Oleg Terletskiy
Verified @ukr.net
Danylo Halytsky Lviv National Medical University
RESEARCH, TEACHING, or OTHER INTERESTS
Medicine, Surgery
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O. Shchur, H. Kurylo, V. Petrov, and O. Terletskiy
Higher State Educational Establishment of Ukraine Bukovinian State Medical University
Introduction. Alagille syndrome (AS) is a syndrome of a decrease in the number of interlobular cells bile ducts, also known as arteriohepatic dysplasia. AS is a genetic multisystemic autosomal dominant disorder with highly variable manifestations, predominantly affecting the liver, heart, face, skeleton and other anomalies may include.Aim. Literature review and analysis of our own experience to update the current knowledge about AS. To introduce new diagnostic and treatment methods, taking into account the need and importance of a systemic multidisciplinary approach to the management of patients with Alaghil syndrome. Pathogenesis. AS, or Watson-Miller syndrome, is a rare disorder caused by mutation of the Jagged1 (JAG1) gene - AGS type 1, and in 2% of cases by mutation of the NOTCH2 gene - AGS type 2, with autosomal dominant inheritance. Mutations of the JAG1 or NOTCH2 genes cause defects in bile duct morphogenesis and angiogenesis, as well as abnormalities of the skeleton, eyes, cardiovascular system, and kidneys.Diagnostics. Since AS manifests itself in different ways, it can be suspected in all age groups and, depending on the variability of symptoms, can be diagnosed by any specialist - neonatologist, pediatrician, ophthalmologist, surgeon, cardiologist, etc. The main diagnostic criteria are primarily liver pathology. The main diagnostic criteria are primarily attributed to liver pathology, 75-100% of cases are hypoplasia of bile ducts, absence of intralobular bile duct, which is clinically manifested by significant persistent cholestasis. The next strong sign of AS is the combination of cholestasis with cardiovascular abnormalities in 85-95% of cases. The most common is stenosis of the peripheral pulmonary arteries or ventricular septal defect, atrial septal defect, tetralogy of Fallot, pulmonary atresia, etc. Other typical anomalies include skeletal pathologies, which occur in 33-80% of affected children. These are "butterfly" vertebrae, inferiorly formed vertebrae, fusion of vertebrae, spina bifida. In the AS group, the frequency of urinary system abnormalities is 20-70% according to the data, they affect the ureters, bladder and pelvis disorders, renal tubular acidosis, etc. In 55-75% of patients with AS there are ocular changes - pigmentary retinopathy, retinal angle vessels, posterior embryotoxon, optic drusen. In 15-35% of patients there are anomalies of peripheral vessels - aneurysms of cerebral vessels, stenosis of internal carotid artery, Moya-Moya disease, as well as anomalies of vessels of abdominal cavity: coarctation of abdominal aorta, stenosis of renal artery. However, the pathognomonic signs of AS include characteristic facial features - 70-95% of patients have a wide forehead, deep-set eyes, slanting upward slits, protruding ears, a straight nose with a bulbous tip, a pointed chin with the effect of a triangular face. Clinical manifestations. In 80-100% of patients with AS, the first clinical manifestation is liver failure of various stages. In neonates and young patients, cholestasis is present with a clinical picture very similar to that of biliary atresia. Jaundice appears on the 2nd or 3rd day of life, i.e. in normal physiological days jaundice period. About 2/3 of the patients studied by us had "light interval" - a decrease in the intensity of jaundice until the end of the 1-2 weeks of life and the following month its gradual increase and the appearance of a greenish tint. Acholia is the earliest and most constant clinical symptom of the disease. It is characterized by the absence of hepatomegaly at birth, followed by an increase in the size of the liver and a change in its consistency from elastic to dense during the first 2 months of life. At about 1 month of life, the development of a hemorrhagic syndrome is possible (bleeding from the mucous membranes of the gastrointestinal tract, umbilical wound, intracranial hemorrhages), which is due to a deficiency of vitamin K-dependent blood coagulation factors as a result of a violation of the processes of absorption of vitamin K in the intestine, which we observed in 3 patients. By 5 years of age, 15-30% of children with AS develop acute liver failure and portal hypertension. Treatment. The main goal of treating a child with AS is to relieve cholestasis and reduce the debilitating symptoms of pruritus. Ursodeoxycholic acid is used, cholestyramine, rifampicin, ondansetron, naltrexone, etc. may be added. It was absolutely revealing the inclusion of marlioxibat, which acts on the inhibitors of transporters of bile acids in the upper parts of the ileum. Liver transplantation, as a rule, becomes necessary in some patients with AS, which meets end-stage liver failure and severe portal hypertension. Another indication for transplantation is hepatocellular carcinoma. According to our experience and data from other centers, transplantation completely solves these problems and has a successful outcome, as it has been proven that AS does not recur in the transplant.