Fatty Liver Index (FLI) is the best score to predict MASLD with 50% lower cut-off value in women than in men.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by the presence of hepatic steatosis, detected on ultrasonography (US) imaging or histology, and at least one of criteria for Metabolic Syndrome diagnosis. Simple non-invasive tests (NITs) have been proposed as an acceptable alternative when US and biopsy are not available or feasible but have not been validated for MASLD. In this observational study, we investigated the reliability of NITs for MASLD detection and whether sex-differences in screening methods should be considered. METHODS: We included 1069 individuals (48% males and 52% females) who underwent their first clinical examination for Metabolic Syndrome in the period between January 2015 and December 2022. Liver steatosis was detected through US and anthropometric and clinical parameters were recorded. RESULTS: Liver steatosis was detected in 648 patients and MASLD was diagnosed in 630 subjects (355 males; 275 females). Women with MASLD showed better metabolic profile and lower prevalence of Metabolic Syndrome criteria than men. Among NITs, Fatty Liver Index (FLI) showed the best ability for detection of MASLD, with a cut-off value of 44 (AUC = 0.82). When considering the two sexes for MASLD detection via FLI, despite no substantial differences regarding FLI correlations with metabolic biomarkers except for age, women showed marked lower FLI cut-off value (32; AUC = 0.80) than men (60; AUC = 0.80). CONCLUSIONS: In this study, we found that FLI is the best non-invasive predictor of both liver steatosis and MASLD. The finding that in women FLI cut-off value for MASLD detection is 50% lower than in men suggests the need of a sex-specific personalized program of screening and prevention of dysmetabolism-related liver diseases, despite outwardly healthy biomarkers profile.

Fatty liver disease is caused by the accumulation of fat into the liver and it is associated to increased risk of chronic diseases. Diagnosis of fatty liver is based on biopsy or ultrasound assessment but when these procedures are not available or feasible also some non-invasive scores have been showed to be reliable measures of this condition. In this study we compared the use of ultrasound and non-invasive scores to assess liver steatosis and associated metabolic disease, finding that Fatty Liver Index (FLI) is the best score for these diagnosis. Surprisingly, in women FLI cut-off value is 50% lower than in men, suggesting that different sex-specific factors may come into play in the development and evolution of liver steatosis. Thus, we suggest the need of a sex-specific personalized program of screening and prevention of dysmetabolism-related liver diseases.

Fasting hyperglycaemia and fatty liver drive colorectal cancer: a retrospective analysis in 1145 patients.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of increased adiposopathy, whose pathogenetic features have been proposed as tumourigenic triggers for colorectal cancer (CRC). We aim to identify specific metabolic signatures involved in CRC development that may be used as non-invasive biomarkers, paving the way for specific and personalized strategies of CRC prevention and early detection. METHODS: We retrospectively assessed CRC onset during a time frame of 8 years in a cohort of 1145 out-patients individuals who had previously been evaluated for Metabolic Syndrome. RESULTS: 28 patients developed CRC. No association between CRC development and visceral and general obesity was detected, while baseline fasting plasma glucose (FPG) and non-invasive liver fibrosis scores were significantly higher in patients with CRC, compared to those who did not develop cancer. Liver steatosis and MASLD were more frequently diagnosed in patients who developed CRC compared to no cancer developers. Canonical correlations among metabolic biomarkers were not present in CRC developers, differently from no cancer group. In ROC analysis, FPG and non-invasive scores also showed good sensitivity and specificity in predicting colon cancer. We then calculated ORs for metabolic biomarkers, finding that higher FPG and non-invasive scores were associated with an increased risk of developing CRC. CONCLUSION: MASLD and increased FPG may play a role in the clinical background of CRC, bringing to light the fascinating possibility of a reversed gut-liver axis communication in the pathogenesis of CRC. Thus, the use of non-invasive scores of fatty liver may be helpful to predict the risk of CRC and serve as novel prognostic factors for prevention and therapeutic strategies.

Low Adherence to Mediterranean Diet Characterizes Metabolic Patients with Gastrointestinal Cancer.

Background. Gastrointestinal (GI) cancers are one of the most relevant causes of death globally, frequently associated with poor dietary patterns. The Mediterranean Diet (MedDiet) contributes to cancer prevention. To assess adherence to MedDiet, our research group validated a new score, the Chrono Med Diet Score (CMDS), that captures increased visceral adiposity. Methods. We enrolled 401 subjects who underwent an evaluation for metabolic diseases and specific screening procedures according to current guidelines and were asked to answer CMDS. A total of 71 new cancer cases were recorded, including 40 GI and 31 non-gastrointestinal (NON-GI) cancers. Results. We found that CMDS was reduced in subjects who were diagnosed with cancers. Patients who reported a CMDS score of 12 or less had an over three times increased risk of being diagnosed with GI cancers and presented increased waist circumference and triglycerides and reduced HDL cholesterol compared to adherent subjects. Conclusions. Low CMDS values capture the risk for cancer diagnosis, especially for GI cancers. Thus, CMDS, along with waist circumference, can be considered as a bona fide marker for increased risk of cancer, requiring anticipated screening procedures for the detection of premalignant and early stage GI cancers in patients with low adherence to MedDiet.

Thyroid nodule malignancy is associated with increased non-invasive hepatic fibrosis scores in metabolic subjects.

Introduction: Thyroid cancer incidence is increasing, and adiposity-related conditions are gaining space in its pathogenesis. In this study, we aimed to detect any anthropometric, biohumoral, and clinical features that might be associated with thyroid nodule malignancy, potentially representing novel non-invasive markers of thyroid cancer. Materials and methods: The study was conducted in a group of 142 consecutive outpatients (47 men and 95 women) who underwent fine-needle aspiration biopsy/cytology (FNAB/C) due to suspicion of malignancy from January 2018 to September 2022. We compared lipid and glycemic blood profiles as well as non-invasive liver fibrosis indexes such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) between patients with benign and malignant newly diagnosed nodules. Then, we performed receiver operating characteristic (ROC) analysis to assess their best cutoff values for discrimination of malignant nodules and chi-squared test to evaluate the association of specific dysmetabolic conditions with malignancy. To understand whether and to what degree dysmetabolic conditions increased the risk of thyroid nodule malignancy, we also calculated the odds ratio (OR) of the main biomarkers. Results: After FNAB/C, 121 (85%) patients were diagnosed with benign thyroid nodules, while 21 (15%) individuals were diagnosed with thyroid cancer. Comparing patients with benign and malignant nodules, we found that individuals with thyroid cancer exhibited increased body mass index (BMI) (p = 0.048) and fasting plasma glucose (p = 0.046). Intriguingly, considering non-invasive scores for liver fibrosis, subjects with thyroid cancer presented increased AAR (p < 0.001) and APRI (p = 0.007), and these scores were associated with malignancy (p < 0.005) with OR = 7.1 and OR = 5, respectively. Moreover, we showed that only in the cancer group, low levels of vitamin D correlated with stigmata of impaired metabolism. Discussion: In our study, AAR and APRI scores were associated with thyroid nodule malignancy and could be used to predict it and to speed up the diagnostic process. From a pathogenic point of view, we speculated that metabolic-associated fatty liver disease (MAFLD) along with hyperglycemia and vitamin D deficiency may represent putative drivers of thyroid carcinogenesis.

AST/ALT-to-platelet ratio (AARPRI) predicts gynaecological cancers: a 8-years follow-up study in 653 women.

Non-alcoholic fatty liver disease (NAFLD), specifically liver steatosis and fibrosis with steatohepatitis (NASH), is often associated with visceral adiposopathy, whose pathogenetic features have been proposed as tumorigenic triggers. We performed a prospective analysis in 653 metabolic women to reveal any conditions that may predict and concur to cancer development during a 8-years period of follow-up. Among clinical and biochemical variables, only AST and non-invasive liver fibrosis scores (AARPRI, APRI, FIB-4, mFIB4) significantly distinguished cancer-developer women (n = 62, 9.5%) from those who did not develop cancer (p < 0.001). In ROC analysis, these scores also showed good sensitivity and specificity in differentiating women who developed cancer (all p < 0.001). We then calculated OR for these indexes finding that increased AARPRI was associated with the highest risk (OR = 6, p < 0.001) of gynaecological cancers development. We further validated these cut-off values in women who had developed other types of cancer, confirming that AARPRI is able to identify the risk for cancer development (OR = 5, p < 0.001). Our findings support the hypothesis that NAFLD, more than obesity per se, is directly associated with the clinical and pathogenic metabolic scenario of gynaecological cancers and encourage the use of liver fibrosis indexes to detect risk of cancer onset in women. Preventing adiposopathy and NAFLD through lifestyle and therapies may represent an instrumental strategy for cancer prevention and/or co-treatment in oncology.

Identification of a Novel Score for Adherence to the Mediterranean Diet That Is Inversely Associated with Visceral Adiposity and Cardiovascular Risk: The Chrono Med Diet Score (CMDS).

Adherence to the Mediterranean diet (MedDiet) leads to reduction of mortality from all causes, especially in subjects with cardiovascular disease, obesity, and diabetes. Numerous scores have been proposed to evaluate the adherence to MedDiet, mainly focused on eating habits. In this study, we verified whether existing validated MedDiet scores, namely, MEDI-LITE and the Mediterranean Diet Score (MDS), could be associated with visceral adiposity. Failing to find a significant association with adiposity, we proposed the validation of a new, easy-to-use adherence questionnaire, the Chrono Med-Diet score (CMDS). CMDS contains eleven food categories, including chronobiology of dietary habits and physical activity. Compared to the MEDI-LITE score and MDS, low values of CMDS are linked to increased waist circumference (WC) and dysmetabolic conditions. CMDS was also inversely correlated with cardiovascular risk (CVR), as well as Fatty Liver Index (FLI). In conclusion, the CMDS is a novel questionnaire to study the adherence to the MedDiet that, focusing on type and timing of carbohydrates intake, has the peculiar capability of capturing subjects with abdominal obesity, thus being an easy-to-use instrument of personalized medicine.

Low HDL-cholesterol levels predict hepatocellular carcinoma development in individuals with liver fibrosis.

Background & Aims: Dysmetabolic conditions could drive liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), increasing susceptibility to hepatocellular carcinoma (HCC). We therefore aimed to identify novel predictive biomarkers of HCC in patients with and without liver fibrosis. Methods: A total of 1,234 patients with putative metabolic conditions and NAFLD were consecutively assessed in our outpatient clinic. Clinical and biochemical data were recorded, and then liver ultrasonography was performed annually for 5 years to detect HCC onset. For the analysis, the population was first divided according to HCC diagnosis; then a further subdivision of those who did not develop HCC was performed based on the presence or absence of liver fibrosis at time 0. Results: Sixteen HCC cases were recorded in 5 years. None of our patients had been diagnosed with cirrhosis before HCC was detected. Compared to patients who did not develop HCC, those who did had higher liver transaminases and fibrosis scores at time 0 (p <0.001). In addition, they presented with increased glycated haemoglobin levels and lower 25-OH vitamin D levels (p <0.05). Intriguingly, patients with higher liver fibrosis scores who subsequently developed HCC had lower HDL-cholesterol (HDL-c) levels at time 0 (p <0.001). Furthermore, in the 484 patients presenting with lower HDL-c at baseline, we found that waist circumference, and then vitamin D and glycated haemoglobin levels, were significantly different in those who developed HCC, regardless of liver fibrosis (p <0.05). Conclusions: This study identifies HDL-c as a bona fide novel marker to predict HCC in patients with NAFLD. Increased waist circumference and deranged metabolic pathways represent additional predisposing factors among patients with low HDL-c, highlighting the importance of studying cholesterol metabolism and integrating clinical approaches with dietary regimens and a healthy lifestyle to prevent HCC. Impact and implications: Visceral adiposity and its associated conditions, such as chronic inflammation and insulin resistance, may play a pivotal role in hepatocellular carcinoma development in patients with non-alcoholic fatty liver disease. We provide new insights on the underlying mechanisms of its pathogenesis, shedding light on the involvement of low levels of "good" HDL-cholesterol. We recommend integrating dietary regimens and advice on healthy lifestyles into the clinical management of non-alcoholic fatty liver disease, with the goal of reducing the incidence of hepatocellular carcinoma.

Monocyte-to-HDL Ratio (MHR) Predicts Vitamin D Deficiency in Healthy and Metabolic Women: A Cross-Sectional Study in 1048 Subjects.

Vitamin D deficiency is often linked with Metabolic Syndrome, both being more frequent with ageing and associated with an increase inflammatory state. Recently, monocytes-to-high density lipoprotein (HDL) ratio (MHR) has emerged as a powerful index to predict systemic inflammation. In this cross-sectional study, we investigated the association between circulating vitamin D level (25-OH vitamin D) and inflammatory status in a population of 1048 adult individuals. Our study reveals an inverse association between 25-OH vitamin D levels and MHR in the overall population. When the population is stratified by gender, waist circumference, and body mass index (BMI), we observed that while in men this relation is strongly significative only in condition of central obesity, in women a lifelong negative correlation exists between circulating 25-OH vitamin D and MHR and it is independent of the metabolic status. These observations underscore the relevance of circulating biomarkers such as MHR in the prediction of systemic inflammatory conditions sustained by vitamin D deficiency also in healthy and young women.

AST to Platelet Ratio Index (APRI) is an easy-to-use predictor score for cardiovascular risk in metabolic subjects.

Visceral obesity is characterized by a low-grade inflammatory systemic state that contributes to the genesis of non-alcoholic fatty liver disease (NAFLD), frequently associated with liver fibrosis. Non-invasive serum markers have recently emerged as reliable, easy-to-use scores to predict liver fibrosis. NAFLD is often linked to metabolic and cardiovascular risk. Thus, in this cross-sectional study, we investigated in a population of 1225 subjects if AST to Platelet Ratio Index (APRI), one of the non-invasive liver fibrosis serum markers, can predict cardiovascular risk (CVR). APRI has been previously validated as an efficient score to predict liver fibrosis in viral hepatitis patients with a cut-off of 0.5 for fibrosis and 1.5 for cirrhosis. Our study showed that APRI significantly correlates with CVR and determines, when elevated, a significant increase in CVR for both genders, especially females. This spike in CVR, observed when APRI is elevated, is relatively high in patients in the age of 51-65 years, but it is significantly higher in younger and premenopausal women, approaching risk values usually typical of men at the same age. Taken together, our data highlighted the role of APRI as a reliable predictor easy-to-use score for CVR in metabolic patients.