Current remarks and future directions on the interactions between metabolic dysfunction-associated fatty liver disease and COVID-19

During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.

Impact of metabolic dysfunction-associated steatotic liver disease on COVID-19 hospitalizations:A propensity-matched analysis of the United States

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),formally known as nonalcoholic fatty liver disease,is the most common chronic liver disease in the United States.Patients with MASLD have been reported to be at a higher risk of developing severe coronavirus disease 2019(COVID-19)and death.However,most studies are single-center studies,and nationwide data in the AIM To study the influence of MASLD on COVID-19 hospitalizations during the initial phase of the pandemic.METHODS We retrospectively analyzed the 2020 National Inpatient Sample(NIS)database to identify primary COVID-19 hospitalizations based on an underlying diagnosis of MASLD.A matched comparison cohort of COVID-19 hospit-alizations without MASLD was identified from NIS after 1:N propensity score matching based on gender,race,and comorbidities,including hypertension,heart failure,diabetes,and cirrhosis.The primary outcomes included inpatient mortality,length of stay,and hospitalization costs.Secondary outcomes included the prevalence of systemic complications.RESULTS A total of 2210 hospitalizations with MASLD were matched to 2210 hospitalizations without MASLD,with a good comorbidity balance.Overall,there was a higher prevalence of severe disease with more intensive care unit admissions(9.5%vs 7.2%,P=0.007),mechanical ventilation(7.2%vs 5.7%,P=0.03),and septic shock(5.2%vs 2.7%,P<0.001)in the MASLD cohort than in the non-MASLD cohort.However,there was no difference in mortality(8.6%vs 10%,P=0.49),length of stay(5 d vs 5 d,P=0.25),and hospitalization costs(42081.5$vs 38614$,P=0.15)between the MASLD and non-MASLD cohorts.CONCLUSION The presence of MAFLD with or without liver cirrhosis was not associated with increased mortality in COVID-19 hospitalizations;however,there was an increased incidence of severe COVID-19 infection.This data(2020)predates the availability of COVID-19 vaccines,and many MASLD patients have since been vaccinated.It will be interesting to see if these trends are present in the subsequent years of the pandemic.

Clinical implications of COVID-19 in patients with metabolicassociated fatty liver disease

People across the world are affected by the"coronavirus disease 2019(COVID-19)",brought on by the"SARS-CoV type-2 coronavirus".Due to its high incidence in individuals with diabetes,metabolic syndrome,and metabolic-associated fatty liver disease(MAFLD),COVID-19 has gained much attention.The metabolic syndrome's hepatic manifestation,MAFLD,carries a significant risk of type-2-diabetes.The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic.Independent of the metabolic syndrome,MAFLD may impact the severity of the viral infections,including COVID-19 or may even be a risk factor.An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics.Many liver markers are seen elevated in COVID-19.MAFLD patients with associated comorbid conditions like obesity,cardiovascular disease,renal disease,malignancy,hypertension,and old age are prone to develop severe disease.There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19.The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19.This review investigates the implications of COVID-19 on liver injury and disease severity and viceversa.We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.

Implications of metabolic dysfunction associated fatty liver disease in COVID-19

Metabolic associated fatty liver disorder(MAFLD)characterizes the contributing etiologies(i.e.,type 2 diabetes mellitus,metabolic syndrome,overweight)of individuals with fatty liver disease that affects 1/3rd of the world population.In 2020,the coronavirus disease 2019(COVID-19)crisis was unprecedented,and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2.MAFLD patients are frequently obese with added metabolic menace like diabetes,hypertension,and dyslipidemia leading to greater jeopardy of COVID-19.MAFLD patients are 4 to 6-fold more prone towards infections.COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin.Hence,MAFLD in COVID-19 patients worsens the condition significantly.The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission.Direct hepatic injury,enhanced levels of inflammatory cytokines,declined hepatic mitochondrial activity,and compromised immunity are considered as some underlying mechanisms.The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients.The review systematically analyzes the effect of striking two worldwide pandemics(MAFLD and COVID-19)together in the present era.

Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

Coronavirus disease 2019 severity in obesity:Metabolic dysfunctionassociated fatty liver disease in the spotlight

The coronavirus disease 2019(COVID-19)outbreak has drawn the scientific community's attention to pre-existing metabolic conditions that could aggravate the infection,causing extended viral shedding,prolonged hospitalization,and high death rates.Metabolic dysfunction-associated fatty liver disease(MAFLD)emerges as a surrogate for COVID-19 severity due to the constellation of metabolic alterations it entails.This review outlines the impact MAFLD exerts on COVID-19 severity in obese subjects,besides the possible mechanistic links to the poor outcomes.The data collected showed that MAFLD patients had poorer COVID-19 outcomes than non-MAFLD obese subjects.MAFLD is generally accompanied by impaired glycemic control and systemic arterial hypertension,both of which can decompensate during the COVID-19 clinical course.Also,MAFLD subjects had higher plasma inflammatory marker concentrations than non-MAFLD subjects,which might be related to an intensified cytokine storm syndrome frequently associated with the need for mechanical ventilation and death.In conclusion,MAFLD represents a higher risk than obesity for COVID-19 severity,resulting in poor outcomes and even progression to non-alcoholic steatohepatitis.Hepatologists should include MAFLD subjects in the high-risk group,intensify preventive measurements,and prioritize their vaccination.

Association of COVID-19 with hepatic metabolic dysfunction

The coronavirus disease 2019(COVID-19)pandemic continues to be a global problem with over 438 million cases reported so far.Although it mostly affects the respiratory system,the involvement of extrapulmonary organs,including the liver,is not uncommon.Since the beginning of the pandemic,metabolic comorbidities,such as obesity,diabetes,hypertension,and dyslipidemia,have been identified as poor prognostic indicators.Subsequent metabolic and lipidomic studies have identified several metabolic dysfunctions in patients with COVID-19.The metabolic alterations appear to be linked to the course of the disease and inflammatory reaction in the body.The liver is an important organ with high metabolic activity,and a significant proportion of COVID-19 patients have metabolic comorbidities;thus,this factor could play a key role in orchestrating systemic metabolic changes during infection.Evidence suggests that metabolic dysregulation in COVID-19 has both short-and long-term metabolic implications.Furthermore,COVID-19 has adverse associations with metabolic-associated fatty liver disease.Due to the ensuing effects on the renin-angiotensin-aldosterone system and ammonia metabolism,COVID-19 can have significant implications in patients with advanced chronic liver disease.A thorough understanding of COVID-19-associated metabolic dysfunction could lead to the identification of important plasma biomarkers and novel treatment targets.In this review,we discuss the current understanding of metabolic dysfunction in COVID-19,focusing on the liver and exploring the underlying mechanistic pathogenesis and clinical implications.

体育锻炼抵御COVID-19发生、发展的作用与可能分子机制

2019冠状病毒病(Coronavirus Disease 2019,COVID-19)于2019年12月暴发以来仍在全球迅速传播,感染和死亡人数还在不断增长。由于COVID-19的症状广泛、患者人群复杂,故开发特定的临床药物尚需一定的时间,需要有其他预防或辅助应对COVID-19的干预策略。根据体育锻炼抗病毒的分子机制及严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)的致病机理,从体育锻炼提高细胞免疫功能、增强机体抗氧化防御能力、改善病毒诱发的铁代谢障碍和内皮功能障碍等方面,探析体育锻炼在抵御SARS-CoV-2入侵、延缓病情发展、降低重症发生率、减少患者并发症中的可能作用,为倡导全民参加体育锻炼积极应对COVID-19提供生理学依据。

成纤维细胞生长因子19(FGF19)与脂代谢的研究进展

成纤维细胞生长因子19(fibroblast growth factor 19,FGF19)是在回肠末端特异性合成并分泌的细胞因子,属于FGFs的特殊成员之一。近年来自动物及细胞学的研究发现,FGF19不仅在胆汁酸代谢的调节中发挥重要作用,而且与多种心血管疾病危险因素密切相关。流行病学研究显示,2型糖尿病、代谢综合征及肥胖者FGF19水平降低。深入研究FGF19的生物学意义可能为肥胖及血脂紊乱的防治提供新的靶点。本文将介绍FGF19与脂代谢相关性的研究进展。

19-去甲类固醇激素的结构、性能及其代谢特点研究

19-去甲类固醇类化合物是临床应用最多的合成类雄性蛋白同化激素,可用于治疗骨质疏松症,蛋白质缺陷型疾病和烧伤等。它还可以提高运动员和赛马比赛的成绩,增强食源性动物瘦肉生产率,进而提高饲料转化率。但19-去甲类固醇及代谢残留引起人的肝功能障碍和心血管系统受损,内分泌失调等副作用,因此在世界上多数国家中,除医疗和科研之外,禁止使用。详尽阐述了19-去甲类固醇类化合物的结构、功能、副作用和代谢特点。

CAPN-10基因Indel-19与非糖尿病血液透析患者的关系研究

目的:研究CAPN-10基因Indel-19与非糖尿病血液透析患者的关系。方法:用聚合酶链反应-限制性片段长度多态性(Polymerase chain reaction-restrictive fragment length polymorphism,PCR-RFLP)法检测30个健康人(A组),60个稳定的非糖尿病血液透析患者(B组)CAPN-10基因Indel-19插入多态性基因型,生化技术测定空腹血糖(Fasting blood glucose,FBG),甘油三脂(Three acids glyceride,TG),高密度脂蛋白胆固醇(High-density lipoprotein cholesterol,HDL-C)水平。结果:B组患者收缩压、舒张压及甘油三酯水平较A组高(P<0.05)。A、B两组比较Indel-19基因型分布无明显差异(P=0.742)。B组基因型为2/2的患者较基因型为1/1,1/2患者有较高的腰围及TG水平(P值分别为0.033,0.002)。同时合并存在"代谢综合征"的B组患者出现CAPN-10基因Indel-19基因型2/2的频率较B组其余患者高(P=0.001)。结论:非糖尿病血液透析患者多同时存在脂质代谢紊乱及高血压。CAPN-10基因Indel-19可能与同时存在"代谢综合征"的终末期肾脏病有关,其可能机制是影响肾病患者脂质代谢,加重患者动脉硬化等的程度,但其具体作用机制尚有待于进一步研究。

成纤维细胞生长因子19对糖尿病大鼠糖代谢的改善及机制研究

目的观察成纤维细胞生长因子19(FGF19)在糖尿病人群中的血清水平,探讨FGF19处理正常大鼠及糖尿病大鼠后,大鼠血糖水平的变化及具体变化的分子机制。方法采用酶联免疫吸附(ELISA)法测定正常人与糖尿病患者血清中FGF19的水平。分别检测野生糖尿病大鼠和同窝野生正常对照大鼠,在有无FGF19处理情况下,大鼠体重、摄食量、空腹血糖、进食后血糖等指标情况。mRNA定量和Western blot法分别检测四组大鼠胰岛组织中INS蛋白磷酸化水平及糖异生关键酶G6Pase表达差异的变化。结果 ELISA法结果表明糖尿病患者血清中FGF19水平较正常人低。大鼠体重、摄食量、空腹血糖、进食后血糖等指标检测结果表明FGF19处理后可以改善糖尿病生理症状。mRNA定量和Western blot结果表明FGF19处理能够与显著改善大鼠胰岛内INS和G6Pase表达水平。结论成纤维细胞生长因子19可以通过提高糖尿病大鼠的胰岛素敏感性,改善糖尿病大鼠的糖代谢,FGF19有望将来成为改善糖尿病的重要分子。

成纤维细胞生长因子19亚家族因子在相关代谢性疾病中的临床研究进展

成纤维细胞生长因子(FGF)19亚家族是新近发现的一类代谢调节因子,包括FGF19、FGF21和FGF23,具有维持全身稳态、调控胆汁酸平衡、调节葡萄糖和脂质代谢、维持磷酸盐/维生素D稳态等作用。鉴于这些功能,FGF19亚家族可作为临床诊断部分相关代谢性疾病的生物标志物,包括糖尿病、肥胖、肿瘤导致的代谢紊乱等。目前正在进行对其类似物、抑制剂的研究,并已进入临床试验阶段,证明FGF19亚家族在治疗相关代谢性疾病方面有很大潜力。但FGF19亚家族的作用机制尚未完全阐明,未来其稳定性和安全性亦需更多研究来证明。

FGF19——新的代谢调节因子

成纤维细胞生长因子19(FGF19)是新近发现的一种代谢调节因子,由胆汁酸分泌进入肠道后刺激肠道分泌和表达。人类的FGF19与小鼠的FGF15同源。FGF19经肠道分泌后可随循环进入肝脏并与肝脏中的FGFR4结合起作用,它具有激素样作用,发挥着重要的代谢调节作用,如调节胆汁酸代谢、调节胆囊的充盈、提高能量代谢降低体质量、改善血糖等。

成纤维细胞生长因子19与糖脂蛋白质代谢的研究进展

成纤维细胞生长因子19(FGF19)是成纤维细胞生长因子家族成员之一,主要功能是调节胆汁酸平衡。近年来研究发现FGF19在糖脂蛋白质代谢中起重要作用,可促进肝脏糖原与蛋白质合成,抑制糖异生及三酰甘油和胆固醇的合成。随着对FGF19研究的不断深入,有望为糖尿病等代谢性疾病的治疗提供新的途径。

Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology

BACKGROUND The coronavirus disease 2019(COVID-19),a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide,was described to be frequently accompanied by extrapulmonary manifestations,including liver dysfunction.Liver dysfunction and elevated liver enzymes were observed in about 53%of COVID-19 patients.AIM To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction.METHODS The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed.Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways.The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis,fibrosis,non-alcoholic fatty liver disease(NAFLD),and hepatitis A/B/C.Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR.RESULTS Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes,DNAJB1,IGF2,EGFR,and HDGF.Concordantly,the differential transcriptome of severe COVID-19 liver tissues substantially overlapped with the disease signature of liver diseases characterized with pathological tissue remodeling(liver cirrhosis,Fibrosis,NAFLD,and hepatitis A/B/C).Moreover,we observed a significant suppression of transcripts implicated in metabolic pathways as well as mitochondrial function,including cytochrome P450 family members,ACAD11,CIDEB,GNMT,and GPAM.Consequently,drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification capacity.In correspondence with the RNA-seq data analysis,we observed a significant upregulation of DNAJB1 and HSP90AB1 as well as significant downregulation of CYP39A1 in the blood plasma of severe COVID-19 patients with liver dysfunction.CONCLUSION Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling,mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction.

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and fibrosis.Liver injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated cholangiopathy.Mechanisms of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell invasion.AIM To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe COVID-19.METHODS ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel classifiers.RESULTS ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct cholangiocytes.Strikingly,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in cirrhosis.ACE2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD spectrum.Hepatic ACE2 levels are also increased in COVID-19 patients,especially those showing evidence of LI,but are not correlated with the presence of SARS-CoV-2 virus in the liver.However,there is a clear association between the hepatic lipid droplet content and the presence of the virus,suggesting a possible functional link.CONCLUSION Hepatic ACE2 levels were elevated in nonfibrotic MASH and COVID-19 patients with LI,while lipid accumulation may promote intra-hepatic SARS-CoV-2 replication,accelerating MASLD progression and COVID-19-mediated liver damage.

老年2型糖尿病视网膜病变患者成纤维细胞生长因子19水平的变化及意义

目的 观察老年2型糖尿病视网膜病变(DR)患者血清成纤维细胞生长因子19(FGF19)水平的变化情况,并分析其意义。方法 选择2018年6月至2020年6月于虞城县人民医院就诊或住院的70例老年2型糖尿病患者作为研究对象。患者就诊时接受检眼镜检查,评估患者网膜病变情况,根据检查结果为DR组与非DR组。记录患者一般资料、血清FGF19水平及其他实验室指标[空腹静脉血糖(FBG)、血清胰岛素(FINS)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、C反应蛋白(CPR)]。分析老年2型DR患者FGF19水平变化及意义。结果 70例老年2型糖尿病患者中30例(42.86%)发生DR。DR组血清FINS、HbA1c、CPR水平高于非DR组,血清FGF19水平低于非DR组,差异有统计学意义(P<0.05);组间其他一般资料比较,差异无统计学意义(P>0.05);logistic回归分析显示血清CPR水平较高、FGF19水平较低是老年2型DR病变的影响因素(P<0.05);绘制受试者工作特征(ROC)曲线,结果显示,FGF19水平预测老年2型DR发病的曲线下面积(AUC)为0.874,当FGF19取7.995 mg·L^(-1)时,可获得最佳预测价值。结论 血清FGF19水平可作为早期预测老年2型DR发生的重要因子。

Lipidome is lipids regulator in gastrointestinal tract and it is a life collar in COVID-19:A review

The term lipidome is mentioned to the total amount of the lipids inside the biological cells.The lipid enters the human gastrointestinal tract through external source and internal source.The absorption pathway of lipids in the gastrointestinal tract has many ways;the 1st way,the lipid molecules are digested in the lumen before go through the enterocytes,digested products are re-esterified into complex lipid molecules.The 2nd way,the intracellular lipids are accumulated into lipoproteins(chylomicrons)which transport lipids throughout the whole body.The lipids are re-synthesis again inside the human body where the gastrointestinal lipids are:(1)Transferred into the endoplasmic reticulum;(2)Collected as lipoproteins such as chylomicrons;or(3)Stored as lipid droplets in the cytosol.The lipids play an important role in many stages of the viral replication cycle.The specific lipid change occurs during viral infection in advanced viral replication cycle.There are 47 lipids within 11 lipid classes were significantly disturbed after viral infection.The virus connects with blood-borne lipoproteins and apolipoprotein E to change viral infectivity.The viral interest is cholesterol-and lipid raft-dependent molecules.In conclusion,lipidome is important in gastrointestinal fat absorption and coronavirus disease 2019(COVID-19)infection so lipidome is basic in gut metabolism and in COVID-19 infection success.

Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is associated with complications and mortality in patients with coronavirus disease 2019(COVID-19).However,there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD,despite its high prevalence.Lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage.Therefore,we propose an index based on lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19.AIM To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases(aspartate aminotransferase/alanine aminotransferase)in patients with COVID-19 and MAFLD[liver fibrosis and nutrition(LNF)-COVID-19 index].METHODS In this retrospective cohort study,two cohorts from two different tertiary centers were included.The first was the derivation cohort to obtain the score cutoffs,and the second was the validation cohort.We included hospitalized patients with severe COVID-19 and MAFLD.Liver steatosis was evaluated by computed tomography scan.Area under the receiver operating characteristic(ROC)curve analysis and survival analysis were used.RESULTS In the derivation cohort,44.6%had MAFLD;ROC curve analysis yielded a LFN-COVID-19 index>1.67 as the best cutoff,with a sensitivity of 78%,specificity of 63%,negative predictive value of 91%and an area under the ROC curve of 0.77.In the multivariate analysis,the LFN-COVID-19 index>1.67 was independently associated with the development of acute kidney injury(odds ratio:1.8,95%confidence interval:1.3-2.5,P<0.001),orotracheal intubation(odds ratio:1.9,95%confidence interval:1.4-2.4,P<0.001),and death(odds ratio:2.86,95%confidence interval:1.6-4.5,P<0.001)in both cohorts.CONCLUSION LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19,which could be useful for the MAFLD population.