A teenage patient with autosomal recessive polycystic kidney disease, a splenorenal shunt, and congenital hepatic fibrosis: a case report / Doença renal policística autossômica recessiva, shunt esplenorrenal e fibrose hepática congênita em adolescente: relato de caso

ABSTRACT A 16-year-old female patient previously diagnosed with autosomal recessive polycystic kidney disease (ARPKD) presented with acute bilateral pneumonia, upper gastrointestinal bleeding caused by ruptured esophageal varices, ascites, and lower limb edema. She required intensive care and an endoscopic procedure to treat the gastrointestinal bleeding. The analysis of the differential diagnosis for chronic liver disease indicated she had a spontaneous splenorenal shunt. Ultrasound-guided biopsy revealed the patient had cirrhosis, as characteristically seen in individuals with ARPKD. She had no symptoms at discharge and was referred for review for a combined transplant.

RESUMO Relato de caso de uma paciente adolescente de 16 anos de idade com diagnóstico prévio de doença renal policística autossômica recessiva (DRPAR), que apresentou quadro agudo de pneumonia bilateral e hemorragia digestiva alta por ruptura de varizes esofágicas, bem como ascite e edema de membros inferiores. Necessitou de estabilização clínica intensiva e tratamento endoscópico do sangramento digestivo. Após investigação dos diagnósticos diferenciais da hepatopatia crônica, diagnosticou-se shunt esplenorrenal espontâneo, e realizou-se biópsia hepática guiada por ecografia com diagnóstico de cirrose, espectro típico da DRPAR. Recebeu alta hospitalar assintomática e foi encaminhada para avaliação de transplante duplo.

A teenage patient with autosomal recessive polycystic kidney disease, a splenorenal shunt, and congenital hepatic fibrosis: a case report.

A 16-year-old female patient previously diagnosed with autosomal recessive polycystic kidney disease (ARPKD) presented with acute bilateral pneumonia, upper gastrointestinal bleeding caused by ruptured esophageal varices, ascites, and lower limb edema. She required intensive care and an endoscopic procedure to treat the gastrointestinal bleeding. The analysis of the differential diagnosis for chronic liver disease indicated she had a spontaneous splenorenal shunt. Ultrasound-guided biopsy revealed the patient had cirrhosis, as characteristically seen in individuals with ARPKD. She had no symptoms at discharge and was referred for review for a combined transplant.

Pregnancy complicated by Caroli's disease with polycystic kidney disease: a case report and following observations.

Caroli's disease and Caroli's syndrome are rare congenital disorders characterized by non-obstructive cystic dilatation of the intrahepatic bile ducts. These disorders are often associated with autosomal recessive polycystic kidney disease. A young woman at 11 weeks of gestation was referred to our hospital for proper management of Caroli's disease during pregnancy. Magnetic resonance imaging and laboratory tests revealed Caroli's disease with chronic renal failure caused by polycystic kidney disease. She received diet control, erythropoietin and prophylactic oral antibiotics. Her pregnancy course was uneventful, and she gave birth at 37 weeks of gestation. Thereafter, her renal function gradually worsened. Hemodialysis was begun 5 years after parturition. Though the courses of pregnancies complicated by Caroli's disease or Caroli's syndrome are variable and can include life-threatening conditions, uneventful outcomes can be expected if careful management prevents biliary and renal infection.

[Cystic liver diseases. Genetics and cell biology]. / Maladies kystiques du foie. Génétique et biologie cellulaire.

In 50% of cases, polycystic liver disease is associated with autosomal dominant polycystic kidney disease, which is caused by mutations in the PKD1 and PKD2 genes that encode polycystin-1 and -2, respectively. These proteins form a polycystin-1/2 complex on the plasma membrane, including that localized on the surface of primary cilia, where they act as mechanosensors. Polycystin-1 acts as a (mechano)receptor of environmental signals, and polycystin-2 as a calcium channel mediating intracellular transduction. Isolated autosomal dominant polycystic liver disease is caused by mutations in PRKCSH that encodes hepatocystin, a protein of the endoplasmic reticulum, which may participate in the N-glycosylation and maturation of proteins addressed to the cell surface. Congenital hepatic fibrosis whether it is accompanied by bile duct dilatations (Caroli's syndrome) or not, may be associated with autosomal recessive polycystic kidney disease, which is caused by mutations in PKHD1 that encodes fibrocystin, a protein of primary cilia. Genetic defects in fibrocystin cause ciliary dysfunction, presently considered as a major pathogenic event in cystogenesis. Excessive cell proliferation, a hallmark of cystic biliary epithelium, occurs in combination with deregulation of the epidermal growth factor (EGF) and probably also estrogen receptors. EGF receptor antagonists inhibit kidney and liver cyst development in animal models, and are currently under investigation in phase I and II clinical trials in patients with autosomal dominant polycystic kidney disease.

Caroli's disease: 6 case studies.

Caroll's disease is characterized by congenital non-obstructive dilatation of the intrahepatic bile ducts of undefined etiology. It is a rare disease usually affecting the whole liver but it may affect a lobe or a segment (11). This study shows the evolution of 6 cases (2 boys and 4 giris) that were diagnosed with Caroli's disease at a referral service. Their ages ranged from 2 to 16 years--median age 10 years. One of the patients presented with cholangitis, while hepatomegaly was observed in 83% of the cases. Four of the patients presented biliary lithiasis and in one of these cholesterol crystals could be observed in the duodenal secretion. The diagnosis was confirmed in 4 cases by endoscopic retrograde cholangiopancreatography, in 1 by cholangioresonance and 1 by echography. Two of the patients also presented congenital hepatic fibrosis. The outpatient clinic follow-up indicated that all the patients evolved well with the exception of one patient who was selected as a candidate for liver transplantation.

Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy.

Long-term antibiotic treatment offers a rare opportunity to study the evolution of bacteria within the same individual. The appearance of new variants has been suggested to take place via the selection of enhanced resistance in compartments of the body in which the antibiotic concentration is low. Laboratory models of protected compartments have elegantly demonstrated their potential in selecting novel variants. However, comparable data from patients have been rare. In this study, extended antibiotic therapy in a single patient suffering from multiple infected liver cysts has provided the opportunity to observe and analyse the molecular evolution of antibiotic resistance. Each isolate has the same basic ompC gene sequence that is distinct from other Escherichia coli isolates, which suggests that they derive from the same founder population. However, the isolates differ in their auxotrophic markers, in the pI values of their dominant beta-lactamase activities and in the mutations in the promoter region of the ampC gene leading to increased expression of the AmpC enzyme. The data provide strong evidence for a single focal infection expanding via parallel pathways of evolution to give a range of antibiotic-resistant isolates. These data suggest that the infected cysts provide numerous protected environments that are the foci for the separate development of distinct variants.

Treatment of chronic active hepatitis and primary biliary cirrhosis with ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA) improves liver function tests in patients with chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC). UDCA will reduce biochemical parameters of both cholestasis and hepatocellular damage. The effects may be less beneficial in patients with advanced stages of chronic liver disease: in PBC we found the improvement of laboratory parameters in stage I and II very impressive, in stage III and IV it was less marked. Data of two controlled trials in PBC showed an improvement in liver histology, in one study the improvement was statistically significant. UDCA can be administered for at least 10 years without any adverse effects, the treatment is safe and improves life quality. The mode of action of UDCA seems to be in its displacement of toxic hydrophobic bile salts from the bile acid pool and the hepatocellular membrane. In in-vitro investigations a direct protective effect of UDCA on isolated sinusoidal hepatocyte membranes against toxic bile salts has been shown. This protective effect of a more general nature may explain the efficacy of UDCA in different chronic, especially cholestatic liver diseases.