ABSTRACT
“Metabolic dysfunction-associated fatty liver disease (MAFLD)” is the term suggested in 2020 to refer to fatty liver disease related to systemic metabolic dysregulation. The name change from nonalcoholic fatty liver disease (NAFLD) to MAFLD comes with a simple set of criteria to enable easy diagnosis at the bedside for the general medical community, including primary care physicians. Since the introduction of the term, there have been key areas in which the superiority of MAFLD over the traditional NAFLD terminology has been demonstrated, including for the risk of liver and extrahepatic mortality, disease associations, and for identifying high-risk individuals. Additionally, MAFLD has been adopted by a number of leading pan-national and national societies due to its concise diagnostic criterion, removal of the requirement to exclude concomitant liver diseases, and reduction in the stigma associated with this condition. The current article explores the differences between MAFLD and NAFLD diagnosis, areas of benefit, some potential limitations, and how the MAFLD terminology has opened up new fields of research.
ABSTRACT
Non-alcoholic fatty liver disease occurring in non-obese subjects (the so-called non-obese NAFLD) is a highly prevalent but neglected liver condition, which is closely associated with metabolic disorders and suboptimal lifestyles. Landmark studies have shown that lifestyle interventions are potentially beneficial in decreasing the risk of developing non-obese NAFLD and in ameliorating NAFLD in non-obese individuals with pre-existing NAFLD. Lifestyle interventions usually refer to changes in eating habits and physical activity, both of which have a powerful effect on non-obese NAFLD and on risk factors for non-obese NAFLD. However, to date, patients and health-care professionals have a poor awareness and understanding of non-obese NAFLD and the beneficial effects of lifestyle interventions in this patient population. The aim of this narrative review is to briefly discuss the evidence for the effects of lifestyle changes and what changes are needed amongst medical personnel and other stakeholders in order to raise awareness of non-obese NAFLD.
ABSTRACT
Background/Aims@#Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic dysfunction. Among the multiple factors, genetic variation acts as important modifiers. Klotho, an enzyme encoded by the klotho (KL) gene in human, has been implicated in the pathogenesis of metabolic dysfunctions. However, the impact of variants in KL on NAFLD risk remains poorly understood. The aim of this study was to investigate the impact of KL rs495392 C>A polymorphism on the histological severity of NAFLD. @*Methods@#We evaluated the impact of the KL rs495392 polymorphism on liver histology in 531 Chinese with NAFLD and replicated that in the population-based Rotterdam Study cohort. The interactions between the rs495392, vitamin D, and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism were also analyzed. @*Results@#Carriage of the rs495392 A allele had a protective effect on steatosis severity (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42–0.89; P=0.010) in Chinese patients. After adjustment for potential confounders, the A allele remained significant with a protective effect (OR, 0.66; 95% CI, 0.45–0.98; P=0.040). The effect on hepatic steatosis was confirmed in the Rotterdam Study cohort. Additional analysis showed the association between serum vitamin D levels and NAFLD specifically in rs495392 A allele carriers, but not in non-carriers. Moreover, we found that the rs495392 A allele attenuated the detrimental impact of PNPLA3 rs738409 G allele on the risk of severe hepatic steatosis. @*Conclusions@#The KL rs495392 polymorphism has a protective effect against hepatic steatosis in patients with NAFLD.
ABSTRACT
Background/Aims@#Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression. @*Methods@#A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited. @*Results@#Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis. @*Conclusions@#LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.
ABSTRACT
The emergence of non-alcoholic fatty liver disease (NAFLD) as the leading chronic liver disease worldwide raises some concerns. In particular, NAFLD is closely tied to sedentary lifestyle habits and associated with other metabolic diseases, such as obesity and diabetes. At the end of the disease spectrum, non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma (HCC), representing a serious health problem to modern society. Recently, an increasing number of HCC cases originating from this progressive disease spectrum have been identified, with different levels of severity and complications. Updating the current guidelines by placing a bigger focus on this emerging cause and highlighting some of its unique features is necessary. Since, the drivers of the disease are complex and multifactorial, in order to improve future outcomes, having a better understanding of NASH progression into HCC may be helpful. The risks that can promote disease progression and currently available management strategies employed to monitor and treat NASH-related HCC make up the bulk of this review.
Subject(s)
Humans , Carcinoma, Hepatocellular/etiology , Liver Cirrhosis , Liver Neoplasms/etiology , Non-alcoholic Fatty Liver Disease , ObesityABSTRACT
Background/Aims@#Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression. @*Methods@#A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited. @*Results@#Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis. @*Conclusions@#LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.
ABSTRACT
<p><b>OBJECTIVE</b>To compare the occurrence of hearing loss in neonates with hyperbilirubinemia, hypoxic-ischemic encephalopathy (HIE) and very low-birth weight infant (VLBW) body mass, and to provide evidence for early intervention.</p><p><b>METHODS</b>Totally 299 high-risk neonates (598 ears) were divided into six groups: pure hyperbilirubinemia group, pure HIE group, hyperbilirubinemia with HIE group, hyperbilirubinemia with VLBW group, HIE with LBWI group, hyperbilirubinemia with VLBW and HIE mass group. Auditory brainstem response (ABR) was detected in all groups.</p><p><b>RESULTS</b>The hearing threshold of ABR and the abnormal rate of hyperbilirubinemia with LBWI and HIE were much higher than that of pure hyperbilirubinemia and pure HIE neonates.</p><p><b>CONCLUSIONS</b>Of the three high-risk factors, hearing loss occurs more often and more serious in neonates with hyperbilirubinemia and with VLBW while as HIE body mass. So the babies should receive hearing screening with ABR and be treated in time or following up as early as possible.</p>