Fibrose hepática congênita e venopatia portal obliterativa sem hipertensão portal - revisão da literatura com base em um caso assintomático / Congenital hepatic fibrosis and obliterative portal venopathy without portal hypertension - a review of literature based on an asymptomatic case

ABSTRACT The disease and the case reported here are relevant especially because of their varied clinical presentation, possibility of being associated with other disorders affecting several organs and possible differential diagnoses. Congenital Hepatic Fibrosis is an autosomal recessive disease due to mutation in the PKHD1 gene, which encodes the fibrocystin/polyductine protein. It is a cholangiopathy, characterized by varying degrees of periportal fibrosis and irregular proliferation of bile ducts. Affected patients are typically diagnosed in childhood, but in some cases the disease may remain asymptomatic for many years. The exact prevalence and incidence of the disease are not known, but it is consider a rare disease, with a few hundred cases described worldwide. It can affect all ethnic groups and occur associated with various hereditary and non-hereditary disorders. The clinical presentation is quite variable, with melena and hematemesis being initial symptoms in 30%-70% of the cases. More rarely, they may present episodes of cholangitis. The disease has been classified into four types: portal hypertension, cholestasis / cholangitis, mixed and latent. Diagnosis begins with imaging tests, but the definition is made by the histopathological sample. So far, there is no specific therapy that can stop or reverse the pathological process. Currently, the therapeutic strategy is to treat the complications of the disease.

RESUMO A patologia e o caso aqui reportados são relevantes especialmente devido sua variada apresentação clínica, possibilidade de estar associada com outras desordens acometendo diversos órgãos e pelos possíveis diagnósticos diferenciais. A fibrose hepática congênita é uma doença autossômica recessiva, devido mutação no gene PKHD1, que codifica a proteína fibrocistina/poliductina. É uma colangiopatia, caracterizada por variados graus de fibrose periportal e proliferação irregular de ductos biliares. Os pacientes acometidos são tipicamente diagnosticados na infância, mas em alguns casos a doença pode permanecer assintomática por muitos anos. Exatas prevalência e incidência da doença não são conhecidas, mas sabe-se que é uma doença bastante rara, com algumas centenas de casos descritos no mundo. Pode afetar todos grupos étnicos e ocorrer associada com diversas desordens hereditárias e não-hereditárias. A apresentação clínica é bastante variável, com melena e hematêmese sendo sintomas iniciais em 30%-70% dos casos. Mais raramente, podem apresentar episódios de colangite. A doença tem sido classificada em quatro tipos: hipertensão portal, colestática/colangite, mista e latente. O diagnóstico inicia com exames de imagem, mas a definição é feita pela amostra histopatológica. Até o momento, não há terapia específica que possa parar ou reverter o processo patológico e a estratégia terapêutica atual é tratar as complicações da doença.

Cryptogenic cirrhosis: Metabolic liver disease due to insulin resistance.

Objective: Etiopathogenesis of cryptogenic cirrhosis (CC) is not yet well established. Up to 20% of non-alcoholic fatty liver disease (NAFLD) may progress to cirrhosis, mostly termed as cryptogenic. Insulin resistance and altered metabolic parameters form a major pathogenic link between NAFLD and CC. CC may thus be actually a metabolic liver disease. Materials and Methods: Thirty-four patients of CC and 32 patients having cirrhosis due to chronic hepatitis B (Hep B) were assessed in a cross-sectional study in a tertiary hospital for insulin resistance, % β-cell activity, obesity indices, plasma glucose, lipid profiles, and many other parameters. Results: CC patients had higher homeostasis model assessment (HOMA)-IR compared to Hep B group (P = 0.000016). A positive correlation between IR values and Child-Pugh score among CC patients was found ("r" = 0.87; P < 0.00001). Out of 34 CC patients, 15 (44.1%) had obesity contrary to 6 (18.8%) in the control group (P = 0.0022). Differences were observed in subcutaneous fat (P = 0.0022), intra-abdominal fat (P = 0.0055), waist circumference (P = 0.014), and percentage body fat (P = 0.047) between the two groups. Significant differences were observed in the levels of triglyceride, total cholesterol, and very low density lipoprotein (VLDL). Conclusion: Most of the CC patients showed significantly higher prevalence of HOMA-IR, obesity indices, and various parameters of "lipotoxicity" and metabolic syndrome, suggesting that CC may be the long-term consequence of a type of "metabolic liver disease." Further studies are required to evaluate the role of therapeutic interventions to enhance insulin sensitivity in such patients.

Síndrome de Caroli: relato de caso clínico / Caroli´s syndrome: clinical case report

Objetivo: apresentar caso clínico de paciente internada em um hospital em Belém do Pará, no qual foi diagnosticado Síndrome de Caroli e sua evolução após terapêutica adequada. Relato do Caso: paciente do sexo feminino, 37 anos, com quadro de hemorragia digestiva alta volumosa, internada de urgência em hospital de grande porte. Ao exame apresentava-se desidratada, descorada, com distensão abdominal e hepatoesplenomegalia. À endoscopia digestiva detectaram-se varizes esofagianas com sangramento ativo, as quais foram submetidas à escleroterapia. A investigação hospitalar posterior constatou hepatopatia crônica e dilatações saculares das vias biliares intra-hepáticas, com fibrose hepática difusa, consolidando-se o diagnóstico de Síndrome de Caroli. A paciente atualmente está em seguimento ambulatórial, aguardando realização de transplante hepático. Considerações finais: o caso de Síndrome de Caroli estudado ratifica a importância da doença como diagnóstico diferencial em pacientes que apresentam quadro clínico compatível com síndrome de hipertensão portal e colangite, com necessidade de diagnóstico precoce devido ao risco caracteristicamente aumentado de colangiocarcinoma, sendo muitas vezes o transplante hepático a melhor opção terapêutica.

Objective: to report the clinical case of a patient admitted to a hospital in Belem, which was diagnosed Caroli's syndrome, and her evolution after appropriate therapy. Case report: A female patient, 37 years old with a massive upper gastrointestinal bleeding was referred for emergency admission in a large hospital. She was referred for gastrointestinal endoscopy, detecting active bleeding from esophageal varices, which were submitted to sclerotherapy. The subsequent investigation confirmed chronic liver disease and diffuse saccular dilatation of intrahepatic bile ducts with diffuse hepatic fibrosis, consolidating the diagnosis of Caroli`s Syndrome. Currently, the patient is in follow up, awaiting liver transplantation. Final considerations: the study of this Caroli's syndrome case confirms the importance of this disease as a differential diagnosis in patients presenting with clinical syndromecompatible with portal hypertension and cholangitis, requiring early diagnosis due to increased risk of cholangiocarcinoma, and often the liver transplant is the best treatment option.

Enfermedad poliquística autosómica recesiva / Illness poliquística autosómica recessive

Como enfermedades renales poliquísticas hereditarias se describen clásicamente la autosómica recesiva y la autosómica dominante, mal llamadas enfermedad poliquística de tipo infantil y de tipo adulto, respectivamente, pues ambas pueden verse tanto en una como en otra edad. Los conceptos cambiantes en cuanto a la enfermedad autosómica recesiva, dados por los progresos en el tratamiento de los recién nacidos con la enfermedad, y la localización del gen, que por su mutación la produce, nos motivan hacer esta breve revisión con la finalidad de contribuir a la comprensión de la enfermedad por los estudiantes de medicina y el médico general básico.

Recessive autosomal and dominant autosomal polycystic kidney diseases are classically described as hereditary illnesses; they are also called polycystic disease of child type and of adult type respectively since both may be seen in any of these two life stages. The changing concepts of recessive autosomal disease, given the advances made in the treatment of newborns with this disease, and the location of the gen, the mutation of which causes it, encouraged us to make a brief literature review to help medical students and general practitioners to understand this disease.

Reversal of severe hepato-pulmonary syndrome in congenital hepatic fibrosis after living-related liver transplantation.

We report a 5-year-old girl with congenital hepatic fibrosis who presented with clubbing and cyanosis. Partial pressure of oxygen was 40 mmHg with oxy-gen saturation of 70% on room air, which improved to 128 mmHg and 92% on inhalation of 100% oxygen. Macroaggregated albumin scan showed 58% shunting to the brain, suggestive of severe hepatopulmonary syndrome. Echocardiogram and pulmonary angiogram ruled out pulmonary hypertension. Four weeks after living-related liver transplantation, she had normal blood gases and reduction in shunting to 7% on macroaggregated albumin scan.

40 years old woman with monolobar Caroli's syndrome treated by left hepatic lobectomy

Caroli's disease [CD] is a rare congenital abnormality characterized by dilatation of intra hepatic bile ducts, which causes stone formation, recurrent cholangitis and higher risk for biliary malignancy. Association of this anomaly with congenital hepatic fibrosis is named Caroli's syndrome [CS]. The monolobar involvement of CS is a very rare condition, curable by partial hepatectomy. We report a 40-year-old woman with recurrent epigastric pain without icterus with normal AST, ALT and alkaline phosphates for 5 years due to left lobe Caroli syndrome which was diagnosed by CT scan and MRCP. Then, the patient underwent successful operation [left hepatic resection]. After 8 months follow up, she was symptom free. Because the presentation of unilobar CS may be as late as middle age, this congenital anomaly should be considered in differential diagnosis of patients with recurrent epigastric pain without icterus in this age group and MRCP is a useful diagnostic tool

Fibrosis hepática congénita: un espectro clínico variable. Casos clínicos / Congenital hepatic fibrosis: report of five cases

Background: Congenital hepatic fibrosis (CHF) is an autosomic dominant disease that has been associated with polycystic kidney disease. Aim: To describe the medical management of 5 children with CHF and to evaluate the presence and extension of the associated renal disease. Patients and methods: Retrospective review of the medical charts of 5 children with CHF, aged 2 to 14 years. Results: Three children presented autosomic recessive polycystic kidney disease, which was diagnosed before the appearance of liver disease manifestations. They presented a more severe liver damage, with a more aggressive clinical course requiring use of transjugular intrahepatic porto-systemic shunts (TIPS) or surgical porto-systemic shunts to control portal hypertension. The other two children, in whom the diagnosed was based on asymptomatic hepatomegaly, had normal renal function and structure with a more benign clinical course. Conclusions: The diagnosis of CHF should be suspected not only in children with polycystic kidney disease but in those children with persistent, hard consistency, left lobe predominance hepatomegaly (Rev Méd Chile 2004; 132: 733-41).

Malformación de la placa ductal en el desarrollo de la fibrosis hepática congénita. Un estudio inmunohistoquímico / Importance of the ductal plate malformation in the development of congenital hepatic fibrosis. An inmunohistochemical study

La fibrosis hepática congénita es una enfermedad autosómica recesiva caracterizada histológicamente por la presencia de tejido fibroconectivo en los espacios porta con numerosos conductos biliares de mediano calibre. Éste es un estudio inmunofenotípico de la placa ductal y su participación en la génesis de la fibrosis hepática congénita . Se estudiaron cuatro casos postmortem con diagnóstico histopatológico de fibrosis hepática congénita y cortes histológicos de hígados de embriones de ocho, nueve y 10 semanas de gestación. Se obtuvieron cortes histológicos y se utilizaron reacciones de inmunohistoquímica (citoqueratina 7, 8, 18, 19 y laminina). Los hepatocitos primitivos que rodean las ramas de la vena porta, muestran reactividad para citoqueratinas 7, 8, 18, 19 y laminina. La falta de remodelación de la placa ductal resulta en persistencia de conductos biliares embrionarios; estas anormalidades de la placa ductal pueden ser responsables de enfermedades congénitas de los conductos biliares intrahepáticos donde se incluye la fibrosis hepática congénita. Los resultados obtenidos demuestran que las células que forman placas ductales son positivas para citoqueratinas 8, 18, 19 y laminina a partir de la semana ocho de gestación y persiste su positividad en conductos biliares en la fibrosis hepática congénita. Estos hallazgos apoyan la hipótesis del desarrollo de la fibrosis hepática congénita por persistencia de la placa ductal.

Diagnostic potential of histochemical demonstration for copper-orcein stain.

The histochemical demonstration of hepatic copper is important in the diagnosis of paediatric copper storage disorders. Conflicting results have been published regarding ability of different histochemical stains to demonstrate copper storage in the liver. Hence the authors retrospectively analysed eighty-two liver biopsies from 82 patients of Indian childhood cirrhosis (ICC), 59 males and 23 females aged between 1-4 years (mean age 3.1 years). All cases were stained with orcein stain. On the basis of histological picture the liver biopsies were divided into the three histological grades I, II and III. Orcein positively was graded from I to IV. All cases showed positivity with orcein stain. Most cases showed grades II and III of orcein positivity. The association between histological and orcein grades was significant. The present study demonstrates the diagnostic utility of orcein stain in liver copper storage disorder, Indian childhood cirrhosis. Variable copper content in the same histological grade of the disease could be due to individual factors such as genetic milieu which determine the amount of copper liver can store without toxicity.

Fisura de paladar blando adquirida por compresión e isquemia / Palatal cleft secondary to the simultaneous use of orotracheal canula and Sengstaken Blakemore tube

Introducción. La fisura palatina adquirida por compresión (con cánula orotraqueal y sonda de Sengstaken-Blakemore) e isquemia (por la compresión y el choque hipovolémico), es una entidad nunca antes reportada. Su origen es tanto mecánico como químico. Caso clínico. Paciente femenino de 8 años de edad, cirrótica que ingresó por choque hipovolémico secundario a várices esofágicas sangrantes. Requirió intubación orotraqueal por 2 semanas, sonda de balones en esófago por 48 horas y manejo intensivo del estado de choque. El día 12 se encontró necrosis en todo el espesor del paladar blando y brida cicatrizal en faringe. Conclusión. Aunque el caso presentado es extremadamente raro, se tiene que vigilar estrechamente a pacientes con intubación orotraqueal, con sonda de balones e hipovolemia poniendo especial atención al daño sobre el paladar

Hemocromatosis neonatal. Informe de tres casos de autopsia / Neonatal hemocrhomatosis. Report of three autopsy cases

Introducción. La hemocromatosis neonatal es una enfermedad que se inicia in utero, caracterizada por fibrosis acentuada o cirrosis y siderosis hepática y extrahepática intensas, pero sin afección del sistema fagocítico mononuclear. Los datos clínicos importantes son falla hepática grave al nacimiento e hipoglicemia. El diagnóstico se hace básicamente por exclusión cuando se reúne al menos dos de los criterios clinicopatológicos establecidos por Knisely. La biopsia de mucosa oral, la resonancia magnética de hígado y de bazo también son útiles en el diagnóstico. Material y método. En el Departamento de Patología del Hospital de Pediatría del Centro Médico Nacional, Siglo XXI del Instituto Mexicano del Seguro Social, que es un hospital de tercer nivel de atención, en un análisis retrospectivo de los casos de autopsia de recién nacidos realizadas en 1989 a 1997 se seleccionaron aquellos cuya enfermedad principal fuera hepática. Se estableció cualitativamente el grado de siderosis en los cortes de hígado y bazo. En el Instituto Nacional de Investigaciones Nucleares se determinó la cantidad de hierro y cobre por medio de fluorescencia de rayos X, principalmente de hígado y bazo, en tejidos fijados en formol, tanto en los casos problema como en dos controles. Resultados. De las 210 autopsias realizadas en recién nacidos, sólo se encontraron cuatro con hepatopatía como enfermedad principal, sin diagnóstico clínico etiopatogénico. En tres de éstos se hizo el diagnóstico anatomopatológico de hemocromatosis neonatal, todos fueron varones, con edades de 29, seis y 36 días, uno de ellos asociado a síndrome de Down. La razón de concentración de hierro en hígado/bazo en los casos de hemocromatosis fue superior a 1.5 en hígado, a diferencia de lo que ocurrió en dos casos control en los cuales fue menor de 1. Conclusiones. Los casos que se presentan muestran la utilidad de la autopsia para establecer un diagnóstico de certeza, ésta nos permitió identificar tres casos de hemocromatosis neonatal, entidad actualmente bien caracterizada. Esta enfermedad evoluciona rápidamente hacia la muerte y no hay más tratamiento que ofrecerles que medidas de apoyo y a veces el trasplante hepático. Se debe alertar a la familia sobre el riesgo de que ocurra esta enfermedad en hijos subsecuentes. La razón de la concentración de hierro en hígado y bazo, en un resultado no descrito previamente que apoya el diagnóstico, ya que descarta otras siderosis secundarias

Fibrose hepática congênita associada à trombose portal: coincidência? / Congenital hepatic fibrosis associated with portal vein thrombosis: Is it coincidental?

Fibrose hepática congênita (FHC), doença fibropolicística, ocorre em várias formas, tendo como manifestação clínica inicial, em crianças, sangramento digestivo alto em pré-escolares entre um e três anos. História clínica similar à trombose portal congenita. Ainda está sob investigação os fatores etiopatogênicos da FHC, e o presente relato de um raro caso de associação entre estas duas afecções, aparentemente congênitas, adiciona argumento para a recente sugestão de que essa associação não seja apenas coincidência

Choledochal cysts in infants and children.

OBJECTIVE: To study the clinical spectrum and management of choledochal cyst in children below 12 years of age. DESIGN: Descriptive study. SETTING: Tertiary care hospital. METHODS: Twenty three children with choledochal cysts were managed between January 1991 to September 1997 and their clinical details, investigations and management were recorded. Choledochal cyst was diagnosed by ultrasonography and confirmed by ERCP or peroperative cholangioram (POC) Children were treated with antibiotics and/or percutaneous transhepatic biliary drainage if there was cholangitis and subsequently subjected to surgery (excision of the cyst and jejunal loop interposition hepaticoduodenostomy). RESULTS: The median age of these children was 3 years with an almost equal sex ratio. Predominant presentation was jaundice in 18, pain abdomen in 15, fever in 12, and lump abdomen in 9 cases. The classical triad of jaundice, pain and lump was present in only 4 cases. ERCP conducted in 7 and POC in 14 cases yielded positive findings in all. Clinically there were two distinct forms of presentation: (i) infantile form (< or = 1 year) comprised 9 infants which presented with jaundice in all, acholic stool in 6, lump abdomen in 4 but only one had classical triad; and (ii) childhood form (> 1 year) presented with pain abdomen in 12 and jaundice and cholangitis in 9 subjects each. Type I cyst was seen in 20 and type IVa in 3. Two children refused surgery, and the rest underwent surgery. Three infants died after surgery, the remaining 18 were alive and well on follow-up (median 25 months). Secondary biliary cirrhosis was seen in 6, extra hepatic biliary artresia in 2 and congenital hepatic fibrosis in 1 on histology. CONCLUSIONS: Choledochal cysts present in two clinically distinct forms. Infantile form is an important cause of cholestasis of infancy. Early diagnosis and referral is essential to prevent complications and death, and prognosis after surgery is good.

Fibrose hepática congênita: Relato de caso / Congenital hepatic fibrosis: A case report

Relata-se um caso de fibrose hepática congênita, näo associada à doença policística renal, num paciente de 11 anos que teve como apresentaçäo inicial hematêmese por hipertensäo portal, hiperesplenismo e hepatoesplenomegalia. As provas de funçäo hepática foram normais. O paciente foi submetido à escleroterapia endoscópica das varizes, näo tendo mais apresentado recorrência da hemorragia

Congenital hepatic fibrosis as a cause of neonatal cholestasis

A 1-month-old Saudi female infant presented with neonatal cholestasis with normal transaminases. Both direct bilirubin and alkaline phosphatase were high. A percutaneous liver biopsy confirmed a diagnosis of congenital hepatic fibrosis in this infant

Fibrosis hepatica congenita: estudio de 26 casos / Congenital hepatic fibrosis: study of 26 cases

Se presentan 26 niños con fibrosis hepática congénita que asistieron al INSTITUTO NACIONAL DE PEDIATRIA durante el período de 1971-1993. Más de la mitad de los casos fueron preescolares y escolares. En 5 casos se documentó antecedente familiar de hepatopatía, pero sólo en 2 hermanos lo fue de fibrosis hepática congénita. La manifestación clínica predominante fue hematemesis con hepatomegalia de predominio de lóbulo izquierdo (34,6 por ciento) se encontró enfermedad renal poliquística asociada. Las pruebas de funcionamiento hepático fueron normales, en la mayoría de los niños. En 22 casos se detectó hipertensión portal demonstrándose várices esófago-gástricas en 20 casos. La biopsia hizo el diagnóstico definitivo en todos los casos. En 9 niños exitó asociación con patología renal. A la fecha, 7 niños han fallecido. En base a nuestras conclusiones es importante que el pediatra sospeche esta enfermedad y refiera al niño a un centro hospitalario especializado