Validation of the European Association for the Study of the Liver algorithm for the noninvasive diagnosis of advanced fibrosis in metabolic-dysfunction associated steatotic liver disease

Metabolic-dysfunction associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD)(1),is characterized by the accumulation of fat in the liver cells,independent of excessive alcohol consumption and has emerged as the most prevalent chronic liver condition in Western countries,underscoring a significant public health concern(2).The progression of MASLD to advanced fibrosis,marked by excessive extracellular matrix deposition and scar tissue formation,is a critical stage in MASLD natural history that significantly increases the risk of liver-related complications mortality(3).Non-invasive tests(NITs),such as liver stiffness measurement(LSM)with transient elastography(TE)and serum biomarkers,have gained prominence for assessing liver fibrosis in patients with suspected/confirmed NAFLD,offering a safer and less invasive alternative to liver biopsy(4).

Advancing towards accurate phenotyping based on metabolic and fibrosis risk in metabolic-dysfunction associated steatotic liver disease:one step closer to personalized care

Relevance of liver fibrosis amongst diabetic patients with metabolic-dysfunction associated steatotic liver disease(MASLD)and knowledge gaps Insulin resistance is paramount in the crosstalk between intrahepatic and extrahepatic pathophysiological mechanisms leading to MASLD(1),hence gaining special relevance in patients diagnosed with type 2 diabetes(T2D).MASLD is the term that was recently endorsed by an international multidisciplinary consensus panel to replace non-alcoholic fatty liver disease[as non-alcoholic steatohepatitis(NASH)was replaced by metabolic dysfunction-associated steatohepatitis(MASH)](2).

Effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease:Clinical implications

In this editorial,we comment on the article by Chen et al recently published in 2024.We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase(ALT)would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease(MAFLD).This is important given the increasing prevalence of MAFLD and obesity globally.Currently,a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT.The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered,particularly as their study found that 83.12%of their study population with a diagnosis of MAFLD had a normal ALT.The main advantages of screening would be to identify patients and provide intervention early,the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis.However,there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered.Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity,although studies have not yet shown a significant improvement in fibrosis regression.It would also require a huge amount of resource if a reduced ALT level alone was used as criteria;it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk.Currently,there is not a good argument to recommend wide-spread screening with a reduced ALT level as this is unlikely to be cost-effective.This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories.Although studies previously have suggested a more pragmatic approach in screening those over the age of 60,this is likely to change with the increasing incidence of obesity within the younger age groups.The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.