Hepatitis autoinmune refractaria: ¿cómo escoger el tratamiento de segunda línea o de rescate? / Refractory autoimmune hepatitis: how to choose second-line or rescue therapy?

Autoimmune hepatitis (AIH) is a liver disease of unknown etiology, with a breakdown in peripheral selftolerance against hepatocytes with both genetic and environmental factors involved. It is characterized by an immune mediated liver injury, with detectable autoantibodies, elevated levels of immunoglobulin G and histological criteria including, necroinflammation, lymphoplasmacytic infiltrates and hepatitis interface. It can be asymptomatic or can present as acute hepatitis or liver cirrhosis. Most patients (70-80%) respond to first line therapy (based on steroids ± azathioprine). In those patients not tolerating azatioprine, in steroid resistant, and those with repeated relapses (20-40%), a long-term second line therapy must be considered to avoid progression of liver disease. This last medications include other immunosuppressants like mycophenolate mophetil, calcineurin inhibitors (cyclosporine or tacrolimus), biologic agents (infliximab and rituximab), and other immunosuppressive agents (sirolimus, everolimus), all with good overall clinical results, but not exempt of side effects. Other difficult scenarios include fulminant AIH, end-stage AIH cirrhosis and the management of post-transplant AIH. In this article we will review the literature related to second- line therapy especially of steroid resistant AIH. Future directions in the treatment of HAI should be guided to the individual patient (personalized) and may include cell therapies, such as infusion of autologous, antigen-specific, and liver-homing regulatory T cells to restore hepatic immune tolerance

La hepatitis autoinmune (HAI) es una hepatopatía de etiología desconocida, con pérdida de la tolerancia inmune contra los hepatocitos con factores genéticos y ambientales asociados. Se caracteriza por fenómenos de daño inmunológicos, con autoanticuerpos circulantes, una concentración elevada de gammaglobulina sérica y en la biopsia de hígado actividad necroinflamatoria, infiltrados linfoplasmocitarios y daño de interfase. La HAI es una entidad que se puede presentar en forma asintomática, como hepatitis aguda o como cirrosis hepática. El 70-80% de los pacientes responden adecuadamente al tratamiento inmunosupresor de primera línea (corticoides ± azatioprina). En los pacientes que no toleran azatioprina, en los corticorresistentes o en aquellos con recaídas repetidas a pesar de terapia (20-40%), es necesario recurrir a terapias de segunda línea de largo plazo, para evitar la progresión de la hepatopatía. Estas últimas incluyen micofenolato mofetil, inhibidores calcineurínicos (ciclosporina o tacrolimus), agentes biológicos (infliximab y rituximab), y otros fármacos inmunosupresores (sirolimus, everolimus), con resultados alentadores, pero no exentos de efectos colaterales. Otros escenarios complejos incluyen: la HAI de presentación aguda grave y fulminante, la cirrosis terminal autoinmune y la HAI post-trasplante. En este trabajo se revisa la literatura en relación a terapias de segunda línea especialmente en HAI corticoide resistente. El futuro del tratamiento de la HAI va encaminado a una terapia personalizada y que podría incluir terapias celulares como la infusión de células T regulatorias, antígeno específicas y autólogas, para reestablecer los mecanismos de tolerancia inmune hepática.

Manejo de la hepatitis B aguda grave y fulminante / Management of acute fulminant hepatitis B

Fulminant hepatitis B virus infection occurs in less than 1percent of acutely infected patients. Acute hepatitis Baccounts for 2-42 percent of the total of fulminant hepatitis cases depending on the geographic area. This infection is associated with 65-93 percent of mortality, without liver transplantation. Its pathogenesis is related to a severe immune response to infected hepatocytes, causing massive cytolysis and liver failure. During the last 3 decades its prognosis has improved due to better medical support in intensive care units, the use of liver transplantation and an improvement in the prevention and management of its complications. More recently the use of liver support devices (MARS, Prometheus, and BAL) has been considered in this situation as a bridge to liver transplantation. Recurrent hepatitis B virus reinfection of the graft was a major issue in the past, but currently with the use of hepatitis B immunoglobulin (HBIg) and oral antiviral therapy, the prognosis has improved, leading to excellent graft and patient outcomes after liver transplantation. There is controversial data on the use of oral antiviral therapy among fulminant hepatitis patients. While some authors have shown beneficial effects, other communications have failed to demonstrate any benefits. Nevertheless, many experts currently recommend the use of oral antiviral therapy in this setting due to their relative safety and potential benefits. This paper reviews the current view on management issues in reference to the patient with fulminant hepatic failure due to acute hepatitis B.

La hepatitis fulminante por virus de hepatitis B ocurre en menos del 1 por ciento de los casos de hepatitis B aguda. Del total de hepatitis fulminantes, entre el 2-42 por ciento son causadas por hepatitis B aguda, dependiendo del lugar geográfico donde se estudia. Se asocia a elevada mortalidad, entre 65-93 por ciento, sin el uso de trasplante hepático. Su patogenia se relaciona a una significativa respuesta inmune a hepatocitos infectados, determinando citolisis masiva y falla hepática. En las últimas 3 décadas el pronóstico de esta patología ha mejorado gracias al soporte médico en unidades de tratamiento intensivo, a la implementación del trasplante hepático, y a la mejoría en la prevención y manejo de sus complicaciones. Más recientemente se ha usado dispositivos de soporte hepático (MARS, Prometheus, BAL), como un puente al trasplante hepático. La reinfección del injerto con hepatitis B era una consideración importante en el pasado, pero con el uso de gamaglobulina específica para hepatitis B y el tratamiento antiviral oral, su pronóstico ha mejorado, determinando un excelente pronóstico del injerto y del paciente a largo plazo post trasplante hepático. Existen datos controversiales referentes al uso de antivirales orales durante una hepatitis fulminante, pues algunos autores muestran beneficios en esta condición, pero otros no han demostrado un beneficio real. Sin embargo, muchos expertos actualmente recomiendan su uso en este escenario, pues son seguros y pueden tener un potencial beneficio. Este artículo revisa el manejo actual del paciente con hepatitis fulminante por hepatitis B aguda.

Actualización en manejo de la Hepatitis B / Update on hepatitis B management

La infección por virus de la Hepatitis B (VHB) constituye un grave problema de salud. Aproximadamente un cuarto de la población mundial presenta evidencia serológica de infección pasada o presente por VHB y 350 millones de personas presentan la infección en forma crónica. La infección por VHB se asocia con 500.000 muertes al año causadas por hepatitis, cirrosis y carcinoma hepatocelular. Chile es considerado un país con baja prevalencia de infección por VHB (menor que 1 por ciento) en que la mayoría de los casos se adquieren en la adultez, contrariamente a lo que ocurre en países de Asia y África, donde la infección crónica por VHB es muy común (5-18 por ciento) y donde esta enfermedad es adquirida generalmente en el período perinatal o durante la infancia. La historia natural de la infección crónica por VHB es variable y fluctúa desde estado de portadores inactivos de HBs Ag a una hepatitis crónica menos progresiva, que potencialmente puede evolucionar a cirrosis y hepatocarcinoma. Programas efectivos de vacunación contra la infección por VHB disminuirán la incidencia de nuevas infecciones por VHB y la carga de enfermedad en las próximas décadas. Los pacientes con infección crónica por VHB deben ser correctamente evaluados para decidir si requerirán o no terapia antiviral. Pacientes adultos con infección crónica por VHB con una carga viral de, mayor 104 copias/ml (mayor que 2.000 UI/mL), con niveles anormales de alanina aminotransferasa (ALT) y evidencia de actividad necroinflamatoria en la biopsia hepática son candidatos para tratamiento antiviral. Actualmente se encuentran disponibles siete drogas para el tratamiento de la hepatitis B crónica: interferón-α convencional, lamivudina, adefovir dipivoxil, interferón pegilado α 2a y 2b, entecavir, telbivudina y tenofovir. Los análogos de nucleósidos/nucleótidos orales actualmente disponibles son muy potentes y pueden producir altas tasas de respuesta virológica, con una alta barrera genética a...

Hepatitis B virus (HBV) infection constitutes a serious health problem, with approximately one-fourth of the world population having serological evidence of past or present infection by HBV and 350 million people being chronically infected. HBV infection is associated to 500,000 deaths per year caused by hepatitis, cirrhosis, and hepatocellular carcinoma. Chile is considered a country with a low prevalence of HVB infection (less than 1 percent) where most cases are acquired in adulthood, as opposed to countries in Asia and Africa, where chronic HBV infection is very common (5-18 percent) and where this disease is usually acquired perinatally or during childhood. The natural history of HBV chronic infection is variable, ranging from an inactive HBsAg carrier state to a more or less progressive chronic hepatitis, potentially evolving to cirrhosis and hepatocarcinoma. Effective vaccination programs against HBV infection will decrease the incidence of new HVB infections and the burden of disease in the next few decades. Patients with chronic HVB infection need to be correctly evaluated to decide whether or not they will require antiviral therapy. Adult patients with chronic HVB infection with a viral load of more than 104 copies/ml (more than 2,000 IU/mL), with abnormal ALT levels and evidence of necroinfl ammatory activity on liver biopsy are candidates for antiviral treatment. Seven drugs are currently available for the treatment of chronic hepatitis B (CHB): conventional interferon-α, lamivudine, adefovir dipivoxil, pegylated interferon α-2a and 2b, entecavir, telbivudine and tenofovir. Currently available oral nucleotide analogues are very potent and can induce high rates of virological response, with a high genetic barrier to resistance in the majority of patients (entecavir and tenofovir).

Trasplante hepático en adultos: casuística de Clínica Alemana de Santiago / Adult liver transplantation: a single center experience from Chile

Background: The success of orthotopic liver transplantation (OLT) has resulted in its widespread use for different liver diseases. Aim: To report our 8 years experience with adult OLT at Clinica Alemana de Santiago. Patients and methods: In all transplantations done at the center, we recorded patient's overall data and survival, postoperative medical and surgical complications and causes of death. Results: Between November 1993 and September 2001, 51 consecutive OLT were performed in 44 patients (22 females, median age 45 years old). Thirty eight patients presented with chronic and 6 with acute or sub-acute liver failure. Cryptogenic cirrhosis and hepatitis C infection were the most common causes for OLT. Postoperative bleeding and extra-hepatic biliary complications were seen in 17.6 and 21.5 percent of cases respectively. Acute rejection, bacterial infections, CMV infection or disease and post OLT hemodialysis were the most common medical complications (51, 31, 19.6 and 19.6 percent of cases respectively). The overall 1 and 5 years survival rates were 80 percent and 73 percent respectively. Considering exclusively the last 22 OLT performed since January 1999, the 1 year survival rate has improved to 91 percent. Conclusions: Liver transplantation in Chile provides a good long term survival with acceptable morbidity, due to a multidisciplinary approach management. The survival rates have improved over the last few years probably due to better surgical techniques, ICU care and immunosuppression. These overall results are comparable with those from other Centers in developed countries

Diverticulosis yeyunal una causa infrecuente de hemorragia digestiva: caso clínico / Jejunal diverticulosis as cause of gastrointestinal hemorrhages: case report

Jejunal diverticulosis is a very uncommon acquired disease. Clinical manifestations include acute life threatening complication such as perforation, obstruction and bleeding. Jejunal diverticulosis is an extremely rare site of origin of gastrointestinal bleeding, with fewer than seventy cases reported in the literature. We report a 77-year -old patient with a recurrent severe gastrointestinal bleeding manifested by melena and hematochaezia. During the hospitalization the tagged red blood cell scanning was positive for bleeding in the jejunum. At laparotomy, several large-mouthed diverticula at the proximal jejunum were identified. Approximately 30 centimeters of the involved segment was resected with primary end-to-end anastomosis. Postoperative 7 month evolution has been favorable, without any evidence of rebleeding. This report reviews the literature concerning this disease, discusses some diagnostic methods of studying small bowel bleeding and highlights the need to consider this diagnosis in old patients with a gastrointestinal hemorrhage of unknown origin