Hiperbilirrubinemias hereditarias: un diagnóstico diferencial a considerar en ictericia / Hereditary hiperbilirrubinemias: a differential diagnosis to considerer in icterus

Las hiperbilirrubinemias hereditarias (HBH) son patologías originadas por defectos en las enzimas y proteínas que participan del metabolismo de la bilirrubina. El clearence de bilirrubina incluye captación y almacenamiento en hepatocitos, conjugación, excreción hacia la bilis y recaptura de su forma conjugada por hepatocitos. Las HBH varían de acuerdo a su patogenia, presentación clínica, niveles de bilirrubinemia y tratamientos disponibles. En general son poco frecuentes, a excepción del Síndrome de Gilbert. Están las que son de predominio indirecto, como el Síndrome de Gilbert y el de Crigler-Najjar, y las de predominio directo, como el Síndrome de Dubin-Johnson y el de Rotor. En general no requieren tratamiento específico y tienen curso benigno, a excepción del Síndrome de Crigler-Najjar para el cual existen medidas terapéuticas específicas a considerar, teniendo un pronóstico reservado para algunas de sus formas de presentación. Es importante el conocimiento de estos síndromes dado el alto índice de sospecha requerido para su diagnóstico y para su diferenciación de otras patologías hepatobiliares de mayor riesgo y severidad.

Hereditary hiperbilirrubinemias (HBH) are pathologies originated from the defect of the enzymes and proteins involved in the metabolism of bilirubin. The bilirubin clearance includes uptake and storage in hepatocytes, conjugation, excretion into bile and recapture of its conjugated form by hepatocytes. HBH vary according to their pathogenesis, clinical presentation, levels of bilirubin and available treatments. Generally they are infrequent, except for Gilbert Syndrome. There are those with indirect bilirubin predominance, such as Gilbert and Crigler-Najjar syndromes, and those with direct bilirubin predominance, including Dubin-Johnson and Rotor syndromes. In general, they do not require specific treatment and have a benign course, with the exception of the Crigler-Najjar Syndrome, for which there are specific therapeutic measures to consider, as well as a reserved prognosis for some of their forms of presentation. The knowledge of these syndromes is important 2 given the high index of suspicion required for its diagnosis and for its differentiation from other hepatobiliary pathologies of greater risk and severity.

Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome?

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have normal liver function tests except for raised transaminases until they have progressed to cirrhosis of liver. The objective of this study was to evaluate patients of NASH for the presence of hyperbilirubinemia at presentation. METHOD: Sixty-seven patients of NASH were studied for the presence of hyperbilirubinemia at presentation. All patients were worked up for the presence of cirrhosis and hemolytic work up and fasting test were done in those found with unconjugated hyperbilirubinemia. RESULTS: Five out of 67 patients (7.5%) of NASH were found to have unconjugated hyperbilirubinemia. Though the fasting test was not positive, they all had a negative hemolytic workup and none of them had underlying cirrhosis. Clinical characteristics of patients with unconjugated hyperbilirubinemia were similar to those with normal serum bilirubin levels. CONCLUSION: Unconjugated hyperbilirubinemia in patients with NASH may suggest an associated Gilbert's syndrome.

Role of overnight rifampin test in diagnosing Gilbert's syndrome.

BACKGROUND: Gilbert's syndrome (GS) is the most common inherited disorder of bilirubin metabolism. Recent data show that the rifampin test can be used as a diagnostic test but there is controversy about its effect on bilirubin level in normal individuals. We studied the effect of administration of rifampin on serum bilirubin level in patients with GS and in healthy individuals. METHODS: Serum total and unconjugated bilirubin levels were measured in 16 patients with GS and 15 healthy individuals before and after a single 600-mg oral dose of rifampin. RESULTS: In patients with GS, mean (SD) serum total and unconjugated bilirubin level increased from 2.15 (0.49) and 1.56 (0.41) mg/dL, respectively to 3.23 (0.72) (p< 0.001) and 2.52 (0.71) mg/dL (p< 0.001), respectively after rifampin administration, and in healthy subjects from 0.69 (0.13) and 0.34 (0.09) mg/dL, respectively to 1.68 (0.56) (p< 0.001) and 0.84 (0.23) mg/dL (p< 0.001), respectively. Elevation of these levels above the normal cut-off levels had poor accuracy for the diagnosis of GS. However, elevation of total serum bilirubin after rifampin above 2.4 mg/dL was 93.8% sensitive and 93.3% specific for the diagnosis of GS, and elevation of unconjugated bilirubin above 1.3 mg/dL was 100% sensitive and 100% specific. CONCLUSIONS: Rifampin elevates bilirubin level to above normal in GS and healthy subjects. Overnight rifampin test may be useful for the diagnosis of GS if cut-off levels for serum total and unconjugated bilirubin level of more than 2.4 and 1.3 mg/dL are used.

A case report of Gilbert Syndrome.

Gilbert syndrome is benign, often familial condition characterized by recurrent but asymptomatic mild unconjugated hyperbilirubinemia in the absence of haemolysis or underlying liver disease. If, it becomes apparent, it is not until adolescence and then usually in association with stress such as intercurrent illness, fasting or strenuous exercise. Virtually all patients have decreased level of UDP-Glucuronosyltransferase, but there also is evidence for a defect in hepatic uptake of bilirubin as well. This case is reported due to its rarity. The prevalence of Gilbert syndrome in U.S is 3-7% of the population.

Diagnóstico presuntivo de Síndrome de Gilbert en una comunidad agraria del centro-este de Argentina / Presumptive diagnosis of Gilbert's syndrome in an agrarian community from the middle-east of Argentina

Introducción.El síndrome de Gilbert es una hiperbilirrubinemia no conjugada,leve,crónica,intermitente,denaturaleza benigna,que ocurre en ausencia de hemólisis o enfermedad hepatocelular y que afecta al 1-5 por ciento

Síndrome de Gilbert estudo clínico e métodos de diagnóstico com apresentaçåo de seis casos observados pelo autor / Gilbert's syndrome

O autor apresenta as observaçÆes de seis pacientes portadores da Síndrome de Gilbert, diagnosticados e acompanhados em sua clínica particular, nos últimos dois anos, tecendo comentários sobre a conceituaçäo de referida síndrome, sua provável etiopatogenia, benignidade do quadro clínico presente e métodos semiológicos utilizados para seu diagnóstico, compreendendo anammese, exame físico, provas laboratoriais, biópsia hepática com exame histopatológico de fragmentos do fígado, dieta baixa em calorias, ou em lipídios, e testes de contra-prova através do uso oral do fenobarbital. Pôde comprovar, no estudo de seus casos, o aumento discreto ou moderado da bilirrubinemia às custas da fraçäo indireta ou näo conjugada; a normalidade das provas hepáticas realizadas; o aparecimento ou desaparecimento das crises de icterícia, pelo menos em alguns casos, após reduçäo do número de calorias e (ou) prática exagerada de exercícios físicos; a ausência de qualquer tipo de anormalidade no exame histopatológico de fragmentos de fígado, obtidos por biópsia hepática, no único caso em que foi utilizado; e, finalmente, a contraprova da baixa da bilirrubinemia mediante o emprego oral de fenobarbital