Treatments for NAFLD: State of Art

Non\u2010alcoholic fatty liver disease (NAFLD) is to date the most common chronic liver dis\u2010 ease in clinical practice and, consequently, a major health problem worldwide. It affects approxi\u2010 mately 30% of adults in the general population and up to 70% of patients with type 2 diabetes (T2DM). Despite the current knowledge of the epidemiology, pathogenesis, and natural history of NAFLD, no specific pharmacological therapies are until now approved for this disease and, con\u2010 sequently, general strategies have been proposed to manage it. They include: (a) lifestyle change in order to promote weight loss by diet and physical activity, (b) control of the main cardiometabolic risk factors, (c) correction of all modifiable risk factors leading the development and progression of advanced forms of NAFLD, and (d) prevention of hepatic and extra\u2010hepatic complications. In the last decade, several potential agents have been widely investigated for the treatment of NAFLD and its advanced forms\u2014shedding some light but casting a few shadows. They include some glu\u2010 cose\u2010lowering drugs (such as pioglitazone, glucagon\u2010like peptide\u20101 (GLP\u20101) receptor agonists, so\u2010 dium\u2010glucose co\u2010transporter\u20102 (SGLT\u20102) inhibitors), antioxidants (such as vitamin E), statins or other lipid lowering agents, bile and non\u2010bile acid farnesoid X activated receptor (FXR) agonists, and others. This narrative review discusses in detail the different available approaches with the potential to prevent and treat NAFLD and its advanced forms

Recent Developments in NAFLD

: The aim of our Special Edition, entitled "Nonalcoholic Fatty Liver Disease/Metabolic Associated Fatty Liver Disease: New Insights", is to point out recent developments in the area of NAFLD pathogenesis and treatment [...]

Coronavirus disease 2019 (COVID-19): we don't leave women alone

Not applicabl

Glucose-lowering agents and reduced risk of incident non-alcoholic fatty liver disease: new insights

Maybe, given the multiple pathways involved in the NAFLD pathogenesis and the single response from single- agent therapies (that stands from 30% to 50%) observed in the RCTs published so far (3), the combination of different agents with various mechanisms of action may be the best way to treat NAFLD and its advanced forms (11). In this regard, for instance, the GLP-1 RA, semaglutide, is being investigated in combination with the nonsteroidal Farnesoid X receptor (FXR) agonist, cilofexor, and with the acetyl- CoA carboxylase inhibitor, firsocostat, in a phase 2 proof- of-concept trial (NCT03987074). Semaglutide is also being investigated in combination with empagliflozin (gliflozin) in a placebo-controlled, double-blind, randomized, 3-arm parallel group trial (NCT04639414). Moreover, considering the heterogeneity of NAFLD patients, it might be even more suitable to identify specific individuals for a definite therapeutic strategy (11). However, the research on this topic is still at the beginning and further studies are needed to improve our understanding for intercepting NAFLD patients who would have a higher probability of treatment response with a specific agent as monotherapy or, better, with a combination therapy (3)

Breastfeeding duration and reduced risk of NAFLD in midlife of parous women

the observational studies available so far and the result of our analysis reinforce the assertion that breastfeeding is relevant for the long-term health of the mother, with a protective effect on the risk of NAFLD

Platelets in Non-alcoholic Fatty Liver Disease

Non alcoholic steatohepatitis (NASH) is the inflammatory reaction of the liver to excessive accumulation of lipids in the hepatocytes. NASH can progress to cirrhosis and hepatocellular carcinoma (HCC). Fatty liver is the hepatic manifestation of metabolic syndrome. A subclinical inflammatory state is present in patients with metabolic alterations like insulin resistance, type-2 diabetes, obesity, hyperlipidemia, and hypertension. Platelets participate in immune cells recruitment and cytokines-induced liver damage. It is hypothesized that lipid toxicity cause accumulation of platelets in the liver, platelet adhesion and activation, which primes the immunoinflammatory reaction and activation of stellate cells. Recent data suggest that antiplatelet drugs may interrupt this cascade and prevent/improve NASH. They may also improve some metabolic alterations. The pathophysiology of inflammatory liver disease and the implication of platelets are discussed in details

Non-Alcoholic Fatty Liver Disease and Risk of Macro- and Microvascular Complications in Patients with Type 2 Diabetes

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. To date, NAFLD is the most frequent chronic liver disease seen day by day in clinical practice across most high-income countries, affecting nearly 25-30% of adults in the general population and up to 70% of patients with T2DM. Over the last few decades, it clearly emerged that NAFLD is a "multisystemic disease" and that the leading cause of death among patients with NAFLD is cardiovascular disease (CVD). Indeed, several observational studies and some meta-analyses have documented that NAFLD, especially its advanced forms, is strongly associated with fatal and non-fatal cardiovascular events, as well as with specific cardiac complications, including sub-clinical myocardial alteration and dysfunction, heart valve diseases and cardiac arrhythmias. Importantly, across various studies, these associations remained significant after adjustment for established cardiovascular risk factors and other confounders. Additionally, several observational studies and some meta-analyses have also reported that NAFLD is independently associated with specific microvascular conditions, such as chronic kidney disease and distal or autonomic neuropathy. Conversely, data regarding a potential association between NAFLD and retinopathy are scarce and often conflicting. This narrative review will describe the current evidence about the association between NAFLD and the risk of macro- and microvascular manifestations of CVD, especially in patients with T2DM. We will also briefly discuss the biological mechanisms underpinning the association between NAFLD and its advanced forms and macro- and microvascular CVD

MAFLD and CKD: An Updated Narrative Review

Accumulating evidence now indicates that non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease observed in clinical practice worldwide, is independently associated with an increased risk of incident chronic kidney disease (CKD). Given that NAFLD is linked to insulin resistance, obesity and type 2 diabetes mellitus, an international panel of experts have recently proposed a name change from NAFLD to metabolic associated fatty liver disease (MAFLD). Since the diagnostic criteria for NAFLD and MAFLD are different, observational studies assessing the potential concordance (or even superiority) of MAFLD, compared with NAFLD, in detecting patients at increased risk of hepatic and extra-hepatic complications (including CKD) are required. Hence, in the last two years, some observational studies have investigated the potential relationship between MAFLD and CKD. The result is that, at present, evidence regarding the concordance or even superiority of MAFLD, compared with NAFLD, in detecting patients at higher risk of CKD is still preliminary, although some data indicate that MAFLD identifies patients with CKD as accurately as NAFLD. In this narrative review, we will discuss: (a) the epidemiological evidence assessing the association between NAFLD and risk of incident CKD, (b) the epidemiological data investigating the association between MAFLD and risk of CKD and (c) the biological mechanisms underlying the association between NAFLD/MAFLD and CKD

Plant cystine-knot peptides: pharmacological perspectives.

The cystine-knot peptides are well represented in several plant species. The pharmacological interest for plant cystine-knot peptides derived from their broad biological activities. The mechanisms of action of plant cystine-knot peptides are still largely undiscovered, although eveidences indicate that they interfere with plasma membranes. In some cases, as tomato TCMPs, the cystine-knot peptides target human growth factor receptors either by acting as growth factor antagonist or by altering their signal transduction pathway. The possibility to identify specific molecular targets of plant cystine-knot peptides in human cells opens novel possibilities for the pharmacological use of these peptides besides their use as scaffold to develop stable disease molecular markers and therapeutic agent

Spur cells in liver cirrhosis are predictive of acute-on-chronic liver failure and liver-related mortality regardless of severe anaemia

Lay SummaryChronic anaemia is a frequent finding in liver cirrhosis and spur cell anaemia has been shown to be an uncommon non-immune haemolytic disease typically related to advanced-liver disease. In our study, spur cell anaemia (spur cells >5%) was found in almost 10% of outpatient cirrhotics and was significantly related to more decompensated disease, higher incidence of ACLF and 1 year liver-related mortality. More importantly, the vast majority of patients with high percentage of spur cells did not have severe anaemia. Therefore, spur cells should be searched for in patients with advanced liver disease by a simple blood smear evaluation, even in the absence of significant anaemia, because of relevant prognostic impact and in order to prioritize patients to intensive management and possibly liver transplantation.Chronic anaemia in advanced liver disease is a frequent finding. The aim was to explore the clinical impact of spur cell anaemia, a rare entity typically associated with end-stage of the disease. One-hundred and nineteen patients (73.9% males) with liver cirrhosis of any etiology were included. Patients with bone marrow diseases, nutrients deficiencies and hepatocellular carcinoma were excluded. In all patients, a blood sample was collected to check for the presence of spur cells on blood smear. A complete blood biochemical panel was recorded together with Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) score. For each patients, clinically relevant events, such as acute-on-chronic liver failure (ACLF) and 1 year liver-related mortality, were registered. Patients were then grouped according to the percentage of spur cells at smear (> 5%, 1-5%, < 1%). Severe anaemia was defined as haemoglobin levels lower than 8 g/dL. 9.2% of subjects had > 5% spur cells, only 2 had evidence of haemolysis. In patients with > 5% spur cells, haemoglobin and albumin were lower compared with the other sub-group, while MELD score, CP score, International Normalized Ratio, ferritin, creatinine and unconjugated bilirubin were higher. Patients with more spur cells were more decompensated and developed more frequently ACLF. ACLF and liver-related mortality were significantly and independently associated with the presence of > 5% spur cells but not with baseline severe anaemia. Cirrhotic patients have a fairly high prevalence of spur cells, not always associated with severe haemolytic anaemia. The presence of spur red cells is per se associated with a worse prognosis and, therefore, should be always evaluated to prioritize patients for intensive management and eventually liver transplantation