Histopathological and doppler findings in children with liver cirrhosis : a correlation study

Cirrhosis is an end stage state of virtually any chronic liver disease. There is great clinical interest in establishing the diagnosis of liver cirrhosis in children by non-invasive means. The aim of this work is to study the correlation between Doppler ultrasound parameters and hepatic histopathological findings in children with liver cirrhosis in an attempt to test the efficacy of these parameters as non-invasive means in diagnosis of cirrhosis. Patients and methods: Twenty two children admitted to Liver Institute, Menoufiya university for evaluation of unknown liver disease were examined prospectively and blindly with Doppler ultrasound prior to liver biopsy. Doppler studies were also preformed on 20 control subjects. Patients only were later subjected to liver biopsy. Histopathological examination of the biopsy specimens showed established cirrhosis in 11 of 22, early cirrhosis in 5 of 22. and no cirrhosis in 6 of 22 children. In patients group, the portal vein velocity was decreased [p < 0.05], the hepatic artery velocity was increased [p<0.05], and the arterio-portal velocity ratio was increased [p< 0.05] relative to the controls. Also, loss of reverse flow component was present in all established cirrhotic patients. For the criteria of the early and established cirrhotic patients, the sensitivities of the loss of reverse flow component in the hepatic vein, portal vein velocity being less than 20 cm/ s,hepatic artery velocity being more than 60 cm/s, arterio-portal velocity ratio being greater than 3.0 were 68.7%, 68.7%, 87.5% and 81.2% respectively. In established cirrhotic patients, the sensitivities of all parameters were 100%. In early cirrhotic patients, the sensitivities of hepatic artery velocity being more than 60 cm/s and arterio-portal velocity ratio being greater than 3.0 were 60% and 40% respectively. Indicators of parenchymal compliance [LRFC], outflow obstruction [decreased PVV] and arterialization [increased HAV, alteration in APVR] were accurate in the diagnosis of established cirrhosis. Also, HAV and APVR were useful in the diagnosis of early cirrhosis. We believe that on the basis of our data, afferent and efferent flow abnormalities monitored with Doppler ultrasound may be useful in the assessment of Patients with liver cirrhosis

Ciculating P53 antibodies in patients with hepatocellular carcinoma

Hepatocellular carcinoma [HCC] is one of the most common malignant tumours worldwide. The poor survival after diagnosis has led to the introduction of screening programs using alpha-fetoprotein [AFP], real time ultrasound scanning and computed tomography. Unfortunately, the accuracy of these programs is limited especially in small HCCs, hence there is clearly a need for other markers of malignant changes that can be used to screen cirrhotic patients. The aim of the present study was to assess the value of using a specific ELISA for the detection of antibodies directed against p53 protein as a scneening test for early detection and characterization of HCC. The present study included 34 patients with HCC and 20 control patients with non-neoplastic chronic liver diseases admitted to Tanta University Hospital and National Liver Institute Menoufeya University. The diagnosis in all the cases was based on histopathological examination of sonar-guided liver biopsies. Tumour size and number were determined at the time of presentation by ultrasound and CT scanning, HBsAg and HCV-antibody status were determined Serum bilirubin, ALT, AST, serum albumin, prothrombin activity, and serum alpha-fetoprotein [AFP] concentrations were measured. Circulating p53 antibodies were looked for using ELISA technique specific for detection of antibodies to p53 protein in serum samples. Positivity for circulating anti-p53 was detected in 16/34 of the HCC patients but in none of the control group with a sensitivity of 47.1%, and specificity of 100%. Positivity for AFP [>500 ng/ml] was found in 14/34 of HCC cases but in none of the control group [sensitivity 41.2%, specificity 100%]. The anti-p53 positivity was not significantly correlated to AFP-positivity [p = 0.4], Screening of patients and controls by both tests increased the sensitivity of detection of HCC up to 73.5%. The positivity for anti-p53 was significantly associated with the degree of HCC differentiation. It was significantly higher in well [9/12; 75%] than in poorly differentiated tumours [7/22; 32%] [p < 0.05], but it had not any significant relation with tumour size and number, nor was it related to hepatitis B or C status, background liver diseases, age, sex, serum bilirubin, serum albumin, ALT, AST, or prothrombin activity. In conclusion, detection of anti-p53 by ELISA is convenient and may be a valuable addition to the current screening tests for HCC with the potential to detect tumours at an early, and therefore more treatable, stage

Circulating anti-p53 antibodies in patients with liver cirrhosis, hepatocellular carcinoma and some non hepatic malignant disorders

Recently, p53 aberrations has been considered as a relevant factor in hepatocarcinogenesis, in tumors from high risk and low risk areas. As p53 mutations result in increased p53 antigen levels, this cellular protein with prolonged half-life might become immunogenic during tumor development. For testing this assumption, in addition to its occurrence or.not in cirrhotic patients and in patients with malignant disease other than hepatocelluar carcinoma, we have analyzed sera from three groups of patients each include 20 individuals; HCCs, cirrhosis, and malignant diseases other than HCCs patients, in addition to 20 healthy individuals with age and sex matched were used as a control group. For the patients and control groups, circulating antibodies against p.53 were measured by anti-p53 ELISA kit provided by Pharma Cell, Paris, France and alpha feto protein assayed using ["one step" Immunoenzymatic mediated assay [IEMA], Sorin Biomedica Kit]. Anti-p53 antibodies were detected in sera of three patients [15%] out of 20 patients with HCCs, the same results were obtained in patients with malignant diseases other than HCCs while anti-p53 antibodies were not detected in sera of cirrhotic patients and healthy control groups. In [65%] [13 of 20] of the hepatocellular carcinoma sera the alpha feto protein levels were elevated. Among the [35%] [7 out of 20] alpha feto protein negative hepatocellular carcinoma patients no one were found to contain anti-p53 antibodies. All anti-p53 positive HCC cases had multiple hepatic focal lesions in this study, also, 33.3% of them showed well differentiated HCC and 66.7% showed moderately differentiated HCC, Also, 33.3% were positive for HBsAg and 66.7% were positive for anti-HCV Ab. In conclusion, the presence of anti-p53 antibodies according to the results obtained in the current study, were specific for malignancy as these antibodies were detected in some HCC patients and patients who suffered from malignant diseases other than HCC with the same percent, but did not detect among cirrhotic patients or healthy individuals, also, these anti-p53 antibodies were independent of AFP status as we did not find any correlation between these anti-p53 antibodies and serum AFP among HCC patients group