Non invasive tools for the diagnosis of liver cirrhosis

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibrosis. Serum markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without complications. They can be classified into direct and indirect markers which may be used alone or in combination to produce composite scores. Diagnostic imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound (US), US Doppler, contrast enhanced US and Elastography. US could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis, in this case Elastography is more reliable. This review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis

An unusual Erdheim-Chester disease with orbital involvement: A case report

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis with multiorgan involvement and a specific tropism for perivascular and fatty connective tissue, of unclear origin, with poor response to therapy. Its identification is difficult because of the variable clinical presentation and its lack of knowledge. We report the case of a 63-years-old woman, with a history of bilateral orbital pseudotumor, who comes to our attention because of progressively worsening asthenia, vomiting and systemic inflammation. Total body computerized tomography scan showed a volumetric increase of choroid plexus of the temporal horn of the left lateral ventricle, presence of solid retrobulbar tissue at the level of both maxillary sinuses, lung fibrosis, and retroperitoneal and peri-aortic infiltration. The association of these signs addressed to a diagnosis of Erdheim-Chester disease. Thus, although extremely rare, the diagnosis of Erdheim-Chester disease must be considered in the case of bilateral retro-orbital tumors and multisystemic involvement

A phenobarbital overdose: a case report

Background: Phenobarbital is a long-acting barbiturate, responsible for many cases of poisoning, from unintentional overdose or attempted suicide. We report a case of phenobarbital overdose in a patient with history of depression. Patients and Methods: A 60 year old woman was admitted to our Internal Medicine Unit for drowsiness, irritability, difficulties in the maintenance of an upright position, dysphasia and weakness. She was suffering from depression and epilepsy and treated with phenobarbital 150 mg/die. Results: At the admittance, she had high fever and neck stiffness; phenobarbital serum levels were 71.2 mcg/ml (3 times u.n.l.); aminotransferases were 12-17u.n.l. Arterial blood pressure was 80/50 mmHg. An inflammatory meningeal process was excluded by lumbar puncture; a brain and spinal cord CT scan excluded spine bone lesions and ischemic stroke. In the suspect of an overdose, a protocol of urine alkalinization was applied resulting in a reduction of phenobarbital levels below the therapeutic range in about 6 days, with state of consciousness, cognitive and behavioral functions improvement. A rapid normalization in aminotransferases levels was noted and serology for hepatitis viruses (HAV, HBV, CMV, EBV, HSV) resulted negative. Conclusions: In our patient phenobarbital was responsible for stupor, hypotension, hypertonicity and aminotransferases elevation, whereas fever was due to a concomitant pulmonary inflammatory process resolved after antibiotic therapy. Despite the use of these drugs has been progressively reduced, the number overdose reports remains still hig

Benign and malignant mimickers of infiltrative hepatocellular carcinoma: tips and tricks for differential diagnosis on CT and MRI

Hepatocellular carcinoma (HCC) may have an infiltrative appearance in about 8–20% of cases. Infiltrative HCC can be a challenging diagnosis and it is associated with the worst overall survival among HCC patients. Infiltrative HCC is characterized by the spread of multiple minute nodules throughout the liver, without a dominant one, ultimately resulting into macrovascular invasion. On CT and MRI, infiltrative HCC appears as an ill-defined, large mass, with variable degree of enhancement, and satellite neoplastic nodules in up to 52% of patients. On MRI, it may show restriction on diffusion weighted imaging, hyperintensity on T2- and hypointensity on T1-weighted images, and, if hepatobiliary agent is used, hypointensity on hepatobiliary phase. Infiltrative HCC must be differentiated from other liver diseases, such as focal confluent fibrosis, steatosis, amyloidosis, vascular disorders of the liver, cholangiocarcinoma, and diffuse metastatic disease. In cirrhotic patients, the identification of vascular tumor invasion of the portal vein and its differentiation from bland thrombosis is of utmost importance for patient management. On contrast enhanced CT and MRI, portal vein tumor thrombosis appears as an enhancing thrombus within the portal vein, close to the main tumor and results into vein enlargement. The aim of this pictorial review is to show CT and MRI features that allow the diagnosis of infiltrative HCC and portal vein tumor thrombosis. A particular point of interest includes the tips and tricks for differential diagnosis with potential mimickers of infiltrative HCC

The role of vitamin deficiency in liver disease: To supplement or not supplement?

Over the past few years, growing interest has been shown for the impact of dietary requirements and nutritional factors on chronic diseases. As a result, nutritional programs have been reinforced by public health policies. The precise role of micronutrients in chronic liver disease is currently receiving particular attention since abnormalities in vitamin levels are often detected. At present, treatment programs are focused on correcting vitamin deficiencies, which are frequently correlated to higher rates of comorbidities with poor outcomes. The literature reviewed here indicates that liver diseases are often related to vitamin disorders, due to both liver impairment and abnormal intake. More specific knowledge about the role of vitamins in liver disease is currently emerging from various results and recent evidence. The most significant benefits in this area may be observed when improved vitamin intake is combined with a pharmacological treatment that may also affect the progression of the liver disease, especially in the case of liver tumors. However, further studies are needed

The establishment of the agricultural landscape of central Sicily between the Middle Neolithic and the beginning of the Iron Age

The possible co-variation of human occupation and vegetation from the Middle Neolithic to the beginning of the Iron Age (7.5–2.8 ka BP) in Central Sicily in the context of the central Mediterranean between Middle and Late Holocene are analysed in this paper to provide new insights on Sicilian prehistoric demography. The demographic and economic trends during these millennia were reconstructed using archaeological, Accelerator Mass Spectrometry 14C dates, palynological, archaeobotanical, and zooarchaeological data from the northern, central, and southern sectors of Central Sicily through a diachronic comparison with variation in Arboreal Pollen, Anthropogenic Pollen Indicators, Olea-Juglans-Castanea pollen, microcharcoals, and Sporormiella from four pollen cores from sites in different ecosystems. A very significant spread of farming activities was found at the end of the Neolithic, together with an apparent demographic gap during the Middle Copper Age, and the emergence of agricultural landscapes at the end of the Copper Age associated with a striking increase in population. A combination of cultural and climatic changes during the late phase of the Bronze Age resulted in a subsequent overall decrease in population

COMEPA (COVID-19 Medicina Policlinico Palermo): a study in hospitalized patients.

Coronavirus disease 2019 (COVID-19) has dramatically changed our lives. In the past months, hospitals were saturated of patients; therefore, it is still important to have simple and standardized prognostic factors and to evaluate the efficacy and safety of medications commonly used for COVID-19. We aimed to collect data of the patients hospitalized in Internal Medicine and Geriatrics Wards at the University Hospital (Policlinico) ‘P. Giaccone’ in Palermo, Italy (COMEPA, COVID-19 Medicina Policlinico Palermo), with the main purpose of finding prognostic tools that can be easily used in clinical practice in order to identify patients hospitalized for/with COVID-19 at higher risk of negative outcomes, such as mortality, transfer to Intensive Care Unit (ICU) and institutionalization, as well as evaluating the efficacy/safety of medications commonly used for COVID-19. For reaching these aims, the medical records of approximately 600 patients will be recorded, having data on several parameters and including as outcomes mortality, ICU placement, institutionalization. With the COMEPA study, we therefore plan to update current literature, giving new data on prognostic factors and on the efficacy/safety of some medications used for COVID-19

Potential uses of olive oil secoiridoids for the prevention and treatment of cancer: A narrative review of preclinical studies

The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and char-acterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammatory, and anti-proliferative properties and, therefore, exhibit anti-cancer activity. This review summarizes the most recent findings regarding the pharmacological properties, molecular targets, and action mechanisms of secoiridoids, focusing attention on their preventive and anti-cancer activities. It provides a critical analysis of preclinical, in vitro and in vivo, studies of these natural bioactive compounds used as agents against various human cancers. The prospects for their possible use in human cancer prevention and treatment is also discussed

ALLELIC VARIANTS OF CYP2E1 GENE IN HEPATOCARCINOMA PATIENTS AND IN HEPATIC TUMOR CELL LINES

Background and Aims: Hepatic enzyme CYP2E1 is involved in the metabolism of a number of exogenous and endogenous substances (i.e. ethanol, drugs and chemical carcinogens). Being polymorphic, CYP2E1 gene can give different xeno-metabolic capabilities in a population and it is well known that inadequate or no enzymatic deactivation of xenobiotics could induce an increased susceptibility to disease and cancer. In particular, one of the 5 -flanking region polymorphisms, able to differentiate CYP2E1 gene transcriptional activity, is caused by the appearance/disappearance of RsaI and PstI restriction sites, which generates two different alleles, namely *C1(Rsa+/Pst−) and *C2(Rsa−/Pst+) respectively, reported to be in complete linkage disequilibrium. Methods: To confirm the existence of a correlation between some particular CYP2E1 genotypes/haplotypes and hepatocarcinoma, we determined CYP2E1 PstI/RsaI genotypes/haplotypes by RFLP-PCR in a cohort of central western Sicily hepatocarcinoma patients and in a population of healthy students from the same geographic area. Results: In hepatocarcinoma patients, modal genotype association was Rsa++/Pst−−, corresponding to CYP2E1 *C1/*C1 haplotype, whereas the Rsa+−/Pst−+ association, equivalent to CYP2E1 *C1/*C2 haplotype, resulted to have the lowest frequency both in patients and in controls. Moreover, both in patients and in controls, noncanonical genotype associations were frequent and arose from a no-linkage disequilibrium between the two polymorphic sites. Other authors reported this finding as a rare occurrence. Thus, from analysis of only one restriction site, Rsa++ genotype was approximately 1.5-fold more frequent in patients than in controls, and the non-canonical Rsa+− genotype was found relatively frequent in patients. Moreover, HuH7 and HA22T transformed hepatocarcinoma cell lines also showed the Rsa+− genotype. Conclusions: These results suggest that the presence in CYP2E1 genotype of at least one allele with an Rsa I restriction site is correlated with hepatocarcinoma. As this site is known a consensus sequence for some specific CYP gene transcription factors, like HNF-1, it may be supposed that a single nucleotide polymorphism can alter the possibility of HNF-1 to bind CYP2E1 promoter. This could determine a marked change in the transcriptional activity of the gene, incompetence in xenobiotic metabolism or in toxic substance deactivation and an increased susceptibility to neoplastic diseases, such as hepatocarcinoma