Worldwide, the leading cause of chronic liver disease is represented by nonalcoholic fatty liver disease (NAFLD) which has now become a global epidemic of the 21st century, affecting 1 in 4 adults, and which appears to be associated with the steadily increasing rates of metabolic syndrome and its components (obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia). NAFLD has been reported to be associated with extrahepatic manifestations such as cardiovascular disease, T2DM, chronic kidney disease, extrahepatic malignancies (e.g., colorectal cancer), endocrine diseases (e.g., hypothyroidism, polycystic ovarian syndrome, psoriasis, and osteoporosis), obstructive sleep apnea, and iron overload. The prevalence of NAFLD is very high, affecting 25–30% of the world population and encloses two steps: (1) nonalcoholic fatty liver (NAFL), which includes steatosis only, and (2) nonalcoholic steatohepatitis (NASH) defined by the presence of steatosis and inflammation with hepatocyte ballooning, with or without fibrosis which can progress to liver fibrosis, hepatocellular carcinoma, and liver transplantation. Current data define a more complex relationship between NAFLD and T2DM than was previously believed, underlining a bidirectional and mutual association between the two entities. This review aims to summarize the current literature regarding the incidence of T2DM among patients with NAFLD and also the prevalence of NAFLD in T2DM patients, highlighting the recent key studies. Clinicians should screen, diagnose, and treat T2DM in patients with NAFLD in order to avoid short- and long-term complications.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent cause of liver disease worldwide, comprising a plethora of conditions, ranging from steatosis to end‐stage liver disease. Cardiovascular disease (CVD) has been associated with NAFLD and CVD‐related events represent the main cause of death in patients with NAFLD, surpassing liver‐related mortality. This association is not surprising as NAFLD has been considered a part of the metabolic syndrome and has been related to numerous CVD risk factors, namely, insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease, and type 2 diabetes. Moreover, both NAFLD and CVD present similar pathophysiological mechanisms, such as increased visceral adiposity, altered lipid metabolism, increased oxidative stress, and systemic inflammation that could explain their association. Whether NAFLD increases the risk for CVD or these diagnostic entities represent distinct manifestations of the metabolic syndrome has not yet been clarified. This review focuses on the relation between NAFLD and the spectrum of CVD, considering the pathophysiological mechanisms, risk factors, current evidence, and future directions.

Nonalcoholic fatty liver disease (NAFLD) has a rising prevalence worldwide. Its potential for evolution towards liver cirrhosis and hepatocellular carcinoma, as well as associations with extrahepatic manifestations, represents a double burden for patients and physicians alike. Recently, there has been increasing evidence of the association between NAFLD and a number of endocrinopathies, such as hypothyroidism, polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency (GHD), hypogonadism, and hypercortisolism. Definite correlations are supported by clear evidence so far, but further studies are needed in order to completely clarify the pathogenic mechanisms and, especially, to identify therapeutic implications. In this review, we present the main relationships between NAFLD and endocrinopathies, emphasizing the reciprocal causality, evolutive interconnections, and current clinical scenarios of presentations of which the clinicians should be aware.

Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP) is a widely used non-invasive technique for concomitant assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the level both of hepatic steatosis and fibrosis as well as the associated risk factors in patients referred to our unit with clinically suspected NAFLD or diagnosed by abdominal ultrasonography. Two hundred four patients were prospectively included in this study and assessed by VCTE with CAP. The final analysis included 181 patients with reliable liver stiffness measurements (LSMs) (53% female, mean age 57.62 ± 11.8 years and BMI 29.48 ± 4.85 kg/m²). According to the cut-off values for steatosis grading, there were 10 (5.5%) patients without steatosis (S0), 30 (16.6%) with mild (S1), 45 (24.9%) moderate (S2), and 96 (53%) severe (S3) steatosis. Based on LSM, there were 73 (40.3%) patients without fibrosis (F0), 42 (23.2%) with mild (F1), 32 (17.7%) significant (F2), 19 (10.5%) advanced (F3) fibrosis, and 15 (8.3%) with cirrhosis (F4). In addition, we found an association between several metabolic components and hepatic steatosis and fibrosis. Thus, in the multivariate analysis, higher BMI, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and serum uric were associated with increased CAP. Furthermore, higher serum uric acid and alpha-fetoprotein together with lower platelets count and albumin levels were associated with increased LSM. The assessment of steatosis and fibrosis using VCTE and CAP should be performed in all patients with suspected or previously diagnosed NAFLD in units with available facilities.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Its incidence is progressively rising and it is possibly becoming a worldwide epidemic. NAFLD encompasses a spectrum of diseases accounting for the chronic accumulation of fat within the hepatocytes due to various causes, excluding excessive alcohol consumption. In this study, we aimed to focus on finding evidence regarding the implications of oxidative stress and inflammatory processes that form the multifaceted pathophysiological tableau in relation to thrombotic events that co-occur in NAFLD and associated chronic liver diseases. Recent evidence on the pathophysiology of NAFLD suggests that a complex pattern of multidirectional components, such as prooxidative, proinflammatory, and prothrombotic components, better explains the multiple factors that promote the mechanisms underlying the fatty acid excess and subsequent processes. As there is extensive evidence on the multi-component nature of NAFLD pathophysiology, further studies could address the complex interactions that underlie the development and progression of the disease. Therefore, this study aimed to describe possible pathophysiological mechanisms connecting the molecular impairments with the various clinical manifestations, focusing especially on the interactions among oxidative stress, inflammation, and coagulation dysfunctions. Thus, we described the possible bidirectional modulation among coagulation homeostasis, oxidative stress, and inflammation that occurs in the various stages of NAFLD.

Background and Objectives: Bacterial infections represent one of the most frequent precipitating events of acute-on-chronic liver failure (ACLF) in a patient with liver cirrhosis (LC). Early diagnosis and treatment could influence the ACLF reversal rate and decrease the mortality rate in these patients. The study aimed to evaluate the role of presepsin, C-reactive protein (CRP), and procalcitonin (PCT) in the early diagnosis of bacterial infections in patients with LC and ACLF, defined according to the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) criteria. Material and Methods: We performed a prospective observational study including all consecutive cirrhotic patients with ACLF admitted to our tertiary university center. The patients were follow-up until discharge. All patients were screened for infection at admission, and we included patients with community-acquired or healthcare-associated bacterial infections. Results: In this study, we included 153 patients with a median age of 60 years, of whom 65.4% were male. Infections were diagnosed in 71 patients (46.4%). The presepsin, CRP, and PCT levels were higher in patients with infections than in those without infections (p < 0.001, p = 0.023, and p < 0.001, respectively). The ROC analysis results demonstrated that the best cut-offs values for infections diagnosis were for presepsin 2300 pg/mL (sensitivity of 81.7%, specificity of 92.7%, AUROC 0.959, p < 0.001), CRP 5.3 mg/dL (sensitivity of 54.9%, specificity of 69.6%, AUROC 0.648, p = 0.023), and PCT 0.9 ng/mL (sensitivity of 80.3%, specificity of 86.6%, AUROC 0.909, p < 0.001). Presepsin (OR 3.65, 95%CI 1.394–9.588, p = 0.008), PCT (OR 9.79, 95%CI 6.168–25.736, p < 0.001), and MELD score (OR 7.37, 95%CI 1.416–18.430, p = 0.018) were associated with bacterial infections in patients with ACLF. Conclusion: Presepsin level ≥2300 pg/mL and PCT level ≥0.9 ng/mL may be adequate non-invasive tools for the early diagnosis of infections in cirrhotics with ACLF.