Comparison between metabolic-associated fatty liver disease and nonalcoholic fatty liver disease:From nomenclature to clinical outcomes

As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis;metabolic-associated fatty liver disease(MAFLD).This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rationale behind the nomenclature change,the main differences,and its clinical implications.

Research on the Mechanism of the treatment of non‑alcoholic fatty liver by Jianwei Gexia Zhuyu Decoction based on network pharmacology and molecular docking

Objective:To analyse the key compounds,targets and pathways of the treatment of non‑alcoholic fatty liver disease(NAFLD)by Jianwei Gexia Zhuyu Decoction based on network pharmacology,in order to explore the molecular mechanism of its therapeutic effects.Methods:The differential genes between sick and normal conditions were screened by GEO‑Datasets,and the heat map and volcano map were drawn.The active compounds in Jianwei Gexia Zhuyu Decoction were searched by TCMSP platform and Drugbank database.OB≥30%and DL≥0.18 were set as thresholds to screen potential active compounds and action targets.The molecular target maps of Jianwei Gexia Zhuyu Decoction and NAFLD differential genes were constructed,and the PPI network and network topology parameters were obtained by STRING database.The PPI network and network topology parameters were visually analyzed by Cytoscape,and the core regulatory genes were screened.At the same time,the SwissDock platform was used to dock the main active components with the target.The main pathways were determined by GO biological function enrichment analysis and KEGG metabolic pathway enrichment analysis by DAVID.Results:After screening,377 differential genes(127 up‑regulated genes and 250 down‑regulated genes),225 active compounds of Jianwei Gexia Zhuyu Decoction,308 corresponding targets were obtained;14 key targets were screened,corresponding to 168 compounds,and the key targets involved MYC,FOSL2,FOS,etc.The results of GO functional enrichment analysis showed that Jianwei Gexia Zhuyu Decoction mainly regulated the activity expression of DNA binding transcriptional activator and the specific transcription of RNA polymeraseⅡ;The results of molecular docking showed that the main active components quercetin and baicalein had good binding activity with VCAM1,HSPB1,MYC,JUN and so on;The results of KEGG enrichment analysis showed that it was mainly involved in IL‑17 signal pathway,Wnt receptor signal pathway,NF‑κB signal pathway,TNF signal pathway and AGE‑RAGE signal pathway in diabetic complications.Conclusion:Through the interaction of multi‑components and multi‑targets,Jianwei Gexia Zhuyu Decoction has achieved the goal of overall treatment of NAFLD from many ways.The application of network pharmacology provides a new research approach and scientific basis for further study on the mechanism of Jianwei Gexia Zhuyu Decoction in the treatment of NAFLD.

Obese children with fatty liver: Between reality and disease mongering

Following the current epidemic of obesity, the worldwide prevalence of nonalcoholic fatty liver disease(NAFLD)has increased with potential serious health implications. While it is established that in adults NAFLD can progress to end-stage liver disease in many cases, the risk of progression during childhood is less well defined. Since most obese children are not adherent to lifestyle modifications and hypocaloric diets, there is a growing number of studies on pharmacological interventions with the risk of disease mongering, the practice of widening the boundaries of illness in order to expand the markets for treatment. Here, we propose a critical appraisal of the best available evidence about long-term course of pediatric NAFLD and efficacy of treatments other than hypocaloric diet and physical exercise. As a result, the number of NAFLD children with a poor outcome is small in spite of the alarming tones used in some papers; large-scale longitudinal studies with longterm follow-up of pediatric NAFLD patients are lacking; the studies on ancillary pharmacological interventions have been performed in few patients with inconclusive and conflicting results.

COVID-19 and liver diseases,what we know so far

Coronavirus disease 2019(COVID-19)pneumonia outbreak started in December 2019.On March 12,2020,the World Health Organization(WHO)declared that the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)constitutes a pandemic,and as of May 2021,SARS-CoV-2 has infected over 167.3 million patients,including 3.4 million deaths,reported to WHO.In this review,we will focus on the relationship between SARS-CoV-2 infection and the liver.We will discuss how chronic liver diseases affect the COVID-19 disease course and outcomes.We will also discuss the SARS-CoV-2 effects on the liver,mechanisms of acute liver injury,and potential management plans.

Histologically proven hepatic steatosis associates with lower testosterone levels in men with obesity

Men with obesity often present with low testosterone(T)and sex hormone-binding globulin(SHBG)levels.Several mechanisms for this have been proposed,but as SHBG is secreted by hepatocytes and sex steroids undergo hepatic metabolization,this study investigates whether severity and histological components of nonalcoholic fatty liver disease(NAFLD)are associated with sex steroid levels in obese men.This cross-sectional study included 80 obese men(age:46±11 years;body mass index:42.2±5.5 kg m^-2).Serum levels of total T and estradiol(E.)were measured using liquid chromatography coupled with tandem mass spectroscopy(LC/MS-MS)and SHBG and gonadotropins by immunoassay.Liver biopsies were evaluated using Steatosis.Activity,and Fibrosis scoring.Participants with steatohepatitis had similar median(1st quartile-3rd quartile)total T levels(7.6[5.0-11.0]nmol l^-1 vs 8.2[7.2-10.9]nmol l^-1;P=0.147),lower calculated free T(cFT)levels(148.9[122.9-188.8]pmol 1-1 s 199.5[157.3-237.6] pmol l^-1;P=0.006),and higher free E.T ratios(10.0[6.4-13.9]×10^-3 vs 7.1[5.7-10.7]×10^-3;P=0.026)compared to men with only nonalcoholic fatty liver.Among the histological components of NAFLD.only steatosis was independently associated with total T(r=-0.331.P=0.003)and cFT levels(r=-0.255.P=0.025).Obese men with.steatohepatitis have even lower cFT levels compared to those without,an association mainly driven by grade of steatosis.Whether this reflects a subgroup of men with a more severe obesity-related phenotype or results from direct relations between hepatic steatosis and sex steroid metabolism needs further investigation.