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Polycystic ovary syndrome (PCOS) represents an endocrine condition affecting 5–18% of adolescents, frequently in association with obesity, metabolic alterations, and liver dysfunction. In this study, we aimed to evaluate the prevalence and risk factors for developing non-alcoholic fatty liver disease (NAFLD) in a cohort of PCOS adolescents. Thirty-two girls were assessed for anthropometric and biochemical markers: total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT). In addition, LH, FSH, 17β-Estradiol (E2), prolactin, testosterone (T), free testosterone, delta 4-androstenedione (D4 A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding protein (SHBG) were also evaluated. All subjects underwent liver ultrasound to detect NAFLD. Our data demonstrated that PCOS adolescents complicated with NAFLD accounted for 37.5%, and those with obesity and lower SHBG were more predisposed to developing NAFLD. Moreover, SHBG showed a negative correlation with several parameters such as blood pressure, body mass index, waist circumference, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR). Our results demonstrated that the assessment of SHBG may allow the identification of PCOS adolescents at risk for developing NAFLD and metabolic alterations. [ABSTRACT FROM AUTHOR]

Aim People experiencing homelessness are often excluded from treatment programs for alcohol use disorder (AUD). The goal of this study was to describe the impact of a multidisciplinary treatment program on alcohol consumption and social reintegration in individuals with AUD experiencing homelessness. Methods Thirty-one individuals with AUD experiencing homelessness were admitted to an inpatient unit for 5–6 days for clinical evaluation and to treat potential alcohol withdrawal syndrome. A group of volunteers, in collaboration with the Community of Sant'Egidio, provided social support aimed to reintegrate patients. After inpatient discharge, all patients were followed as outpatients. Alcohol intake (number drinks/day), craving and clinical evaluation were assessed at each outpatient visit. Biological markers of alcohol use were evaluated at enrollment (T0), at 6 months (T1) and 12 months (T2). Results Compared with T0, patients at T1 showed a significant reduction in alcohol consumption [10 (3–24) vs 2 (0–10); P  = 0.015] and in γ-glutamyl-transpeptidase [187 (78–365) vs 98 (74–254); P  = 0.0021]. The reduction in alcohol intake was more pronounced in patients with any housing condition [10 (3–20) vs 1 (0–8); P  = 0.008]. Similarly, compared with T0, patients at T2 showed significant reduction in alcohol consumption [10 (3–24) vs 0 (0–15); P  = 0.001], more pronounced in patients with any housing condition [10 (3–20) vs 0 (0–2); P  = 0.006]. Moreover, at T2 patients showed a significant reduction in γ-glutamyl-transpeptidase [187 (78–365) vs 97 (74–189); P  = 0.002] and in mean cell volume [100.2 (95–103.6) vs 98.3 (95–102); P  = 0.042]. Conclusion Patients experiencing homelessness may benefit from a multidisciplinary treatment program for AUD. Strategies able to facilitate and support their social reintegration and housing can improve treatment outcomes. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemia due to the SARS-CoV-2 coronavirus, in its first 4 months since its outbreak, has to date reached more than 200 countries worldwide with more than 2 million confirmed cases (probably a much higher number of infected), and almost 200,000 deaths. Amplification of viral RNA by (real time) reverse transcription polymerase chain reaction (rRT-PCR) is the current gold standard test for confirmation of infection, although it presents known shortcomings: long turnaround times (3-4 hours to generate results), potential shortage of reagents, false-negative rates as large as 15-20%, the need for certified laboratories, expensive equipment and trained personnel. Thus there is a need for alternative, faster, less expensive and more accessible tests. We developed two machine learning classification models using hematochemical values from routine blood exams (namely: white blood cells counts, and the platelets, CRP, AST, ALT, GGT, ALP, LDH plasma levels) drawn from 279 patients who, after being admitted to the San Raffaele Hospital (Milan, Italy) emergency-room with COVID-19 symptoms, were screened with the rRT-PCR test performed on respiratory tract specimens. Of these patients, 177 resulted positive, whereas 102 received a negative response. We have developed two machine learning models, to discriminate between patients who are either positive or negative to the SARS-CoV-2: their accuracy ranges between 82% and 86%, and sensitivity between 92% e 95%, so comparably well with respect to the gold standard. We also developed an interpretable Decision Tree model as a simple decision aid for clinician interpreting blood tests (even off-line) for COVID-19 suspect cases. This study demonstrated the feasibility and clinical soundness of using blood tests analysis and machine learning as an alternative to rRT-PCR for identifying COVID-19 positive patients. This is especially useful in those countries, like developing ones, suffering from shortages of rRT-PCR reagents and specialized laboratories. We made available a Web-based tool for clinical reference and evaluation (This tool is available at https://covid19-blood-ml.herokuapp.com/). [ABSTRACT FROM AUTHOR]

Summary: Objectives: The liver‐specific miR‐122 was proposed as biomarker for NAFLD in adults. Here, we investigated the relationship between miR‐122 levels, parameters of liver metabolism and NAFLD in pre‐pubertal obese children. Methods: Parameters of liver metabolism (ALT, AST and GGT) of three European cohorts were included (German cohort [n = 71; age: 11.53 ± 1.29 years; BMI z‐score: 2.96 ± 0.64], Italian cohort [n = 45; age: 9.60 ± 2.11 years; BMI z‐score: 3.57 ± 1.16], Slovenian cohort [n = 31; age: 7.53 ± 1.47 years; BMI z‐score: 3.66 ± 0.88]). MiR‐122 levels and CK18 concentrations were measured in fasting blood samples. In the German and Italian cohort, the diagnosis of NAFLD and grading of NAFLD was assessed by ultrasound. Results: NAFLD was diagnosed in n = 50 patients of the German cohort (29.6%) and in n = 29 patients (72.5%) of the Italian cohort. In all three cohorts, miR‐122 was positively correlated with ALT and AST as well as with CK18 concentrations. MiR‐122 levels were higher in children with NAFLD compared with healthy controls. Conclusions: MiR‐122 levels in pre‐pubertal obese children could be a potential biomarker for paediatric NAFLD. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the prevalence and the clinical implication of persistently elevated liver enzymes in diabetic subjects, with no evidence of viral hepatitis infection or alcohol abuse.Methods: Clinical, lifestyle, anthropometric data and laboratory test values were collected in 916 type 2 diabetic subjects, examined for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (γ-GT) levels at two different time points.Results: Five hundred forty four patients (59.4%) showed normal (NLT group) and 182 (19.9%) persistently elevated (ELT group) liver tests in both determinations. ELT patients were prevalently men (P=0.016), younger (P<0.0001) and with a lower duration of diabetes (P=0.008). Adjusting for age and sex, ELT subjects had significantly higher BMI (P<0.001), waist circumference (P=0.010), systolic (P=0.017) and diastolic blood pressure (P<0.001), and higher levels of fasting blood glucose (P=0.023), and triglycerides (P<0.0001). Current hypoglycemic and/or hypolipidemic drugs were comparable between the two groups. At multivariate analysis, male gender (OR=3.017, P=0.012), worse metabolic control (HbA1c, OR=1.408, P=0.017), and a younger age (OR=1.054, P=0.007) predicted the presence of persistently elevated liver enzymes.Conclusions: Persistently elevated liver enzymes are a common finding in outpatient type 2 diabetic subjects, particularly in young men with suboptimal metabolic control and with the features of metabolic syndrome. The persistence of abnormal liver tests may be of potential utilization in clinical practice for the screening of patients at high risk of NAFLD. [ABSTRACT FROM AUTHOR]

Objectives Gamma-glutamyltransferase ( GGT) is a biomarker of liver disease and oxidative stress which was associated with all-cause and cardiovascular ( CV) mortality in the general population and in patients with high risk conditions. This study aims at assessing whether ox LDL modifies the relationship between GGT, all-cause, and CV mortality in elderly individuals from the general population. Design Observational longitudinal study. Setting Population-based cohort of older individuals (>65 years) free of liver disease. Participants One thousand and thirty-eight individuals from the Invecchiare in Chianti (In CHIANTI) study. Measurements Serum GGT level, oxidized low-density lipoprotein (ox LDL), CV comorbidities, all-cause and CV mortality. Results The median age of the study population (n = 1,038) was 74 years (inter-quartile range: 69-79), 152 individuals (15%) had past CV events. During a median follow-up of 9 years, 401 individuals died, 168 of them (42%) for CV causes. In adjusted analyses, GGT predicted all-cause mortality ( HR for 20 U/L increase in serum GGT: 1.11, 95% CI: 1.02-1.21, P = .02) and CV mortality ( HR: 1.17, 95% CI: 1.03-1.33; P = .02). Furthermore, in an analysis for interaction circulating ox LDL amplified the effect of GGT on all-cause mortality ( P = .003). Conclusion Circulating ox LDL amplifies the effect of GGT on mortality in the elderly. The mechanism for this association remains unknown and requires further research, including studying the potential role of GGT in oxidative stress. These results are consistent with the hypothesis of a causal role of GGT in the CV morbidity and mortality in older individuals and indicate that ox LDL plays a crucial role in the interpretation of the link between GGT and the risk of adverse clinical events in this population. [ABSTRACT FROM AUTHOR]

The evaluation of serum liver enzyme levels is the most used surrogate marker of liver injury in clinical practice. The prevalence and association of abnormal enzyme values with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and with other major causes of liver damage (obesity, diabetes, dyslipidemia, and alcohol abuse) were evaluated in individuals attending the surgeries of 14 general practitioners (GPs) working in Messina. Alanine-amino-transferase, aspartate-amino-transferase, and gamma-glutamyl-transpeptidase measurements were measured in 7816 individuals consecutively attending the GP surgeries between January 1, 2011 and June 30, 2012. Five-thousand-eight-hundred-six subjects (74.3 %) had the tests performed, and 1189 of them (20.5 %) showed increased liver enzyme levels. Sixty-nine of these 1189 individuals (5.8 %) were HCV positive and 12 HBV positive (1 %), 755 (63.5 %) were overweight or obese, 288 (24.2 %) had diabetes, and 351 (29.5 %) had dyslipidemia; 262 (22 %) drank >2 alcoholic units/day. Overall, 57 % of individuals with abnormal liver enzymes had multiple possible causes of liver disease, 28 % one cause, and 15 % no apparent cause. In conclusion, this study shows that 1/5 of individuals attending GP surgeries have altered liver biochemistry and that overweight and metabolic disorders have become the major causes of liver damage even in South Italy, where HBV and HCV were endemic in the past century. Notably, many HCV and HBV patients are still unaware of their infected status, and GPs are essential for their timely identification. [ABSTRACT FROM AUTHOR]

Background: The relative contribution of visceral (VAT) and subcutaneous (SAT) adipose tissue to cardiometabolic disease is controversial. The aim of this study was to evaluate whether dissecting abdominal fat in VAT and SAT using US may detect stronger and more specific association with MS, MS components, hyperuricemia and altered liver enzymes compared to waist circumference.Methods: We performed a cross-sectional study on 2414 subjects aged 18 to 66 years (71 % women) followed at the International Center for the Assessment of Nutritional Status (ICANS, Milan, Italy). VAT and SAT were measured using ultrasonography. Multivariable logistic regression controlling for age and gender was used to evaluate the association of the parameters of interest (waist circumference (WC), VAT, SAT and VAT + SAT) with the MS (international harmonized definition), its components (high triglycerides, low HDL, high blood pressure, high glucose), high uric acid (≥7 mg/dl), high alanine transaminase (ALT, ≥ 30 U/l) and high gamma-glutamyl-transferase (GGT, ≥ 30 U/l).Results: VAT was independently associated with all the outcomes of interest, while SAT was independently associated with MS and only with high blood pressure and high ALT when we considered the single parameters of MS and NAFLD. VAT had the strongest association with high triglycerides, high ALT and high GGT. The VAT + SAT association had the strongest association with MS. WC had the strongest association with low HDL and high blood pressure. VAT and WC were similarly associated to high glucose and high uric acid.Conclusion: US-determined VAT and SAT are both independently associated with MS. Moreover, to our knowledge, we are the first to show that VAT, being associated to all of the MS components in addition to hyperuricemia and altered liver enzymes, performs equally or better than WC except for high blood pressure and low HDL. [ABSTRACT FROM AUTHOR]

Background: There are few prospective data on the prognosis of insulin-sensitive and insulin-resistant normal-weight (NW) or obese individuals. Objectives: The estimated liver fat content, incidences of hyperglycemia and cardiovascular disease, and all-cause and cardiovascular mortality rates were investigated in a population-based cohort of 1658 individuals who were categorized according to BMI and insulin resistance as defined by HOMA-IR values ≥2.5 and the presence of metabolic syndrome. Design: This was a prospective cohort study with a 9-y follow-up. Anthropometric values, blood pressure, and blood metabolic variables were measured, and information on vital status was collected from demographic files at follow-up. Results: A total of 137 of 677 NW individuals (20%) were classified as insulin resistant and normal weight (IR-NW), and 72 of 330 obese individuals (22%) were classified as insulin sensitive and obese (IS-obese). Incidences of diabetes, impaired fasting glucose, and cardiovascular events were 0.4%, 6.3%, and 3.3%, respectively, in insulin-sensitive and normal-weight (IS-NW) individuals (reference category); 5.8%, 10.2%, and 6.6%, respectively, in IR-NW individuals; and 5.6%, 8.3%, and 8.3%, respectively, in IS-obese individuals. In a multiple logistic regression model, risks of incident hyperglycemia and cardiovascular events increased in both groups compared with in the reference category [HR (95% CI): 2.54 (1.42, 4.55) and 1.98 (0.86, 4.54) in IR-NW subjects; 2.16 (1.01, 4.63) and 2.76 (1.05, 7.28) in IS-obese subjects]. The estimated liver fat content significantly increased during follow-up only in the IR-NW group in the same model. Cardiovascular mortality was 2-3-fold higher in IR-NW and IS-obese than in IS-NW individuals in a Cox regression model. Conclusions: Our data refute the existence of healthy obese phenotypes because IS-obese individuals showed increased cardiometabolic risk. The existence of unhealthy NW phenotypes is supported by their increased risk of incident hyperglycemia, fatty liver, cardiovascular events, and death. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the relation between consumption of coffee and other methylxanthine-containing beverages and liver cirrhosis.METHODS: A hospital-based case-control study of digestive tract and liver diseases was conducted in Greater Milan, Italy, including 101 cases with liver cirrhosis and 1538 controls.RESULTS: Compared with coffee non-drinkers, the multivariate odds ratio (OR) was 0.77 for one cup of coffee per day, 0.57 for two, and 0.29 for three or more. The OR for 40 years of coffee consumption or more was 0.45. Trends in risk were significant for both number of cups and duration of coffee drinking. No significant association was observed with decaffeinated coffee, tea and cola-containing beverages. The relation between coffee consumption and liver cirrhosis was not attributable to confounding and was observed across strata of tobacco, alcohol, and other major covariates of interest. In particular, an inverse relation was observed also in subjects reporting moderate alcohol drinking.CONCLUSIONS: The present study confirms, and further quantifies, the existence of an inverse association between coffee consumption and liver cirrhosis. However, the metabolism of caffeine is impaired in fasting subjects with liver cirrhosis, and the association could be due to a reduction of coffee drinking in subjects with liver cirrhosis. [Copyright &y& Elsevier]

The article describes a case-control study of the correlation of serum enzyme gamma glutamyltransferase (GGT) levels with functional abilities in a group of older patients in Naples, Italy who were diagnosed with acute ischemic stroke (IS). Associations were found between high GGT level and disability and impairment, suggesting that GGT is a biochemical marker of oxidative stress and inflammation risk factors for stroke. Statistical methods used include analysis of variance and chi squares.

Background & Aims: Four gamma-gultamyltransferases (GGT) fractions (b-, m-, s-, and f-GGT) have been identified in human plasma and their concentrations and ratios vary in different pathological conditions. To assess the behaviour of fractional GGT in cirrhotic patients evaluated for liver transplantation., Methods: This was a single-centre, cross-sectional study; GGT fractions were determined by gel-filtration chromatography., Results: 264 cirrhotic patients (215 males; median age 54.5 years) were included and compared against a group of 200 healthy individuals (100 males; median age 41.5). Median (25th-75th percentile) total and fractional GGT were higher in cirrhotics, with s-GGT showing the greatest increase [36.6 U/L (21.0-81.4) vs. 5.6 U/L (3.2-10.2), P<0.0001], while the median b-GGT/s-GGT ratio was lower in cirrhotics than in healthy controls [0.06 (0.04-0.10)] vs. 0.28 (0.20-0.40), P<0.0001]. The ratio showed higher diagnostic accuracy (ROC-AUC, 95% CI: 0.951, 0.927-0.969) then either s-GGT (0.924, 0.897-0.947; P<0.05) or total GGT (0.900, 0.869-0.925; P<0.001). The diagnostic accuracy of the ratio was maintained (0.940, 0.907-0.963) in cirrhotic patients (n=113) with total GGT values within the reference range. The s-GGT fraction consisted of two components, with one (s2-GGT) showing a significant positive correlation with serum aspartate aminotransferases, alanine aminotransferase, lactate dehydrogenases (LDH), alkaline phosphatases and bilirubin, and negative with albumin. The b-GGT fraction showed a positive correlation with albumin, fibrinogen, and platelet counts, and negative with international normalized ratio, bilirubin and LDH., Conclusions: The ratio performs as a sensitive biomarker of the liver parenchymal rearrangement, irrespective of aetiology of cirrhosis and presence of hepatocellular carcinoma, even in patients with total GGT values within the reference range., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)