Review article: the diagnosis of non-alcoholic fatty liver disease -- availability and accuracy of non-invasive methods.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of clinical conditions, actually representing an emerging disease of great clinical interest. Currently, its diagnosis requires liver biopsy, an invasive procedure not free from potential complications. However, several non-invasive diagnostic strategies have been proposed as potential diagnostic alternatives, each with different sensitivities and accuracies. AIM: To review non-invasive diagnostic parameters and tools for NAFLD diagnosis and to formulate a diagnostic and prognostic algorithm for a better classification of patients. METHODS: A literature search was carried out on MEDLINE, EMBASE, Web of Science and Scopus for articles and abstracts in English. The search terms used included 'NAFLD', 'non invasive method and NAFLD', 'transient elastography' and 'liver fibrosis'. The articles cited were selected based on their relevancy to the objective of the review. RESULTS: Ultrasonography still represents the first-line diagnostic tool for simple liver steatosis; its sensitivity could be enhanced by the complex biochemical score SteatoTest. Serum cytokeratin-18 is a promising and accurate non-invasive parameter (AUROCs: 0.83; 0.91) for the diagnosis of non-alcoholic steatohepatitis (NASH). The staging of liver fibrosis still represents the most important prognostic problem: the most accurate estimating methods are FibroMeter, FIB-4, NAFLD fibrosis score (AUROCs: 0.94; 0.86; 0.82) and transient elastography (AUROC: 0.84-1.00). CONCLUSIONS: Different non-invasive parameters are available for the accurate diagnosis and prognostic stratification of non-alcoholic fatty liver disease which, if employed in a sequential algorithm, may lead to a reduced use of invasive methods, i.e. liver biopsy.

Multislice CT cholangiography without biliary contrast agent: technique and initial clinical results in the assessment of patients with biliary obstruction.

Our objective was to describe our technique for multislice CT cholangiography without cholangiographic contrast agent, and to present our preliminary clinical results. Thirty-seven patients with suspected biliary obstruction were studied. A multislice CT unit was used with the following technical parameters: 2.5-mm collimation; 7.5-mm/s table speed; pitch 6; 0.8-s rotation time; 300 mA; 120 kVp; 18- to 24-s scan time; scan volume ranging from the hepatic dome to below the pancreatic head; 70-s delay after injection of 150 ml of iodinated contrast agent at 4 ml/s. No biliary contrast material was given; oral iodinated contrast agent was administered to opacify bowel loops. Axial, multiplanar reformatted, and minimum intensity projection images were evaluated. The CT findings were compared with the gold standard techniques: endoscopic retrograde cholangiography (ERCP) in 30 patients, percutaneous transhepatic cholangiography in 5, and intraoperative cholangiography in 2. In 5 patients with ampullary lesions biopsy was made during ERCP, 9 underwent surgery, and 11 US-guided fine-needle aspiration. Bile ducts appeared hypodense within the surrounding enhanced structures. Regarding the site of obstruction, agreement between multislice CT and conventional cholangiography was observed in all cases. One patient presented negative findings on both CT and ERCP. In 31 of 36 (86%) patients, multislice CT cholangiography without cholangiographic contrast agent correctly assessed the cause of bile duct obstruction. Multislice CT cholangiography without cholangiographic contrast agent seems to be a promising diagnostic tool in the assessment of patients with bile duct obstruction.

[Intra-arterial chemotherapy in locally advanced or recurrent breast neoplasms]. / La chemioterapia intraarteriosa nella neoplasia mammaria localmente avanzata o recidiva.

Intraarterial chemotherapy is studied as an alternative procedure for the neoadjuvant treatment of locally advanced and recurrent breast cancer. Our study was aimed at investigating the feasibility, the toxicity and the local response rate of an intraarterial chemotherapy regimen including 5-fluorouracil, epirubicin and mitomycin. These drugs were administered angiographically into the subclavian and internal mammary arteries ipsilateral to the lesion. We treated 20 women with a median age of 58 years (range: 42-74 years); 12 patients had locally advanced breast cancer with a median tumor size of 12 cm (range: 6-20 cm) and 8 patients exhibited cutaneous, thoracic or axillary recurrences, with a median lesion size of 6 cm (range: 3-12 cm). In all, we administered 54 cycles of chemotherapy drugs (mean: 2.7 cycles a patient). Most patients were submitted to selective catheterization of the internal mammary artery (44/54 cycles); all the drugs were injected into the subclavian artery only when catheterization of this vessel was unfeasible. No angiography-related toxicity was observed. No systemic, particularly hematological, toxicity was observed. Four patients exhibited skin erythema in the feeding region of the internal mammary artery, 2 hemialopecia, 1 cutaneous steatonecrosis and 1 transient hemiplegia. We obtained 1 complete remission and 11 partial responses, with 60% overall response rate (12/20 patients). All the patients with locally advanced breast cancer had an objective response and the mean interval between the start of therapy and radical mastectomy was only 49 days. In conclusion, intraarterial chemotherapy for locally advanced or recurrent breast cancer is a feasible and well-tolerated tool which needs further studies, particularly to assess its efficacy.

[CT evaluation of sacrococcygeal chordoma]. / Aspetti TC dei cordomi sacrococcigei.

From June 1985 to September 1986, eight patients affected by sacrococcygeal chordoma were examined by means of conventional radiography and tomography first, and then by high-resolution CT. All patients underwent surgery and an histologic examination of the surgical specimen was carried out. CT always allowed to detect the sacro-coccygeal neoplasm, which looked like a solid non-homogeneous mass; in 50% of cases coarse calcifications were found. CT made it possible to evaluate the growing side of the tumor, its relation with the adjacent anatomical structures-especially the longitudinal extension and the involvement of the sacral hiatus; these findings proved to be very useful in order to choose the most appropriate surgical technique. CT findings also suggested the nature of the tumor but rarely allowed a definitive diagnosis. CT is, at any rate, mandatory in order to evaluate the real extent of the tumor and to plan surgery.

[Value and limitations of computerized tomography in the study of benign tumors of the bone]. / Valore e limiti della Tomografia Computerizzata nello studio dei tumori benigni dell'osso.

In order to stress the role of CT in the evaluation of benign tumors of the bone the authors studied by means of a high-resolution CT scanner 74 patients that later underwent surgery (70 cases) and histological examination (all cases). CT findings were compared with the surgical and histological data. The results prove that the diagnostic contributions of CT are less important in the evaluation of benign than in malignant bone tumors. The major contributions of CT were:--the capability of detecting the presence of osteoid osteoma not found by means of conventional radiographic techniques;--differentiation between benign osteochondroma and peripheral chondrosarcoma by measurement of the peripheral cartilaginous cap: this criterion, on the other hand, does not seem to be always reliable and useful;--differential diagnosis of different types of cystic and fibrocystic diseases (simple and aneurysmal bone cyst, fibrous dysplasia);--evaluation of soft-tissue tumoral masses and of their extra-osseus extent in giant cell tumor and chondroblastoma; this allows us to establish the real extension of the tumor and to plan surgery more accurately.

Symptoms, signs and findings in humans exposed to PCBs and their derivatives.

The records of the health effects caused by some accidental exposure and findings from medical examination in cases exposed to polybrominated biphenyls (PBB) as well as to polychlorinated biphenyls (PCB) and their derivatives polychlorinated dibenzofurans (PCDF) and dibenzodioxins (PCDD) have provided some information for the recognition and classification of their toxicity in humans. The most impressive clinical features have been presented by the yusho episode of exposure. Dermatologic signs are the most persistent indicator of a considerable uptake. Neurological symptoms, respiratory findings and impairment of liver function are further aspects of the contamination. Skin manifestations have been observed also in the newborn infants from mothers exposed to high levels of the substances. However, the available data make it still hard to assess the clinical picture of the effects on humans in cases of acute exposure and even more the effects on reproduction and long-term effects. Furthermore it would still be arbitrary to draw a line between the symptoms which can be referred to PCBs and PBBs alone and those which can be related qualitatively and quantitatively to PCB derivatives (PCDFs, PCDDs, PCQs).

Elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxine in goat milk.

2,3,7,8-Tetrachlorodibenzo-p-dioxine (TCDD) 200 ng/day, was given orally to 7 goats for 2 months, followed by an elimination period of 1 month. Then a daily dose of 400 ng TCDD was given for 1 month to the same animals. Two animals were killed and the rest of the animals were observed for several months. The excretion of TCDD in milk was studied by glass capillary gas fragmentography, where the minimal detectable concentration was below 5 ppt. After the first feeding the concentration of TCDD in milk achieved a maximum of 20.8 +/- 6.6 ppt while a similar value of 19.3 +/- 6.6 ppt was observed after the second feeding. After this period, the concentration of TCDD decreased slowly with values, after 18 weeks, of 4, 2 +/-, 3 and 6 ppt. The concentration of TCDD in the liver in the two animals killed was 1039.0 and 898.0 ppt. There were no differences in clinical observations or blood and urine analyses when experimental animals were compared with controls.

Alcohol-induced biphasic background and stimulus-elicited EEG changes in relation to blood alcohol levels.

The effects of 0.8 g alcohol kg-1 on CNS processes as reflected in EEG changes were studied in controlled experiments in 14 subjects in relation to BAC levels. A Two Period Change-Over Design with repeated trials over time allowed us to ascertain the time course and to isolate alcohol-induced changes from diurnal variations and effects of sequence and period. Based on spectral analysis of analog EEG recordings, the study has shown differential patterns of bi-phasic or tri-phasic alcohol-induced EEG changes over time in a number of parameters in background and in stimulus-elicited EEG responses varying with the BAC level and the metabolic phase of alcohol biotransformation. An increase in alpha activity during the absorption phase, a shift in the median of the total spectral power to the right (upwards), a decrease in slow activity in the delta and theta bands, and a decrease in variability of the background EEG on one hand and a reduction in stimulus-elicited EEg responses in total spectral alpha, theta and delta bands on the other are all interpreted as a stimulating excitatory effect during the absorption phase, parallel to the increase in BAC. The reverse pattern in the first part of the elimination phase infers a decrease in cerebral activation reflecting the sedative, depressant action of alcohol in this phase. The effects observed in the last trial, to a certain extent interpreted as stimulating, were simultaneous with the beginning of the post-alcohol hangover phase.

Acute human exposure to TCDD in Seveso, Italy.

The children and adults who suffered injuries after exposure to chemicals that escaped in July 1976 from a reactor during the production of trichlorophenol is Seveso, Italy, have been repeatedly examined by a medical commission appointed by the judge holding the legal inquest. All patients suffered burnlike skin lesions and all but two recovered without residual effects. Chloracne occurred in 12 of these cases; it was mild in almost all and has now disappeared. Systemic functions were repeatedly evaluated in all cases and no evidence of visceral lesions was obtained. Immunocapability was normal and chromosome aberrations were within the normal range.

Estimation of the TCDD toxic potential in the light of the Seveso accident.

Two years after the TCDD release in Sevesco from the assessment of the acute and midterm effects on the health of the population exposed to known level of contamination the following facts emerged. Chloracne appeared mainly in a small nuber of children mostly with mild severity and quick recovery. Immunoresponse remained normal and susceptibility to infectious diseases was not increased. Peripheral nervous system was not affected in these children nor were the hepatic functions and the urinary porphyrin excretion. Fetal losses and birth defects remained within the expected rates. Newborn growth and development proceeded normally. Chromosome examinations did not reveal abnormalities in number and patterns. A case of intercurrent death provided for the first time TCDD tissue levels in man 6 months after the exposure.

The heart rate response as an indicator of changes in activation induced by alcohol.

This experiment was conducted in order to examine different alcohol-induced states of activation as indicated by the acoustic evoked heart rate response (HRR). Twelve healthy male subjects received 0.7 g/kg alcohol in one session of a cross-over designed experiment. In the control session no alcohol was given. The measurements of three parameters of the heart rate response as well as the self-assessments of mood were repeated five times along the course of the venous blood alcohol concentration. Significant depressant alcohol effects were reflected in a decrease in the HRR acceleration as well as in a decrease in vitality, vigilance, and self-estimated startle reaction. Stimulating effects could be observed in an increase of the mean heart rate and the second HRR deceleration. We conclude that different alcohol-induced states of activiation represent different patterns of inhibitory and facilitatory processes, each manifesting itself in different parameters. The results suggest three major components of alcohol action: 1) an inhibition release with immediate onset,2) a slower processing inhitition,3) attention focussing as a compensatory response to inhibition.

[The time-course of alcohol induced changes in self-rating-scales of mood (author's transl)]. / Der zeitliche Verlauf der Alkoholwirkung in Skalen der Selbstbefindlichkeit

Alcohol was administered in a dose of 0.77 g per kg bodyweight to 16 healthy male subjects in a cross-over-design. A study was made of a number of psychological and physiological variables to determine the modifications that accompany the alcohol-induced changes in the orienting response to an auditory stimulus. Five determinations were made at intervals following a dose of alcohol and five in a control session when no alcohol was given. The results obtained for the psychological variables (self-ratings of the intensity of intoxication and the degree of being startled by the first stimulus; and self-assessment of mood) show alcohol to have stimulant as well as depressant effects. Some of the variables show stimulant effects, mainly at the beginning of the absorption phase, whereas other variables show depressant effects, both in the absorption phase and the postabsorption phase. Changes in physiological variables (such as parameters of electrodermal activity and of the heart rate response) support these findings. The simultaneous presence of both stimulant and depressant effects is pointed out as well as the difficulties in describing these findings in terms of a unidimensional model of activation.

Relation between drug-induced central nervous system effects and plasma levels of diazepam in man.

Pharmacodynamic effects and plasma levels of diazepam were studied in healthy male volunteers at different dose levels. Responses to diazepam were quantified, using instruments which measured body sway (statometry) and psychomotor performance (stressalyser tests). High dose-related correlations were obtained between drug-induced changes in test parameters and drug plasma levels, both with regard to stimulant and depressive effects. Techniques were devised for evaluating and comparing the efficacy and usefulness of different types of tests, taking into account critical thresholds, slopes and error estimates, correcting for changes in predrug levels and control (nondrug) trials.