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.

Cutaneous polyarteritis nodosa and pulmonary arterial hypertension: An unexpected liaison. A case report.

BACKGROUND: Cutaneous polyarteritis nodosa (cPAN) is a form of medium-sized vessel necrotizing vasculitis. It is a rare, skin-limited variant of polyarteritis nodosa, characterized by dermal and subcutaneous tissue involvement. The most common findings in cPAN include digital gangrene, livedo reticularis, and tender subcutaneous nodules. However, while limited to the skin, cPAN results in significant morbidity and mortality due to the accompanying skin ischemia and necrosis, such that patients are vulnerable to superinfection. Here, we describe a unique presentation of cPAN associated with pulmonary arterial hypertension (PAH). METHODS: A 78-year-old female presented with digital ischemia and leg ulcers associated with PAH. Skin biopsy showed necrotizing fibrinoid necrosis of the small- and middle-sized vessels of the dermis. A diagnosis of cPAN and PAH was made. The patient was treated with glucocorticoids, vasodilators, and cyclophosphamide. RESULTS: She died due to severe sepsis complications. CONCLUSION: To date, this is the first case report describing the association between cPAN and PAH. In this case, PAH is a complication of the cutaneous vasculitides suggesting that vasculopathy could play a role in the pathophysiology of PAH. However, the underlying pathophysiological mechanisms still have to be firmly established.

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.

Analysis of hepatic stiffness after viral eradication in a population with chronic hepatitis C treated with DAAs

Introduction and objectives: Despite chronic hepatitis C (CHC) is still a global burden as the high morbidity and mortality, the recently approved direct-acting antivirals (DAAs) permit a very high rate of sustained virologic response (SVR) in these patients. The clinical improvement due to viral eradication is being documented, however it is not clear why a subset of patients does not benefit in terms of fibrosis regression or hepatocellular carcinoma (HCC) development. Aim of the study was to assess the hepatic stiffness regression at SVR24 and detect factors impacting stiffness course.Patients and methodsHepatic stiffness assessed by acoustic radiation force impulse (ARFI) and anthropometric- and biochemical parameters were retrospectively collected by 166 CHC patients treated with DAAs, form baseline and SVR24.ResultsViral eradication significantly improved overall hepatic stiffness and other related hepatitis hallmarks such as ALT, AST, γGT, platelets count, AST to Platelets ratio Index (APRI), total- and LDL cholesterol. The multiple regression analysis showed that patients with baseline glucose > 110mg/dl presented a stiffness regression significantly lower when compared to low glucose patients (<110mg/dl), moreover baseline HbA1c strongly correlated with DeltaStiffness. 7 patients (4.2%) developed HCC and importantly, presented hyperglycaemia and no stiffness regression nor platelets count recover.ConclusionsAlthough viral eradication with DAAs entails overall benefits, glycaemic decompensation negatively affects fibrosis regression and probably facilitates HCC development. (AU)

Introducción y objetivos: Aunque la hepatitis C crónica (CHC) sigue siendo una carga global debida a la alta morbilidad y mortalidad, los antivirales de acción directa (AAD) recientemente aprobados, permiten un índice muy alto de respuesta virológica sostenida (RVS) en estos pacientes. La mejoría clínica debida a la erradicación viral está siendo documentada, pero no está claro por qué un subconjunto de pacientes no se beneficia en términos de regresión de fibrosis o desarrollo de carcinoma hepatocelular (HCC). El objetivo de este estudio fue evaluar la regresión de la rigidez hepática en SVR24 y detectar los factores que afectan el curso de la rigidez.Pacientes y métodosLa rigidez hepática evaluada por la radiación acústica de la fuerza de impulso (ARFI) y los parámetros antropométricos y bioquímicos fueron recolectados retrospectivamente por 166 pacientes con CHC tratados con ADD, desde el punto de partida y SVR24.ResultadosLa erradicación viral mejoró significativamente la rigidez hepática general y otros signos relacionados con la hepatitis, como ALT, AST, γGT, conteo de plaquetas, índice da razão AST/plaquetas (APRI), colesterol total y LDL. El análisis de regresión múltiple mostró que los pacientes con glucosa basal >110 mg/dL tuvieron una regresión de rigidez significativamente inferior en comparación con los pacientes con glucosa baja (<110 mg/dL), además la HbA1c de referencia se correlacionó fuertemente con DeltaStiffness. Siete pacientes (4,2%) desarrollaron CHC y, lo que es más importante, presentaron hiperglucemia y no hubo regresión de rigidez ni recuperación del conteo de plaquetas.ConclusionesA pesar de que la erradicación viral con AAD conlleva diversos beneficios, la descompensación glucémica afecta negativamente la regresión de la fibrosis y probablemente facilita el desarrollo de CHC. (AU)

A large asymptomatic portal vein aneurysm in an old man.

Ultrasound (US) is a useful tool in diagnosis and follow-up of portal vein aneurysms (PVA). In the absence of international surgical guidelines on PVAs, US can be effectively used in follow-up of asymptomatic patients not suitable for surgery.

Analysis of hepatic stiffness after viral eradication in a population with chronic hepatitis C treated with DAAs.

INTRODUCTION AND OBJECTIVES: Despite chronic hepatitis C (CHC) is still a global burden as the high morbidity and mortality, the recently approved direct-acting antivirals (DAAs) permit a very high rate of sustained virologic response (SVR) in these patients. The clinical improvement due to viral eradication is being documented, however it is not clear why a subset of patients does not benefit in terms of fibrosis regression or hepatocellular carcinoma (HCC) development. Aim of the study was to assess the hepatic stiffness regression at SVR24 and detect factors impacting stiffness course. PATIENTS AND METHODS: Hepatic stiffness assessed by acoustic radiation force impulse (ARFI) and anthropometric- and biochemical parameters were retrospectively collected by 166 CHC patients treated with DAAs, form baseline and SVR24. RESULTS: Viral eradication significantly improved overall hepatic stiffness and other related hepatitis hallmarks such as ALT, AST, γGT, platelets count, AST to Platelets ratio Index (APRI), total- and LDL cholesterol. The multiple regression analysis showed that patients with baseline glucose > 110mg/dl presented a stiffness regression significantly lower when compared to low glucose patients (<110mg/dl), moreover baseline HbA1c strongly correlated with DeltaStiffness. 7 patients (4.2%) developed HCC and importantly, presented hyperglycaemia and no stiffness regression nor platelets count recover. CONCLUSIONS: Although viral eradication with DAAs entails overall benefits, glycaemic decompensation negatively affects fibrosis regression and probably facilitates HCC development.

Gender, BMI and fasting hyperglycaemia influence Monocyte to-HDL ratio (MHR) index in metabolic subjects.

Metabolic Syndrome (MS) is characterized by a low-grade inflammatory state causing an alteration of non-invasive indexes derived from blood count, namely monocyte-to-HDL ratio (MHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). We analyse a population of 771 subjects (394 controls and 377 MS patients) to evaluate the best predictive index of MS. The diagnosis of MS was made according to the 2006 criteria of the International Diabetes Federation (IDF). We performed ROC curve analyses to evaluate the best predictor index of MS. MHR cut-off value was used to classify the population in two different groups and to create the outcome variable of the Recursive Partitioning and Amalgamation (RECPAM) analysis. This method is a tree-structured approach that defines "risk profiles" for each group of dichotomous variables. We showed that MHR index is significantly linked to body mass index (BMI), waist circumference, creatinine, C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR). ROC curve defined an MHR cut-off value of 6.4, which was able to identify two patient groups with significant differences in waist circumference, blood pressure, creatinine, estimated glomerular filtration rate and fasting plasma glucose. RECPAM analysis demonstrated that gender, BMI categorization and hyperglycaemia were the most important risk determinants of increased MHR index that can be considered bona fide a useful and easily obtainable tool to suggest the presence of peculiar metabolic features that predict MS.

Hyperhomocysteinemia is an independent risk factor of atherosclerosis in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a clinical condition potentially promoting the development of atherosclerotic disease. To date, the clinical impact of elevated serum homocysteine (Hcy) levels in MetS is still under discussion. The aim of this cross sectional study was to evaluate the relationship between MetS and hyperhomocysteinemia and the potential role of Hcy in the pathogenesis of atherosclerotic complications of MetS. METHODS: We recruited 300 outpatients with MetS. All patients underwent a medical history collection, physical examination, blood sampling and carotid ultrasound echo-color Doppler. According to Hcy levels, MetS patients were divided into two groups: "normal" (< 10.7 µmol/l; n = 140, group 1) and "high" Hcy (≥ 10.7 µmol/l; n = 160, group 2). Comparisons between groups were made by Student's t-test or Chi-square test. The effects of potential covariates on group differences were evaluated by general linear models. The relationships between continuous variables were assessed by simple or multiple correlation and by linear regression. Multiple regression models were built to evaluate the effects of Hcy, together with other potential risk factors, on carotid atherosclerosis. RESULTS: Patients with high Hcy were predominantly male and slightly older than group 1 patients. Smokers and non-smokers exhibited similar Hcy levels, nor was a statistical relationship between pack-years and Hcy observed. Group 2 showed lower levels of folic acid, vitamin D, high density lipoprotein (HDL)-cholesterol and glomerular filtration rate (e-GFR) than group 1, but higher levels of C-peptide, uric acid and triglycerides. In all patients, Hcy was positively correlated with C-peptide and uric acid and negatively with folic acid and e-GFR. Intima-media thickness (IMT) and carotid stenosis degree were significantly higher in patients with high Hcy and a positive relationship between Hcy and both IMT and carotid stenosis was detected in all patients. Finally, Hcy atherogenic effects were independent of other well-known atherosclerosis risk factors. CONCLUSIONS: Our results highlight a link between MetS and hyperhomocysteinemia and a direct effect of Hcy on atherogenic process during MetS. Early correction of folic acid levels may contribute to prevent cardiovascular complications in MetS patients.

Liver stiffness and portal blood flow modifications induced by a liquid meal consumption: pathogenetic mechanisms and clinical relevance.

OBJECTIVE: The correlation between liver stiffness (LS) variations and portal blood flow (PBF) modifications induced by a standardized liquid meal consumption and the clinical relevance of this matter are two aspects not yet fully elucidated. Herein, we evaluated the variations of LS and PBF after a standardized liquid meal intake in patients with chronic liver disease. MATERIAL AND METHODS: PBF and LS were determined after an overnight fasting period in 54 patients. They were divided in three groups according to baseline LS (absent, moderate, and severe). They consumed 200 ml of water and a standardized liquid meal (300 Kcal/200 ml) after 60 min. PBF and LS were measured at 30 min after water and liquid meal consumption. RESULTS: In all groups, LS and PBF values significantly increased only after meal consumption. A significant correlation between baseline LS values and post-meal increase of LS was observed. Moreover, higher basal stiffness values were associated to a larger increase of LS variation after meal consumption. The effect of the meal on LS remained statistically significant after multiple regression analysis. A significant correlation between increase of LS and PBF was found in patients with absent and moderate baseline LS. Nine patients (17%) switched from a lower to a higher level of LS after meal consumption. CONCLUSION: A low calories/low-volume meal is capable of significantly increasing LS regardless of the grade of stiffness, determining a reclassification rate of 17%. In presence of minimal or moderate stiffness, the increase of LS is significantly correlated with the augment of PBF.