Elżbieta Skiba

Serum concentration of adiponectin, leptin and resistin in obese children with non-alcoholic fatty liver disease

PURPOSE Obesity, insulin resistance and dyslipidemia are the most significant risk factors of non-alcoholic fatty liver disease (NAFLD) but the role of adipokines in patomechanism of this disease is not clear. The aim of the study was to evaluate the serum levels of leptin, adiponectin and resistin in obese children with NAFLD. MATERIAL/METHODS The fasting serum levels of adipokines were determined in 44 consecutive obese children with suspected liver disease and in 24 lean controls. The degree of the ultrasound liver steatosis was graded according to Saverymuttu. RESULTS The fatty liver was confirmed in 33 children by ultrasonography (16 of them also showed an increased ALT activity). The serum leptin level was significantly higher and adiponectin level was lower in the obese children with NAFLD when compared to controls. Only adiponectin correlated with homeostasis model assessment of insulin resistance (HOMA-IR). Significant negative correlations were found between the ultrasonographic grades of liver steatosis and adiponectin and resistin levels. Serum adiponectin and resistin levels were lower in children with an advanced liver steatosis (grade 3, n=10) compared to patients with a mild steatosis (grade 1-2, n=23). The ability of serum adiponectin and resistin to differentiate children with an advanced liver steatosis from those with mild steatosis was significant. CONCLUSIONS These data suggest a role of both adiponectin and resistin in the pathogenesis of NAFLD in obese children and confirm the association between adiponectin and insulin resistance. Adiponectin and resistin may be suitable serum markers in predicting an advanced liver steatosis in children with NAFLD.

Tumor necrosis factor alpha and its soluble receptors in obese children with NAFLD.

PURPOSE To evaluate the serum levels of tumor necrosis factor (TNF) alpha and its soluble receptors in obese children with non-alcoholic fatty liver disease (NAFLD). MATERIAL/METHODS Fasting serum levels of TNFalpha and its receptors were determined in 45 consecutive obese children with suspected liver disease and 20 lean controls. The degree of liver steatosis was graded in ultrasound according to Saverymuttu. 1H-MR spectroscopy was performed with 1.5T scanner with PRESS sequence. RESULTS A fatty liver was confrmed in 32 children by ultrasonography (group I); 16 of them also had increased ALT activity (group Ia - NAFLD). Serum concentrations of TNFalpha and its receptors were significantly higher in obese children with NAFLD compared to controls. Significant correlation was found between ultrasonographic grade of liver steatosis and TNFalpha level but serum level of this adipokine was not significantly different in children with advanced liver steatosis (grade 2-3, n=13) compared to patients with mild steatosis (grade 1, n=19). The ability of TNFalpha and its receptors (R1, R2) to differentiate children with advanced liver steatosis from those with mild steatosis was insignificant. However, the ability of serum TNFalpha to differentiate obese children with liver steatosis from those without steatosis was significant (AUC=0.7448, p=0.0291). CONCLUSION Although TNFalpha does not predict advanced liver steatosis, it may be suitable serum marker in predicting liver steatosis in obese children.

Extrahepatic manifestations associated with chronic hepatitis C infections in Poland

PURPOSE To assess the prevalence and predictive factors of extrahepatic manifestation (EM) in patients with chronic hepatitis C (CHC) infection in Poland. MATERIAL AND METHODS 340 consecutive patients (mean age: 42 years) with untreated CHC were studied between 2000 and 2006. The HCV infection was defined by positive serology and serum HCV RNA. The inflammation grade and fibrosis stage were assessed according to Ishak. Demographic, laboratory and liver biopsy data were collected. The patients with liver cirrhosis, concomitant HBV or HIV infection, autoimmune liver diseases and alcohol abusers were excluded from the analysis. RESULTS 210 patients with CHC (61.7%) presented at least 1 extrahepatic manifestation, including mixed cryoglobulinemia (37.1%), thrombocytopenia (27.6%), thyroid autoimmunity (16.2%), dermatological disorders (4.1%) and type 2 diabetes (4.1%). Other EM such as the sicca syndrome, nephropathy, polyneuropathy and B-cell lymphoma were observed in single cases. In multivariate analysis lower platelet count was found as a predictive factor of EM in patients with CHC. CONCLUSIONS The majority of patients with CHC, living in Poland, have EM, of which cryoglobulinemia, thrombocytopenia, thyroid autoimmunity, dermatological disorders and type 2 diabetes are most common. Through the multivariate analysis the lower platelet predicts extrahepatic manifestations associated with chronic hepatitis C.

Hepatoblastoma as a result of APC gene mutation.

H epatoblastoma is a rare early childhood neoplasm occurring in patients with genetic disorders, such as trisomies of chromosomes 18, or inherited predispositions to some neoplastic diseases, including Beckwith-Wiedemann syndrome and familial adenomatous polyposis (FAP) (1). The observed increase in the risk of hepatoblastoma in APC (adenomatous polyposis coli) gene mutation carriers is low, not exceeding 1%, which is associated with APC gene mutation located in the region of codons 459 to 1309, where most mutations identified in families affected by FAP in Poland are found. Tissues obtained from patients with hepatoblastoma but without the diagnosis of FAP show loss of heterozygocity at the locus of APC or MCC (mutated in colorectal cancers) genes. Hepatoblastoma growth is the result of the sequence of changes in genetic material. A major role can be ascribed to the Wnt pathway where somatic mutations have been observed in the genes of B-cathenin (CTNNB1, Cathenin [cadherin-associated protein], b-1.88 kD), and AXIN1 (axis inhibitor 1) (2,3). We present a case of familial hepatoblastoma in a 3-month-old infant with a constitutional mutation in the APC gene. A female infant ages 3 months (Fig. 1. IV, 4) was admitted to the department for the diagnosis and treatment of abdominal tumor. The index case was born after an uneventful pregnancy with routine antenatal scanning carried out during the pregnancy, which was unremarkable. Parents are healthy and unrelated. This was her mother’s fourth pregnancy; the first and third pregnancies ended with miscarriages in 1st trimester (Fig. 1. IV, 1 and 3). Second pregnancy resulted in a girl born at 36th week who died at age 14 months with the diagnosis of multiple congenital defects: congenital hydrocephalus, spina bifida, anorectal malformations, and cardiac anomaly. Her chromosomal analysis was normal: 46, XX (Fig. 1. IV, 2). On admission, the physical examination revealed a large hard tumor, bulging in the whole abdominal cavity. Additional tests found thrombocythemia (701 10 /mL) and elevated levels of a-fetoproteins (331.000 ng/mL) and b-human chorionic gonadotropin (75.81 mU/mL). The ophthalmic examination showed congenital hypertrophy of the retinal pigment epithelium (CHRPE) in the eye fundus. Computed tomography scan visualized a pathological 120 95 74-mm mass, visible from the left dome of the

The case of the youngest infant with hepatoblastoma with APC gene mutation

Hepatoblastoma is a rare early malignant liver neoplasm occurring in infants and children. Some cases of hepatoblastoma are associated with genetic conditions such as trisomies of chromosomes 18, Beckwith-Wiedemann syndrome and familial adenomatous polyposis (FAP). The observed increase in the risk of hepatoblastoma in APC (adenomatous polyposis coli) gene mutation carriers is low, not exceeding 1%, which is associated with APC gene mutation located in the region of codons 459-1309, where most mutations identified in families affected by FAP in Poland are found. Tissues obtained from patients with hepatoblastoma but without the diagnosis of FAP show loss of heterozygocity at the locus of APC or MCC (mutated in colorectal cancers) genes. Hepatoblastoma growth is the result of the sequence of changes in genetic material. However, a major role can be ascribed to the Wnt pathway where somatic mutations have been observed in the genes of Bcathenin (CTNNB1, Cathenin (cadherin-associated protein), beta 1.88kD) and AXIN1 (Axis inhibitor 1). We present a case of familial hepatoblastoma in a 3-month-old infant with a constitutional mutation in the APC gene.