Hepatitis autoinmune en pediatría, una revisión del Grupo de Trabajo de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (LASPGHAN) / Autoimmune hepatitis in pediatrics, a review by the Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology, and Nutrition

La hepatitis autoinmunitaria es una enfermedad inflamatoria crónica del hígado caracterizada por una interacción compleja entre factores genéticos, respuesta inmunitaria a antígenos presentes en los hepatocitos y alteraciones de la regulación inmunitaria. Presenta una distribución global, con predominio en individuos de sexo femenino. Se clasifica en dos grupos, según el tipo de autoanticuerpos séricos detectados. La forma de presentación más frecuente es la hepatitis aguda (40 %), con síntomas inespecíficos, elevación de aminotransferasas e hipergammaglobulinemia. El tratamiento estándar consiste en la administración de fármacos inmunosupresores. Es una patología compleja, a veces difícil de diagnosticar. Si no se trata de manera adecuada, la mortalidad puede alcanzar el 75 % a los 5 años de evolución.

Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by a complex interaction among genetic factors, immune response to antigens present in hepatocytes, and immune regulation alterations. Its distribution is global and there is a female predominance. AIH is divided into 2 groups, depending on the type of serum autoantibodies detected. The most common presentation is acute hepatitis (40%), with nonspecific symptoms, high aminotransferase levels, and hypergammaglobulinemia. Standard treatment consists of the administration of immunosuppressive drugs. It is a complex condition, often difficult to diagnose. If not managed adequately, the 5-year mortality rate may reach 75%.

Autoimmune hepatitis in pediatrics, a review by the Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. / Hepatitis autoinmune en pediatría, una revisión del Grupo de Trabajo de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (LASPGHAN).

Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by a complex interaction among genetic factors, immune response to antigens present in hepatocytes, and immune regulation alterations. Its distribution is global and there is a female predominance. AIH is divided into 2 groups, depending on the type of serum autoantibodies detected. The most common presentation is acute hepatitis (40%), with non-specific symptoms, high aminotransferase levels, and hypergammaglobulinemia. Standard treatment consists of the administration of immunosuppressive drugs. It is a complex condition, often difficult to diagnose. If not managed adequately, the 5-year mortality rate may reach 75%.

La hepatitis autoinmunitaria es una enfermedad inflamatoria crónica del hígado caracterizada por una interacción compleja entre factores genéticos, respuesta inmunitaria a antígenos presentes en los hepatocitos y alteraciones de la regulación inmunitaria. Presenta una distribución global, con predominio en individuos de sexo femenino. Se clasifica en dos grupos, según el tipo de autoanticuerpos séricos detectados. La forma de presentación más frecuente es la hepatitis aguda (40 %), con síntomas inespecíficos, elevación de aminotransferasas e hipergammaglobulinemia. El tratamiento estándar consiste en la administración de fármacos inmunosupresores. Es una patología compleja, a veces difícil de diagnosticar. Si no se trata de manera adecuada, la mortalidad puede alcanzar el 75 % a los 5 años de evolución.

Hepatitis C: ¿un virus que podríamos erradicar? / Hepatitis C: Could we eradicate this virus?

La infección crónica con el virus C de la hepatitis constituye un problema de salud a nivel mundial, tanto en niños como en adultos. Su eliminación espontánea puede ocurrir durante la infancia temprana, y luego es infrecuente. Aunque la mayoría de los casos son asintomáticos en la infancia y adolescencia, al llegar a la edad adulta, los pacientes pueden evolucionar a la cirrosis y presentar complicaciones, que incluyen el carcinoma hepatocelular. Un tratamiento eficaz debe tener como meta la eliminación del virus, lo que significaría la curación de la enfermedad. Recientemente, el advenimiento de varios agentes antivirales de acción directa ha posibilitado una alta resolución de la infección, del 97-100 % de los casos. Para lograr este objetivo costo-efectivo, es fundamental la concientización de los pediatras en la detección de los pacientes infectados y su derivación al especialista hepatólogo pediatra para la implementación del tratamiento adecuado.

Chronic hepatitis C virus infection is a health problem worldwide, both in children and adults. Its spontaneous resolution may occur during early childhood, and then it becomes uncommon. Although most cases are asymptomatic during childhood and adolescence, as adults, patients may progress to cirrhosis and develop complications, including hepatocellular carcinoma. The goal of an effective treatment should be virus elimination, i.e., disease cure. Recently, the emergence of several direct-acting antivirals has enabled a high rate of infection resolution in 97-100 % of cases. To achieve this cost-effective objective, it is critical to raise awareness among pediatricians so that they can detect infected patients and refer them to a pediatric liver specialist for an adequate management.

Hepatitis C: Could we eradicate this virus? / Hepatitis C: ¿un virus que podríamos erradicar?

Chronic hepatitis C virus infection is a health problem worldwide, both in children and adults. Its spontaneous resolution may occur during early childhood, and then it becomes uncommon. Although most cases are asymptomatic during childhood and adolescence, as adults, patients may progress to cirrhosis and develop complications, including hepatocellular carcinoma. The goal of an effective treatment should be virus elimination, i.e., disease cure. Recently, the emergence of several direct-acting antivirals has enabled a high rate of infection resolution in 97-100 % of cases. To achieve this cost-effective objective, it is critical to raise awareness among pediatricians so that they can detect infected patients and refer them to a pediatric liver specialist for an adequate management.

La infección crónica con el virus C de la hepatitis constituye un problema de salud a nivel mundial, tanto en niños como en adultos. Su eliminación espontánea puede ocurrir durante la infancia temprana, y luego es infrecuente. Aunque la mayoría de los casos son asintomáticos en la infancia y adolescencia, al llegar a la edad adulta, los pacientes pueden evolucionar a la cirrosis y presentar complicaciones, que incluyen el carcinoma hepatocelular. Un tratamiento eficaz debe tener como meta la eliminación del virus, lo que significaría la curación de la enfermedad. Recientemente, el advenimiento de varios agentes antivirales de acción directa ha posibilitado una alta resolución de la infección, del 97-100 % de los casos. Para lograr este objetivo costo-efectivo, es fundamental la concientización de los pediatras en la detección de los pacientes infectados y su derivación al especialista hepatólogo pediatra para la implementación del tratamiento adecuado.

Hepatitis B crónica en pediatría: tratar o no tratar, esa es la pregunta / Chronic hepatitis B in pediatrics: To treat or not to treat, that is the question

La infección crónica con el virus B de la hepatitis es una de las enfermedades de mayor prevalencia mundial. Puede evolucionar a la cirrosis y carcinoma hepatocelular. La detección temprana, evitar la utilización de drogas intravenosas, la educación sexual y la vacunación son fundamentales para la prevención. La infección neonatal y durante el primer año de vida evoluciona hacia la cronicidad en más del 90 % de los niños. La transmisión vertical, de una madre con virus B de la hepatitis al recién nacido, es, actualmente, la forma más frecuente de infección. Su detección y la administración de inmunoglobulinas y vacuna disminuyen esta vía de infección. El tratamiento antiviral puede acelerar en dos o tres años el pasaje de la fase activa a la inactiva de la infección, sin influir en el proceso hacia la recuperación. El tratamiento oportuno de algunos casos elegidos puede evitar la progresión de la enfermedad

Chronic hepatitis B virus infection is one of the most prevalent diseases worldwide. It may progress to cirrhosis and hepatocellular carcinoma. An early detection, not using intravenous drugs, sex education, and immunization are critical for prevention. An infection in the neonatal period and in the first year of life becomes chronic in more than 90 % of children. Vertical transmission from a mother with hepatitis B virus to the newborn infant is currently the most common mode of transmission. Detection, immunoglobulin administration, and immunization help to reduce it. Antiviral therapy may accelerate the transition from the active to the inactive phase of infection by two or three years, without affecting the recovery process. A timely treatment of some selected cases may prevent hepatitis B progression.

Chronic hepatitis B in pediatrics: to treat or not to treat, that is the question. / Hepatitis B crónica en pediatría: tratar o no tratar, esa es la pregunta.

Chronic hepatitis B virus infection is one of the most prevalent diseases worldwide. It may progress to cirrhosis and hepatocellular carcinoma. An early detection, not using intravenous drugs, sex education, and immunization are critical for prevention. An infection in the neonatal period and in the first year of life becomes chronic in more than 90 % of children. Vertical transmission from a mother with hepatitis B virus to the newborn infant is currently the most common mode of transmission. Detection, immunoglobulin administration, and immunization help to reduce it. Antiviral therapy may accelerate the transition from the active to the inactive phase of infection by two or three years, without affecting the recovery process. A timely treatment of some selected cases may prevent hepatitis B progression.

La infección crónica con el virus B de la hepatitis es una de las enfermedades de mayor prevalencia mundial. Puede evolucionar a la cirrosis y carcinoma hepatocelular. La detección temprana, evitar la utilización de drogas intravenosas, la educación sexual y la vacunación son fundamentales para la prevención. La infección neonatal y durante el primer año de vida evoluciona hacia la cronicidad en más del 90 % de los niños. La transmisión vertical, de una madre con virus B de la hepatitis al recién nacido, es, actualmente, la forma más frecuente de infección. Su detección y la administración de inmunoglobulinas y vacuna disminuyen esta vía de infección. El tratamiento antiviral puede acelerar en dos o tres años el pasaje de la fase activa a la inactiva de la infección, sin influir en el proceso hacia la recuperación. El tratamiento oportuno de algunos casos elegidos puede evitar la progresión de la enfermedad.

Autoimmune Hepatitis in Children: Prednisone Plus Azathioprine Versus Cyclosporine: A Randomized Trial.

OBJECTIVE: The aim of this study was to find the outcome and adverse effects of 2 initial treatments in children with autoimmune hepatitis, prednisone (PRED) plus azathioprine (AZA) versus cyclosporine (CsA). STUDY DESIGN: Between December 2008 and February 2012, 50 consecutive patients were centrally randomized to 1 of 2 treatment arms. Group 1: PRED was indicated at a dose of 1 to 2 mg ·â€Škg ·â€Šday (up to 60 mg/day) and AZA at a dose of 1 to 2 mg ·â€Škg ·â€Šday. Group 2: CsA was administered at a dose of 4 mg ·â€Škg ·â€Šday orally divided into 2 doses. After remission, all patients were given a combination of PRED at 0.3 to 0.5 mg ·â€Škg ·â€Šday and AZA at 1 to 2 mg ·â€Škg ·â€Šday. Children presenting liver failure were placed on a triple immunosuppressive regimen if this condition persisted after 1 week of treatment, after liver function normalization they were switched back to their initial scheme. RESULTS: A total of 26 patients received PRED-AZA and 24 CsA. Both treatments showed similar initial results in effectiveness and safety, although remission was achieved earlier with PRED-AZA: 8.6 versus CsA: 13.6 weeks (P < 0.0081). All children recovered liver function in a mean time of 32 ±â€Š26 days. Cushingoid syndrome was more frequently observed with PRED-AZA (P < 0.001) and gingival hypertrophy with CsA (P < 0.001). A significant increase in body mass index was observed in all patients from initial treatment to remission, being greater with PRED-AZA. CONCLUSIONS: Similar outcomes were obtained with PRED plus AZA or CsA treatments. Either therapeutic strategy could be used according to the particular characteristics of each patient. Triple immunosuppression was beneficial in patients with liver failure at onset.

Changing Etiologies and Prognostic Factors in Pediatric Acute Liver Failure.

After the implementation of universal hepatitis A virus vaccination in Argentina, the outcome of pediatric acute liver failure (PALF) remains unknown. We aimed to identify variables associated with the risk of liver transplantation (LT) or death and to determine the causes and short-term outcomes of PALF in Argentina. We retrospectively included 135 patients with PALF listed for LT between 2007 and 2016. Patients with autoimmune hepatitis (AIH), Wilson's disease (WD), or inborn errors of metabolism (IEM) were classified as PALF-chronic liver disease (CLD), and others were classified as "pure" PALF. A logistic regression model was developed to identify factors independently associated with death or need of LT and risk stratification. The most common etiologies were indeterminate (52%), AIH (23%), WD (6%), and IEM (6%). Overall, transplant-free survival was 35%, whereas 50% of the patients underwent LT and 15% died on the waiting list. The 3-month risk of LT or death was significantly higher among patients with pure PALF compared with PALF-CLD (76.5% versus 42.5%; relative risk, 1.8 [1.3-2.5]; P < 0.001), and 3 risk factors were independently associated with worse outcome: international normalized ratio (INR) ≥3.5 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3-7.2]), bilirubin ≥17 mg/dL (OR, 4.4; 95% CI, 1.9-10.3]), and pure PALF (OR, 3.8; 95% CI, 1.6-8.9). Patients were identified by the number of risk factors: Patients with 0, 1, or ≥2 risk factors presented a 3-month risk of worse outcome of 17.6%, 36.6%, and 82%, respectively. In conclusion, although lacking external validation, this simple risk-staging model might help stratify patients with different transplant-free survival rates and may contribute to establishing the optimal timing for LT.

Management of cirrhotic ascites in children: Review and recommendations. Part 2: Electrolyte disturbances, nonelectrolyte disturbances, therapeutic options. / Manejo de la ascitis secundaria a cirrosis en el paciente pediátrico: Revisión y recomendaciones. Parte 2: Complicaciones electrolíticas, complicaciones no electrolíticas, opciones terapéuticas.

Ascites is a major complication of cirrhosis. There are several evidence-based articles and guidelines for the management of adults, but few data have been published in relation to children. In the case of a pediatric patient with cirrhotic ascites (PPCA), the following questions are raised: How are the clinical assessment and ancillary tests performed? When is ascites considered refractory? How is it treated? Should fresh plasma and platelets be infused before abdominal paracentesis to prevent bleeding? What are the hospitalization criteria? What are the indicated treatments? What complications can patients develop? When and how should hyponatremia be treated? What are the diagnostic criteria for spontaneous bacterial peritonitis? How is it treated? What is hepatorenal syndrome? How is it treated? When should albumin be infused? When should fluid intake be restricted? The recommendations made here are based on pathophysiology and suggest the preferred approach to diagnostic and therapeutic aspects, and preventive care.

La ascitis es una complicación grave de la cirrosis. Existen numerosos artículos y guías basadas en la evidencia para adultos, pero poco se ha publicado para niños. Ante un paciente pediátrico con ascitis secundaria a cirrosis (PPAC), se plantean las siguientes preguntas: ¿Cómo se realiza la evaluación clínica y los exámenes complementarios? ¿Cuándo se considera que la ascitis es refractaria; cómo se trata? ¿Debe infundirse plasma fresco y plaquetas antes de la paracentesis abdominal para evitar el sangrado? ¿Cuáles son los criterios de hospitalización? ¿Cuáles son los tratamientos indicados? ¿Qué complicaciones puede presentar? ¿Cuándo y cómo debe tratarse la hiponatremia? ¿Qué criterios diagnósticos tiene la peritonitis bacteriana espontánea; cómo se trata? ¿Qué es el síndrome hepatorrenal; cómo se trata? ¿Cuándo debe infundirse albúmina? ¿Cuándo debe restringirse el aporte líquido? Las recomendaciones que efectuamos, basadas en la fisiopatología, sugieren el enfoque preferido para encarar sus aspectos diagnósticos, terapéuticos y los cuidados preventivos.

Management of cirrhotic ascites in children. Review and recommendations. Part 1: Pathophysiology, diagnostic evaluation, hospitalization criteria, treatment, nutritional management. / Manejo de la ascitis secundaria a cirrosis en el paciente pediátrico. Revisión y recomendaciones. Parte 1: Fisiopatología, evaluación diagnóstica, criterios de hospitalización, tratamiento, manejo nutricional.

Ascites is a major complication of cirrhosis. There are several evidence-based articles and guidelines for the management of adults, but few data have been published in relation to children. In the case of pediatric patients with cirrhotic ascites (PPCA), the following questions are raised: How are the clinical assessment and ancillary tests performed? When is ascites considered refractory? How is it treated? Should fresh plasma and platelets be infused before abdominal paracentesis to prevent bleeding? What are the hospitalization criteria? What are the indicated treatments? What complications can patients develop? When and how should hyponatremia be treated? What are the diagnostic criteria for spontaneous bacterial peritonitis? How is it treated? What is hepatorenal syndrome? How is it treated? When should albumin be infused? When should fluid intake be restricted? The recommendations made here are based on pathophysiology and suggest the preferred approach to its diagnostic and therapeutic aspects, and preventive care.

La ascitis es una complicación grave de la cirrosis. Existen numerosos artículos y guías basadas en la evidencia para adultos, pero poco se ha publicado para niños. Ante un paciente pediátrico con ascitis secundaria a cirrosis (PPAC), se plantean las siguientes preguntas: ¿Cómo se realiza la evaluación clínica y los exámenes complementarios? ¿Cuándo se considera que la ascitis es refractaria; cómo se trata? ¿Debe infundirse plasma fresco y plaquetas antes de la paracentesis abdominal para evitar el sangrado? ¿Cuáles son los criterios de hospitalización? ¿Cuáles son los tratamientos indicados? ¿Qué complicaciones puede presentar? ¿Cuándo y cómo debe tratarse la hiponatremia? ¿Qué criterios diagnósticos tiene la peritonitis bacteriana espontánea; cómo se trata? ¿Qué es el síndrome hepatorrenal; cómo se trata? ¿Cuándo debe infundirse albúmina? ¿Cuándo debe restringirse el aporte líquido? Las recomendaciones que efectuamos, basadas en la fisiopatología, sugieren el enfoque preferido para encarar sus aspectos diagnósticos, terapéuticos y los cuidados preventivos.

Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An update. / Enfermedad hepática y dislipemia como manifestación de deficiencia de lipasa acida lisosomal (LAL-D). Aspectos clínicos, diagnósticos y nuevo tratamiento. Actualización.

Lysosomal acid lipase deficiency (LAL-D) is still a little recognized genetic disease with significant morbidity and mortality in children and adults. This document provides guidance on when to suspect LAL-D and how to diagnose it. It is recommended to add lysosomal acid lipase deficiency to the List of differential diagnoses of sepsis, oncological diseases, storage diseases, persistent diarrhea, chronic malnutrition, and hemophagocytic lymphohistiocytosis. It should also be considered in young patients with dyslipidemia and atherosclerosis as well as diseases associated with fatty liver and/or hepatomegaly. LAL-D should be suspected in patients with hepatomegaly, hyperlipidemia and /or elevated transaminases found during routine checks or testing for other conditions, and in patients with cryptogenic cirrhosis. At present, there is the option of a specific enzyme replacement treatment.

La deficiencia de lipasa ácida lisosomal es una enfermedad genética aún poco reconocida, con significativa morbimortalidad en niños y en adultos. Esta guía orienta sobre cuándo sospechar la enfermedady cómo diagnosticarla. Serecomienda agregar la deficiencia de lipasa ácida lisosomal a la lista de diagnósticos diferenciales de las sepsis, enfermedades oncológicas, enfermedades de depósito, diarrea prolongada y desnutrición crónica y linfohistiocitosis hemofagocítica. Asimismo, se sugiere considerarla en pacientes jóvenes con dislipemia y arterioesclerosis y en enfermedades que ocurran con hígado graso y/o hepatomegalia. La hepatomegalia, hiperlipidemia y/o elevación de las transaminasas en ocasión de controles de rutina o de otras afecciones deberían hacer sospechar la deficiencia de lipasa ácida lisosomal, al igual que en pacientes con cirrosis criptogénica. Hoy existe la opción de un tratamiento de remplazo enzimático específico.

[Pediatric acute liver failure. Working group of the Latinamerican Society of Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN).] / Insuficiencia hepática aguda pediátrica. Grupo de trabajo de la Sociedad Latinoamericana de Gastroenterología, Heapatología y Nutricion Pediátrica (SLAGHNPP).

Pediatric acute liver failure is a syndrome ofsevere and sudden dysfunction of the hepatocytes which produces a failure in synthetic and detoxifyingfunction. It is an infrequent and severe disease butpotentiallyfatal, occurring in children with no prior history of liver disease. Etiology is related to the age and geographic region of the patient, recognizing the origin: metabolic, infectious, drug exposure, autoinmune, vascular and oncologic. Indeterminate cause where all the etiological search is negative, can range between 18 and 47%, depending on the center and access to the realization of etiological studies. The process which determines the liver injury is still not well known and is considered multifactorial. Essentially, it depends on host susceptibility, the cause and severity of the damage and the ability of liver regeneration. The clinical presentation depends on the etiology, which usually begins with an episode ofacute hepatitis, that in the following days or weeks presents unfavorable outcome, deepening jaundice, affecting the general state and presenting severe coagulopathy that characterizes the syndrome. The treatment consists of general measures which take into account the metabolic disorders, nutritional aspect, and the prevention and treatment of all complications that occur in the evolutionary course (infectious, neurological, etc). Besides it is also vital to implement the specific treatment of those diseases which can benefit from it (alloimmune hepatitis, galactosemia, tyrosinemia, herpes simplex infection, Wilson's disease, etc.). However, despite therapeutic advances, acute liver failure results in death or liver transplantation in over 45% ofcases.

Hepatitis autoinmune en niños: perspectivas actuales / Autoimmune hepatitis in children. Current perspectives

La hepatitis autoinmune es una enfermedad inflamatoria crónica progresiva del hígado de etiología desconocida. Afecta predominantemente al sexo femenino en la etapa prepuberal. Se caracteriza por presentar niveles elevados de transaminasas e inmunoglobulina G, niveles bajos del factor 4a del complemento y de IgA circulantes, autoanticuerpos en suero, prevalencia del antígeno leucocitario humano B8, haplotipos DR3 y DR4, y hepatitis de interfase en la histología. El curso puede ser fluctuante, con períodos de remisión espontánea. Se describen dos tipos de acuerdo con los autoanticuerpos hallados en suero. El mecanismo de producción del daño hepático es secundario a reacciones inmunes contra antígenos hepáticos no controladas adecuadamente por las células T reguladoras. La mayoría de los pacientes responden favorablemente al tratamiento inmunosupresor. Librada a su evolución espontánea, la enfermedad progresa hacia la destrucción hepática, por lo que, en su etapa terminal, requiere un trasplante hepático.

[Hepatitis C virus infection in children]. / Infección por virus de la hepatitis C en niños.

The modes of transmission of hepatitis C virus are parenteral, sexual and maternal-fetal. It affects 3% of the population worldwide. Currently, vertical infection is the main way of virus spreading. Most children are clinically asymptomatic, but progression of liver disease has been described. The positivity of antibodies against hepatitis C virus does not discriminate between active and resolved infection, so determination of serum HCV-RNA is necessary. The combination of peginterferon and ribavirin appears to be the most effective treatment. Future challenges are the development of new drugs and a vaccine.

Infección por virus de la hepatitis C en niños / Hepatitis C virus infection in children

La hepatitis C se adquiere por las vías parenteral, materno-fetal y sexual. Afecta al 3 por ciento de la población mundial. La transmisión vertical constituye la principal forma de diseminación del virus actualmente. La mayoría de los niños desarrolla enfermedad crónica asintomática; sin embargo, puede observarse progresión de la enfermedad en la edad pediátrica. Los anticuerpos contra el virus de la hepatitis C no permiten discriminar entre infección activa y resuelta. Se requiere la determinación por PCR del HCV-ARN. La combinación de peginterferón y ribavirina parece ser el tratamiento más eficaz. El desarrollo de nuevos fármacos, así como el de una vacuna, constituyen los próximos desafíos.

The modes of transmission of hepatitis C virus are parenteral, sexual and maternal-fetal. It affects 3 percent of the population worldwide. Currently, vertical infection is the main way of virus spreading. Most children are clinically asymptomatic, but progression of liver disease has been described. The positivity of antibodies against hepatitis C virus does not discriminate between active and resolved infection, so determination of serum HCV-RNA is necessary. The combination of peginterferon and ribavirin appears to be the most effective treatment. Future challenges are the development of new drugs and a vaccine.

Immunosuppressive therapy allows recovery from liver failure in children with autoimmune hepatitis.

BACKGROUND & AIMS: Patients with autoimmune hepatitis (AIH) frequently have liver failure (LF) at the time of diagnosis; their response to immunosuppressive therapy has not been thoroughly analyzed. We evaluated the outcomes of children with AIH and LF who received immunosuppressive therapy and analyzed predictors of liver function recovery. METHODS: We collected data from 237 children that had AIH between September 1996 and December 2008; 50 had LF (defined as prothrombin time <50%) and had not received prior treatment. Patients were treated with either 2 mg/kg/day prednisone at doses up to 60 mg/day (n = 13) or 1 mg/kg/day prednisone at doses up to 40 mg/day plus cyclosporine at blood levels of 200 ± 50 ng/mL (n = 37). RESULTS: Of the 50 patients studied, 45 (90%) achieved prothrombin time >50% in a median time of 24 days (range of 4-257 days); 93% of these patients achieved this within the first 90 days of treatment. Two of the 45 patients who responded to immunosuppression required liver transplantation because of complications related to portal hypertension, and 3 died because of infection. Three of the 5 nonresponders received liver transplants - 1 remained on the waiting list, and the other died because of central nervous system bleeding. Infection was the only independently associated significant factor that delayed recovery from LF (odds ratio = 7.7, 95% confidence interval, 1.5-40). Each therapeutic approach had similar efficacy. CONCLUSIONS: Most pediatric patients with AIH recover after LF with immunosuppressive therapy; liver transplantation could be avoided or delayed. Infection was the most frequent cause of morbidity and mortality in these patients.

The simultaneous high expression of Vα24, IFN-γ and FoxP3 characterizes the liver of children with type I autoimmune hepatitis.

The immunopathogenesis of type I autoimmune hepatitis (AIH-I) might involve the deregulation of different cellular processes. Here, we investigated the liver expression of selected cytokines and genes of regulatory cell populations in children both at diagnosis and during biochemical remission following immunosuppressive treatment (AIH-Ir). We found a higher Vα24, IFN-γ, FoxP3, IL-27p28, IL-12p40 and IL-21 expression at diagnosis as well as a positive correlation between IL-21 and transaminase levels. Interestingly, only IFN-γ and FoxP3 were decreased in AIH-Ir. An "AIH-I phenotype" (high Vα24, IFN-γ and FoxP3 expression at diagnosis) was observed in only 5 out of 22 AIH-Ir patients but not in controls. These results indicate a local deregulation of the innate and adaptive immune responses with an increased transcriptional activity of immunoregulatory cells at diagnosis. In addition, IL-21 is highlighted as a mediator of liver injury. AIH-Ir is characterized by a partial reversal of the deregulated response.