ABSTRACT
Cirrhosis is a primary cause of liver-related mortality and morbidity. The basic process driving chronic liver disease to cirrhosis is accelerated fibrogenesis. Although the pathogenesis of liver cirrhosis is a multifactorial process, the essential step in the evolution of liver fibrosis is the activation of hepatic stellate cells, which are the main source of collagen produced in the extracellular matrix. This activation process is mediated by multiple growth factors, cytokines, and chemokines. One of the hepatic stellate cell-activating signaling molecules (and also one associated with cell injury and fibrosis) is osteopontin (OPN). OPN concentration in the plasma has been found to be predictive of liver fibrosis in various liver diseases. OPN concentrations correlate significantly with the stage of fibrosis, liver insufficiency, portal hypertension, and the presence of hepatocellular cancer. However, due to its versatile signaling functions, OPN not only contributes to the development of liver cirrhosis, but is also implicated in the pathogenesis of other chronic hepatic diseases such as viral hepatitis, both alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and hepatocellular cancer. Thus, the targeting of OPN pathways seems to be a promising approach in the treatment of chronic liver diseases.
Subject(s)
Liver Diseases/metabolism , Osteopontin/metabolism , Biomarkers , Carcinoma, Hepatocellular , Chemical and Drug Induced Liver Injury/metabolism , Hepatic Insufficiency/metabolism , Hepatic Stellate Cells/metabolism , Humans , Hypertension, Portal/metabolism , Liver Cirrhosis/metabolism , Liver Neoplasms/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Signal TransductionSubject(s)
Humans , Infant , Child, Preschool , Child , Aged , History, 19th Century , History, 20th Century , History, 21st Century , Neuromuscular Depolarizing Agents/administration & dosage , Neuromuscular Depolarizing Agents , Neuromuscular Depolarizing Agents/pharmacokinetics , Neuromuscular Depolarizing Agents/pharmacology , Neuromuscular Depolarizing Agents/therapeutic use , Neuromuscular Nondepolarizing Agents/administration & dosage , Neuromuscular Nondepolarizing Agents , Neuromuscular Nondepolarizing Agents/pharmacokinetics , Neuromuscular Nondepolarizing Agents/pharmacology , Neuromuscular Nondepolarizing Agents/therapeutic use , Anesthesiology/history , Cardiovascular Diseases/chemically induced , Hepatic Insufficiency/metabolism , Renal Insufficiency/metabolism , Pancuronium , Vecuronium BromideABSTRACT
Esplenectomia e ligadura da veia gátrica esquerda em crianças portadoras de hepatoesplenomegalia esquistossomótica com varizes sangrantes de esôfago determinam uma diminuiçÝo no fluxo portal e um aumento do fluxo arterial hepático. Os efeitos dessa alteraçÝo hemodinâmica no fígado poderiam, teoricamente, agravar a reserva funcional hepática desses pacientes. Quarenta crianças portadoras desta patologia submetidas àquele tipo de tratamento foram seguidas prospectivamente, em média de 42 meses, com relaçÝo a reserva funcional hepática. No pré-operatório, treze crianças foram diagnosticadas como grau A, na classificaçÝo de Child, enquanto vinte e sete eram grau B. A concentraçÝo média de albumina desses pacientes pacientes foi de 3,16g/dl+/-0,62g/dl. Apenas um paciente apresentou bilirrubina discretamente superior a 2mg/dl. Após seguimento entre dezoito e setenta e dois meses, quinze pacientes foram diagnosticados como grau A e vinte e cinco como grau B. A concentraçÝo média de albumina foi de 3,25g/dl+/-0,50g/dl. De forma similar ao pré-operatório um paciente vem apresentando bilirrubina acima de 2mg/dl. Os achados nÝo indicam que tenha havido agravamento da reserva funcional hepática desses pacientes