Effects of Albumin on Survival after a Hepatic Encephalopathy Episode: Randomized Double-Blind Trial and Meta-Analysis

No therapies have been proven to increase survival after a hepatic encephalopathy (HE) episode. We hypothesize that two doses of albumin could improve 90-day survival rates after a HE episode. Methods: (1) A randomized double-blind, placebo-controlled trial (BETA) was conducted in 12 hospitals. The effect of albumin (1.5 g/kg at baseline and 1 g/kg on day 3) on 90-day survival rates after a HE episode grade II or higher was evaluated. (2) A meta-analysis of individual patient's data for survival including two clinical trials (BETA and ALFAE) was performed. Results: In total, 82 patients were included. Albumin failed to increase the 90-day transplant-free survival (91.9% vs. 80.5%, p = 0.3). A competing risk analysis was performed, observing a 90-day cumulative incidence of death of 9% in the albumin group vs. 20% in the placebo (p = 0.1). The meta-analysis showed a benefit in the albumin group, with a lower rate of clinical events (death or liver transplant) than patients in the placebo (HR, 0.44; 95% CI, 0.21-0.82), when analyzed by a competing risk analysis (90-days mortality rate of 11% in the albumin group vs. 30% in the placebo, p = 0.02). Conclusions: Repeated doses of albumin might be beneficial for patient's survival as an add-on therapy after an HE episode, but an adequately powered trial is needed

Enfermedades vasculares del hígado. Guías Clínicas de la Sociedad Catalana de Digestología y de la Asociación Española para el Estudio del Hígado

Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide.Las enfermedades vasculares hepáticas, a pesar de su relativamente baja prevalencia, representan un problema de salud importante en el campo de las enfermedades hepáticas. Una característica común a muchas de estas enfermedades es que pueden causar hipertensión portal, con la elevada morbimortalidad que ello conlleva. Con frecuencia estas enfermedades se diagnostican en pacientes jóvenes y el retraso en su diagnóstico y/o un tratamiento inadecuado pueden reducir de forma importante la esperanza de vida. El presente artículo revisa la evidencia actual en el síndrome de Budd-Chiari, la trombosis venosa portal en pacientes no cirróticos, la hipertensión portal idiopática, el síndrome de obstrucción sinusoidal, las malformaciones vasculares hepáticas en la telangiectasia hemorrágica hereditaria, la trombosis portal en la cirrosis, otras patologías vasculares menos frecuentes como las fístulas arterioportales, así como un apartado sobre el diagnóstico por imagen de las enfermedades vasculares hepáticas y su tratamiento desde el punto de vista hematológico (estudio de la diátesis trombótica y tratamiento anticoagulante). Las recomendaciones se han realizado de acuerdo a los estudios publicados extraídos de Pubmed. La calidad de la evidencia y la intensidad de las recomendaciones fueron graduadas de acuerdo al sistema Grading of Recommendations Assessment Development and Evaluation (GRADE). Cuando no existían evidencias suficientes, las recomendaciones se basaron en la opinión del comité que redactó la guía

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% to 80% 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.<br>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%-80% 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