Immune checkpoint inhibitors (ICIs) have revolutionized oncology, providing a groundbreaking therapeutic option for patients with various advanced-stage cancers. While these treatments can significantly extend survival, they also carry a substantial risk of immune-related adverse events, among which hypophysitis is particularly detrimental to endocrine function. This narrative review synthesizes current knowledge on the pathogenesis, clinical features, diagnosis, and management of ICI-induced hypophysitis (IH) based on an in-depth analysis of the recent literature and clinical trials. The diagnosis of IH presents unique challenges due to its overlap with systemic symptoms commonly associated with the underlying malignancy. These symptoms can include asthenia, anorexia, headache, vomiting, weight loss, hypotension, dizziness, decreased libido, and visual disturbances. Diagnostic evaluation typically combines clinical assessment, hormonal profiling, and findings from magnetic resonance imaging (MRI). Effective management of IH requires a personalized, multidisciplinary approach, focusing on hormone replacement therapy and vigilant monitoring. Long-term care depends on the severity of hypophysitis, and the specific hormonal axes involved. This review aims to enhance awareness of the critical aspects of recognizing and managing IH, underscoring the importance of early diagnosis and timely intervention to reduce its long-term effects on patient quality of life.

The most common form of chronic liver disease, recently defined as MASLD, is strongly linked to obesity and metabolic syndrome. Lifestyle changes are part of MASLD prevention. The very low-calorie ketogenic diet (VLCKD) is a useful option for treating MASLD and reducing liver steatosis in patients with obesity. We assessed whether a greater degree of steatosis could have a positive or negative impact on how well 8 weeks of using the VLCKD improve steatosis and fibrosis in a patient population of overweight and obese individuals. Anthropometric parameters, along with changes in hormone and metabolic biomarkers, were also assessed both before and after the dietary change. The study population included 111 overweight (14.41%) or obese subjects (85.59%) aged between 18 and 64 years; the 75 women and 36 men involved were not taking any medicine. In both the raw (0.37 95% CI 0.21; 0.52) and the multivariate models (model a: 0.439 95% CI 0.26; 0.62; model b: 0.437 95% CI 0.25; 0.63), there was a positive and statistically significant correlation between the CAP delta value and the CAP before using the VLCKD. Additionally, the liver stiffness delta was found to be positively and statistically significantly correlated with liver stiffness before the use of the VLCKD in both models: the multivariate model (model a: 0.560 95% CI 0.40; 0.71; model b: 0.498 95% CI 0.34; 0.65) and the raw model (0.52 95% CI 0.39; 0.65). Systolic and diastolic blood pressure, insulin resistance (measured by HOMA-IR), insulin, HbA1c, fasting blood glucose, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, BMI, waist circumference, and fat mass, were all decreased (p < 0.001) following the use of the VLCKD. However, following the use of the VLCKD, there was an increase in vitamin D levels. (p < 0.001). We found that using the VLCKD for 8 weeks has a greater effect on improving steatosis and fibrosis in subjects who initially have more severe forms of these conditions.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly correlated with the severity of obesity, and the extent of liver fibrosis is associated with a higher risk of liver-related complications, cardiovascular events, and overall mortality. Leptin circulating levels are directly correlated with the amount of adipose tissue. Aims: In the present study, we investigated the association between circulating leptin levels and liver steatosis and fibrosis. Methods: Eighty-six patients (41.7 ± 12.6 yrs, 35 men, 41%), naïve to medications, who attended the Nutrition Center for the Research and Care of Obesity and Metabolic Diseases at the National Institute of Gastroenterology “Saverio de Bellis” for weight management, were cross-sectionally evaluated. Demographic, anthropometric, clinical, and laboratory data were collected and analyzed. All patients underwent liver ultrasonographic assessment by FibroScan to diagnose liver steatosis (controlled attenuation parameter, CAP > 275 dBm) and fibrosis (liver stiffness measurement, LSM > 8.2 kPa). Results: Sixty-three individuals (73.3%) had liver steatosis, and 17 (19.8%) had liver fibrosis. The mean leptin levels were 22.3 ± 14.1 ng/mL, while the BMI and waist circumference were 36.7 ± 7.2 kg/m² and 114.5 ± 16.4 cm, respectively. CAP values exhibited no correlation with leptin (r = 0.09, p = 0.436), while a significant connection was seen between leptin and LSM (β = 0.065; p = 0.038). Specifically, for each unit increase in leptin, LSM values were varied by +0.065 units (p = 0.038). This association was independent of gender, age, insulin resistance, adiponectin, RBP4, and visfatin. This is the first study showing these results by using FibroScan assessment in patients naïve to medications. Conclusions: Circulating leptin concentrations are independently correlated with hepatic fibrosis in individuals with a BMI ≥ 25 kg/m². These findings indicate a function for leptin in promoting liver fibrosis; however, longitudinal studies are required to elucidate the causal nature of this interaction.

BTC overall incidence is globally increasing. CCA, including its subtypes, is a form of BTC. MetS, obesity, MASLD, and diabetes are all linked to CCA in interconnected ways. The link between obesity and CCA is less well-defined in Eastern countries as compared to Western. Although more research is needed to determine the relationship between MASLD and extrahepatic CCA (eCCA), MASLD may be a concurrent risk factor for intrahepatic CCA, particularly in populations with established or unidentified underlying liver disease. Interestingly, the risk of biliary tract cancer (BTC) seemed to be higher in patients with shorter diabetes durations who were not treated with insulin. Therefore, early detection and prevention of chronic liver disease, as well as additional intervention studies, will undoubtedly be required to determine whether improvements to MetS, weight loss, and diabetes therapy can reduce the risk and progression of BTC. However, further studies are needed to understand how reproductive hormones are involved in causing BTC and to develop consistent treatment for patients. Finally, it is critical to carefully assess the cardiological risk in BTC patients due to their increased intrinsic cardiovascular risk, putting them at risk for thrombotic complications, cardiovascular death, cardiac metastasis, and nonbacterial thrombotic endocarditis. This review aimed to provide an updated summary of the relation between the abovementioned cardio-metabolic conditions and BTC.

Background/Objectives: Chronotype describes individual preferences regarding the timing of sleep, food intake, and other daily activities and is commonly evaluated using the Morningness–Eveningness Questionnaire (MEQ). Individuals with a morning chronotype generally prefer earlier sleep–wake schedules, whereas those with an evening chronotype exhibit delayed circadian timing and achieve peak alertness later in the day. Previous evidence has linked evening chronotype to an elevated risk of obesity and metabolic dysfunction; however, its association with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), particularly with hepatic steatosis and fibrosis, has not yet been fully elucidated. Methods: This cross-sectional study included 119 medication-naïve adults, predominantly with obesity (mean age 41.5 ± 11.9 years; 58 men, 49%), recruited at the Nutrition Center of the National Institute of Gastroenterology “Saverio de Bellis.” Hepatic steatosis (controlled attenuation parameter [CAP] > 275 dB/m) and liver fibrosis (liver stiffness > 8.2 kPa) were assessed by transient elastography (FibroScan). Results: Hepatic steatosis was detected in 62% of participants (n = 74), whereas fibrosis was identified in 15% (n = 18). When chronotype was analyzed as a continuous variable, no significant correlations were observed with either CAP (r = 0.017, p = 0.852) or liver stiffness measurements (r = −0.045, p = 0.629). Although these associations did not reach statistical significance, the corresponding confidence intervals remained compatible with small-to-moderate effect sizes, particularly for fibrosis, reflecting the limited number of participants with fibrotic disease. Conclusions: In this sample, chronotype was not significantly associated with FibroScan-derived measures of hepatic steatosis or fibrosis. Associations with selected metabolic and behavioral characteristics were identified, although these findings require confirmation in adequately powered longitudinal investigations. To our knowledge, only a limited number of studies have explored these relationships using objective FibroScan-derived measurements in medication-naïve individuals. Consequently, the present findings should be considered hypothesis-generating and warrant validation in larger prospective cohorts.