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In recent decades, following the spread of obesity, metabolic dysfunction has come to represent the leading cause of liver disease. The classical clinical presentation of the cirrhotic patient has, therefore, greatly changed, with a dramatic increase in subjects who appear overweight or obese. Due to an obesogenic lifestyle (lack of physical activity and overall malnutrition, with an excess of caloric intake together with a deficit of proteins and micronutrients), these patients frequently develop a complex clinical condition defined as sarcopenic obesity (SO). The interplay between cirrhosis and SO lies in the sharing of multiple pathogenetic mechanisms, including malnutrition/malabsorption, chronic inflammation, hyperammonemia and insulin resistance. The presence of SO worsens the outcome of cirrhotic patients, affecting overall morbidity and mortality. International nutrition and liver diseases societies strongly agree on recommending the use of food as an integral part of the healing process in the comprehensive management of these patients, including a reduction in caloric intake, protein and micronutrient supplementation and sodium restriction. Based on the pathophysiological paths shared by cirrhosis and SO, this narrative review aims to highlight the nutritional interventions currently advocated by international guidelines, as well as to provide hints on the possible role of micronutrients and nutraceuticals in the treatment of this multifaceted clinical condition. [ABSTRACT FROM AUTHOR]

Simple Summary: One out of four patients with NAFLD and metabolic syndrome is also affected by psychological distress. In this study, we evaluated the impact of a stressful contingency such as the COVID-19 lockdown on a cohort of Italian patients affected by NAFLD. Our data confirmed the association between psychological distress and NAFLD. They also showed how psychological suffering was associated with a worse efficacy of the behavioral therapeutic approach in patients with NAFLD. Non-alcoholic fatty liver disease (NAFLD) is a potentially progressive condition characterized by the presence of fat in more than 5% of hepatocytes, representing the hepatic expression of metabolic syndrome (MetS). A reduction of at least 5–7% in initial body weight improves the metabolic profile underlying NAFLD. The aim of our study was to evaluate the effects of the COVID-19 lockdown on a cohort of non-advanced NAFLD Italian outpatients. We identified 43 patients with 3 available time point visits in our center: first visit (T0) when behavioral indications aimed at controlling MetS were provided, a pre-COVID visit (T1) and a post-COVID visit (T2). During the lockdown, an online compilation of validated psychological tests (SRQ-20, EQ5D, SF-12 and STAI) and a specifically formulated questionnaire for NAFLD was presented to our cohort and completed by 14 consenting patients. Patients who had lost more than 5% of the initial weight at T1 (9 subjects, 21%) maintained the results even at T2, with an overall reduction in BMI and liver stiffness; patients who had not lost the desired weight at T1 (34 subjects, 79%) displayed a further increase in BMI and visceral adiposity at T2. Of interest is that patients in the latter group reported signs of psychological suffering. Our data demonstrated that the setting of good counseling was effective in controlling the metabolic disorder underlying NAFLD in our cohort of outpatients. Given the need for patients to play an active role in the behavioral therapy for NAFLD, we advocate that a multidisciplinary approach be adopted, including a psychological support to obtain the best results over time. [ABSTRACT FROM AUTHOR]

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes' comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called "Diabetes Comorbidome". (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The "Diabetes Comorbidome" represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes. [ABSTRACT FROM AUTHOR]

The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The European (EASL) and American (AASLD) guidelines for the management of hepatocellular carcinoma (HCC) suggest different management of nodules with indeterminate imaging in cirrhosis. In particular, nodules classified as LR-3 and LR-4 by the CEUS LI-RADS algorithm (indeterminate for HCC) are suggested to be biopsied according the EASL guidelines, but may be only monitored with follow-up imaging, with biopsy left to selected LR-4/LR-M cases, according to the AASLD ones. The present study shows that CEUS LI-RADS classes LR-3 and LR-4 HCC have no better clinical outcome than typical HCC (LR-5). Such data support the EASL policy, aimed at conclusive diagnostic investigations of indeterminate nodules up to obtaining histological proof to avoid leaving aggressive HCC not timely treated. The American College of Radiology (ACR) released the Liver Imaging Report and Data System (LI-RADS) scheme, which categorizes hepatic nodules in risk classes from LR-1 to LR-5 (according to the degree of risk to be HCC) and LR-M (probable malignancy not specific for HCC). The aim of this study was to test whether HCC with different LR patterns on CEUS have different overall survival (OS) and recurrence-free survival (RFS). We retrospectively enrolled 167 patients with the first definitive diagnosis of single HCC (by using CT/MRI or histological techniques if CT/MRI were inconclusive) for whom CEUS examination was available. The median size of HCC lesions was 2.2 cm (range 1.0–7.2 cm). According to CEUS LI-RADS classification, 28 patients were in LR-3, 48 in LR-4, 83 in LR-5, and 8 in LR-M. Patient liver function and nodule characteristics were not statistically different between CEUS LI-RADS classes. Using univariate analysis, CEUS LI-RADS class was not found to be a predictor of survival (p = 0.347). In conclusion, HCC showing the CEUS LI-RADS classes LR-3 and LR-4 have no better clinical outcome than typical HCC. Such data support the EASL policy, aimed at conclusive diagnostic investigations of indeterminate nodules up to obtaining histological proof to avoid leaving aggressive HCC not timely treated. [ABSTRACT FROM AUTHOR]

Background: Currently, diabetes represents the seventh leading cause of death worldwide, with a significant economic burden. The number and severity of comorbidities increase with age, and are identified as important determinants that influence the prognosis. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients affected by diabetes. Methods: In this observational study, we retrospectively analyzed data collected from the REgistro dei pazienti per lo studio delle POlipatologie e politerapie in reparti della rete Simi (RePoSi) registry. Socio-demographic, clinical characteristics, and laboratory findings were considered. The association between variables and in-hospital and 1-year follow-up were analyzed. Results: Among 4708 in-patients, 1378 (29.3%) had a diagnosis of diabetes. Patients with diabetes had more previous hospitalization, a clinically significant disability, and more need for a urinary catheter in comparison with subjects without diabetes. Patients affected by diabetes took more drugs, both at admission, at in-hospital stay, at discharge, and at 1-year follow-up. Thirty-five comorbidities were more frequent in patients with diabetes, and the first five were hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and chronic obstructive pulmonary disease (22.7%). Heart rate was an independent predictor of in-hospital mortality. At 1-year follow-up, cancer and male sex were strongly independently associated with mortality. Conclusions: Our findings showed the severity of the impact of diabetes and its comorbidities in the real life of internal medicine and geriatric wards, and provide data to be used for a better tailored management of elderly in-patients with diabetes. [ABSTRACT FROM AUTHOR]

Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of "NAFLD as a manifestation of the Metabolic Syndrome", to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research. [ABSTRACT FROM AUTHOR]

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary liver cancer. It is constituted by neoplastic cells of both hepatocellular and cholangiocellular derivation. Different histology types of HCC-CC have been reported, hinting at heterogeneous carcinogenic pathways leading to the development of this cancer. Due to its rarity and complexity, mixed HCC-CC is a scantly investigated condition with unmet needs and unsatisfactory outcomes. Surgery remains the preferred treatment in resectable patients. The risk of recurrence, however, is high, especially in comparison with other primary liver cancers such as hepatocellular carcinoma. In unresectable or recurring patients, the therapeutic options are challenging due to the dual nature of the neoplastic cells. Consequently, the odds of survival of patients with HCC-CC remains poor. We analysed the literature systematically about the treatment of mixed HCC-CC, reviewing the main therapeutic options and their outcomes and analysing the most interesting developments in this topic with a focus on new potential therapeutic avenues. [ABSTRACT FROM AUTHOR]