Histopathology of nonalcoholic fatty liver disease

Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD,i.e.nonalcoholic steatohepatitis(NASH) and fibrosis.Included in the lesions of NAFLD are steatosis,lobular and portal inflammation,hepatocyte injury in the forms of ballooning and apoptosis,and fibros...     

Association between UCP3 gene polymorphisms and nonalcoholic fatty liver disease in Chinese children

AIM:To confirm the hypothesis that polymorphisms of the uncoupling protein 3(UCP3)gene are associated with the occurrence of nonalcoholic fatty liver disease(NAFLD).METHODS:A total of 250 NAFLD patients(147 malesand 103 females)and 200 healthy individuals who served as controls(control,109 males and 91 females),aged between 6 and 16 years were enrolled in this study.The four non-synonymous single nucleotide polymorphisms(SNPs)in the UCP3 gene polymorphisms of rs1726745,rs3781907,rs11235972 and rs1800849,were genotyped using MassArray.Body mass index(BMI),waist and hip circumference,blood pressure(BP),fasting blood glucose(FBG),insulin and lipid profiles were measured and B-ultrasound examination was performed in all subjects.RESULTS:NAFLD patients showed risk factors for metabolic syndrome:elevated BMI,waist-to-hip ratio,BP,FBG,homeostasis model assessment-estimated insulin resistance,total triglyceride,total cholesterol and low-density lipoprotein-cholesterol,while decreased high-density lipoprotein-cholesterol level compared with the control group.The GG genotype distributions of rs11235972 in the NAFLD group differed significantly from that in the control group.We found that waist circumference between CC(58.76±6.45 cm)and CT+TT(57.00±5.59 cm),and hip circumference between CC(71.28±7.84 cm)and CT+TT genotypes(69.06±7.75 cm)were significantly different with and without rs1800849 variation(P<0.05).CONCLUSION:A higher prevalence of rs11235972 GG genotype was observed in the NAFLD group compared with the control group.No differences were observed for the other SNPs.However,there was a significant difference in body height in addition to waist and hip circumference between the CC(mutant type group)and CT+TT group with and without rs1800849 variation.     

外周血PNPLA3 rs738409基因多态性与非酒精性脂肪性肝病遗传易感性研究

目的 分析patatin样磷脂酶结构域蛋白3(PNPLA3)rs738409基因多态性与非酒精性脂肪性肝病(NAFLD)遗传易感性的关系。方法 2017年11月～2019年11月我院诊治的162例NAFLD患者和同期体检的100例健康人,采用聚合酶链式反应-限制性片段长度多态性检测外周血PNPLA3 rs738409位点多态性。结果 NAFLD组PNPLA3基因rs738409位点GG基因型频率为37.0%,G等位基因频率为58.3%,显著高于健康人(分别为11.0%和34.0%,P<0.05),而GC和CC基因型频率分别为42.6%和20.4%,C等位基因频率为41.7%,与健康人的46.0%、43.0%和66.0%比,差异无统计学意义(P>0.05);73例GG基因型的NAFLD患者血清ALT和AST水平分别为(118.5±20.3)U/L和(85.2±14.7)U/L,显著高于65例GC基因型患者[分别为(93.3±16.4)U/L和(59.6±10.3)U/L,P<0.05]或24例CC基因型患者[分别为(65.9±11.8)U/L和(31.9±5.5)U/L...     

Noninvasive biomarkers in pediatric nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide among children and adolescents. It encompasses a spectrum of disease, from its mildest form of isolated steatosis, to nonalcoholic steatohepatitis (NASH) to liver fibrosis and cirrhosis, or end-stage liver disease. The early diagnosis of pediatric NAFLD is crucial in preventing disease progression and in improving outcomes. Currently, liver biopsy is the gold standard for diagnosing NAFLD. However, given its invasive nature, there has been significant interest in developing noninvasive methods that can be used as accurate alternatives. Here, we review noninvasive biomarkers in pediatric NAFLD, focusing primarily on the diagnostic accuracy of various biomarkers as measured by their area under the receiver operating characteristic, sensitivity, and specificity. We examine two major approaches to noninvasive biomarkers in children with NAFLD. First, the biological approach that quantifies serological biomarkers. This includes the study of individual circulating molecules as biomarkers as well as the use of composite algorithms derived from combinations of biomarkers. The second is a more physical approach that examines data measured through imaging techniques as noninvasive biomarkers for pediatric NAFLD. Each of these approaches was applied to children with NAFLD, NASH, and NAFLD with fibrosis. Finally, we suggest possible areas for future research based on current gaps in knowledge.     

Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH.     

Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is the commonest chronic liver disease and includes simple steatosis and nonalcoholic steatohepatitis(NASH). Since NASH progresses to cirrhosis more frequently and increases liver-related and cardiovascular disease risk substantially more than simple steatosis, there is a great need to differentiate the two entities. Liver biopsy is the gold standard for the diagnosis of NAFLD but its disadvantages, including the risk of complications and sampling bias, stress the need for developing alternative diagnostic methods. Accordingly, several non-invasive markers have been evaluated for the diagnosis of simple steatosis and NASH, including both serological indices and imaging methods. The present review summarizes the current knowledge on the role of these markers in the diagnosis of NAFLD. Current data suggest that ultrasound and the fibrosis-4 score are probably the most appealing methods for detecting steatosis and for distinguishing NASH from simple steatosis, respectively, because of their low cost and relatively high accuracy. However, currently available methods, both serologic and imaging, cannot obviate the need for liver biopsy for diagnosing NASH due to their substantial false positive and false negative rates. Therefore, the current role of these methods is probably limited in patients who are unwilling or have contraindications for undergoing biopsy.     

Gender and racial differences in nonalcoholic fatty liver disease

Due to the worldwide epidemic of obesity, nonalcoholic fatty liver disease(NAFLD) has become the most com-mon cause of elevated liver enzymes. NAFLD represents a spectrum of liver injury ranging from simple steato-sis to nonalcoholic steatohepatitis(NASH) which may progress to advanced fibrosis and cirrhosis. Individuals with NAFLD, especially those with metabolic syndrome, have higher overall mortality, cardiovascular mortality, and liver-related mortality compared with the general population. According to the population-based studies, NAFLD and NASH are more prevalent in males and in Hispanics. Both the gender and racial ethnic differences in NAFLD and NASH are likely attributed to interaction between environmental, behavioral, and genetic fac-tors. Using genome-wide association studies, several genetic variants have been identified to be associated with NAFLD/NASH. However, these variants account for only a small amount of variation in hepatic steatosis among ethnic groups and may serve as modifiers of the natural history of NAFLD. Alternatively, these variants may not be the causative variants but simply markers representing a larger body of genetic variations. In this article, we provide a concise review of the gender and racial differences in the prevalence of NAFLD and NASHin adults. We also discuss the possible mechanisms for these disparities.     

Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

It is estimated that 30%of the adult population in Japan is affected by nonalcoholic fatty liver disease(NAFLD).Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography(US)and computed tomography(CT),but the sensitivity of these imaging techniques is low in cases of mild steatosis.Alanine aminotransferase levels may be normal in some of these patients,warranting the necessity to establish a set of parameters useful for detecting NAFLD,and the more severe form of the disease,nonalcoholic steatohepatitis(NASH).Although liver biopsy is currently the gold standard for diagnosing progressive NASH,it has many drawbacks,such as sampling error,cost,and risk of complications.Furthermore,it is not realistic to perform liver biopsies on all NAFLD patients.Diagnosis of NASH using various biomarkers,scoring systems and imaging methods,such as elastography,has recently been attempted.The NAFIC score,calculated from the levels of ferritin,fasting insulin,and typeⅣcollagen 7S,is useful for the diagnosis of NASH,while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis.This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.     

Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice

With the increasing number of individuals with diabetes and obesity,nonalcoholic fatty liver disease(NAFLD) is becoming increasingly prevalent,affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver(NAFL) to nonalcoholic steatohepatitis(NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden,and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD,including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice.     

Fibrosis in nonalcoholic fatty liver disease: Noninvasive assessment using computed tomography volumetry

AIM To evaluate the diagnostic performance of computed tomography(CT) volumetry for discriminating the fibrosis stage in patients with nonalcoholic fatty liver disease(NAFLD).METHODS A total of 38 NAFLD patients were enrolled. On the basis of CT imaging, the volumes of total, left lateral segment(LLS), left medial segment, caudate lobe, and right lobe(RL) of the liver were calculated with a dedicated liver application. The relationship between the volume percentage of each area and fibrosis stage was analyzed using Spearman's rank correlation coefficient. A receiver operating characteristic(ROC) curve analysis was performed to determine the accuracy of CT volumetry for discriminating fibrosis stage.RESULTS The volume percentages of the caudate lobe and the LLS significantly increased with the fibrosis stage(r = 0.815, P 0.001; and r = 0.465, P = 0.003, respectively). Contrarily, the volume percentage of the RL significantly decreased with fibrosis stage(r =-0.563, P 0.001). The volume percentage of the caudate lobe had the best diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating fibrosis stage were as follows: ≥ F1, 0.896; ≥ F2, 0.929; ≥ F3, 0.955; and ≥ F4, 0.923. The best cut-off for advanced fibrosis(F3-F4) was 4.789%, 85.7% sensitivity and 94.1% specificity.CONCLUSION The volume percentage of the caudate lobe calculated by CT volumetry is a useful diagnostic parameter for staging fibrosis in NAFLD patients.     

Metabolic aspects of adult patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome(MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance(IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.     

Validation of PNPLA3 polymorphisms as risk factor for NAFLD and liver fibrosis in an admixed population

Introduction and aimStudies have shown that two polymorphisms were associated with steatosis and progression of non-alcoholic fatty liver disease (NAFLD) in different populations: the Patatin-like Phospholipase Domain Containing 3 (PNPLA3) and Transmembrane 6 Superfamily Member 2 (TM6SF2). However, the frequency and significance of these polymorphisms in an admixed population, i.e., Brazilian, is unknown. Therefore, we aimed to evaluate them in healthy subjects in comparison to patients with NAFLD.Material and methodsThis was a multicenter cross-sectional study in 248 patients with biopsy-proven NAFLD and in 134 healthy controls from two tertiary centers in Brazil. PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) polymorphisms were evaluated.ResultsIn controls, the frequencies of PNPLA3 CC and CG + GG were 49.25% and 50.74%, respectively; in NAFLD patients, this was 31.05% and 68.88% (p = 0.0044, 95% CI 1.037–2.977). PNPLA3 GG subjects had an increased risk (3.29-fold) of having NAFLD when compared to CC subjects (p = 0.0044, 95% CI 1.504–7.225). In patients with nonalcoholic steatohepatitis (NASH), PNPLA3 GG compared to CC was associated with higher AST levels [38.4 ± 25.3 versus 36.7 ± 40.1 IU/L, p = 0.0395)] and with the presence of liver fibrosis (≥F2 fibrosis, p = 0.0272). TM6SF2 polymorphisms were not in Hardy-Weinberg equilibrium in our NAFLD group precluding further analysis.ConclusionWe demonstrated for the first time that PNPLA3 CG + GG increase the risk of NAFLD among Brazilian subjects. Moreover, PNPLA3 GG was associated with liver enzyme elevation and fibrosis in NASH patients.     

Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population

Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease(NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms(SNPs) in the regulatory region of genes encoding NADPH oxidase 4(NOX4) and p22 phox(CYBA) in NAFLD.Methods: A total of 207 biopsy-proven NAFLD patients [simple steatosis(n = 27); nonalcoholic steatohepatitis(NASH)(n = 180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA(unregistered) and NOX4(rs3017887) were determined by direct sequencing of PCR.Results: Associations of CYBA-675 T/A with high-density lipoprotein(HDL)(TT vs TA vs AA; P 0.01) and triglycerides(TGL)(TT vs XA; P 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4(rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase(ALT)(CA + AA vs CC; P = 0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus(66.9% vs 37.5%, P 0.01) and those who were more obese(32.2 vs 29.0 kg/m2,P 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH.Conclusions: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.     

Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease (NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.     

Promising diagnostic biomarkers of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: From clinical proteomics to microbiome

Fatty liver has been present in the lives of patients and physicians for almost two centuries. Vast knowledge has been generated regarding its etiology and consequences, although a long path seeking novel and innovative diagnostic biomarkers for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is still envisioned. On the one hand, proteomics and lipidomics have emerged as potential noninvasive resources for NAFLD diagnosis. In contrast, metabolomics has been able to distinguish between NAFLD and NASH, even detecting degrees of fibrosis. On the other hand, genetic and epigenetic markers have been useful in monitoring disease progression, eventually functioning as target therapies. Other markers involved in immune dysregulation, oxidative stress, and inflammation are involved in the instauration and evolution of the disease. Finally, the fascinating gut microbiome is significantly involved in NAFLD and NASH. This review presents state-of-the-art biomarkers related to NAFLD and NASH and new promises that could eventually be positioned as diagnostic resources for this disease. As is evident, despite great advances in studying these biomarkers, there is still a long path before they translate into clinical benefits.     

非酒精性脂肪性肝病合并2型糖尿病患者肝组织病理学变化研究

目的 研究非酒精性脂肪性肝病（NAFLD）合并2型糖尿病（T2DM）患者肝脏组织病理学变化。方法 分析240例行肝活检术的NAFLD患者临床资料,比较NAFLD合并T2DM与未合并T2DM患者肝组织病理学表现和评分的差异。结果 在240例NAFLD患者中,合并2型糖尿病者80例（33.3%）,未合并T2DM 者160例（66.7%）;在NAFLD合并T2DM患者中非酒精性脂肪性肝炎（NASH）60例、肝纤维化20例,未合并T2DM患者中分别为68例和92例;在NAFLD合并T2DM患者中检出肝纤维化评分≥2者30例（37.5%）、肝细胞气球样变评分≥2者23例（28.8%）和马洛里小体22例（27.5%）,均显著高于未合并T2DM患者的【20例（12.5%）、22例（13.8%）和30例（18.8%）,P<0.05】;T2DM为发生NASH（OR=3.27,95%CI：1.42~7.55）和肝纤维化（OR=3.35,95%CI：1.55~7.63）的独立危险因素。结论 合并T2DM的NAFLD患者肝组织病理学损伤更趋严重,应注意防治。     

Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease

AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was performed.Cases were 40 obese children with NAFLD.The diagnosis of NAFLD was based on magnetic resonance imaging(MRI)with high hepatic fat fraction(HFF≥5%),and confirmed by liver biopsy with≥5%of hepatocytes containing macrovesicular fat.Controls were selected from obese children with normal levels of aminotransferases,and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases.Controls were matched(1-to 1)with the cases on age,gender,pubertal stage and as closely as possible on body mass index-standard deviation score.All participants underwent clinical examination,laboratory testsincluding zonulin,inflammatory and metabolic parameters,and MRI for measurement of HFF and visceral adipose tissue.RESULTS:Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD[median(interquartile range),4.23(3.18-5.89)vs 3.31(2.05-4.63),P<0.01].In patients with NAFLD,zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis(r=0.372,P<0.05);however,we did not find a significant correlation between zonulin and lobular inflammation(P=0.23),ballooning(P=0.10),fibrosis score(P=0.18),or presence of nonalcoholic steatohepatitis(P=0.17).Within the entire study population,zonulin levels were positively associated with gamma-glutamyl transferase,2-h insulin,HFF,and negatively associated with whole-body insulin sensitivity index(WBISI),after adjustment for age,gender and pubertal status.When the associations were restricted to the group of NAFLD patients,2-h insulin,hepatic fat,and WBISI retained statistical significance.CONCLUSION:Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.     

ALDH2 rs671基因多态性与非酒精性脂肪性肝病相关性研究*

目的 研究乙醛脱氢酶2（ALDH2）基因rs671多态性与非酒精性脂肪性肝病（NAFLD）发病的相关性。方法 在120例研究对象,行肝脏硬度和受控衰减参数（CAP）及血ALDH2 rs671多态性检测,采用非条件Logistic回归控制混杂因素,计算比值比（OR）及其95%可信区间（CI）,判断基因多态性与NAFLD患病的相对风险度。结果 根据CAP检测结果发现脂肪肝73例,无脂肪肝人群47例;脂肪肝组和无脂肪肝组ALDH2 rs671基因GA/AA型比例分别为52.1%和34.0%（P<0.05）;女性和超重人群中脂肪肝组GA/AA型比例分别为48.8%和53.3%,显著高于无脂肪肝组的22.2%和23.1%（P<0.05）;GA/AA型者脂肪肝患病风险升高3.756倍,其体质量、臀围、腰高比超标比例显著高于GG型者（P<0.05）,血清GGT水平为（55.57±99.97） U/L,显著高于GG型者[（38.17±48.02）U/L,P<0.05]。结论 ALDH2 rs671突变可增加NAFLD的患病风险,其发病机制和防治措施还需要进一步研究。     

Pediatric nonalcoholic fatty liver disease: overview with emphasis on histology

Nonalcoholic fatty liver disease(NAFLD) is a disease in which excessive fat accumulates in the liver of a patient without a history of alcohol abuse.This disease includes simple steatosis and nonalcoholic steatohepatitis(NASH).NAFLD/NASH is recognized as a hepatic manifestation of metabolic syndrome.In recent years,pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity.The estimated prevalence of pediatric NAFLD is 2.6%-9.6%,and it is associated with sex,age,and ethnicity.W...     

Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.