Comparison of lipid profile in different grades of non-alcoholic fatty liver disease diagnosed on ultrasound

Objective:To detect and compare serum lipid abnormalities in patients diagnosed with different grades of non-alcoholic fatly liver on ultrasonography.Methods:A total of 70 cases which included 30 males and 40 females,diagnosed as nonalcoholic fatty liver disease(NAFLD)on ultrasound were investigated with serum lipid profile.Then a comparison of lipid abnormalities between different grades of fatty liver diagnosed on ultrasound was done.P value was calculated by using analysis of variance lest(ANOVA)and P value<0.05 was considered as statistically significant.Results:Out of 70 cases which were diagnosed as NAFLD on ultrasonography,gradeⅠNAFLD cases were 47.15%,gradeⅡwere 42.85%and gradeⅢwere 10%.The mean age of the patients was49.14 years.Male to female ratio was 3:4.Serum triglycerides,total cholesterol,LDL and VLDL levels were raised in 67.14%,45.71%34.28%,25.71%of cases respectively.Low serum HDL levels were seen in 62.85%of patients.On statistical analysis we found increasing grades of NAFLD were significantly associated with increasing values of total cholesterol(P value-0.001),LDL(P value-0.000)and VLDL(P value-0.003)and decreasing HDL(P value-0.000).Conclusion:Most of the patients of NAFLD in India is asymptomatic,non-diabetic and non-hypertensive.Though liver biopsy is the gold standard melhod for diagnosis of NAFLD,Ultrasonography which is non-invasive,simple tool,can be used for the early detection of NAFLD in asymptomatic patients.

LEARN algorithm:a novel option for predicting non-alcoholic steatohepatitis

Background:There is an unmet need for accurate non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH).Since impedance-based measurements of body composition are simple,repeatable and have a strong association with non-alcoholic fatty liver disease(NAFLD)severity,we aimed to develop a novel and fully automatic machine learning algorithm,consisting of a deep neural network based on impedance-based measurements of body composition to identify NASH[the bioeLectrical impEdance Analysis foR Nash(LEARN)algorithm].Methods:A total of 1,259 consecutive subjects with suspected NAFLD were screened from six medical centers across China,of which 766 patients with biopsy-proven NAFLD were included in final analysis.These patients were randomly subdivided into the training and validation groups,in a ratio of 4:1.The LEARN algorithm was developed in the training group to identify NASH,and subsequently,tested in the validation group.Results:The LEARN algorithm utilizing impedance-based measurements of body composition along with age,sex,pre-existing hypertension and diabetes,was able to predict the likelihood of having NASH.This algorithm showed good discriminatory ability for identifying NASH in both the training and validation groups[area under the receiver operating characteristics(AUROC):0.81,95%CI:0.77-0.84 and AUROC:0.80,95%CI:0.73-0.87,respectively].This algorithm also performed better than serum cytokeratin-18 neoepitope M30(CK-18 M30)level or other non-invasive NASH scores(including HAIR,ION,NICE)for identifying NASH(P value<0.001).Additionally,the LEARN algorithm performed well in identifying NASH in different patient subgroups,as well as in subjects with partial missing body composition data.Conclusions:The LEARN algorithm,utilizing simple easily obtained measures,provides a fully automated,simple,non-invasive method for identifying NASH.

Heterogeneous population of macrophages in the development of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is characterized by a spectrum of hepatic diseases,including fatty liver,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.NAFLD is a hepatic manifestation of metabolic syndrome and has become the leading cause of liver transplantation,necessitating an in-depth understanding of its underlying pathogenic mechanisms and the identification of viable drug targets.Although fatty liver is benign and does not exert marked liver damage or inflammation,NAFLD progression involves inflammatory processes facilitated by immune cells.Macrophages and monocytes constitute the pool of innate immune cells that contribute to NAFLD development in association with other cell types,such as neutrophils,T cells,and natural killer cells.The concept that macrophages contribute to the inflammatory processes in NAFLD development has long been debated;however,the remarkable advances in experimental techniques have rapidly uncovered new subpopulations of macrophages and monocytes,whose functions need to be comprehensively elucidated.The current review focuses on the recent expansion of our knowledge of the heterogeneous population of macrophages crucially involved in NAFLD development.In addition,the present paper discusses ongoing efforts to target macrophages and inflammatory processes to develop optimal therapeutic agents against non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease:Dietary and nutraceutical approaches

Non-alcoholic fatty liver disease(NAFLD),defined as the presence of fat accumulation in imaging or histology in more than 5%of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation,is one of the major causes of chronic liver disease worldwide.Metabolic syndrome is associated with an increased risk of progression from NAFLD to non-alcoholic steatohepatitis(NASH),fibrosis,and forthcoming liver failure.Also,genetic predisposition contributes to the risk of NAFLD development.This review explores the role of diets and nutraceuticals in delaying the development and the evolution of NAFLD to chronic liver disease.The Mediterranean diet,high-protein diet,lowcarbohydrate/high-fat diet,high-carbohydrate/low-fat diet,and intermittent fasting are the dietary approaches investigated given the presence of relevant literature data.Moreover,this review focused on nutraceuticals with proven efficacy in ameliorating NAFLD and grouped them into four different categories:plant-based nutraceuticals(Ascophyllum nodosum and Fucus vesiculosus,Silymarin,Berberine,Curcumin,Resveratrol,Nigella sativa,Quercetin),vitamin-like substances(vitamin E,vitamin D,vitamin C,coenzyme Q10,inositol),fatty acids(omega-3),and microbiota-management tools(probiotics).

Practice guidance documents for the diagnosis and management of non-alcoholic fatty liver disease-recent updates and open questions

Primarily driven by an increasingly sedentary lifestyle and hypercaloric nutritionally imbalanced diets,non-alcoholic fatty liver disease(NAFLD)has emerged as the most prevalent liver disease in the US and Europe.NAFLD constitutes an umbrella term that includes a spectrum of disease from non-alcoholic fatty liver(NAFL)to non-alcoholic steatohepatitis(NASH),NASH fibrosis and NASH cirrhosis that are all characterized by≥5%of all hepatocytes being steatotic in patients with little alcohol intake and no apparent alternative causes.

Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models

Background and objective:Noninvasive non-alcoholic steatohepatitis(NASH)assessment is a clinical challenge to the management of non-alcoholic fatty liver disease.We aim to develop diagnostic models based on sequential ultrasound molecular imaging(USMI)for the noninvasive identification of NASH in mouse models.Methods:Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University.Forty-nine C57BL/6 mice were divided into normal control,non-alcoholic fatty liver,NASH,and hepatitis groups.Sequential USMI was implemented using CD36-targeted microbubbles(MBs-CD36)and intercellular adhesion molecule-1(ICAM-1)-targeted microbubbles(MBs-ICAM-1)to visualize hepatic steatosis and inflammation.The targeting signal of USMI was quantified as the normalized intensity difference(NID)with the destruction-replenishment method.Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBsICAM-1 and pathological inflammation score.Finally,diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.Results:MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice.NID-MBs-CD36 values increased with the progression of steatosis,while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation.A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade(r_(s)=0.9078,P<0.0001)and between NIDMBs-ICAM-1 and pathological inflammation grade(r_(s)=0.9071,P<0.0001).Among various sequential USMI-based diagnostic models,the serial testing model showed high diagnostic performance in detecting NASH,with 95%sensitivity,97%specificity,95%positive predictive values,97%negative predictive values,and 96%accuracy.Conclusions:Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation.Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.

Fibroscan-AST(FAST)score and other non-invasive tests for the diagnosis of fibrotic non-alcoholic steatohepatitis

The Fibroscan-AST(FAST)score was developed based on the data of patients who had a liver biopsy for non-alcoholic fatty liver disease(NAFLD)at several liver centres in England,and it was validated using data from seven clinical studies from North America,Europe and Asia(1).The FAST score requires only controlled attenuation parameter(CAP)and liver stiffness measurement(LSM)from a vibration-controlled transient elastography(VCTE)examination and serum aspartate aminotransferase(AST)level in its calculation.

健脾化痰祛瘀中药联合干扰素治疗慢性乙型肝炎合并非酒精性脂肪肝临床观察

目的观察健脾化痰祛瘀中药联用干扰素对慢性乙型病毒性肝炎合并脂肪肝患者抗病毒疗效的影响。方法将64例慢性乙型病毒性肝炎合并脂肪肝患者随机分对照组和治疗组,对照组用干扰素治疗(长效或短效),治疗组在对照组基础上加用健脾化痰祛瘀中药治疗。治疗前后分别进行体重、腰围、臀围、肝功能、血脂、乙型肝炎病毒血清学标志物和HBVDNA定量、超声学检查,治疗6个月后评估疗效。结果治疗组血脂、体重指数及腰臀比均明显降低,治疗后两组比较,差异有统计学意义(P<0.05);治疗组脂肪肝的好转率明显升高,两组比较差异有统计学意义(P<0.05);治疗组抗病毒有效率明显升高,两组比较差异有统计学意义(P<0.05)。结论健脾化痰祛瘀中药能显著改善慢性乙肝合并非酒精性脂肪肝患者的脂肪肝程度,并能提高干扰素对该类患者的抗病毒疗效。

Non-alcoholic Fatty Liver Disease in South Asians:A Review of the Literature

Non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)are national and global epidemics.The disease is characterized by a spectrum of liver steatosis(fat deposition),inflammation(in NASH)and fibrosis.NAFLD and specifically NASH can lead to cirrhosis,which carry risks of progression to portal hypertension and hepatocellular carcinoma(HCC).NASH is also associated with higher mortality from cardiovascular causes.Most of the data for NAFLD has been obtained from the perspective of developed nations,although the disease is increasing and threatening to reach epidemic proportions across the world.Emerging data is notable for high prevalence of NAFLD in South Asian populations,presumably resulting from a combination of underlying genetic polymorphisms and changes in socio-economic status.It is also notable that an‘Asian Paradox'has been defined for NAFLD based upon the observation of lower than predefined body mass index(BMI),otherwise termed as"lean NAFLD",among this population.Yet,data remains limited in regards to the characteristics of NAFLD/NASH in this population.In this article,we present a review of the literature and discuss the prevalence,associated risk factors and burden of HCC in South Asians with NAFLD.

Bile acid-based therapies for non-alcoholic steatohepatitis and alcoholic Iiver disease

Bile acids are synthesized from cholesterol only in hepatocytes.Bile acids circulating in the enterohepatic system act as physiological detergent molecules to help solubilize biliary cholesterol and emulsify dietary lipids and fat-soluble vitamins in small intestine.Bile acids are signaling molecules that activate nuclear receptor farnesoid X receptor(FXR)and cell surface G protein-coupled receptor TGR5.FXR critically regulates bile acid homeostasis by mediating bile acid feedback inhibition of hepatic bile acid synthesis.In addition,bile acid-activated cellular signaling pathways regulate metabolic homeostasis,immunity,and cell proliferation in various metabolically active organs.In the small and large intestine,gut bacterial enzymes modify primary bile acids to generate secondary bile acids to help shape the bile acid pool composition and subsequent biological effects.In turn,bile acids exhibit anti-microbial properties and modulate gut microbiota to influence host metabolism and immunity.Currently,bile acid-based therapies including systemic and intestine-restricted FXR agonists,TGR5 agonists,fibroblast growth factor 19 analogue,intestine FXR antagonists,and intestine apical sodium-bile acid transporter(ASBT)inhibitors have been developed as promising treatments for non-alcoholic steatohepatitis(NASH).These pharmacological agents improved metabolic and inflammatory disorders via distinct mechanisms of action that are subjects of extensive research interest.More recently,human and experimental alcoholic liver disease(ALD)has been associated with disrupted bile acid homeostasis.In additional,new findings showed that targeting bile acid metabolism and signaling may be promising therapeutic approaches for treating ALD.

Vitamins and non-alcoholic fatty liver disease: A molecular insight

The incidence of non-alcoholic fatty liver disease(NAFLD)is rising rapidly across the globe.NAFLD pathogenesis is largely driven by an imbalance in hepatic energy metabolism,and at present,there is no approved drug for its treatment.The liver plays a crucial role in micronutrient metabolism,and deregulation of this micronutrient metabolism may contribute to the pathogenesis of NAFLD.Vitamins regulate several enzymatic processes in the liver,and derangement in vitamin metabolism is believed to play a critical role in NAFLD progression.The anti-oxidant activities of vitamins C and E have been attributed to mitigate hepatocyte injury,and alterations in the serum levels of vitamin D,vitamin B12 and folate have shown a strong correlation with NAFLD severity.This review aims to highlight the role of these vitamins,which represent promising therapeutic targets for the management of NAFLD.

Bile acid activated receptors: Integrating immune and metabolic regulation in non-alcoholic fatty liver disease

Bile acids are a family of atypical steroids generated at the interface of liver-intestinal microbiota acting on a ubiquitously expressed family of membrane and nuclear receptors known as bile acid activated receptors.The two best characterized receptors of this family are the nuclear receptor,farnesoid X re-ceptor(FXR)and the G protein-coupled receptor,G protein-coupled bile acid receptor 1(GPBAR1).FXR and GPBAR1 regulate major aspects of lipid and glucose metabolism,energy balance,autophagy and immunity and have emerged as potential pharmaceutical targets for the treatment of metabolic and inflammatory disorders.Clinical trials in non-alcoholic fatty liver disease(NAFLD),however,have shown that selective FXR agonists cause side effects while their efficacy is partial.Because FXR and GPBAR1 exert additive effects,dual FXR/GPBAR1 ligands have been developed for the treatment of metabolic disorders and are currently advanced to clinical trials.Here,we will review the role of FXR and GPBAR1 agonism in NAFLD and how the two receptors could be exploited to target multiple components of the disease.

Extracellular vesicles in non-alcoholic and alcoholic fatty liver diseases

Fatty liver diseases,non-alcoholic fatty liver disease(NAFLD)and alcoholic liver disease(ALD)are the most common causes of chronic liver diseases around the world.NAFLD and ALD can progress towards a more severe form of the disease,including as non-alcoholic steatohepatitis(NASH)and alcoholic steatohepatitis(ASH).In both instances central pathogenic events include hepatocyte death,liver inflammation,pathological angiogenesis,and fibrosis,followed by cirrhosis and cancer.Over the last few years,extracellular vesicles(EVs)have been identified as effective cell-to-cell communicators that contain a cell-and stressspecific cargo from the cell of origin and are capable of transferring this cargo to a target or acceptor cell.In this review,we focus on the growing evidence supporting a role for EVs in the pathophysiology of NASH and ASH as well as their potential roles as targets for novel biomarkers for these conditions.

Non-alcoholic fatty liver disease development:A multifactorial pathogenic phenomena

Non-alcoholic fatty liver disease(NAFLD),characterized by the accumulation of excessive intrahepatic fat,is a leading metabolic disorder also considered as the hepatic manifestation of metabolic syndrome(MS).Though more commonly observed in obese individuals and those with metabolic risk factors,it also develops in a considerable number of non-obese individuals as well as participants without having any component of MS.The basic mechanism involved in the development of fatty liver is the imbalance between lipid uptake,synthesis,and metabolism in the liver,normally controlled by several mechanisms to maintain lipid homeostasis.As a complex progressive liver disorder,the NAFLD pathogenesis is multifactorial,and several new pathogenic phenomena were discovered over time.The available literature suggests the role of both genetic and environmental factors and associated metabolic factors;however,the mechanism of progression is not completely understood.In this review,we discuss different pathogenic mechanisms and their interplay to provide an elaborate idea regarding NAFLD development and progression.Better understanding of pathogenic mechanisms will be useful in finding new treatment for patients with NAFLD.

Endogenously increased n-3 PUFA levels in fat-1 transgenic mice do not protect from non-alcoholic steatohepatitis

Background:Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver diseaseworldwide,ranging from simple steatosis to non-alcoholic steatohepatitis(NASH)and fibrosis.Possiblereasons for the NAFLD epidemic in industrialized countries are the high intake of pro-inflammatory n-6polyunsaturated fatty acids(n-6 PUFAs)and low consumption of healthy n-3 PUFAs.Due to their antiinflammatoryproperties,n-3 PUFAs may have the potential to alleviate chronic liver disease.Herein,weexamined the therapeutic effect of increased n-3 PUFA tissue levels in fat-1 transgenic mice on progressiveNASH.Methods:Disease was induced in mice by streptozotocin and high fat diet(STZ/HFD)resulting in NASH.NAFLD in 6 and 8 weeks old wild type and fat-1 transgenic STZ/HFD treated mice was analyzed.Unlikeall other mammals,fat-1 transgenic mice ubiquitously express an n-3 fatty acid desaturase,which converts n-6to n-3 PUFAs,leading to increased n-3 and decreased n-6 PUFA tissue contents.Results:Liver damage,NAFLD activity score(NAS),hepatic lipid accumulation and inflammation weresignificantly reduced in fat-1 transgenic STZ/HFD treated mice in the early(6 weeks)but not late(8 weeks)phase of NASH.Simultaneously,mRNA expression of genes involved in fatty acid uptake and storage(Cd36and Plin3,respectively)was significantly down-regulated in 6 week old but not 8 week old fat-1 transgenicSTZ/HFD treated mice.Conclusions:Endogenously elevated n-3 PUFA levels in fat-1 transgenic mice transiently delay the onsetof STZ/HFD induced NASH but failed to efficiently protect from NASH development.

Hepatic transcriptome profiling reveals early signatures associated with disease transition from non-alcoholic steatosis to steatohepatitis

Background and aim:Non-alcoholic fatty liver disease(NAFLD)is becoming a leading cause of chronic liver disease worldwide.The molecular events that influence disease progression from non-alcoholic fatty liver(NAFL)to aggressive non-alcoholic steatohepatitis(NASH)remain incompletely understood,leading to lack of mechanism-based targeted treatment options for NASH.This study aims to identify early signatures associated with disease progression from NAFL to NASH in mice and humans.Materials and methods:Male C57BL/6J mice were fed a high-fat,-cholesterol,and-fructose(HFCF)diet for up to 9 months.The extent of steatosis,inflammation,and fibrosis was evaluated in liver tissues.Total RNA sequencing(RNA-seq)was conducted to determine liver transcriptomic changes.Results:After being fed the HFCF diet,mice sequentially developed steatosis,early steatohepatitis,steatohepatitis with fibrosis,and eventually spontaneous liver tumor.Hepatic RNA-seq revealed that the key signatures during steatosis progression to early steatohepatitis were pathways related to extracel-lular matrix organization and immune responses such as T cell migration,arginine biosynthesis,C-type lectin receptor signaling,and cytokine-cytokine receptor interaction.Genes regulated by transcription factors forkhead box M1(FOXM1)and negative elongation factor complex member E(NELFE)were significantly altered during disease progression.This phenomenon was also observed in patients with NASH.

Comparative effectiveness of medical treatment vs.metabolic surgery for histologically proven non-alcoholic steatohepatitis and fibrosis:a matched network meta-analysis

Background:Non-alcoholic steatohepatitis(NASH)comprises a major healthcare problem affecting up to 30%of patients with obesity and the associated risk for cardiovascular and liver-related mortality.Several new drugs for NASH-treatment are currently investigated.No study thus far directly compared surgical and non-surgical therapies for NASH.This network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical approach.Methods:The study was conducted according to the PRISMA guidelines for network meta-analysis.PubMed,CENTRAL and Web of Science were searched without restriction of time or language using a validated search strategy.Studies investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were selected.Patients with liver cirrhosis were excluded.Risk of bias was assessed with ROB-2 and ROBINS-I-tools.A novel method for population-adjusted indirect comparison to include and compare single-arm trials was applied.Main outcomes were NASH-resolution and improvement of fibrosis.Results:Out of 7,913 studies,twelve randomized non-surgical studies and twelve non-randomized surgical trials were included.NASH-resolution after non-surgical intervention was 29%[95%confidence interval(CI):23-40%]and 79%(95%CI:72-88%)after surgery.The network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication[odds ratio(OR)=2.68;95%CI:1.44-4.97]while drug treatment was superior to placebo(OR=2.24;95%CI:1.55-3.24).Surgery(OR=2.18;95%CI:1.34-3.56)and medication(OR=1.79;95%CI:1.39-2.31)were equally effective to treat fibrosis compared to placebo without difference between them.The results did not change when only new drugs specifically developed for the treatment of NASH were included.Conclusions:Metabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of fibrosis.Trials directly comparing surgery with medication must be urgently conducted.Patients with NASH should be informed about surgical treatment options.

Effects of apical sodium-bile acid transporter inhibitor and obeticholic acid co-treatment in experimental non-alcoholic steatohepatitis

Background and aims:Several bile acids-based monotherapies have been developed for non-alcoholic steatohepatitis(NASH)treatment but clinical trial findings suggest that they do not satisfactorily improve NASH and liver fibrosis in many patients.Recently,we have shown that combining a gut-restricted apical sodium-bile acid transporter(ASBT)inhibitor GSK2330672(GSK)with adeno-associated virus(AAV)-mediated liver fibroblast growth factor 15(FGF15)overexpression provides significantly improved efficacy than either single treatment against NASH and liver fibrosis in a high fat,cholesterol,and fructose(HFCFr)diet-induced NASH mouse model.The beneficial effects of the com-bined treatment can be attributed to the markedly reduced bile acid pool that reduces liver bile acid burden and intestinal lipid absorption.The aim of this study is to further investigate if combining GSK treatment with the orally bioavailable obeticholic acid(OCA),which induces endogenous FGF15 and inhibits hepatic bile acid synthesis,can achieve similar anti-NASH effect as the GSKþAAV-FGF15 co-treatment in HFCFr-diet-fed mice.Materials and methods:Male C57BL/6J mice were fed HFCFr diet to induce NASH and liver fibrosis.The effect of GSK,OCA,and GSKþOCA treatments on NASH development was compared and contrasted among all groups.Results:Findings from this study showed that the GSKþOCA co-treatment did not cause persistent reduction of obesity over a 12-week treatment period.Neither single treatment nor the GSKþOCA co-treatment reduce hepatic steatosis,but all three treatments reduced hepatic inflammatory cytokines and fibrosis by a similar magnitude.The GSKþOCA co-treatment caused a higher degree of total bile acid pool reduction(~55%)than either GSK or OCA treatment alone.However,such bile acid pool reduction was insufficient to cause increased fecal lipid loss.The GSKþOCA co-treatment prevented GSK-mediated induction of hepatic cholesterol 7alpha-hydroxylase but failed to induce ileal FGF15 expression.GSK did not reduce gallbladder OCA amount in the GSKþOCA group compared to the OCA group,suggesting that ASBT inhibition does not reduce hepatic OCA distribution.Conclusions:Unlike the GSKþAAV-FGF15 co-treatment,the GSKþOCA co-treatment does not provide improved efficacy against NASH and liver fibrosis than either single treatment in mice.The lack of synergistic effect may be partly attributed to the moderate reduction of total bile acid pool and the lack of high level of FGF15 exposure as seen in the GSKþAAV-FGF15 co-treatment.

The alteration of immune cells in the pathogenesis of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

The prevalence of non-alcoholic fatty liver disease(NAFLD)increases rapidly in recent decades.NAFLD has become a major public health problem in China and the whole world,and it is considered as the main cause for the chronic liver diseases.However,there is still not specific and effective treatment for non-alcoholic steatohepatitis(NASH),the advanced form of NAFLD.The inflammation in the liver is the hallmark of NASH.Actually,the dysregulation of immune cells happened in the early stage of NAFLD.Targeting immune cells in the liver may represent one of the effective ways for NASH treatment.A better understanding of the change of immune cells in the pathogenesis of NAFLD will be very helpful for developing new treatments for NAFLD and NASH.Here we summarized how the immune cells were affected in different stages of NAFLD and how these immune cells contributed to the development of NAFLD.

Therapies for non-alcoholic steatohepatitis

Current phase 3 trials for the treatment of non-alcoholic steatohepatitis(NASH)are discussed in this review.Modalities that are based on weight loss include therapeutic lifestyle changes,pharmacological weight loss drugs(e.g.,orlistat),and bariatric surgery.Traditionally,insulin resistance has been targeted using pioglitazone,but liraglutide and elafibranor are emerging as potential treatments.With regard to the farnesoid X receptor(FXR)pathway,obeticholic acid has been approved for primary biliary cholangitis and is being studied as a treatment for NASH.Antioxidants include vitamin E and statins.Medications that target fibrogenesis directly instead of NASH include selonsertib.