Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

Role of Cone-Beam CT in the Intraprocedural Evaluation of Chemoembolization of Hepatocellular Carcinoma

Purpose. To assess the ability of Cone-Beam CT (CBCT), performed during the Transcatheter Arterial Chemoembolization (TACE), in predicting the response to treatment of hepatocellular carcinoma (HCC). Materials and Methods. We evaluated fifty patients (M/F = 40/10, mean age: 66.7 years ± 8.22) with hepatocellular carcinoma (HCC), for a total of 82 nodules evaluated (mean diameter: 21.4 ± 11 mm). All patients performed a CT scan one month before and one month after TACE. After TACE is completed, a CBCT was performed to assess the degree of drug retention in the lesions. For each lesion, the major diameter, volume, and density of the vital portion were evaluated. The response to TACE was assessed using the mRECIST criteria on the CT scan carried out one month after the procedure. The receiver operating characteristic (ROC) curves were performed to assess the accuracy of the CBCT in predicting the response to treatment and to identify the cut-off points for each parameter under examination. Results. A complete response (CR) was observed in 24/50 patients (48%), a partial response (PR) in 16/50 (32%), stable disease (SD) in 8/50 (16%), and progressive disease (PD) in 2/50 (4%). Evaluation of the area under the ROC curve showed that the diameter, volume, and density of the lesion, measured with CBTC, had an accuracy of 94%, 96%, and 98%, respectively, in discriminating a complete response from a not complete response. Conclusion. CBCT is effective in predicting short-term response at 1-month follow-up of HCC treated by chemoembolization

Recurrence of insulin resistant metabolic syndrome following liver transplantation

Insulin resistant metabolic syndrome is a major clinical disorder including hyperlipidaemia, hypertension, impaired glucose tolerance and/or type 2 diabetes and central obesity, which are well established cardiovascular risk factors. We report the case of a 61-year-old woman who developed severe hypercholesterolaemia and hypertriglyceridaemia after liver transplantation. In her forties she had hypertension, mixed hyperlipidaemia, mild hyperglycaemia and moderate abdominal obesity, suggesting the presence of the metabolic syndrome. She had liver enzyme elevation and severe steatosis and hepatomegaly at ultrasonography. At age 52, cryptogenic liver cirrhosis was diagnosed and rapidly progressing liver failure developed. In 1992 she underwent liver transplantation. Seven years after transplant the patient had abdominal obesity, high blood pressure, marked hypercholesterolaemia, hypertriglyceridaemia and moderate elevation of alanine aminotransferase. She also had impaired glucose tolerance and markedly increased basal and post-glucose load plasma insulin levels. Steatohepatitis was demonstrated by serial liver biopsies. This is the first case that reports the recurrence of the metabolic syndrome following liver transplantation. We postulate that metabolic syndrome may have promoted fatty liver and subsequent progression to end stage liver disease. We also stress the need for careful management of the metabolic syndrome in order to decrease the long-term risk for cardiovascular disease. © 2003 Lippincott Williams & Wilkins

Association between common metabolic diseases and severity of liver steatosis

Association between common metabolic diseases and severity of liver steatosi

Non-alcoholic fatty liver syndrome: A hepatic consequence of common metabolic diseases

Background and Aims: The association of liver steatosis with a number of common metabolic conditions has been suggested. The aim of the present study was to evaluate the clinical features of subjects with different severities of steatosis. Methods: The present study was performed in 282 consecutive patients with 'bright liver' at ultrasonography and in 58 subjects without steatosis. They had no history of alcohol abuse and negative tests for the presence of hepatitis B and C virus. Patients underwent clinical examination, anthropometry, laboratory tests and routine liver ultrasonography. Steatosis was graded as absent, mild, moderate and severe. Results: A progressive increase in the prevalence of obesity (P < 0.001), type 2 diabetes (P < 0.001), alanine aminotransferase (ALT) elevation (P < 0.001) and hypertriglyceridemia (P < 0.001), and a decrease of hypercholesterolemia (P < 0.05) was observed from the control group to the groups with mild, moderate and severe steatosis. More than half the subjects with liver steatosis had insulin resistance metabolic syndrome. Obesity, diabetes and hypertriglyceridemia were more common by 5.3-fold, 4.0-fold, and 6.7-fold, respectively, in subjects with severe steatosis, as compared to controls. Prevalence of obesity, diabetes and hyperlipidemia was significantly higher in subjects with fatty liver and ALT elevation. Conclusion: Fatty liver can be considered as the hepatic consequence of common metabolic diseases. (C) 2003 Blackwell Publishing Asia Pty Ltd

Fetal MRI of the cardiovascular system: role of steady-state free precession sequences for the evaluation of normal and pathological appearances

Purpose. This study aimed to evaluate the feasibility of fetal magnetic resonance imaging (MRI) with steady-state free precession (SSFP) sequences to visualise the normal and pathological appearances of the cardiovascular system. Materials and methods. This is a prospective observational study of 83 pregnant women who underwent fetal cardiac MRI: 43 patients (cases) had echocardiographic suspicion of congenital heart disease; 40 patients (controls) did not. Fetal cardiac MRI consisted of a static phase with multiplanar SSFP sequences and a dynamic phase with real-time SSFP sequences. Two radiologists evaluated the diagnostic quality of the SSFP images in both the controls and cases, the MRI morphological and functional features in the controls and the MRI signs of congenital heart disease in the cases. Results. In both groups, SSFP sequences produced good-quality MR images and good visualisation of morphological features. Functional data appeared to be unavailable due to the current small temporal resolution and the technical impossibility of fetal cardiac triggering. MRI detected direct signs of congenital heart disease in 21 fetuses, indirect signs in six and both signs in 15. Conclusions. SSFP sequences are effective in demonstrating the morphological features of the cardiovascular system, whereas dynamic SSFP cine-MRI sequences may provide adjunctive albeit suboptimal functional information

Attitudes and approach to cardiovascular risk factors in Italy: Results of an electronic questionnaire survey

Background. The advent of computer-based technology has led to innovative epidemiological research methods to exploit the advantages of computer-mediated communications. The aim of the present study was to develop and evaluate a self-administered electronic questionnaire for acquiring information on cardiovascular health, knowledge and behaviours in a representative, stratified sample of the Italian population. Methods. We report information on the attitudes and approach to cardiovascular disease prevention in a representative sample of Italian families who were interviewed at home by electronic questionnaires. The panel of families is currently used for national opinion polls and marketing surveys. Electronic questionnaires were filled out by 1683 males and 1736 females during a weekend period. Results. Two-thirds of respondents reported having their blood pressure measured while only half reported having blood lipid and glucose tests over the previous 2 years. Prevalence of reported hypertension, hypercholesterolaemia, diabetes and smoking were 15.2, 13.0, 9.8 and 37.1% in men and 10.1, 8.1, 2.6 and 28.0% in women, respectively. More than 50% of hypertensives and diabetics were on drug treatment, while only 20% of subjects reporting hyperlipidaemia were on medication. Conclusions. The results suggest the usefulness of self-administered electronic questionnaires for acquiring quick, low-cost and high response rate information in epidemiological surveys. © 2003 The Royal Institute of Public Health. Published by Elsevier Science Ltd. All rights reserved

Hyaluronan-cholesterol nanohydrogels: characterisation and effectiveness in carrying alginate lyase

Although in recent years several methods have been studied and developed to obtain different types of nanosized drug delivery systems, the set up of suitable procedures and materials remains highly expensive, their preparation is time consuming and often not feasible for a scale-up process. Furthermore, the sterilisation and storage of nanocarrier formulations represents a complicated but mandatory step for their effective use. In our previous work we assessed the use of an autoclaving process to achieve, in one simple step, sterile self-assembled hyaluronan-cholesterol (HA-CH) and hyaluronan-riboflavin (HA-Rfv) nanohydrogels (NHs). In the present work, the effect of the high temperature on HA-CH has been studied in detail. HA-CH suspensions were characterised in terms of size and polydispersity by Dynamic Light Scattering at different temperatures and conditions; the HA-CH chemical structure and its molecular weight were assessed via FT-IR and GPC analysis after the sterilising cycle in an autoclave at 121°C for 20min. The obtained NHs were then observed with TEM and AFM microscopy, in both dry and liquid conditions. The Young's modulus of the NHs was determined, evidencing the soft nature of these nanosystems; the critical aggregation concentration (c.a.c) of the nanosuspension was also assessed. Thereafter, alginate lyase (AL) was conjugated to NHs, with the aim of developing a useful system for therapies against bacterial infections producing alginate biofilms. The conjugation efficiency and the enzymatic activity of AL were determined after immobilisation. The AL-NHs system showed the ability to depolymerise alginate, offering an opportunity to be a useful nanosystem for the treatment of biofilm-associated infections