Nonalcoholic Fatty Liver Disease (NAFLD) represents the leading cause of liver disease in developed countries but its diffusion is currently also emerging in Asian countries, in South America and in other developing countries. It is progressively becoming one of the main diseases responsible for hepatic insufficiency, hepatocarcinoma and the need for orthotopic liver transplantation. NAFLD is linked with metabolic syndrome in a close and bidirectional relationship. To date, NAFLD is a diagnosis of exclusion, and liver biopsy is the gold standard for diagnosis. NAFLD pathogenesis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. New concepts are constantly arising in the literature promising new diagnostic and therapeutic tools. One of the challenges will be to better characterize not only NAFLD development but overall NAFLD progression, in order to better identify NAFLD patients at higher risk of metabolic, cardiovascular and neoplastic complications. This review analyses NAFLD epidemiology and the different prevalence of the disease in distinct groups, particularly according to sex, age, body mass index, type 2 diabetes and dyslipidemia. Furthermore, the work expands on the pathophysiology of NAFLD, examining multiple-hit pathogenesis and the role of different factors in hepatic steatosis development and progression: genetics, metabolic factors and insulin resistance, diet, adipose tissue, gut microbiota, iron deposits, bile acids and circadian clock. In conclusion, the current available therapies for NAFLD will be discussed.

The classic description of diabetic kidney disease (DKD) involves progressive stages of glomerular hyperfiltration, microalbuminuria, proteinuria, and a decline in the estimated glomerular filtration rate (eGFR), leading to dialysis. In recent years, this concept has been increasingly challenged as evidence suggests that DKD presents more heterogeneously. Large studies have revealed that eGFR decline may also occur independently from the development of albuminuria. This concept led to the identification of a new DKD phenotype: non-albuminuric DKD (eGFR < 60 mL/min/1.73 m², absence of albuminuria), whose pathogenesis is still unknown. However, various hypotheses have been formulated, the most likely of which is the acute kidney injury-to-chronic kidney disease (CKD) transition, with prevalent tubular, rather than glomerular, damage (typically described in albuminuric DKD). Moreover, it is still debated which phenotype is associated with a higher cardiovascular risk, due to contrasting results available in the literature. Finally, much evidence has accumulated on the various classes of drugs with beneficial effects on DKD; however, there is a lack of studies analyzing the different effects of drugs on the various phenotypes of DKD. For this reason, there are still no specific guidelines for therapy in one phenotype rather than the other, generically referring to diabetic patients with CKD.

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic pathology in industrialized countries, affecting about 25% of the general population. NAFLD is a benign condition, however, it could evolve toward more serious diseases, including non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard for NAFLD diagnosis. Due to the risks associated with liver biopsy and the impossibility to apply it on a large scale, it is now necessary to identify non-invasive biomarkers, which may reliably identify patients at higher risk of progression. Therefore, several lines of research have tried to address this issue by identifying novel biomarkers using omics approaches, including lipidomics, metabolomics and RNA molecules’ profiling. Thus, in this review, we firstly report the conventional biomarkers used in clinical practice for NAFL and NASH diagnosis as well as fibrosis staging, and secondly, we pay attention to novel biomarkers discovered through omics approaches with a particular focus on RNA biomarkers (microRNAs, long-noncoding RNAs), showing promising diagnostic performance for NAFL/NASH diagnosis and fibrosis staging.

The controlling nutritional status (CONUT) score represents poor nutritional status and has been identified as an indicator of adverse outcomes. Our aim was to evaluate the prognostic role of the CONUT score on in-hospital outcomes in an Internal Medicine Department. This is a retrospective study analyzing data from 369 patients, divided into four groups based on the CONUT score: normal (0–1), mild–high (2–4), moderate–high (5–8), and marked high (9–12). In-hospital all-cause mortality increased from normal to marked high CONUT score group (2.2% vs. 3.6% vs. 13.4% vs. 15.3%, p < 0.009). Furthermore, a higher CONUT score was linked to a longer length of hospital stay (LOS) (9.48 ± 6.22 vs. 11.09 ± 7.11 vs. 12.45 ± 7.88 vs. 13.10 ± 8.12, p < 0.013) and an increased prevalence of sepsis. The excess risk of a high CONUT score relative to a low CONUT score remained significant after adjusting for confounders (all-cause mortality: OR: 3.3, 95% CI: 1.1–9.7, p < 0.02; sepsis: OR: 2.7, 95% CI: 1.5–4.9, p < 0.01; LOS: OR: 2.1, 95% CI: 1.2–3.9, p < 0.007). The present study demonstrated that an increased CONUT score is related to a higher risk of short-term in-hospital death and complications.

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice.

Prediabetes (preD) carries increased risk of cardiovascular (CV) events than normal-glucose-tolerance (NGT). Insulin resistance, a hallmark of preD, is closely linked to CV-risk, making its assessment crucial. Triglycerides-to-high-density-lipoprotein-cholesterol-ratio (TG/HDL) and triglycerides-and-glucose-product (TyG) have emerged as surrogate of insulin resistance. We aimed to evaluate the association of these indexes with CV-risk assessed through arterial stiffness in preD. 377 individuals without diagnosis of diabetes underwent: (1) complete biochemistry and oral-glucose-tolerance-test; (2) CV-risk assessment through arterial stiffness (pulsed-wave-velocity - PWV - and augmentation-index - AugI) and intima-media-thickness (IMT). Participants were split according to current guidelines: NGT (n = 100), preD (n = 216), and newly-diagnosed-type-2-diabetes (ND-T2D) (n = 61). TG/HDL and TyG were higher in preD than NGT, with no difference between preD and ND-T2D regarding TG/HDL. PreD showed higher PWV, AugI, and IMT than NGT. In preD group, after adjusting for major confounders, PWV was correlated with TG/HDL (β = 0.16; P = 0.03), but not with TyG, and there was a trend of association with HOMA-IR (β = 0.19, P = 0.07). In logistic regression, being in the higher tertile of TG/HDL was associated with higher PWV (odds-ratio 2.51, 95 %CI 1.01-6.29, P = 0.048). In preD, TG/HDL was independently associated with PWV, suggesting its possible role as a simple, cost-effective tool for assessing CV risk.