Glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

Non-alcoholic fatty liver disease(NAFLD)is the predominant cause of chronic liver disease worldwide.NAFLD progresses in some cases to non-alcoholic steatohepatitis(NASH),which is characterized,in addition to liver fat deposition,by hepatocyte ballooning,inflammation and liver fibrosis,and in some cases may lead to hepatocellular carcinoma.NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus(T2DM).Currently,lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD.Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are used in the management of T2DM and do not have major side effects like hypoglycemia.In patients with NAFLD,the GLP-1 receptor production is down-regulated.Recently,several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation,alleviating the inflammatory environment and preventing NAFLD progression to NASH.In this review,we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH.Finally,as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD,we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.

Nonalcoholic fatty liver disease in lean subjects:Prognosis,outcomes and management

Nonalcoholic fatty liver disease(NAFLD)accounts for most cases of chronic liver disease worldwide,with an estimated global prevalence of approximately 25%and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis.NAFLD is strongly connected to metabolic syndrome,and for many years,fatty liver was considered to be an exclusive feature of obese patients.However,recent studies have highlighted the presence of NAFLD in non-obese subjects,with or without increased visceral fat or even in lean subjects without increased waist circumference.“Lean NAFLD”is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology,prognosis and management compared with NAFLD in overweight/obese patients.In the present editorial,we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries.Moreover,we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population.Finally,we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and nonlean cohorts.

Non-alcoholic fatty liver disease and hepatocellular carcinoma:Clinical challenges of an intriguing link

Non-alcoholic fatty liver disease(NAFLD)has emerged as the most common liver disorder worldwide mainly attributed to the epidemic spread of obesity and type 2 diabetes mellitus.Although it is considered a benign disease,NAFLD can progress to non-alcoholic steatohepatitis,liver cirrhosis and hepatocellular carcinoma(HCC).Most data regarding the epidemiology of NAFLD-related HCC are derived from cohort and population studies and show that its incidence is increasing as well as it is likely to emerge as the leading indication for liver transplantation,especially in the Western World.Although cirrhosis constitutes the main risk factor for HCC development,in patients with NAFLD,HCC can arise in the absence of cirrhosis,indicating specific carcinogenic molecular pathways.Since NAFLD as an underlying liver disease for HCC is often underdiagnosed due to lack of sufficient surveillance in this population,NAFLDHCC patients are at advanced HCC stage at the time of diagnosis making the management of those patients clinically challenging and affecting their prognostic outcomes.In this current review,we summarize the latest literature on the epidemiology,other than liver cirrhosis-pathogenesis,risk factors and prognosis of NAFLD-HCC patients.Finally,we emphasize the prevention of the development of NAFLD-associated HCC and we provide some insight into the open questions and issues regarding the appropriate surveillance policies for those patients.

Acute Severe Hepatitis of Unknown Origin in Children Across the World: A 2022 Source of Concern

At the beginning of April 2022,the World Health Organization(WHO)identified 10 cases of acute severe hepatitis in children younger than 10 years of age,across central Scotland.1 None of the typical hepatitis viruses(A–E)that are known to cause acute viral hepatitis were isolated from any of those cases,and no common environmental exposures were found.Based on the latest data(up to 26 May 2022),approximately 152 cases of acute severe hepatitis were reported in the European Union and 222 cases in the UK.2 Moreover,more than 38 of the cases received a liver transplant and at least 14 deaths were reported(Table 1).2,3 The WHO,European Centre for Disease Prevention and Control,and UK Health Security Agency have posted reports trying to inform about the recent cases of acute hepatitis of unknown origin.Concerning the case definition by WHO,a description of a confirmed case is not available at present,while a probable case is considered a person presenting with acute hepatitis that cannot be attributed to the hepatitis viruses A–E,with serum aminotransferase levels>500 IU/L(aspartate aminotransferase or alanine aminotransferase),who is 16 years or younger,since October 2021(Table 2).