Under-prescription of statins in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with high cardiovascular risk. Management of dyslipidaemia plays a pivotal role in the prevention of CV events and statins have proved to be safe in these patients. However, in everyday clinical practice statin prescription is sometimes limited because of the concern of physicians about side-effects. The aim of the study was to investigate if the presence of NAFLD affects the prescription of lipid-lowering treatment in a large series of patients with cardio-metabolic disorders. METHODS AND RESULTS: Cardiovascular risk and LDL-C targets were defined according to ESC/EAS Guidelines in 605 consecutive adult subjects referred for screening of suspected metabolic diseases. Liver steatosis was assessed by ultrasound Hamaguchi criteria. In the whole cohort, 442 patients had indication for cholesterol-lowering treatment. Lack of statin prescription was present in 230 (52.0%) patients. Of these, 77 (33.5%) were very high-risk, 48 (20.8%) high-risk, and 105 (45.6%) moderate risk patients. Only 44% of the NAFLD patients with indication for statin treatment were on therapy. NAFLD patients on statin treatment had significantly lower ALT values as compared to those not on treatment (p < 0.05). CONCLUSIONS: Our findings show that about 50% of patients with indication to statin treatment do not receive any cholesterol-lowering medication. Statin under-use was particularly high in subjects with NAFLD. Use of statin treatment should be encouraged in the context of NAFLD, as it may improve lipid profile and reduce the cardiovascular risk in this setting.

Low-grade endotoxemia, gut permeability and platelet activation in patients with impaired fasting glucose.

BACKGROUND AND AIM: Impaired fasting glucose (IFG) is associated with an increased risk of cardiovascular disease but the underlying mechanisms are still unclear. Aim of the study was to investigate the interplay between platelet activation, lipopolysaccharides (LPS) and markers of oxidative stress in patients with IFG and control subjects. METHODS AND RESULTS: We performed a cross-sectional study including 35 patients with IFG and 35 control subjects who were well comparable for age, sex, body mass index and smoking history. Serum levels of LPS, zonulin (a marker of gut permeability), oxidized LDL and plasma levels of soluble P-selectin, were measured. Patients with IFG had significantly higher levels of sP-selectin, LPS, zonulin and oxLDL compared to control subjects. The IFG status (beta coefficient: 0.518, p < 0.001), higher LPS (beta coefficient: 0.352, p = 0.001) and female sex (beta coefficient: 0.179, p = 0.042) were independently associated with higher sP-selectin; in addition, oxLDL was positively associated with sP-selectin (r = 0.530, p < 0.001) and LPS (r = 0.529, p = 0.001). In IFG patients, we found a significant association between LPS and zonulin (r = 0.521, p = 0.001); this association was confirmed at multivariable analysis (beta coefficient: 0.512, p = 0.007). CONCLUSION: Our study provides evidence that patients with IFG have increased platelet activation, and suggests LPS as a potential trigger for in vivo platelet activation in this patient population.

Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis.

BACKGROUND AND AIM: Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH. METHODS: In a cross-sectional study we analysed endothelial function, as assessed by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx), in patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we performed a randomized, cross-over study in 19 subjects with NASH comparing the effect of 14-days administration of 40 g of chocolate at high (dark chocolate, cocoa >85%) versus low content (milk chocolate, cocoa <35%) of polyphenols on FMD and oxidative stress. Compared to controls, NASH and FLD patients had higher Nox2 activity and isoprostanes levels and lower FMD and NOx, with a significant gradient between FLD and NASH. The interventional study showed that, compared to baseline, FMD and NOx increased (from 2.9 ± 2.4 to 7.2 ± 3.0% p < 0.001 and from 15.9 ± 3.6 to 20.6 ± 4.9 µM, p < 0.001, respectively) in subjects given dark but not in those given milk chocolate. A simple linear regression analysis showed that Δ (expressed by difference of values between before and after 14 days of chocolate assumption) of FMD was associated with Δ of Nox2 activity (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs: 0.557; p < 0.001). CONCLUSIONS: Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients.

Type IIB von Willebrand factor with normal sialic acid content induces platelet aggregation in the absence of ristocetin. Role of platelet activation, fibrinogen, and two distinct membrane receptors.

Three preparations of purified von Willebrand factor (vWF), obtained from unrelated patients affected by type IIB von Willebrand disease, were found to have normal sialic acid content (between 129 and 170 nmol/mg of vWF, as compared with 158 +/- 17 nmol/mg in four normal preparations) and to induce platelet aggregation in the presence of physiologic levels of divalent cations and without addition of ristocetin. A monoclonal antibody that blocks the vWF binding domain of the platelet glycoprotein (GP)Ib caused complete inhibition of IIB vWF-induced aggregation. In contrast, a monoclonal antibody that blocks the receptor for adhesive proteins on the platelet GPIIb/IIIa complex failed to inhibit the initial response of platelets to high concentrations of IIB vWF. Moreover, IIB vWF caused agglutination of formalin-fixed platelets that was blocked only by the anti-GPIb antibody, suggesting that the binding of vWF to GPIb, even in the absence of ristocetin, results in platelet-platelet interaction that is followed by exposure of the GPIIb/IIIa receptors for adhesive proteins. Endogenous ADP, normally active platelet metabolism and fibrinogen binding to GPIIb/IIIa were necessary for maximal and irreversible platelet aggregation. In the absence of fibrinogen, however, aggregation was mediated by vWF binding to GPIIb/IIIa. A 52/48-kD tryptic fragment containing the GPIb binding domain of normal vWF completely blocked the aggregation induced by all three IIB vWF preparations. The present study defines in detail the mechanisms involved in IIB vWF-induced platelet aggregation. Moreover, it establishes that the GPIb binding domain of normal and IIB vWF are closely related and that desialylation is not required for the direct interaction of IIB vWF with GPIb.

Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. It is suspected in persons with elevated aminotransferase levels and features of insulin resistance (or metabolic) syndrome. The pathogenesis of NAFLD is not clear and there is no universal treatment. OBJECTIVES: To assess beneficial and harmful effects of drugs improving insulin resistance for NAFLD and/or NASH. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and The Chinese Biomedical Database until February 2006. SELECTION CRITERIA: We included randomised clinical trials assessing the effects of drugs improving insulin resistance for patients with NAFLD or NASH. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two independent observers extracted data from each trial. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Only three randomised clinical trials could be included. Two of the trials had unclear allocation concealment. None was blinded regarding outcome assessment. In two trials, metformin was associated with significantly higher normalization of serum alanine aminotransferase (OR fixed 2.83, 95% CI 1.27 to 6.31 versus diet and OR fixed 7.75, 95% CI 2.37 to 25.35 versus vitamin E) and improvement of liver echographic response (OR fixed 5.25, 95% CI 1.09 to 25.21). An improvement of fatty infiltration was observed in a limited number of patients undergoing liver biopsy. In the single pioglitazone trial, a statistically significant improvement of NASH histology was demonstrated. AUTHORS' CONCLUSIONS: At present, there is insufficient data to either support or refute the use of drugs improving insulin resistance for patients with NAFLD, although current limited information suggests a favourable role of drugs improving insulin resistance. It is advisable to carry out large randomised trials on this topic employing clinically relevant outcome measures and adequate methodology, including blinded outcome assessment.

Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis.

BACKGROUND: Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non-alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans. AIM: To analyse the effect of cocoa polyphenols on NADPH oxidase isoform 2 (NOX2) activation, oxidative stress and hepatocyte apoptosis in a population affected by NASH. METHODS: In a cross-sectional study comparing 19 NASH and 19 controls, oxidative stress, as assessed by serum NOX2 activity and F2-isoprostanes, and hepatocyte apoptosis, as assessed by serum cytokeratin-18 (CK-18) levels, were measured. Furthermore, the 19 NASH patients were randomly allocated in a crossover design to 40 g/day of dark chocolate (>85% cocoa) or 40 g/day of milk chocolate (<35% cocoa), for 2 weeks. sNOX2-dp, serum isoprostanes and CK-18 were assessed at baseline and after 2 weeks of chocolate intake. RESULTS: Compared to controls, NASH patients had higher sNOX2-dp, serum isoprostanes and CK-18 levels. A significant difference for treatments was found in subjects with respect to sNOX2-dp, serum isoprostanes and serum CK-18. The pairwise comparisons showed that, compared to baseline, after 14 days of dark chocolate intake, a significant reduction in sNOX2-dp serum isoprostanes and CK-18 M30 was found. No change was observed after milk chocolate ingestion. A simple linear regression analysis showed that ∆ of sNOX2-dp was associated with ∆ of serum isoprostanes. CONCLUSION: Cocoa polyphenols exert an antioxidant activity via NOX2 down-regulation in NASH patients.

Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease.

BACKGROUND/AIMS: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. METHODS AND RESULTS: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median. CONCLUSIONS: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.

Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan.

Previous observations have shown that oral administration of 5-hydroxytryptophan (5-HTP) without dietary prescriptions causes anorexia, decreased food intake, and weight loss in obese subjects. To confirm these data over a longer period of observation and to verify whether adherence to dietary restriction could be improved by 5-HTP, 20 obese patients were randomly assigned to receive either 5-HTP (900 mg/d) or a placebo. The study was double-blinded and was for two consecutive 6-wk periods. No diet was prescribed during the first period, a 5040-kJ/d diet was recommended for the second. Significant weight loss was observed in 5-HTP-treated patients during both periods. A reduction in carbohydrate intake and a consistent presence of early satiety were also found. These findings together with the good tolerance observed suggest that 5-HTP may be safely used to treat obesity.

INTERSALT in Italy: findings and community health implications.

In INTERSALT, an international cooperative study on electrolytes and blood pressure, significant associations were found, in the pooled data for 52 centres, between systolic BP and sodium (Na) excretion, body mass index (BMI), high alcohol intake and low potassium (K) excretion. We have assessed the status of the four Italian centres (Mirano, Gubbio, Bassiano, Naples) on these variables. The four centres examined a total of 794 men and women aged 20-59 years. Combined values were similar to overall INTERSALT levels for daily Na excretion (170 mmol) and BMI (25 kg/m2). The Italian centres had slightly higher potassium excretions (57 vs. 55 mmol/day), a higher prevalence of drinkers and a greater average alcohol consumption. Participants were divided into those below or above median levels of Na, K, BMI, and by alcohol intake (below or above 300 ml/week). Both systolic BP and diastolic BP were found to be lower in the more favourable stratum, for each variable. When all four factors were combined, those below median Na excretion and BMI, above median K, and with alcohol intake less than 300 ml/week had age-adjusted systolic BP 7.5 mmHg lower than those with less favourable levels of all four variables. The difference in adjusted diastolic BP was 4.3 mmHg. The data indicate the potential for lower population average BP with improved lifestyles.

Nutritional habits in the Mediterranean Basin. The macronutrient composition of diet and its relation with the traditional Mediterranean diet. Multi-centre study of the Mediterranean Group for the Study of Diabetes (MGSD).

OBJECTIVE: To compare the nutritional habits among six Mediterranean countries and also with the various official recommendations and the 'Mediterranean diet' as originally described. DESIGN: Cross-sectional study. SETTINGS: Three centres in Greece, two in Italy and one in Algeria, Bulgaria, Egypt and Yugoslavia. SUBJECTS: Randomly selected non-diabetic subjects from the general population, of age 35-60, not on diet for at least 3 months before the study. INTERVENTIONS: A dietary questionnaire validated against the 3-Day Diet Diary was used. Demographic data were collected and anthropometrical measurements done. RESULTS: All results were age adjusted. Energy intake varied in men, from 1825 kcal/day in Italy-Rome to 3322 kcal/day in Bulgaria and in women, from 1561 kcal/day in Italy-Rome to 2550 kcal/day in Algeria. Protein contribution (%) to the energy intake varied little, ranging from 13.4% in Greece to 18.5% in Italy-Rome, while fat ranged from 25.3% in Egypt to 40.2% in Bulgaria and carbohydrates from 41.5% in Bulgaria to 58.6% in Egypt. Fibre intake, g/1000 kcal, ranged from 6.8 in Bulgaria to 13.3 in Egypt and the ratio of plant to animal fat from 1.2 in Bulgaria to 2.8 in Greece. The proportion of subjects following the WHO and the Diabetes and Nutrition Study Group (DNSG) of the EASD recommendations for carbohydrates, fat and protein ranged from 4.2% in Bulgaria to 75.7% in Egypt. Comparison with the Mediterranean diet, as defined in the seven Country Study, showed significant differences especially for fruit, 123-377 vs 464 g/day of the Mediterranean diet, meat, 72-193 vs 35 g/day, cheese, 15-79 vs 13 g/day, bread, 126-367 vs 380 g/day. CONCLUSIONS: (a) Dietary habits of the 'normal' population vary greatly among the Mediterranean countries studied. (b) Egypt is closest to the DNSG recommendations. (c) Significant differences from the originally described Mediterranean diet are documented in most Mediterranean countries, showing a Westernization of the dietary habits.

Modular uncemented prosthetic reconstruction after resection of tumours of the distal femur.

We report the use of the uncemented Kotz modular femur and tibia reconstruction system after 95 distal femoral resections performed from 1983 to 1989. The average follow-up was 51 months; 62 patients had at least 36 months' follow-up and 36 at least 60 months. Complications required reoperation in 55%. The postoperative infection rate was 5% for primary cases, 6% for revision cases, and 43% for revision of previously infected cases. The polyethylene bushes failed in 42% of cases at an average of 64 months postoperatively. Stem breakage occurred in 6% and was associated with the use of narrow stems and extensive quadriceps excision. The radiological results were excellent or good in most cases and were related to the initial screw fixation, but not to age, chemotherapy, length of resection or size of stem. The clinical results were excellent or good in 75%, failure usually being associated with a complication, especially infection.

Intracranial hemorrage due to brain metastases in an Italian HCV patient with hepatocellular carcinoma.

Brain metastases from hepatocarcinoma are exceptional and only a few cases have been reported in the literature, mainly from Far-Eastern countries. Clinical diagnosis in asymptomatic patients with preserved liver function is difficult and usually late. In some cases, cerebral metastasis is the initial manifestation of HCC and patients may develop intracerebral hemorrage and have a stroke-like presentation. We report on the first Italian case of cerebral metastases from multifocal hepatocellular carcinoma in an asymptomatic HbsAg negative patient with unknown HCV related chronic hepatitis and no evidence of liver cirrhosis. For many years he had a mild liver enzyme elevation and the presence of multiple misinterpreted hypoechogenic hepatic lesions. The hepatic tumor spread to the lungs and the brain and the patient developed two major episodes of intracranial hemorrage. He had two nodular lesions in the brain and alpha-fetoprotein levels were more than 10,000 ng/ml. He died from neurologic causes, without major signs of liver failure.

[Reliability and power of genetic studies]. / Affidabilità e potenzialità dello studio genetico.

During the last few years new powerful diagnostic methods have been developed in the field of molecular and cell biology. It is now possible to work out the molecular pathology of many genetic diseases and to institute new techniques for the detection of carriers and neonatal diagnosis. However, it is in the field of polygenic diseases such as degenerative vascular disease, diabetes, cancer and other chronic diseases that molecular biology will play its most important part and perhaps change in the long term our clinical approach. There is considerable debate among geneticists on the safest strategy for obtaining and long term storing sufficient DNA from an individual for projects requiring large but unknown amounts of DNA. As little as 0.5 ml whole, blood samples (or white cells) which have been frozen with 10% DMSO or anticoagulants will provide sufficient DNA by direct extraction methods and also permit to establish lymphoblastoid cell lines providing an infinite source of DNA.

Rotationplasty in segmental resections of the femur.

The authors report 26 cases of high-grade malignant tumors of the distal femur (23 osteosarcomas, 3 Ewing's tumors) submitted to rotation-plasty. The five-years actuarial survival rate (in the 23 cases of osteosarcoma) was 69% and there was no incidence of local recurrence. The following complications were observed: wound dehiscence (6 cases), arterial thrombosis (in 2 patients submitted to resection and vascular termino-terminal suturing), paralysis of the sciatic nerve (2 cases), delay in consolidation (2 cases), traumatic fracture of the neo-femur (3 cases). All of the complications were resolved favorably, 5 of these requiring surgical treatment (33%). Satisfactory functional results were obtained in all of the cases, except in one patient who had limitation of the ankle joint subsequent to vascular compartmental syndrome. On the basis of the oncological, functional and biomechanical results reported in this study and in the literature, the authors discuss current indications for rotation-plasty.

The use of massive bone allografts for intercalary reconstruction and arthrodeses after tumor resection. A multicentric European study.

A multicentric study was conducted by the European Musculoskeletal Oncology Society on 113 cases of resection for tumors of the major long bones and reconstruction with massive allografts, as intercalary diaphyseal or for arthrodesis. The follow-up was at least 12 months. There was a 14% incidence of infection, with a higher frequency (18.5%) in intercalary grafts as compared to arthrodeses (7%). Fracture of the graft occurred in 15.5% of the cases with a prevalence in the humerus (28.5%) as compared to the tibia (21.4%) and femur (14.7%). Fracture constantly occurred after osteosynthesis with screws, in 16% of the cases after osteosynthesis with a plate, and in 12.5% of the cases after osteosynthesis with an intramedullary nail. It was observed in 32% of the grafts preserved at -30 degrees, in 17% of those irradiated, and in 7% and 7.6% of those preserved at -180 degrees and -80 degrees, respectively. Delayed union and non-union was observed in 57% of the cases: 63% in intercalary grafts, 48% in arthrodeses. Final results after treatment of complications were excellent and good in 63% of the entire series. The results should, however, be evaluated after 3 years, as during this period of time important transformation phenomena of the graft occur. Complications are observed in 75% of the cases, but they may be reduced if planning is correct and surgery is accurate. Each complication may be dealt with and resolved without high risks for preservation of the limb.

[Residual gastric mucosa after gastrectomy: development of precancerous lesions]. / Mucosa gastrica residua a gastroresezione: dinamica delle lesioni precorritrici del carcinoma.

The gastric remnant can be regarded as a model to investigate the events of gastric carcinogenesis of intestinal type. Histologic changes precursor of the malignancy develop in higher incidence in the postoperative stomachs than in non-resected ones. 316 patients hemi-gastrectomized for peptic ulcer were assessed by an endoscopic-histologic study to provide further informations on the sequential chain of histologic lesions that precede the development of cancer. The anastomosis was by far the commonest diseased area at endoscopy, particularly in the patients with a Billroth II resection (p < 0.0004). The 10% of the 233 patients biopsied evidenced a normal gastric mucosa, in the others Superficial Gastritis 74%, Chronic Atrophic Gastritis 36%, Cystic Dilatation 52%, Foveolar Hyperplasia 29%, Intestinal Metaplasia 39%, moderate-severe Dysplasia 6% as single abnormality or variously associated were observed. The stoma was the most damaged area at histology. The occurrence of the DC, the FI and the IM at the anastomotic site was significative (p values between 0.02 and 0.001). The earliest postoperative histologic lesion was the CAG, evidenced, in mean 13 years after operation, the latest the DC observed in mean 18 years after surgery (p < 0.004). The IM, the IF, the CD, and the dysplasia in association with the CAG were observed at postoperative intervals shorter when non-associated with CAG (respective p value: NS, < 0.03, < 0.0002, NS). The probability of transition from an histologic lesions to a more advanced one in our patients was similar to that of a non resected population at medium--high risk of gastric cancer.

Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver.

Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis. Methods. Steatosis severity was defined according to Hamaguchi's echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2 α , soluble NOX2-derived peptide, and adiponectin were measured. Results. Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5) µ IU/mL in mild, moderate, and severe steatosis, respectively; P < 0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2 α , soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchi's score, urinary 8-iso-PGF2 α , and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjusted R (2) = 0.36). Conclusion. We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.

Non-alcoholic fatty liver disease, metabolic syndrome and patatin-like phospholipase domain-containing protein3 gene variants.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease was traditionally interpreted as a condition which may progress to liver-related complications. However, the increased mortality is primarily a result of cardiovascular diseases. It has been suggested that fatty liver can be considered as the hepatic consequence of the metabolic syndrome. The aim was to describe the different clinical presentations of non-alcoholic fatty liver disease on the basis of the patatin-like phospholipase domain-containing protein3 (PNPLA3) rs738409 gene variant. METHODS: Fatty liver was defined by ultrasonographic Hamaguchi's criteria in 211 consecutive subjects with non-alcoholic fatty liver disease. The rs738409 polymorphism was determined by TaqMan assays. Metabolic syndrome was defined according to ATPIII modified criteria. RESULTS: Prevalence of PNPLA3-148II, PNPLA3-148IM, and PNPLA3-148MM genotypes was 45.0%, 40.7%, and 14.3% respectively. Prevalence of metabolic syndrome progressively increased with the severity of liver steatosis (from 52.5% to 65.2%, and 82.3% respectively, p<0.01). The PNPLA3-148MM group had significantly lower mean serum triglycerides (p<0.001), Framingham cardiovascular risk score (p<0.01) and lower prevalence of metabolic syndrome (p<0.05) and its components. Age and HOMA-IR were positive independent predictors of metabolic syndrome, while a negative independent association was found between metabolic syndrome and the homozygotes PNPLA3 I148M variant. CONCLUSIONS: We suggest a lower prevalence of MetS and reduced cardiovascular risk in NAFLD patients with PNPLA3MM genotype.