The debate over Diagnostic and Therapeutic Care Pathways (DTCP) existed for at least twenty years it is therefore necessary to contextualize the thinking with respect to the historical context and in accordance to the disciplinary bases. In the last twenty years, health care companies, Region - health care and medicine relations have undergone a major transformation, so there is a need to resume the historical positions by updating them or referring to those contributions of the debate that best capture the most recent transformations. The reference to the disciplinary roots of the various contributions in the literature allows for a common denominator to avoid building proposals that risk being based on very different conceptual basis or referring to distant issues in the complex world of healthcare services.This article compares three trials implemented in the Lombardy region with regard to the management of chronicity in general practice first, the proactive taking in charge of chronicity; second, the Chronic Related Groups (CReGs); and third, the clinical government of Brescia's ATS. The analysis of the Lombardy reforms uses the cycle of public policies as an interpretative tool, with particular reference to the causal theories of the problem proposed by the policies, and to the strategies adopted to encourage change, understood as higher effectiveness and appropriateness in the treatment of chronic diseases with a high prevalence in the area.The Research and Health Foundation led a preliminary analysis to understand how drugs are cited and what their weight is within the current diagnostic-therapeutic care pathways (PDTA) referring to chronic diseases.  https://www.selleckchem.com/products/rbn013209.html  The results highlight the need to provide for the specification of which drugs to use and the related methods of use. The issue is also important due to the connection between specific decisions of the Italian Medicines Agency concerning the access and reimbursement of the drug and their use.The Farnesoid X nuclear receptor (FXR) is a nuclear receptor of bile acids whose activation suppresses the synthesis of bile acids stimulates their excretion in the bile and inhibits its uptake in hepatocytes. FXR is also involved in the regulation of over 250 genes including those responsible for the control of lipid and carbohydrate metabolism. The activation of FXR also induces anti-inflammatory effects and antifibrotics. Over the past 10 years they have been synthesized and studied various FXR agonists which have demonstrated beneficial effects in the treatment of the main pathologies cholestatic diseases including primary biliary cholangitis, cholangitis primary sclerosing and cholangiocarcinoma.Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that may develop at any point of the biliary tree. Their incidence is rising worldwide, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent nature of these tumours combined with their high aggressiveness and refractory nature contribute to their alarming mortality rates, representing nowadays ~2% of all cancer-related deaths yearly. In the past decade, increasing efforts have been made in order to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to increase patient's welfare.Hepatocellular carcinoma is diagnosed in more than half of all cases at unresectable stage when no potentially curative treatments are feasible. Since 2008, sorafenib had represented the only effective first line systemic therapy over the last decade until the approval of lenvatinib, who showed to be non-inferior to sorafenib. Recently, for the first time, a combination of immunotherapy and antiangiogenic drug, atezolizumab plus bevacizumab, was associated with a significantly longer overall survival and progression free survival compared to sorafenib, becoming the new best performing first-line approach for unresectable HCC. After several randomized controlled trials (RCTs) that have attempted to find an effective second-line therapy, regorafenib, cabozantinib, ramucirumab, nivolumab and pembrolizumab represent approved treatments for patients who failed first-line treatment. However, inclusion criteria of second-line RCTs are quite heterogeneous and no direct comparisons exist among these agents. Exciting opportunities have been found either in the combination or in the sequencing of these agents, but the optimal therapeutic strategy for these patients remains elusive. Moreover, the coexistence of cirrhosis and the competing risk of liver decompensation increase the complexity of the assessment of the net health benefit of the available therapeutic approaches. The aim of this review is to summarize the evidence on systemic treatments for unresectable HCC and to explore the future perspectives on this topic.This review explores the latest guidelines on nutrition in patients with chronic liver diseases of the European Association for the Study of the Liver (EASL) and recent studies on physiopathology, clinical outcomes and possible treatments of malnutrition and sarcopenia in liver cirrhosis. Chronic liver diseases are frequently associated with malnutrition, changes in skeletal muscle and bone quality and quantity. About 20% of patients with compensated liver cirrhosis and 50% of those with decompensated cirrhosis are sarcopenic. Malnutrition and sarcopenia are associated with a higher complication rate (ascites, bacterial infections and hepatic encephalopathy) and are independent predictors of lower survival in cirrhotic patients. In recent years, concomitant with the decline of post-viral cirrhosis, patients affected by post-metabolic cirrhosis are increasing. These patients are more frequently overweight or obese, but sarcopenia may also coexist. Sarcopenic obesity has been shown to worsen the prognosis in patients with liver cirrhosis. There is a general consensus about the need of improving the nutritional status and implementing skeletal muscle mass in cirrhotic patients, but this is not always achievable. Osteoporosis is present in about 30% of cirrhotic patients, with a higher prevalence in patients with cholestasis. Treatment with phosphonates, calcium and vitamin D are recommended in association with a periodic follow-up.