Corticoterapia con intención de rescate en pacientes con hepatitis autoinmune severa: ¿el trasplante hepático es evitable?

Resumen: Introducción: La hepatitis autoinmune es una enfermedad cuya presentación clínica inicial puede manifestarse de diversas formas, siendo su presentación aguda con aumento de los niveles de bilirrubina, caída de la función biosintética y necrosis masiva/submasiva o cirrosis en la histología, marcadores de severidad de la misma. La decisión de iniciar tratamiento con corticoides en este escenario resulta un desafío en la práctica clínica. Los objetivos del presente trabajo fueron evaluar el grado de respuesta al tratamiento, los predictores de respuesta, y la supervivencia global y libre de trasplante en pacientes cuyo debut clínico fue de forma aguda y severa. Resultados: Fueron incluidos 33 pacientes con bilirrubina total mayor a 2.5 mg/dl, sin tratamiento previo (naive), que cumplían criterios diagnósticos según el grupo internacional de hepatitis autoinmune. El 97% eran mujeres con una mediana de edad de 52 años, el 58% se encontraba en etapa de cirrosis con un MELD promedio de 24, y el 15% presentaba una necrosis masiva/submasiva en la muestra de biopsia hepática. En 27 casos se inició corticoterapia. El 66.7 % evolucionó con remisión completa, 14.8 % con remisión parcial, y en 18.5% hubo falla al tratamiento corticoideo. La colesterolemia basal y la presencia de encefalopatía hepática fueron predictores de no respuesta al tratamiento corticoideo, mientras que el MELD pre-tratamiento y la colesterolemia basal fueron las variables estadísticamente significativas asociadas a falla en el rescate del trasplante hepático. En los pacientes tratados con corticoides, la supervivencia global y libre de trasplante a 5 años en función del MELD (<25 vs ≥ 25) fue del 90% vs 60% respectivamente. Conclusión: Las altas tasas supervivencia logradas bajo tratamiento médico que fueron evidenciadas en esta serie reafirman la necesidad de priorizar el uso de corticoides en pacientes con hepatitis autoinmune aguda y severa.

Abstract: Introduction: Autoimmune hepatitis can initially manifest itself in various clinical ways. Its acute presentation with increased levels of bilirubin, fall of biosynthetic function and massive/submassive necrosis or cirrhosis in histology, is a marker of severity of it. The decision to start corticosteroid treatment in this scenario is a challenge in clinical practice. The objectives of this work were to assess the degree of response to treatment, response predictors, and overall and transplant-free survival in patients whose clinical debut was acute and severe. Results: 33 patients with total bilirubin greater than 2.5 mg/dL, without prior (naive) treatment, who met diagnostic criteria according to the international autoimmune hepatitis group, were included. 97% were women with a median age of 52, 58% were in the cirrhosis stage with an average MELD of 24, and 15% had massive/submassive necrosis in the liver biopsy sample. In 27 cases treatment with cortiocosteroids was initiated, 66.7% evolved with complete remission, 14.8% with partial remission, and in 18.5% there was failure of corticosteroid treatment. Basal cholesterol and the presence of hepatic encephalopathy were predictors of non-response to corticosteroid treatment, while pre-treatment MELD and basal cholesterol were the statistically significant variables associated with liver transplant rescue failure. In patients treated with corticosteroids, overall and transplant-free survival at 5 years based on MELD (<25 vs ≥ 25) was 90% vs 60% respectively. Conclusion: The high survival rates achieved under medical treatment that were demonstrated in this series reaffirm the need to prioritize the use of corticosteroids in patients with acute and severe autoimmune hepatitis.

Resumo: Introdução: A hepatite autoimune é uma doença cuja apresentação clínica inicial pode se manifestar de várias formas, sendo sua apresentação aguda com níveis elevados de bilirrubina, descida na função biossintética e necrose maciça/submassiva ou cirrose em histologia, marcadores de gravidade dela. A decisão de iniciar o tratamento corticosteroide nesse cenário é um desafio na prática clínica. Os objetivos deste trabalho foram avaliar o grau de resposta ao tratamento, preditores de resposta e sobrevida geral e livre de transplantes em pacientes cuja estréia clínica foi aguda e grave. Resultados: Foram incluídos 33 pacientes com bilirrubina total superior a 2,5 mg/dL, sem tratamento prévio (ingênuo), que atendiam aos critérios diagnósticos segundo o grupo internacional de hepatite autoimune. 97% eram mulheres com idade mediana de 52 anos, 58% estavam em estágio de cirrose com um MELD médio de 24, e 15% tinham necrose maciça/submassiva na amostra de biópsia hepática. Em 27 casos foi iniciado o tratamento médico e, em 6 casos, o transplante de fígado foi alcançado sem terapia prévia. 66,7% evoluíram com remissão completa, 14,8% com remissão parcial e, em 18,5%, houve falha no tratamento corticosteroide. O colesterol basal e a presença de encefalopatia hepática foram preditores de não resposta ao tratamento corticosteroide, enquanto o meld pré-tratamento e o colesterol basal foram as variáveis estatisticamente significativas associadas à falha de resgate do transplante de fígado. Em pacientes tratados com corticosteroides, a sobrevida geral e livre de transplante aos 5 anos com base no MELD (<25 vs ≥ 25) foi de 90% vs 60%, respectivamente. Conclusão: As altas taxas de sobrevivência alcançadas sob tratamento médico demonstrado nesta série reafirmam a necessidade de priorizar o uso de corticosteroides em pacientes com hepatite autoimune aguda e grave.

[Hepatocellular carcinoma within Milan criteria and beyond: outcomes of liver transplantation in a single Argentinian institution]. / Hepatocarcinoma dentro y fuera de los criterios de Milán: resultados de un centro de trasplante hepático en la Argentina.

Hepatocellular carcinoma (HCC) recurrence following liver transplantation is associated to bad prognosis. We retrospectively analyzed the data of 95 patients who underwent liver transplantation for HCC. Recurrence rate and variables associated with recurrence were reviewed. According to the findings on the explanted livers they were divided in two groups: Milan (M) 67% and non-Milan (NM) 33%. Global recurrence rate, and M-group and NM-group recurrence rates were 19%; 12% and 32%, respectively (P = 0.001). Although in the univariate analysis we found some factors associated to recurrence (hemocromathosis, year of transplant, bilobar distribution, vascular invasion and previous chemoembolization), they were not independent predictors of recurrence in the multivariate analysis. Actuarial survival in cirrhotic patients with and without HCC at 1, 3 and 5 years was 86% and 91% (NS), 77% and 88% (NS), and 67% and 86% (P = 0.002), respectively; whereas actuarial survival of the M and NM groups was 86% and 71%; 82% and 61%, and 78% and 58%, respectively (P = 0.02). We had a satisfactory five-year global survival in our series even though one third of our patients grafted for HCC were outside Milan criteria.

[Hepatitis E: an infrequent virus or an unfrecuently investigated agent?]. / Hepatitis E: un virus infrecuente o un agente infrecuentemente pensado?

Two cases of hepatitis E that were assisted in our Unit of Hepatology and Liver Transplantation are described in this article. The first patient had prior hepatic involvement and therefore a more severe course, whereas the second case, with normal liver function, only developed a self-limited acute hepatitis.

Hepatitis E: un virus infrecuente o un agente infrecuentemente pensado? / [Hepatitis E: an infrequent virus or an unfrecuently investigated agent?].

Two cases of hepatitis E that were assisted in our Unit of Hepatology and Liver Transplantation are described in this article. The first patient had prior hepatic involvement and therefore a more severe course, whereas the second case, with normal liver function, only developed a self-limited acute hepatitis.

Hepatocarcinoma dentro y fuera de los criterios de Milán: resultados de un centro de trasplante hepático en la Argentina / [Hepatocellular carcinoma within Milan criteria and beyond: outcomes of liver transplantation in a single Argentinian institution].

Hepatocellular carcinoma (HCC) recurrence following liver transplantation is associated to bad prognosis. We retrospectively analyzed the data of 95 patients who underwent liver transplantation for HCC. Recurrence rate and variables associated with recurrence were reviewed. According to the findings on the explanted livers they were divided in two groups: Milan (M) 67

. Global recurrence rate, and M-group and NM-group recurrence rates were 19

, respectively (P = 0.001). Although in the univariate analysis we found some factors associated to recurrence (hemocromathosis, year of transplant, bilobar distribution, vascular invasion and previous chemoembolization), they were not independent predictors of recurrence in the multivariate analysis. Actuarial survival in cirrhotic patients with and without HCC at 1, 3 and 5 years was 86

(NS), and 67

(P = 0.002), respectively; whereas actuarial survival of the M and NM groups was 86

, and 78

, respectively (P = 0.02). We had a satisfactory five-year global survival in our series even though one third of our patients grafted for HCC were outside Milan criteria.

Hepatocarcinoma dentro y fuera de los criterios de Milán: resultados de un centro de trasplante hepático en la Argentina. / [Hepatocellular carcinoma within Milan criteria and beyond: outcomes of liver transplantation in a single Argentinian institution].

Hepatocellular carcinoma (HCC) recurrence following liver transplantation is associated to bad prognosis. We retrospectively analyzed the data of 95 patients who underwent liver transplantation for HCC. Recurrence rate and variables associated with recurrence were reviewed. According to the findings on the explanted livers they were divided in two groups: Milan (M) 67

and non-Milan (NM) 33

. Global recurrence rate, and M-group and NM-group recurrence rates were 19

; 12

and 32

, respectively (P = 0.001). Although in the univariate analysis we found some factors associated to recurrence (hemocromathosis, year of transplant, bilobar distribution, vascular invasion and previous chemoembolization), they were not independent predictors of recurrence in the multivariate analysis. Actuarial survival in cirrhotic patients with and without HCC at 1, 3 and 5 years was 86

and 91

(NS), 77

and 88

(NS), and 67

and 86

(P = 0.002), respectively; whereas actuarial survival of the M and NM groups was 86

and 71

; 82

and 61

, and 78

and 58

, respectively (P = 0.02). We had a satisfactory five-year global survival in our series even though one third of our patients grafted for HCC were outside Milan criteria.

Hepatitis E: un virus infrecuente o un agente infrecuentemente pensado? / [Hepatitis E: an infrequent virus or an unfrecuently investigated agent?].

Two cases of hepatitis E that were assisted in our Unit of Hepatology and Liver Transplantation are described in this article. The first patient had prior hepatic involvement and therefore a more severe course, whereas the second case, with normal liver function, only developed a self-limited acute hepatitis.

How common is delayed cyclosporine absorption following liver transplantation?

The mean time to peak absorption of cyclosporine (CsA) in liver transplant patients is approximately 2 hours, but in some patients the peak occurs later. The goal of this study was, therefore, to investigate the incidence of delayed absorption in 27 de novo liver transplant recipients receiving CsA > or =10 mg/kg/day (C(2) monitoring) and in 15 maintenance patients. Patients were categorized as 'normal' absorbers (C(2) exceeding C(4) and C(6)) or 'delayed' absorbers (C(4) or C(6) exceeding C(2)), and as 'good' (>800 ng/mL at C(0), C(2), C(4), or C(6)) or 'poor' absorbers (C(0), C(2), C(4) and C(6) <800 ng/mL) on the day of study. Among de novo patients, 15 (56%) had 'normal' CsA absorption and 12 (44%) 'delayed' absorption. Good CsA absorption occurred in 16 patients (59%) and poor absorption in 11 (41%). The proportion of poor absorbers was similar in patients with normal (6/15, 40%) or delayed (5/12, 42%) absorption. Among the 12 delayed absorbers, 11 had peak CsA concentration at C(4). Mean C(0) level was significantly higher in delayed absorbers (282 +/- 96 ng/mL) than in normal absorbers (185 +/- 88 ng/mL; P = .01). Delayed absorbers reverted to normal absorption (C(2) > C(4)) after a median of 6 days from the day of study, and no cases of delayed absorption were found among maintenance patients. In conclusion, almost 50% of the patients had delayed CsA absorption early posttransplant; around half of these exhibited normal CsA exposure. Measurement of C(4) in addition to C(2) differentiates effectively between delayed and poor absorbers of CsA such that over- or underimmunosuppression can be avoided.