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.

Objective: Statin therapy has been linked to an increased risk of type 2 diabetes in high-risk populations; however, the pathophysiology of this association remains to be clarified. We investigated glucagon suppression and its relationship with insulin resistance in prediabetic subjects undergoing atorvastatin therapy; in addition, we studied molecular insulin signaling in pancreatic α-cells exposed to atorvastatin in vitro. Design and methods: Fifty subjects with prediabetes were divided into two groups based on atorvastatin therapy. All subjects underwent an oral glucose tolerance test. Early (0–30 min), late (30–120 min) and overall (0–120 min) glucagon suppression were evaluated. Insulin sensitivity was estimated by the insulin sensitivity index (ISI_0–120). Insulin signaling pathway and insulin-mediated glucagon suppression were investigated in pancreatic αTC1-6 cells chronically exposed (24 or 48 h) to atorvastatin (100 ng/mL). Results: Individuals on statin therapy (n = 26) showed a significantly reduced early (0–30 min) (P = 0.003) and overall (0–120 min) (P = 0.01) glucagon suppression compared with controls (n = 24). In multivariate regression analysis, early glucagon suppression (0–30 min) exhibited a significant correlation with statin therapy. Regression analysis showed a significant association between ISI _0-120 and early_0-30 (r = 0.33, P < 0.05) and overall₀-₁₂₀ (r = 0.38, P < 0.05) glucagon suppression. Moreover, in αTC1-6 cells atorvastatin treatment affected insulin-mediated glucagon suppression, insulin receptor phosphorylation and IRS-1-AKT pathway signaling. Conclusions: Prediabetic patients undergoing statin therapy exhibit impaired glucagon suppression associated with lower insulin sensitivity. Our data revealed a new molecular aspect behind the deregulation of insulin sensitivity secondary to statin exposure.

The coronavirus disease 19 (COVID-19) emergency led to rearrangements of healthcare systems with a significant impact on those internal medicine departments that had not been converted to COVID-19 wards. A reduced number of departments, indeed, had to cope with the same number of patients along with a lack of management of patients’ chronic diseases. We conducted a retrospective study aimed at examiningthe consequences of the COVID-19 pandemic on internal medicine departments that were not directly managing COVID-19 patients. Data from 619 patients were collected: 247 subjects hospitalized in 2019 (pre-COVID-19 era), 178 in 2020 (COVID-19 outbreak era) and 194 in 2021 (COVID-19 ongoing era). We found that in 2020 in-hospital mortality was significantly higher than in 2019 (17.4% vs. 5.3%, p = 0.009) as well as length of in-hospital stay (LOS) (12.7 ± 6.8 vs. 11 ± 6.2, p = 0.04). Finally, we performed a logistic regression analysis of the major determinants of mortality in the entire study population, which highlighted an association between mortality, being bedridden (β = 1.4, p = 0.004), respiratory failure (β = 1.5, p = 0.001), glomerular filtration rate (β = −0.16, p = 0.03) and hospitalization in the COVID-19 outbreak era (β = 1.6, p = 0.005). Our study highlights how the COVID-19 epidemic may have caused an increase in mortality and LOS even in patients not directly suffering from this infection.