Patología del trasplante hepático, aspectos más relevantes del período postrasplante tardío / Most Relevant Pathology Issues in the Late Post Liver Transplant Period

La sobrevida de los pacientes postrasplante hepático supera el 90% al año y el 75% a los 5 años. Entender las causas de pérdida del injerto, o inclusive la muerte del paciente, es esencial para mejorar aún más los resultados a largo plazo. La evaluación de las biopsias hepáticas tiene un papel importante en la explicación y manejo de la disfunción del injerto de hígado, que ocurre después del primer año del trasplante. La interpretación de estas biopsias puede ser muy difícil, en especial por la alta incidencia de enfermedades recurrentes que pueden mostrar un cuadro clínico y unas características histopatológicas que semejan varias condiciones, especialmente cuando el rechazo agudo o crónico pueden sobreponerse a una patología ya existente o presentarse de manera simultánea y contribuir a la disfunción tardía del injerto, por lo que el análisis de la biopsia puede ayudar a determinar el componente principal de la lesión. Es indispensable la correlación clínico patológica, teniendo en cuenta la enfermedad original, el tipo de inmunosupresión, las pruebas de función hepática, las serologías virales, los autoanticuerpos y los hallazgos radiológicos. En este artículo comentaré las patologías más frecuentes y las que causan más problemas en su diagnóstico durante el período postrasplante tardío

One year survival rates of liver transplant patients exceed 90% while five year survival rates exceed 75%. Understanding the causes of graft losses and patient deaths is essential for further improvement of long-term results. Evaluation of liver biopsies has an important role in explaining liver graft dysfunction that occurs more than one year after transplantation, and thus is key for post-transplant patient management. The interpretation of these biopsies can be very difficult especially because of the high incidence of recurrent diseases that sometimes have clinical and histopathological features that resemble various other conditions. This is especially true for acute and chronic rejection which can overwhelm an existing condition and which can develop simultaneously with other conditions that contribute to late graft dysfunction. Analysis of the biopsy can help determine the main component of a lesion. Clinical findings must be correlated to pathological findings, and the correlation must take into account the original disease, the type of immunosuppression, liver function tests, viral serology, autoantibodies and radiological findings. In this article I will discuss the most common diseases and those that cause the most problems for diagnosis during the late post-transplant period

Colestasis neonatal e infantil: Aproximación al diagnóstico histopatológico / Neonatal and Infantile Cholestasis: An Approach to Histopathological Diagnosis

Aun cuando el papel de la biopsia hepática está cambiando con el desarrollo de nuevos métodos de diagnóstico y del avance de las técnicas de imagen, de biomarcadores no invasivos, estudios proteómicos y genómicos, la biopsia hepática realizada en el momento y con la indicación adecuadas continúa siendo una importante herramienta para la evaluación y diagnóstico de los niños con colestasis tanto en el periodo neonatal como durante la infancia temprana o tardía, no solo para determinar una etiología o establecer un pronóstico sino para guiar una terapia (1). Son múltiples las causas y varios los patrones morfológicos observados, puede estar relacionada a un defecto genético del metabolismo hepático incluyendo la síntesis de ácidos biliares, la formación y función de transportadores de membrana o a alteraciones en el desarrollo de las vías biliares, muchos de los cuales pueden sobreponerse y deben interpretarse en conjunto con los hallazgos clínicos, genéticos y de laboratorio. Los síndromes heredados que producen colestasis intrahepática y la atresia biliar son las causas más comunes de enfermedad hepática crónica y la indicación principal para el trasplante hepático en niños. El enfoque que aquí daremos hace hincapié en la estrecha colaboración que debe existir entre pediatras, gastroenterólogos, cirujanos pediátricos y los patólogos para la correcta identificación y posterior manejo sea médico o quirúrgico incluyendo el trasplante hepático, de muchas de las patologías colestásicas que afectan este grupo etario (2, 3).

Although the role of liver biopsies is changing with the development of new diagnostic methods and advances in imaging techniques, non-invasive biomarkers, proteomic and genomic studies, a liver biopsy performed at the right time and with appropriate indications continues to be an important tool for assessment and diagnosis of children with cholestasis. This is equally true in the neonatal period, in early childhood, and in late childhood not only for determination of an etiology and establishing a prognosis, but also for guiding treatment of the patient (1). There are multiple causes and morphological patterns that may be related to a genetic defect in aspects of hepatic metabolism including synthesis of bile acids, formation and function of membrane transporters, and alterations in the development of the bile ducts. Many of these may overlap and should be interpreted in conjunction with clinical, genetic and laboratory findings. Inherited syndromes that produce intrahepatic cholestasis and biliary atresia are the most common causes of chronic liver disease and the leading indication for liver transplantation in children. The approach we present here emphasizes the close cooperation that should exist between pediatricians, gastroenterologists, pediatric surgeons and pathologists for proper identification of many of the cholestatic diseases that can affect this age group. Subsequent surgical or medical management may include liver transplantation (2, 3).

A Case of Idiopathic Adulthood Ductopenia

Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic liver disease of unknown etiology characterized by adult onset, an absence of autoantibodies, inflammatory bowel disease, and a loss of interlobular bile ducts. In the present report, a case fulfilling the IAD criteria is described. A 19-year-old man was admitted to the hospital for persistent elevation of transaminases and alkaline phosphatase without clinical symptoms. Viral hepatitis markers and autoantibodies were absent. The patient had a normal extrahepatic biliary tree and had no evidence of inflammatory bowel disease. A liver biopsy specimen showed absence of interlobular bile ducts from 58% of the portal tracts. He was diagnosed with IAD and was treated with ursodeoxycholic acid.

A case of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis / 대한간학회지

Allopurinol-induced hypersensitivity syndrome is characterized by an idiosyncratic reaction involving multiple-organs, which usually begins 2 to 6 weeks after starting allopurinol. In rare cases, the adverse reactions to allopurinol are accompanied by a variety of liver injury, such as reactive hepatitis, granulomatous hepatitis, vanishing bile duct syndrome, or fulminant hepatic failure. Here we report a case with granulomatous hepatitis and ductopenia. A 69-year-old man with chronic renal failure, hyperuricemia, and previously normal liver function presented with jaundice, skin rash, and fever 2 weeks after taking allopurinol (200 mg/day). In histopathology, a liver biopsy specimen showed mild spotty necrosis of hepatocytes, marked cholestasis in parenchyma, and some granulomas in the portal area. There were vacuolar degeneration in the interlobular bile ducts and ductopenia in the portal tracts. Pathologic criteria strongly suggested the presence of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis. The patient fully recovered following the early administration of systemic corticosteroid therapy.

Clinical Features of Cholestatic Hepatitis / 영남의대학술지

BACKGROUND: Cholestatic hepatitis is failure of bile to reach the duodenum with hepatocellular damage and no demonstable obstruction of the major bile ducts. The prognosis of usually good with recovery in less than 4 weeks after withdrawal of the offending drug. However, a prolonged causes of Chronic liver disease is needed. MATERIALS AND METHODS: From January 1991 through January 2000, 14 patients diagnosed as cholestatic hepatitis by liver biopsy were included. The possible causative drug, clinical features, laboatory findings, and progression of cholestatic hepatitis were evaluated. The semiquantitative study of liver lesions was performed by two independent observers. RESULTS: Causes of cholestatic hepatitis are 5 cases of oriental medicine, 3 cases of anti-tuberculosis medication, 1 case of ticlopidine and antibiotics and 4 cases of unknown causes. The clinical features of cholestatic hepatitis were jaundice, itching, urine color change, and general weakness. During 6 to 50 months, LFT of 5 patients showed prolonged elevation. Elevated total cholesterol > or =250 mg/dL in 6 patients, pheripheral blood eosinophilia in 5 patients, auto-antibody positive in 6 patients were observed respectively. The biopsies showed intralobular bilirubinostasis with a mixed portal inflammatory infiltration. CONCLUSION: In chlestatic hepatitis, durations of abnormal LET are variable regardless of causative drugs. If chlestatic hepatitis progresses toward chronic course, viral hepatitis, primary biliary cirrhosis, and autoimmune hepatitis should be differentially diagnosed and sequential liver biopsies are needed.