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Hepatic ultrasound scan showing marked nodularity (cirrhosis).
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This study analyzes the prevalence and the role of possible clinical and genetic risk factors for the development of cystic fibrosis (CF)-related liver disease (LD) in a Macedonian CF population. All patients older than three years (n=52) were screened for LD. LD was defined by the finding of hepatomegaly and/or splenomegaly, significant and persis...
Context in source publication
Context 1
... ultrasonographic changes (Table II). Abnormal imagings on hepatobiliary scintigraphy were seen in 12 patients and functional scintigraphic abnormalities suggested delayed biliary flow in 3 patients with LD. Echographic evidence of hepatic cirrhosis (coarsely nodular liver; score 8 or 9) was found in 7 patients, 3 of them with portal hypertension (Fig. 1). The diagnosis of cirrhosis was confirmed by liver biopsy findings in 4 ...
Citations
... 13,24,25 However, the role of such factors in the development of CFld is controversial. 26 In addition, correlation to the degree of pancreatic sufficiency has been proposed where CFld is generally not observed in patients with pancreatic sufficiency. 27 The phenotypic variability of CFld in patients with CF may be explained by other insults and factors. ...
Cystic fibrosis (CF) is a multisystem disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CFTR is expressed in the apical surface of cholangiocytes. Homozygous CFTR gene mutation results in viscous and acidic bile secretions secondary to deficient surface fluid and bicarbonate efflux. Viscous, inspissated bile causes ductular obstruction and hepatotoxicity from retained bile components, leading to fibrosis and ultimately cirrhosis, known as CF liver disease (CFLD). CFLD is the third leading cause of death in CF patients. CFLD manifestations can take many forms. They range from asymptomatic elevation of transaminases to cirrhosis and end-stage liver disease. CFLD is diagnosed after excluding other causes of chronic liver disease. To date, there is no effective therapy to prevent or treat CFLD. Management of CFLD emphasizes on optimizing nutritional status. Ursodeoxycholic acid is the only available treatment that may prevent progression of CFLD at present. All CF patients with CFLD need annual investigations and follow-up for early detection of the disease. Liver transplantation should be considered in patients with decompensated cirrhosis and portal hypertension, with acceptable long-term outcomes. Novel therapies of CFLD are promising. This review article aims to summarize the published literature on CFLD, its pathophysiology, clinical features and complications, and management including new therapeutic options.
... In pathogenesis some genes were suspected as a factor inducing pathological processes in the liver and bile duct in patients with cystic fibrosis (gene of plasminogen activator inhibitor type 1, genes relating to metalloproteinases, P1 glutation s-transferase gene, transforming growth factor beta gene, uridylyltransferase gene (UGT1A1). But the role is not strictly confirmed [12][13][14][15][16][17]. ...
... Nesses estudos, não foi observada associação entre doença hepática e estado nutricional. 27,28 Como exceção, há apenas um estudo recente de Ayoub et al., 29 que analisaram os fatores de risco para EH em pacientes adultos com FC, contudo não foi possível a comparação dos resultados por se tratar de pacientes com diferença importante de faixa etária (mediana de 29 anos) e também porque os autores encontraram associação da EH com sobrepeso e concluíram que a EH em pacientes adultos com FC compartilha semelhanças com a doença hepática gordurosa não alcoólica. ...
Objective:
To determine the prevalence of hepatic steatosis (HS) in children and adolescents with cystic fibrosis (CF) and associate it with nutritional status.
Methods:
Cross-sectional study with children and adolescents with CF diagnosis. Weight and height were used to calculate the body mass index (BMI) and subsequent classification of the nutritional status. The midarm circumference (MAC), triceps skinfold thickness (TSF) and midarm muscle circumference (MAMC) were used to evaluate body composition. Abdominal ultrasonography was performed for diagnosis of HS. The statistical tests used were Student's t test, Mann-Whitney test and chi-square test with significance level of 5%.
Results:
50 patients with CF were evaluated, 18 (36%) were diagnosed with HS (Group A) and 32 (64%) without HS (Group B). The mean age of Group A was 13,2±4,9 years old and Group B 11,7±4,9; for BMI, the value for Group A was 18,0±4,1 and Group B was 15,7±3,8; the TSF of Group A was 8,4±3,5 mm and Group B was 7,0±2,5 mm. For these variables, there was no significant difference between the groups. The mean of MAC and MAMC differed significantly between the groups, being higher in the HS group, with p values of 0,047 and 0,043.
Conclusions:
The frequency of HS in patients with CF is high and it is not related to malnutrition, according to the parameters of BMI, TSF and MAMC. The values of MAC and MAMC indicated a greater reserve of muscle mass in patients with HS.
... All patients with LD had severe mutations: DeltaF508, G542X, N1303K, CFTRdel.21Kb, 1811+1G-->C and Y1092X[14]. ...
Cystic fibrosis is a genetic disorder in which the mutation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that codes the protein forming a chloride channel of epithelial cells results in its distorted functioning. The products of the damaged gene cause irregular transport of water and electrolytes through epithelial cells, leading to chronic diseases of the respiratory and gastrointestinal tract, increase in saliva concentration in the saliva, and damage to reproductive functions. Oral manifestations are mild and may manifest in the form of enlargement of the lips or erythema, as well as a gingivitis with a concomitant mild dryness in the mouth. Prior to oral surgery, consultations with a doctor who treats the child are necessary, because if there is cirrhosis of the liver then there is certainly a lack of coagulation factor, as well as a disorder in the mechanism of blood coagulation. Dental interventions under general anesthesia should be avoided due to the poor condition of the respiratory system. Nowadays with a modern therapy possibilities is possible to extend patients' life expectancy, although cystic fibrosis remains incurable. The multidisciplinary team of doctors should include a pediatric dentist with the aim to take into consideration the specific prevention and treatment needs of this group of young patients. Knowledge of dentists about clinical signs and characteristics of cystic fibrosis is essential for the successful dental treatment of these patients and the enabling of their better quality of life.
... The role these factors play in the development of CFLD is, however, controversial. Some reports correlate meconium ileus or its equivalent (ie, distal intestinal obstruction syndrome) with increased liver disease prevalence (173,176,183), yet others fail to support this finding (175,184,185). No specific CFTR mutations are associated with the presence and/or severity of CFLD, and the same CFTR mutation yields variable liver phenotypes (183,184). ...
Hepatic involvement is often encountered in gastrointestinal (GI) diseases, in part because of the close anatomic and physiologic relations between the liver and GI tract. Drainage of the mesenteric blood supply to the portal vein permits absorbed and/or translocated nutrients, toxins, bacterial elements, cytokines, and immunocytes to gain hepatic access. Liver problems in digestive disorders may range from nonspecific hepatocellular enzyme elevations to significant pathologic processes that may progress to end-stage liver disease. Hepatobiliary manifestations of primary GI diseases in childhood and adolescence are not uncommon and include several well-described associations, such as sclerosing cholangitis with inflammatory bowel disease. Liver damage may also result from the effects of drugs used to treat GI diseases, for example, the hepatotoxicity of immunomodulatory therapies. This review highlights the important features of the hepatic and biliary abnormalities associated with 3 common pediatric GI conditions: inflammatory bowel disease, celiac disease, and cystic fibrosis.
... As a result, chronic liver disease has become an important issue among patients with CF and its severity may determine the prognosis of this group. The reported prevalence of liver disease among CF patients ranges between 9% and 37%, depending on the study and criteria for defining the liver disease [11,14,15,16]. Higher prevalence has been reported in studies in which liver disease had been actively searched for and diagnosed through a combination of diagnostic tools (clinical, biochemical, ultrasonographic evaluation). ...
As the expected survival improves in individuals with the cystic fibrosis (CF), so they may be faced with a number of medical complications.
The aim of this study was to analyze the prevalence of liver cirrhosis in our CF population as well as the clinical and genetic characteristics of these patients.
All patients older than 2 years (n = 96) were screened for liver disease. Liver cirrhosis was defined by ultrasonographic findings of distinct heterogeneity of liver parenchyma and nodular liver surface and/or by liver biopsy findings. Enlarged spleen, distended portal vein and abnormal portal venous flow indicated portal hypertension. Clinical and genotype data were analyzed.
Sixteen patients were found to have liver cirrhosis, three of them with portal hypertension. All patients had pancreatic insufficiency. Nutritional status expressed as standard deviation score (Z score) for weight, height, and body mass index was as follows: zW = -0.40 +/- 1.24, zH = -0.83 +/- 1.02, and BMI = 20.1 +/- 2.3. CF patients with liver cirrhosis generally had mild-to-moderate lung disease, with average FVC and FEV1 values of 97.1 +/- 16.5% of predicted and 87.9 +/- 23.5% of predicted, respectively. Genetic analysis showed high frequency of F508del mutation in the group with cirrhosis (90.6%).
The prevalence of liver cirrhosis in our CF population older than 2 years was 16.6%. Patients with pancreatic insufficiency and severe CFTR mutations, especially F508del, were exposed to higher risk of developing liver cirrhosis. Liver cirrhosis has no significant impact on the pulmonary function and the nutritional status, until the end-stage liver disease.
... So far, no specific mutations related exclusively to liver damage in the course of cystic fibrosis have been detected. Such mutations are usually "serious mutations" of the CFTR gene (delta F508, G524X, N1303K, CFTRdel21kB, 1811+1G-> C) [9,10]. Mutation delta 508 is a special risk factor of hepatic disease development in patients with cystic fibrosis; it stimulates increased loss of bile acids in faeces and enhances formation of more hydrophobic bile salts. ...
Liver changes observed in the course of cystic fibrosis comprise a group of complex processes of fibrosis, inflammation, remodelling, apoptosis and cholestasis as a result of abnormal functioning of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, immunological reactions and response to oxidation stress. Liver lesions are only observed in 5-20% of patients with diagnosed cystic fibrosis; however, they increase mortality, reduce the lifespan and deteriorate the quality of life. Liver diseases are the most common extrapulmonary causes of death in patients with cystic fibrosis. The aim of the study was to analyse the hitherto performed studies on the aetiopathogenesis of liver changes in the course of cystic fibrosis considering disturbances of the bile acid profile as well as genetic and immunological factors.
... Характерная морфологическая картина поражения печени при муковисцидозе: фокальный билиарный фиброз с явлениями отёка, хронической воспалительной инфильтрацией, пролиферацией жёлчных протоков, скоплениями эозинофильных масс во внутрипечёночных протоках. У некоторых больных эти изменения прогрессируют и ведут к мультилобулярному билиарному циррозу и портальной гипертензии [7,17]. ...
Presented was an overview of domestic and foreign literature on the condition of the hepatobiliary system in children with cystic fibrosis. Due to an increasing life expectancy of cystic fibrosis patients in the last decade, the frequency of complications from the hepatobiliary system (cholestatic hepatitis, portal hypertension, liver cirrhosis), which, according to various authors, range from 20 to 80%, also increases. The most pronounced changes in the liver and the gall bladder are characteristic for children with moderate pulmonary symptoms and predominantly with the intestinal form of the disease. The risk factors for liver damage in cystic fibrosis are - pancreatic insufficiency, «severe» mutation, male sex, meconium ileus in the past medical history and earlier age at which the disease was diagnosed. Complex ultrasound assessment of the liver parenchyma and blood flow in the portal vascular system and in the celiac trunk make it possible to specify the severity of fibrosis and to identify early signs of portal hypertension. Magnetic resonance imaging can confirm the presence of liver cirrhosis and determine collateral circulation associated with portal hypertension. Magnetic resonance cholangiography and radionuclide imaging make it possible to determine the status of intra- and extrahepatic biliary system. There is currently no effective treatment that could prevent the progression of liver damage. There are reports of the beneficial effects of ursodeoxycholic acid drugs. Perspective directions of treatment - liver transplantation and genetic engineering. Methods of conservative, endoscopic and surgical treatment of bleeding esophageal varices are used during the portal hypertension syndrome.
Liver damage observed in the course of cystic fibrosis is a group of complicated processes of fibrogenesis, inflammation, remodeling, apoptosis and cholestasis. The complexity of processes which take place in the liver and bile ducts in the course of this disease is not explained. Changes in the liver are observed in only 5-20% of patients with diagnosed cystic fibrosis, however, they increase mortality, shorten the length of life and deteriorate the quality of life. The aim of the study was evaluation of risk factors, clinical symptoms, diagnostic methods and treatment of liver changes in the course of cystic fibrosis.
