brazilian real was the currency used in the analysis, and the results were converted to US dollars. Results: After selection, eligibility, and evaluation of the quality of publications, the results demonstrated that administration of terlipressin or norepinephrine in combination with albumin in patients diagnosed with HRS type 1 was efficacious. The cost of treatment with terlipressin in combination with albumin was USD $1,644.06, administration of albumin alone was USD $912.02, and norepinephrine plus albumin was USD $2,310.78. Considering that the combination therapies demonstrated effectiveness, the incremental cost of terlipressin and norepinephrine in combination with albumin was USD $666.73, and an effectiveness of 0.570 was found for terlipressin in combination with albumin and 0.200 for norepinephrine in combination with albumin. The incremental effectiveness was 0.370, and the ICER was USD $1,801.97. Thus, the parameters of increasing cost per therapy and ICER indicated that the combined therapy of terlipressin plus albumin was cost effective compared to albumin alone or norepinephrine plus albumin in a public single-payer healthcare system. Conclusion: A cost-effectiveness analysis showed that terlipressin in combination with albumin when administered concomitantly to patients who were diagnosed with type 1 HRS is cost-effective compared to norepinephrine in combination with albumin administered in a controlled environment.

RESUMO Contexto: A Síndrome Hepatorrenal (SHR) é a forma mais grave de lesão renal aguda em pacientes com cirrose avançada, estando diretamente associada a alta taxa de mortalidade. Normalmente é diagnosticada seguindo critérios definidos pela International Ascites Club (IAC). Atualmente, as terapias farmacológicas mais indicadas no tratamento da SHR são a combinação de vasoconstritores esplâncnicos (terlipressina ou norepinefrina) associados à albumina. Com o aumento progressivo dos gastos em saúde, torna-se relevante realizar uma análise de custo-efetividade do tratamento farmacológico em pacientes com diagnóstico de SHR. Objetivo: Realizar avaliação de custo-efetividade do uso da terlipressina associada à albumina no tratamento da SHR em pacientes com cirrose. Métodos: Avaliação econômica de custo-efetividade, com base em dados secundários de estudos publicados com resultado da eficácia da terapia com terlipressina, em comparação com norepinefrina combinada com albumina ou apenas albumina. A análise de custo-efetividade foi calculada usando a razão de custo-efetividade incremental (RCEI) e uma análise de sensibilidade foi desenvolvida variando os valores das terapias e probabilidades. O real foi a moeda utilizada na análise. Resultados: Após a seleção, elegibilidade e avaliação da qualidade das publicações, os resultados demonstraram que a administração da associação de terlipressina ou norepinefrina com albumina em pacientes diagnosticados com SHR tipo 1 possui eficácia comprovada. Os custos do tratamento com a terapia combinada de terlipressina com albumina foram de USD $1,644.06, administração de somente albumina USD $912.02 e norepinefrina mais albumina USD $2,310.78. Considerando as terapias combinadas com efetividade terapêutica comprovada, isto é, terlipressina e norepinefrina associada a albumina, o custo incremental foi de USD $666.73 e efetividade de 0,570 para o grupo da terlipressina associada a albumina e de 0,200 para o grupo da norepinefrina associada a albumina. A efetividade incremental foi de 0,370 e o valor da RCEI foi de USD $1,801.97. Assim, os fatores de incremento do custo por terapia e razão de custo-efetividade incremental definem que a terapia combinada de terlipressina mais albumina é custo efetiva quando comparada a administração de somente albumina ou norepinefrina no cenário do sistema único de saúde. Conclusão: O estudo demonstrou por meio de uma análise de custo-efetividade que a terlipressina associada à albumina quando administrada concomitantemente a pacientes com diagnóstico de SHR tipo 1 é custo-efetiva quando comparada à albumina sozinha e com norepinefrina associada à albumina administrada em um ambiente controlado.

Síndrome hepatorrenal: revisión de la literatura

Contexto: el síndrome hepatorrenal es una disfunción renal que ocurre en pacientes con enfermedad hepática crónica como cirrosis hepática o enfermedad hepática aguda, caracterizada por la activación de mecanismos reguladores que conducen a la disminución de la tasa de filtrado glomerular. Clínicamente, el síndrome hepatorrenal se divide en dos tipos: el tipo 1 se caracteriza por una pérdida rápida y progresiva de la función renal, mientras que el tipo 2 se caracteriza por ser de progresión lenta y de mejor pronóstico. Objetivo: analizar la historia natural de la enfermedad que presentan los pacientes que desarrollan síndrome hepatorrenal. Metodología: se realizó una revisión de la literatura científica de manuscritos publicados sobre síndrome hepatorrenal, para evaluar la historia natural de esta patología. Resultados: no existen hallazgos clínicos específicos, sin embargo, sus manifestaciones clínicas reflejan la enfermedad hepática avanzada subyacente, la insuficiencia renal y las anomalías circulatorias presentes. Conclusiones: la opción terapéutica más adecuada es el trasplante hepático, pero no todos los pacientes pueden recibirlo, mientras se accede a dicho manejo una opción es el tratamiento medicamentoso con vasoconstrictores y albúmina.

Background: Hepatorenal syndrome is a renal dysfunction that occurs in patients with chronic liver disease such as liver cirrhosis or acute liver disease, characterized by the activation of regulatory mechanisms that lead to a decrease in the glomerular filtration rate. Clinically, hepatorenal syndrome is divided into two types, type 1 and type 2. Type 1 is characterized by a rapid and progressive loss of kidney function while type 2 is characterized by slow progression and a better prognosis. Purpose: To analyze the natural history of the disease presented by patients who develop hepatorenal syndrome. Methodology: A review of the scientific literature of published manuscripts on hepatorenal syndrome was carried out to evaluate the natural history of this pathology. Results: There are no specific clinical findings, however, its clinical manifestations reflect the underlying advanced liver disease, kidney failure, and circulatory abnormalities present. Conclusions: The most appropriate therapeutic option is liver transplantation, but not all patients can receive it, while accessing said management an option is drug treatment with vasoconstrictors and albumin.

Síndrome hepatorrenal en falla hepática aguda sobre crónica / Hepatorrenal syndrome in acute on chronic hepatic failure

Resumen La insuficiencia hepática aguda sobre crónica (ACLF, por su nombre en inglés: Acute-on-Chronic Liver Failure) es una entidad de reciente caracterización que se presenta como una descompensación aguda de una hepatopatía crónica, la cual puede ir asociada a falla en diferentes órganos y presentar una alta mortalidad. Su incidencia alcanza hasta un 30% de pacientes que consultan por complicaciones asociadas a cirrosis de base. Dentro de los factores precipitantes más frecuentes se encuentran las infecciones bacterianas, el alcoholismo y la reactivación de hepatitis virales; no obstante, hasta en un 40% de los casos no se identifica ningún factor precipitante. La fisiopatología de esta entidad aún es desconocida en cierta medida, pero se plantea la existencia de una respuesta inflamatoria excesiva en su desarrollo. No existe ningún tratamiento específico y su manejo se basa en el tratamiento para complicaciones asociadas, soporte y finalmente trasplante hepático. La disfunción renal es un hallazgo común en pacientes con enfermedad hepática. Se pensaba que el síndrome hepatorrenal era de carácter meramente funcional. Ahora, ante la evidencia de algún grado de daño tubular relacionado, se ha mejorado la comprensión de la fisiopatología de dicha entidad, lo que ha obligado recientemente a replantear los criterios diagnósticos y la clasificación de la enfermedad. Describimos el caso clínico de una paciente atendida en un centro hospitalario en la ciudad de Pereira, Risaralda. Ella presentó bacteriemia por cocos Gram positivos de origen no claro, lo que se consideró como el factor precipitante; tuvo deterioro clínico, con aparición de síndrome hepatorrenal y falla multiorgánica, lo que finalmente la llevo a la muerte, a pesar del manejo multidisciplinario.

Abstract Acute-on-chronic liver failure (ACLF) is a recently characterized entity that presents as an acute decompensation of chronic liver disease. It can be associated with failure in different organs and presents a high mortality rate. Its incidence reaches up to 30% on patients consulting for complications derived from cirrhosis. Among the most frequent precipitating factors, there are bacterial infections, alcoholism, and reactivation of viral hepatitis; however, in up to 40% of the cases, no precipitating factor is identified. The pathophysiology of this entity is still unknown to a certain extent, but the existence of an excessive inflammatory response in its development is suggested. There is no specific treatment and its management is based on treatment for associated complications, support, and finally liver transplantation. Kidney dysfunction is a common finding in patients with liver disease. The understanding of the pathophysiology of this entity, previously thought to be purely functional in nature, yet now given the evidence of some degree of related tubular damage, has improved and has recently entailed a rethink of the diagnostic criteria and the classification of the illness. We describe the clinical case of a patient treated at a hospital in the city of Pereira, Risaralda, who presented bacteremia due to Gram-positive cocci of unclear origin, considered as the precipitating factor. The patient had clinical deterioration, as well as the onset of hepatorenal syndrome and multi-organ failure, finally leading to death despite multidisciplinary treatment.

Disfunción renal en el paciente cirrótico / Renal dysfunction in the cirrhotic patient

La disfunción renal es una complicación común en pacientes con cirrosis avanzada y está asociadaa un incremento significativo en la mortalidad. Este deterioro de la función renal puede ser reversible en algunos casos, si se identifica y se trata su etiología. La lesión renal aguda (LRA) de origen prerrenal y la necrosis tubular aguda (NTA) son las entidades más frecuentes en pacientes con enfermedad hepática crónica y cirrosis, constituyendo un desafío en los escenarios clínicos actuales. La aparición de nuevos biomarcadores como la lipocalina asociada a la gelatinasa de neutrófilos (NGAL), puede ser un factor determinante para esclarecer el origen de estas dos entidades. En la actualidad, la clasificación de la enfermedad renal establece que un aumento en la creatinina sérica basal >0,3 mg/dL dentro de las primeras 48 horas, o un incremento mayor al 50% desde la línea de base, son suficientes para definir lesión renal aguda, por lo cual, cambios leves en la creatinina sérica en un periodo corto de tiempo, contribuyen a una identificación temprana y previenen desenlaces negativos. Esta revisión de tema abordará la lesión renal aguda en cirrosis desde la fisiopatología, la clasificación actual según guías internacionales, los avances en biomarcadores y las principales etiologías, finalizando con un abordaje general y estrategias de prevención.

Kidney dysfunction is a common complication in patients with advanced cirrhosis and is associated with a significant increase in mortality. This deterioration of kidney function may be reversible in some cases, if its etiology is identified and treated. Acute kidney injury (AKI) of prerenal origin and acute tubular necrosis (ATN) are the most frequent entities in patients with chronic liver disease and cirrhosis, constituting a challenge in current clinical scenarios. The emergence of new biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), may be a determining factor in clarifying the origin of these two entities. Currently, the classification of renal disease establishes that an increase in basal serum creatinine >0,3 mg/dL within the first 48 hours, or an increase higher than 50% from the baseline, are enough to define acute kidney injury, therefore slight changes in serum creatinine in a short period of time contribute to an early identification and prevent negative outcomes. This literature review will address acute kidney injury in cirrhosis from its pathophysiology, current classification according to international guidelines, advances in biomarkers and the main etiologies associated with it, ending with a general approach and prevention strategies.

Características clínicas y complicaciones de la cirrosis hepática en una población de altura (Huancayo, 3250 m s. n. m.) / Clinical features and complications of liver cirrhosis in a high-altitude population (Huancayo, 3,250 m a.s.l.)

RESUMEN Objetivo La cirrosis hepática ocasiona significativa mortalidad y morbilidad. Esta investigación trata de determinar la presentación clínica, la etiología y las complicaciones de los pacientes con cirrosis hepática en una población que habita en una región de altura del Perú. Materiales y métodos Evaluación retrospectiva de la presentación clínica y las complicaciones de la cirrosis hepática. Se estudiaron 108 historias clínicas de pacientes cirróticos ingresados en el Servicio de Medicina del Hospital Nacional Ramiro Prialé Prialé de la ciudad de Huancayo entre el 2010 y el 2012. Resultados El promedio de edad de los pacientes fue de 60,50 años (rango 12-82 años) y el 62,90 % fueron varones. La etiología más frecuente fue la ingesta alcohólica (63,00 %) seguida por las hepatitis B y C crónicas (7,40 % y 2,80 %, respectivamente). El 58,30 % de los casos correspondía al estadio B de la clasificación de Child-Pugh y el 31,30 % se encontraba en estadio C. La manifestación clínica más frecuente fue la distensión abdominal (87,00 %). Las complicaciones más comunes fueron la ascitis (56,00 %), la encefalopatía hepática (47,20 %) y el síndrome hepatorrenal (8,30 %). Conclusiones La cirrosis alcohólica fue la etiología más común y las complicaciones más frecuentes fueron la ascitis y la encefalopatía hepática.

ABSTRACT Objective Liver cirrhosis is responsible for significant morbidity and mortality. This research aims to determine the clinical presentation, etiology and complications of patients with liver cirrhosis from a population living at a high altitude region in Peru. Materials and methods A retrospective study of the clinical presentation and complications of liver cirrhosis was conducted. One hundred eight (108) medical records of patients with liver cirrhosis admitted to the Internal Medicine Service of the Hospital Nacional Ramiro Prialé Prialé, Huancayo, were evaluated between 2010 and 2012. Results Patients' mean age was 60.5 years (range: 12-82 years) and 62.9 % were males. The most common etiology was alcohol consumption (63 %), followed by chronic hepatitis B and C (7.4 % and 2.8 %, respectively). Fifty-eight point three percent (58.3 %) of the patients had a Child-Pugh class B score and 31.30 % of them had a Child-Pugh class C score. The most frequent clinical presentation was abdominal distension (87 %). The most common complications were ascites (56 %), hepatic encephalopathy (47.2 %) and hepatorenal syndrome (8.3 %). Conclusions Alcoholic liver cirrhosis was the most common etiology. The most frequent complications were ascites and hepatic encephalopathy.

Insuficiencia renal aguda en cirrosis hepática / Acute renal failure in hepatic cirrhosis

Resumen La asociación de la insuficiencia renal aguda en pacientes con cirrosis hepática siempre se ha establecido en el contexto del síndrome hepatorrenal, pero hay varias causas además de ésta. La insuficiencia renal aguda es un desafío terapéutico en pacientes con cirrosis hepática. La insuficiencia renal aguda se debe a factores prerrenales, factores intrínsecos del riñón o posrenales. La prevalencia de insuficiencia renal aguda en la cirrosis se ha informado de 14 a 50% en pacientes con cirrosis. Su prevalencia es de aproximadamente 50% en pacientes con cirrosis y ascitis y de 20% en los pacientes con cirrosis en etapa avanzada que están hospitalizados. En 2015, el Club Internacional de Ascitis estableció una nueva definición y estadificación de la insuficiencia renal aguda en pacientes con cirrosis hepática.

Abstract The association of acute renal failure in patients with liver cirrhosis has always been established in the context of hepatorenal syndrome, but there are several etiologies in addition to this cause. Acute renal failure is a therapeutic challenge in patients with liver cirrhosis. Acute renal failure is due to prerenal factors, intrinsic factors of the kidney or post-renal. The prevalence of acute renal failure in cirrhosis has been reported from 14 to 50% in patients with cirrhosis. Its prevalence is approximately 50% in patients with cirrhosis and ascites and 20% in patients with advanced stage cirrhosis who are hospitalized. In 2015, the International Ascitis Club established a new definition and staging of acute renal failure in patients with liver cirrhosis.

Falla hepática aguda sobre crónica / Acute-On-Chronic Liver Failure

La falla hepática aguda sobre crónica (ACLF, del inglés Acuteon Chronic Liver Failure) comprende el deterioro agudo de la función hepática en un paciente que tiene de base una enfermedad hepática crónica de novo o conocida y desencadenada por diferentes factores precipitantes que pueden ser hepáticos o extrahepáticos. Dentro de las manifestaciones clínicas se encuentran: disfunción renal, encefalopatía hepática y falla orgánica multisistémica, que de no ser tratadas oportunamente se traducen en mal pronóstico. Se han utilizado varias puntuaciones para valorar la función hepática y el pronóstico de los pacientes. A pesar de que la falla orgánica multisistémica es una contraindicación para el trasplante hepático, este sigue siendo la mejor opción de tratamiento para estos pacientes

Acute-on-chronic liver failure (ACLF) includes acute deterioration of liver functions in patients with either chronic de novo liver disease or already diagnosed liver disease. ACLF can be triggered by various hepatic or extrahepatic precipitating factors. Among its clinical manifestations are renal dysfunction, hepatic encephalopathy, and multisystem organ failure. If not treated promptly translate the prognosis can be poor. Several scoring systems have been used to assess liver function and patient prognosis. Although multisystem organ failure contraindicates liver transplantation, it remains the treatment of choice for this patients

Síndrome hepatorrenal: fisiopatología, diagnóstico y manejo / Pathophysiology, Diagnosis and Management of Hepatorenal Syndrome

El síndrome hepatorrenal es la forma de disfunción renal que complica a los pacientes con enfermedad hepática avanzada o insuficiencia hepática aguda. En él se presentan alteraciones notables en la circulación renal arterial, lo cual conlleva a una elevación progresiva de los niveles de creatinina y ascitis. En la actualidad su esquema de tratamiento farmacológico es limitado, por lo que la mejor opción terapéutica resulta ser el trasplante hepático.

Hepatorenal syndrome is a form of renal dysfunction develops as a complication in patients with advanced liver disease and in patients with acute liver failure. Significant alterations in renal blood flow lead to progressively increasing levels of creatinine and to ascites. Currently, the best treatment option is liver transplantation because options for treatment with drugs are very limited.

Patogenia, diagnóstico y tratamiento de la disfunción renal en cirrosis / Pathogenesis, Diagnosis and Treatment of Renal Dysfunction in Cirrhosis

Los pacientes con cirrosis hepática son susceptibles a presentar un deterioro de la función renal que puede ser de naturaleza funcional y/o estructural. La insuficiencia renal aguda (IRA) prerrenal representa la forma más frecuente en el 68% de los casos, e incluye un tipo especial de insuficiencia renal funcional conocida como síndrome hepatorrenal (SHR). La creatinina sérica permanece como el mejor biomarcador de IRA en cirrosis a pesar de sus reconocidas limitaciones. La diferenciación entre necrosis tubular aguda (NTA) y SHR se puede establecer con el uso de biomarcadores urinarios como la uNGAL. Los factores de riesgo de IRA en cirrosis incluyen las infecciones bacterianas, la hemorragia digestiva, las pérdidas de líquidos gastrointestinales y renales, la paracentesis sin albúmina y los agentes nefrotóxicos, entre otros. Los nuevos criterios por estadios de la AKI-IAC para el diagnóstico de IRA en cirrosis, que inician por un aumento de la creatinina sérica ≥0,3 mg/dL en menos de 48 horas, mejoran el pronóstico de los pacientes al permitir una intervención más temprana. El diagnóstico del SHR se establece al excluir las causas de azoemia prerrenal, NTA y expandir el volumen con albúmina. El uso de vasoconstrictores esplácnicos, como la terlipresina junto con la albúmina, permite revertir hasta el 40% de los casos de SHR. El trasplante hepático representa el tratamiento definitivo en pacientes con SHR.

Patients with cirrhosis of the liver are susceptible to deterioration of renal function which may be functional or structural. Prerenal acute renal failure which occurs in 68% of these cases is the most common form. It includes a special type of functional renal failure known as hepatorenal syndrome (HRS). Serum creatinine remains the best biomarker for acute renal failure in cirrhosis despite its recognized limitations. Acute tubular necrosis and HRS can be differentiated by using urinary biomarkers such as urinary neutrophil gelatinase-associated lipocalin (uNGAL). Risk factors for acute renal failure in cirrhosis include bacterial infections, gastrointestinal bleeding, loss of gastrointestinal and renal fluids, paracentesis without albumin, and nephrotoxic agents. The new criteria for staging acute kidney injury (AKI) in cirrhosis have improved patient outcomes by enabling earlier interventions by starting when serum creatinine increases above 0.3 mg/dl in less than 48 hours. The diagnosis of HRS is established by excluding causes of pre-renal azotemia, acute tubular necrosis and volume expansion with albumin. The use of splanchnic vasoconstrictors such as terlipressin together with albumin can reverse up to 40% of cases of SHR. Liver transplantation is the definitive treatment for patients with hepatorenal syndrome.

Síndrome hepatorrenal: abordaje clínico y estrategia terapéutica / Hepatorenal Syndrome: clinical approach and therapeutic strate

El síndrome hepatorrenal (SHR) se define como el desarrollo de injuria renalen un paciente cirrótico en ausencia de una causa identificable que la explique. De acuerdo con la velocidad de instalación y la severidad de la fallarenal, se describen 2 tipos (tipo I y tipo II). El SHR tipo I se caracteriza por un rápido y progresivo deterioro de la función renal con un pronóstico ominoso, mientras que en el SHR tipo II el desarrollo de la falla renal es de instalación más insidiosa y de menor gravedad, pero de todas formas con un mal pronóstico a corto plazo. La media de sobrevida global de esta entidad es deaproximadamente 3 meses (2 semanas para el SHR tipo I vs. 4 a 6 meses para el SHR tipo II), aunque la implementación de estrategias terapéuticas tiene un claro impacto en el pronóstico. Dado que no existen pruebas de laboratorio específicas para su diagnóstico, éste se basa en datos clínico-analíticos y en la exclusión de otras causas de injuria renal en este contexto. El tratamiento definitivo de esta entidad es el trasplante hepático, siendo los fármacos vasoconstrictores sistémicos análogos de la vasopresina en combinación con albúmina la terapéutica puente de elección a él

Hepatorenal syndrome (HRS) is defined as the onset of renal failure without an identifiable cause in a cirrhotic patient. According with the installation speed and the severity of the renal failure, two types are described: type I and type II. Type I is characterized by a rapid and progressive deterioration of renal function with an ominous prognosis. Type II, presents with an insidious and less severe development of renal failure, but always bears a poor short-term prognosis. Although the implementation of therapeutic strategies has a clear impact on the prognosis, the median overall survival of these patients is approximately 3 months (2 weeks for type I HRS vs. 4 to 6 months for type II HRS). Since there are no specific tests for the diagnosis, it is based on a combination of clinical and laboratory data as well as the exclusion of other kinds of renal injury. Systemic vasoconstrictors drugs analogues of vasopressin combined with albumin are the treatment of choice before liver transplantation, which constitutes the definitive treatment of this entity.

Enfoque clínico del síndrome hepatorrenal / Clinical approach to hepatorenal syndrome

Introducción: el síndrome hepatorenal es un tipo de insuficiencia renal que ocurre en pacientes con cirrosis hepática. Es el resultado de la vasodilatación arterial esplácnica, la vasoconstricción renal, la reducción del volumen arterial eficaz, y la disminución potencial del gasto cardíaco. Desarrollo: el síndrome hepatorenal es una complicación fatal, y el único tratamiento definitivo actualmente disponible es el trasplante hepático o del hígado-riñón. Se han realizado otras modalidades terapéuticas en el manejo del síndrome hepatorenal, pero la gran mayoría se basan en estudios no controlados y con muestras muy pequeñas. El papel principal de estas opciones de tratamiento es proporcionar un puente al trasplante hepático. El tratamiento también puede proporcionar una regresión del fallo renal agudo y algún alivio sintomático, pero la recaída es la regla. Las mejores opciones terapéuticas parecen ser las que revierten la hipertensión portal, la vasodilatación esplácnica y la vasoconstricción renal. Conclusiones: las terapias artificiales de apoyo han demostrado la posibilidad de mejorar las anormalidades del laboratorio, y el cuadro clínico de estos pacientes, pero su efecto en la evolución al final no ha sido determinado. Las terapias de reemplazo renal, o las nuevas terapias de apoyo artificial del hígado necesitan de una extensa evaluación antes de que puedan recomendarse rutinariamente.

Introduction:hepatorenal syndrome is a type of renal insufficiency that occurs in patients with cirrhosis of liver. It is the result of splanchnic arterial vasodilatation, renal vasoconstriction, reduction of the effective arterial volume, and potential reduction of the cardiac output. Development: hepatorenal syndrome is a fatal complication and the only definitive treatment currently available is the liver or liver-kidney transplant. Some other therapeutic treatment modalities have been conducted in the management of hepatorenal syndrome, but most of them are based on non-controlled studies and small samples. The primary role of these treatment options is to provide a door to liver transplant. Treatment may also lead to a regression to renal insufficiency or may produce some symptomatic relief, but relapse is the most frequent occurrence. The best therapeutic options seem to be those that revert to portal hypertension, splanchnic vasodilatation, and/or renal vasoconstriction. Conclusions: artificial support therapies have demonstrated the possibilities to improve laboratory abnormalities and the clinical picture of these patients, but their effect on clinical outcomes has not been determined. Renal replacement therapies or the new artificial support therapies need further evaluation before they can be routinely recommended.

Ultrasonido Doppler dúplex y color en el estudio de los pacientes con hepatopatías crónicas / Duplex and color Doppler ultrasound in the study of patients presenting with chronic liver diseases

El ultrasonido continúa siendo la primera investigación imaginológica en el estudio de los pacientes con hepatopatías crónicas, pues le permite al médico de asistencia, de manera rápida y eficaz, conocer el estado morfológico de los órganos involucrados y, además, mediante el estudio Doppler, valorar las características del flujo del sistema portal desde el punto de vista cuantitativo (velocidad del flujo) y cualitativo (permeabilidad y dirección del flujo así como la presencia de vasos de circulación colateral). Permite también evaluar todas las estructuras de la cavidad abdominal e investigar patologías asociadas, como es el caso del síndrome hepatorrenal. A favor de esta técnica están además; su bajo costo, fácil manejo, reproductibilidad y ausencia de intervensionismo, todo ello con alta sensibilidad y especificidad, superiores al de otras técnicas complejas de diagnóstico por imagen, como es la tomografía axial computarizada o la resonancia magnética nuclear. Con este trabajo nos proponemos realizar una revisión del tema y mostrar, mediante la literatura consultada y los resultados de nuestra experiencia, el valor del ultrasonido Doppler en el estudio de los pacientes con hepatopatías crónicas

Ultrasound (US) still is the first imaging research in the study of patients presenting with chronic liver diseases allowing to assistance physician to know in a fast and effective way the morphologic state of involved organs and also, be Doppler study, to evaluate the features of portal system flow from the quantitative point of view (flow speed) and the qualitative one (flow permeability and direction as well as the presence of collateral circulation vessels). Also allows to assess the structures of the abdominal cavity and to investigate the associated pathologies such as the hepatorenal syndrome. Favoring this technique are the following: its low cost, easy management, reproducibility and lack of interventions with a high sensitivity and specificity level superior to that of other complex techniques of imaging diagnosis by example, the computerized axial tomography (CAT) or the nuclear magnetic resonance (MNR)

Cirrosis hepática: medidas preventivas de algunas de sus complicaciones / Liver cirrhosis: some complications preventive measures

Cirrosis hepática es una enfermedad prevalente en el mundo. Su diagnóstico y tratamiento debe ser dominio de todo médico general e internista. En los últimos años han ocurrido notables avances en el diagnóstico, fisiopatología, tratamiento y en la identificación de factores pronósticos de cirrosis y de sus complicaciones mayores. Particular atención ha existido en desarrollar medidas preventivas de sus complicaciones como por ejemplo: hemorragia por várices esofágicas, peritonitis bacteriana espontánea, síndrome hepatorrenal. Estas medidas preventivas han influido de forma muy favorable en el pronóstico de los pacientes cirróticos. En este artículo se discuten las diversas estrategias preventivas que han demostrado su efectividad en cirrosis hepática

Liver cirrhosis is a prevalent disease around the world. Its diagnosis and treatment must be in the knowledge of every general physicians and internist.Over the last years, there have been notorious advances in the diagnosis, pathophysiology, treatment and the identification of prognosis factors for cirrhosis major complications.There has been particular attention to the development of preventive measures for its complications, such as variceal bleeding, spontaneous bacterial peritonitis, hepatorenal syndrome. These preventive measures have had a favorable influence on the prognosis of cirrhotic patients. This article discusses several preventive strategies that have proven its effectiveness in hepatic cirrhosis

Poor outcomes with treatment of hepatorenal syndrome type 1 with splancnic vasoconstrictors and albumin: report of seven cases and review of the literature / Resultados adversos com o emprego de vasoconstritores esplâncnicos e albumina para tratamento da síndrome hepatorrenal do tipo 1: relato de sete casos e revisão da literatura

CONTEXT: Treatment of hepatorenal syndrome type 1 (HRS-1) with splancnic vasoconstrictors and high-dose albumin has been associated with reversal of renal failure in approximately 60 percent to 80 percent of the cases in pilot or uncontrolled studies. OBJECTIVE: To evaluate the results of treatment of HRS-1 with terlipressin and high-dose albumin. METHODS: All patients with HRS-1 that underwent treatment with terlipressin and high-dose albumin at our unit were retrospectively reviewed. Outcomes including reversal of renal failure and death were recorded and compared to baseline clinical and laboratory parameters. RESULTS: Seven subjects (median age 64 [47-69] years, 5 males) with median Child-Pugh and MELD scores of 12 [10-15] and 22 [17-38], respectively, hospitalized with decompensated chronic liver disease secondary to tense ascitis and infections, who exhibited criteria for HRS-1, were submitted to therapy with terlipressin and high-dose albumin according to a predefined standard protocol. Baseline creatinine levels were 2.9 [2.3-4.0] mg/mL. None of the patients achieved reversal of HRS-1 and five subjects died on-treatment due to sudden-death (n = 1), multiple organ dysfunction associated with end-stage liver failure (n = 2) and sepsis (n = 2). CONCLUSIONS: Treatment of HRS-1 with terlipressin and high-dose albumin was not associated with reversal of renal failure, but most of the treated subjects had severe end-stage liver disease with high MELD scores as well as high baseline creatinine values, parameters previously associated with bad outcomes.

CONTEXTO: O tratamento da síndrome hepatorrenal do tipo 1 (SHR-1) com vasoconstritores esplâncnicos e albumina intravenosa tem se associado, em relatos de caso e estudos piloto não-controlados, à reversão da insuficiência renal em 60 por cento-80 por cento dos pacientes tratados. OBJETIVO: Avaliar os resultados do tratamento da SHR-1 com terlipressina e albumina. MÉTODOS: Foram avaliados, retrospectivamente, todos os pacientes hospitalizados com o diagnóstico de SHR-1 que se submeteram a tratamento com terlipressina associada à albumina em altas doses. As frequências de reversão de insuficiência renal e óbito foram comparados com parâmetros clínicos e laboratoriais pré-tratamento. RESULTADOS: Sete pacientes (5 homens, idade mediana 64 [47-69] anos) com mediana de pontuação Child-Pugh e MELD respectivamente de 12 [10-15] e 22 [17-38], admitidos na unidade de terapia intensiva por desconforto respiratório secundário à ascite tensa ou por infecções, que apresentaram critérios para SHR-1 e eligibilidade para o transplante de fígado foram submetidos a tratamento com terlipressina e albumina, de acordo com protocolo pré-definido. Níveis de creatinina prévios ao tratamento foram de 2.9 [2.3-4.0] mg/mL. Nenhum paciente apresentou reversão da SHR-1 e cinco faleceram por morte súbita (n = 1), disfunção de múltiplos órgãos associada a falência hepática (n = 2) e sepse (n = 2), a maioria antes de completar o tratamento. CONCLUSÕES: O tratamento da SHR-1 com terlipressina e albumina, em altas doses, não foi associado à reversão da insuficiência renal em nenhum dos pacientes tratados, mas a maioria dos pacientes apresentava doença hepática em fase avançada, com altos valores de MELD, e níveis elevados de creatinina pré-tratamento, parâmetros previamente associados com pior resposta e prognóstico mais reservado.

Insuficiencia renal en pacientes con cirrosis y ascitis: incidencia, etiología y factores predictivos / Renal failure in patients with cirrhosis and ascites: incidence, etiology and predictive factors

BACKGROUND: renal insufficiency (RI) is a frequent complication in patients with cirrhosis and ascites. OBJECTIVE: to assess the incidence, causes, predictive factors and prognosis of RI in cirrhotic patients with ascites. PATIENT AND METHODS: descriptive study of cases and controls. Clinical histories of 162 admissions in 103 patients during 3 years were reviewed. It was considered RI when there was an increase of creatininemia > 1.5 mg/dl. The predictive factors, clinical features, and mortality of the patients with and without RI were compared. RESULTS: a diagnosis of RI was made in 35 cases (21.6%). Hospital mortality rate was 18.5%: with RI 57.1%, controls 7.8% (p<0.01). Etiology: reversible prerrenal failure (54.3%), SHR 1 (14.2%) and 2 (5.7%), septic shock by spontaneous bacterial peritonitis (SBP) (11.4%), NTA (8.5%). The patients with and without RI had a Child-Pügh score average (+/-DS): 12.8 (1.8) and 11.4 (1.9) (p=0.0002) respectively. The patients with RI had higher values of total bilirubin, AST, ALT, white blood cells, time prothrombin, and minors values of serum sodium, Hto, Hb, protein, albumin and cholinesterase that controls (p<0.05). The clinical variables associated with RI included infections (OR 1.4), SBP (OR 4) and hepatic encephalopathy (OR 2.4). In the multivariate analysis, the independent predictive factors for RI were hyponatremia, bilirubinemia greater to 10 mg/dl and SPB. CONCLUSION: in cirrhotic patients RI have high mortality. The most frequent cause was reversible prerrenal failure. The risk of RI was increased significantly in patients with hyponatremia, marked hyperbilirubinemia and SPB.

Background: renal insufficiency (RI) is a frequent complication in patients with cirrhosis and ascites. Objective: to assess the incidence, causes, predictive factors and prognosis of RI in cirrhotic patients with ascites. Patient and methods: descriptive study of cases andcontrols. Clinical histories of 162 admissions in 103 patients during 3 years were reviewed. It was consideredRI when there was an increase of creatininemia > 1,5 mg/dl. The predictive factors, clinical features, andmortality of the patients with and without RI were compared. Results: a diagnosis of RI was made in 35 cases (21.6%). Hospital mortality rate was 18.5%: with RI 57.1%, controls 7.8% (p< 0.01). Etiology: reversible prerrenal failure (54.3%), SHR 1 (14.2%) and 2 (5.7%), septic shock by spontaneous bacterial peritonitis (SBP) (11.4%), NTA (8.5%). The patientswith and without RI had a Child-Pügh score average (± DS): 12.8 (1.8) and 11,4 (1.9) (p=0.0002) respectively.The patients with RI had higher values of total bilirubin, AST, ALT, white blood cells, time prothrombin, and minors values of serum sodium, Hto, Hb, protein,albumin and cholinesterase that controls (p<0.05). The clinical variables associated with RI included infections (OR 1.4), SBP (OR 4) and hepatic encephalopathy (OR 2.4). In the multivariate analysis, the independent predictive factors for RI were hyponatremia, bilirubinemia greater to 10 mg/dl and SPB. Conclusion: in cirrhotic patients RI have high mortality.The most frequent cause was reversible prerrenal failure. The risk of RI was increased significantly in patients with hyponatremia, marked yperbilirubinemiaand SPB.

Hepatorenal syndrome: an update

Hepatorenal syndrome (HRS) is the development of renal failure in patients with chronic previous liver disease, without clinical or laboratory evidence of previous kidney disease. It affects up to 18 percent of cirrhotic patients with ascites during the first year of follow-up, reaching 39 percent in five years and presenting a survival of about two weeks after its establishment. HRS diagnosis is based on clinical and laboratory data. The occurrence of this syndrome is related to the mechanism for ascites development, involving vasoconstriction, low renal perfusion, water and sodium retention, increased plasma volume, and consequent overflow at the splanchnic level. Renal vasoactive mediators like endothelin 1, thromboxane A2, and leukotrienes are also involved in the genesis of this syndrome, which culminates in functional renal insufficiency. The treatment of choice can be pharmacological or surgical, although liver transplantation is the only permanent and effective treatment, with a four-year survival rate of up to 60 percent. Liver function recovery is usually followed by renal failure reversion. Early diagnosis and timely therapeutics can increase life expectancy for these patients while they are waiting for liver transplantation as a definitive treatment.

A síndrome hepatorrenal (SHR) é o desenvolvimento do quadro de insuficiência renal em pacientes com doença hepática crônica prévia sem evidências clínica ou laboratorial de nefropatia prévia. Atinge até 18 por cento dos pacientes cirróticos com ascite em um ano, chegando a 39 por cento em cinco anos, com uma sobrevida média em torno de duas semanas após estabelecido o quadro. O diagnóstico da SHR baseia-se em critérios clínicos e laboratoriais. Seu aparecimento está relacionado ao mecanismo de formação de ascite, que envolve vasoconstrição e hipofluxo renal, retenção de água e sódio, aumento do volume plasmático, e conseqüentemente hiperfluxo no território esplâncnico. Mediadores vasoativos renais e humorais, como a endotelina 1, tromboxano A2 e leucotrienos, estão ainda envolvidos na gênese desta síndrome que culmina com insuficiência renal funcional. O tratamento preconizado da SHR pode ser farmacológico ou cirúrgico, sendo o transplante de fígado o único efetivo e permanente, com sobrevida de até 60 por cento em quatro anos. Após melhora da função hepática, geralmente há a reversão da insuficiência renal. O diagnóstico precoce e a rápida terapêutica podem ampliar a expectativa de vida destes hepatopatas enquanto se aguarda o transplante hepático para seu tratamento definitivo.

Síndrome hepatorrenal: Revisión de la literatura y análisis crítico de los criterios diagnósticos / Hepatorenal Syndrome: Review of the literature and critical analysis of diagnostic criteria

El síndrome hepatorrenal es una falla renal funcional que ocurre en pacientes con enfermedad hepática avanzada e hipertensión portal. Su fisiopatología es hoy en día materia de numerosos estudios. Se propone en esta revisión unos nuevos criterios diagnósticos y se revisa la fisiopatología y numerosas modalidades de tratamiento.

Hepatorenal syndrome a review of literature and critique analysis of diagnostic criteria. The hepatorenal syndrome is a functional renal failure that occurs in patients with severe liver disease and portal hypertension. Its pathophysiology is not clear and theme of several studies. New diagnostic criteria, pathophysiolgy and treatments are reviewed in this article.