Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease

Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease (NAFLD). The change in gut microbiota may alter nutritional absorption and storage. In addition, gut microbiota are a source of Toll-like receptor (TLR) ligands, and their compositional change can also increase the amount of TLR ligands delivered to the liver. TLR ligands can stimulate liver cells to produce proinflammatory cytokines. Therefore, the gut-liver axis has attracted much interest, particularly regarding the pathogenesis of NAFLD. The abundance of the major gut microbiota, including Firmicutes and Bacteroidetes, has been considered a potential underlying mechanism of obesity and NAFLD, but the role of these microbiota in NAFLD remains unknown. Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD. For instance, a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability, which allows the leakage of bacterial components. Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD. In children, the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis (NASH) compared with those in obese control. Escherichia can produce ethanol, which promotes gut permeability. Thus, normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD. In addition, TLR signaling in the liver is activated, and its downstream molecules, such as proinflammatory cytokines, are increased in NAFLD. To data, TLR2, TLR4, TLR5, and TLR9 have been shown to be associated with the pathogenesis of NAFLD. Therefore, gut microbiota and TLRs are targets for NAFLD treatment.     

Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis

A growing body of evidence from multiple areas proposes that periodontal disease, accompanied by oral inflammation and pathological changes in the microbiome, induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A subgroup of NAFLD patients have a severely progressive form, namely nonalcoholic steatohepatitis (NASH), which is characterized by histological findings that include inflammatory cell infiltration and fibrosis. NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma. The oral microbiota may serve as an endogenous reservoir for gut microbiota, and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis. Gut dysbiosis increases the production of potential hepatotoxins, including lipopolysaccharide, ethanol, and other volatile organic compounds such as acetone, phenol and cyclopentane. Moreover, gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall, leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation. In particular, many animal studies support that oral administration of Porphyromonas gingivalis, a typical periodontopathic bacterium, induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis. NAFLD, also known as the hepatic phenotype of metabolic syndrome, is strongly associated with metabolic complications, such as obesity and diabetes. Periodontal disease also has a bidirectional relationship with metabolic syndrome, and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively. In this review, we will describe the link between periodontal disease and NAFLD with a focus on basic, epidemiological, and clinical studies, and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome. In conclusion, it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease, gut microbiota, and metabolic syndrome. Thus, the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics, prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.     

Nonalcoholic fatty liver disease – current status and future directions

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide with a reported prevalence ranging 6–33%, depending on the studied populations. It encompasses a spectrum of liver manifestations ranging from simple steatosis (also known as nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. NAFLD is strongly associated with the components of metabolic syndrome, mainly obesity and type 2 diabetes mellitus. NAFLD patients are at increased risk of liver‐related as well as cardiovascular mortality. Current paradigm suggests a benign course for NAFL whereas NASH is considered to be the progressive phenotype. Although previously under‐recognized accumulating evidence suggests that NAFL may also progress, suggesting a higher number of patients at risk than previously appreciated. Liver biopsy remains the gold standard for definitive diagnosis, but the majority of patients can be diagnosed accurately by noninvasive methods. Approved therapies for NAFLD are still lacking and lifestyle modifications aiming at weight loss remain the mainstay of NAFLD treatment. Intensive research could identify insulin resistance, lipotoxicity and dysbiosis of the gut microbiota as major pathophysiological mechanisms, leading to the development of promising targeted therapies which are currently investigated in clinical trials. In this review we summarized the current knowledge of NAFLD epidemiology, natural history, diagnosis, pathogenesis and treatment and considered future directions.     

Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by fat accumulation combined with low‐grade inflammation in the liver. A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue and de novo lipogenesis can lead to NAFLD and insulin resistance. Thus, individuals with obesity, insulin resistance, and dyslipidaemia are at the greatest risk of developing NAFLD. Conversely, NAFLD is a phenotype of cardiometabolic syndrome. Notably, researchers have discovered a close association between NAFLD and impaired glucose metabolism and focused on the role of NAFLD in the development of type 2 diabetes. Moreover, recent studies provide substantial evidence for an association between NAFLD and atherosclerosis and cardiometabolic disorders. Even if NAFLD can progress into severe liver disorders including nonalcoholic steatohepatitis (NASH) and cirrhosis, the majority of subjects with NAFLD die from cardiovascular disease eventually. In this review, we propose a potential pathological link between NAFLD/NASH and cardiometabolic syndrome. The potential factors that can play a pivotal role in this link, such as inflammation, insulin resistance, alteration in lipid metabolism, oxidative stress, genetic predisposition, and gut microbiota are discussed.     

Gut microbiota and nonalcoholic fatty liver disease

Recent evidence has linked obesity and the metabolic syndrome with gut dysbiota. The precise mechanisms underlying that association are not entirely understood; however, microbiota can enhance the extraction of energy from diet and regulate whole-body metabolism towards increased fatty acids uptake from adipose tissue and shift lipids metabolism from oxidation to de novo production. Obesity and high fat diet relate to a specific gut microbiota, which is enriched in Firmicutes and with less Bacterioidetes. Microbiota can also play a role in the development of hepatic steatosis, necroinflammation and fibrosis. In fact, some studies have shown an association between small intestinal bacterial overgrowth, increased intestinal permeability and nonalcoholic steatohepatitis (NASH). That association is, in part, due to increased endotoxinaemia and activation of the Toll-like receptor-4 signaling cascade. Preliminary data on probiotics suggest a potential role in NASH treatment, however randomized controlled clinical trials are still lacking.     

The Gut Microbiome and Ferroptosis in MAFLD

Metabolic-associated fatty liver disease (MAFLD) is a new disease definition, and is proposed to replace the previous name, nonalcoholic fatty liver disease (NAFLD). Globally, MAFLD/NAFLD is the most common liver disease, with an incidence rate ranging from 6% to 35% in adult populations. The pathogenesis of MAFLD/NAFLD is closely related to insulin resistance (IR), and the genetic susceptibility to acquired metabolic stress-associated liver injury. Similarly, the gut microbiota in MAFLD/NAFLD is being revaluated by scientists, as the gut and liver influence each other via the gut-liver axis. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Emerging evidence suggests that ferroptosis has a key role in the pathological progression of MAFLD/NAFLD, and inhibition of ferroptosis may become a novel therapeutic strategy for the treatment of NAFLD. This review focuses on the main mechanisms behind the promotion of MAFLD/NAFLD occurrence and development by the intestinal microbiota and ferroptosis. It outlines new strategies to target the intestinal microbiota and ferroptosis to facilitate future MAFLD/NAFLD therapies.     

Apoptosis and non-alcoholic fatty liver diseases

The number of patients with nonalcoholic fatty liver diseases(NAFLD) including nonalcoholic steatohepatitis(NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma(HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.     

饮食干预对非酒精性脂肪性肝病肠道菌群的影响

非酒精性脂肪性肝病(NAFLD)的发生与遗传和环境密切相关,肠道菌群在其发生和发展中发挥了重要作用,调节肠道菌群已成为干预NAFLD的重要靶点之一.无论是饮食总量还是结构都会对肠道菌群产生直接且长期的影响.通过低脂饮食、增加饮食中不饱和脂肪酸或者增加难以吸收的多糖等方式调整饮食结构,可以有效调节肠道菌群并治疗NAFLD,但高蛋白饮食的作用还存在争议.     

Gut–liver axis: The impact of gut microbiota on non alcoholic fatty liver disease

AimTo examine the impact of gut microbiota on non alcoholic fatty liver disease (NAFLD) pathogenesis.Data synthesisEmerging evidence suggests a strong interaction between gut microbiota and liver. Receiving approximately 70% of its blood supply from the intestine, the liver represents the first line of defence against gut-derived antigens. Intestinal bacteria play a key role in the maintenance of gut–liver axis health. Disturbances in the homeostasis between bacteria- and host-derived signals at the epithelial level lead to a break in intestinal barrier function and may foster “bacterial translocation”, defined as the migration of bacteria or bacterial products from the intestinal lumen to mesenteric lymph nodes or other extraintestinal organs and sites. While the full repertoire of gut-derived microbial products that reach the liver in health and disease has yet to be explored, the levels of bacterial lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver diseases. Derangement of the gut flora, particularly small intestinal bacterial overgrowth, occurs in a large percentage (20–75%) of patients with chronic liver disease. In addition, evidence implicating the gut–liver axis in the pathogenesis of metabolic liver disorders has accumulated over the past ten years.ConclusionsComplex metabolic diseases are the product of multiple perturbations under the influence of triggering factors such as gut microbiota and diet, thus, modulation of the gut microbiota may represent a new way to treat or prevent NAFLD.     

Current and novel therapies for the treatment of nonalcoholic steatohepatitis

The worldwide epidemic of obesity and the metabolic syndrome has made nonalcoholic fatty liver disease (NAFLD), one of the most important liver diseases of our time. NAFLD is now the commonest cause of abnormal liver test results in industrialized countries and its incidence is rising. The current treatment of nonalcoholic steatohepatitis (NASH) has focused on lifestyle modification to achieve weight loss and modification of risk factors, such as insulin resistance, dyslipidemia, and hyperglycemia associated with the metabolic syndrome. With our increasing understanding of the pathogenesis of NASH, have come a plethora of new pharmacologic options with great potential to modify the natural history of NAFLD and NASH. This article focuses on a number of novel molecular targets for the treatment of NASH as well as the evidence for currently available therapy. It should be noted, however, that in part because of the long natural history of NASH and NAFLD, no therapy to date has been shown to unequivocally alter liver-related morbidity and mortality in these patients.     

Gut microbiota and non-alcoholic fatty liver disease

BACKGROUND: Non-alcoholic fatty liver disease(NAFLD) is a common disorder with poorly understood pathogenesis. Beyond environmental and genetic factors,cumulative data support the causative role of gut microbiota in disease development and progression.DATA SOURCE: We performed a Pub Med literature search with the following key words: "non-alcoholic fatty liver disease","non-alcoholic steatohepatitis","fatty liver","gut microbiota" and "microbiome",to review the data implicating gut microbiota in NAFLD development and progression.RESULTS: Recent metagenomic studies revealed differences in the phylum and genus levels between patients with fatty liver and healthy controls. While bacteroidetes and firmicutes remain the dominant phyla among NAFLD patients,their proportional abundance and genera detection vary among different studies. New techniques indicate a correlation between the methanogenic archaeon(methanobrevibacter smithii) and obesity,while the bacterium akkermanshia municiphila protects against metabolic syndrome. Among NAFLD patients,small intestinal bacterial overgrowth detected by breath tests might induce gut microbiota and host interactions,facilitating disease development.CONCLUSIONS: There is evidence that gut microbiota participates in NAFLD development through,among others,obesity induction,endogenous ethanol production,inflammatory response triggering and alterations in choline metabolism. Further studies with emerging techniques are needed to further elucidate the microbiome and host crosstalk in NAFLD pathogenesis.     

Non-alcoholic fatty liver disease and the metabolic syndrome： An update

Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic in westernized countries, subsequently increasing the risk for developing the metabolic syndrome and nonalcoholic fatty liver disease （NAFLD）. NAFLD is estimated to affect approximate 30% of the general US population and is considered the hepatic manifestation of the metabolic syndrome. Recent findings linking the components of the metabolic syndrome with NAFLD and the progression to nonalcoholic steatohepatitis （NASH） will be reviewed; in particular, the role of visceral adipose tissue, insulin resistance, and adipocytokines in the exacerbation of these conditions. While no therapy has been proven effective for treating NAFLD/NASH, common recommendations will be discussed.     

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.     

Bariatric surgery in patients with non-alcoholic fatty liver disease-from pathophysiology to clinical effects

Non-alcoholic fatty liver disease(NAFLD) is increasingly recognized as a significant liver disease,and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis(NASH) to fibrosis,subsequent cirrhosis,end-stage liver failure,and liver cancer with a potential need for liver transplantation.NAFLD and NASH are closely related to obesity,metabolic syndrome,and type 2 diabetes(T2 D).The role of gut hormones,especially glucagon-like peptide 1(GLP-1),is important in NAFLD.Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2 D.Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD.Therefore,bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients.In the present review,we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways.We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients.The specific focus was liver histopathology as assessed by the invasive liver biopsy.Additionally,we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.     

Microbiota and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH)

Genetic predisposition, the intestinal microbiota (IM) and environmental factors, such as sedentary lifestyle and inadequate diet, should be considered as critical factors for the development of nonalcoholic fatty liver disease (NAFLD). Recently, some studies have demonstrated an association between dysbiosis and NAFLD; however, the exact mechanisms that lead to intestinal membrane damage, bacterial translocation and inflammation are not well elucidated. Due to the relevance of this theme, the IM and its metabolites have received special attention in recent years in an attempt to better understand the mechanisms related to the prevention, physiopathology, and treatment of NAFLD. In this paper, we provide a review of the human IM and its role in diet, obesity, and the development/progression of NAFLD/NASH, as well as the use of prebiotics and probiotics in the modulation of IM.     

Potential mechanisms linking gut microbiota and portal hypertension

Gut microbiota is the largest collection of commensal micro‐organisms in the human body, engaged in reciprocal cellular and molecular interactions with the liver. This mutually beneficial relationship may break down and result in dysbiosis, associated with disease phenotypes. Altered composition and function of gut microbiota has been implicated in the pathobiology of nonalcoholic fatty liver disease (NAFLD), a prevalent condition linked to obesity, insulin resistance and endothelial dysfunction. NAFLD may progress to cirrhosis and portal hypertension, which is the result of increased intrahepatic vascular resistance and altered splanchnic circulation. Gut microbiota may contribute to rising portal pressure from the earliest stages of NAFLD, although the significance of these changes remains unclear. NAFLD has been linked to lower microbial diversity and weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defence and inflammation. Moreover, disrupted host‐microbial metabolic interplay alters bile acid signalling and the release of vasoregulatory gasotransmitters. These perturbations become prominent in cirrhosis, increasing the risk of clinically significant portal hypertension and leading to bacterial translocation, sepsis and acute‐on‐chronic liver failure. Better understanding of the gut‐liver axis and identification of novel microbial molecular targets may yield specific strategies in the prevention and management of portal hypertension.     

Nonalcoholic steatohepatitis in nonalcoholic fatty liver disease patients of Bangladesh

AIM: To explore the prevalence and risk factors for nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: We have included 493 patients with sonographic evidence of a fatty change, and 177 of these individuals were evaluated and confirmed after liver biopsy. The exclusion criteria consisted of significant alcohol abuse (< 20 g daily), evidence of hepatitis B and C, evidence of drug-induced fatty liver disease and other specific liver diseases such as hemochromatosis, Wilson’s disease or autoimmune liver disease. The patients were assessed for metabolic syndrome, and biochemical, anthropometric and histopathological evaluations were carried out. The degree of disease activity in the NAFLD patients was evaluated using the NAFLD Activity Score. The data were analyzed by SPSS, version 16.0. RESULTS: Females predominated among the study participants (250, 57.0%), and the mean age was 40.8 ± 10.2 years. The numbers of overweight, obeseⅠ and obese Ⅱ patients were 58 (13.2%), 237 (53.9%) and 93 (21.2%), respectively. However, there were 422 (96.2%) centrally obese patients. NASH was absent in 10 (5.6%) cases, borderline in 92 (52.6%) cases and present in 75 (42.4%) cases. The presence of diabetes could significantly (P = 0.001) differentiate NASH from simple steatosis. The following parameters did not influence the development of NASH: age, sex, basal metabolic index, waist circumference, serum high-density lipoprotein, triglyceride, insulin resistance index, hypertension and metabolic syndrome. The serum gammaglutamyl transpeptidase (GGT) level was significantly higher (P = 0.05, 51.7 ± 32.8 and 40.4 ± 22.6 U/L) in the NASH patients, with a sensitivity of 45% and a specificity of only 68%. The serum alanine aminotransferase and aspartate aminotransferase levels were not able to predict NASH. CONCLUSION: Females were the predominant sufferers of NAFLD in Bangladesh. The prevalence of NASH was high. Diabetes was found to be the main culprit in developing NASH. GGT was the only biochemical marker of NASH. We recommend liver biopsy in NAFLD patients who have diabetes and elevated GGT.     

From the metabolic syndrome to NAFLD or vice versa?

The metabolic syndrome encompasses metabolic and cardiovascular risk factors which predict diabetes and cardiovascular disease (CVD) better than any of its individual components. Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum which includes variable degrees of simple steatosis (nonalcoholic fatty liver, NAFL), nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the hepatic manifestation of the metabolic syndrome, with insulin resistance as the main pathogenetic mechanism. Recent data indicate that hyperinsulinemia is probably the consequence rather than cause of NAFLD and NAFLD can be considered an independent predictor of cardiovascular disease. Serum free fatty acids derived from lipolysis of visceral adipose tissue are the main source of hepatic triglycerides in NAFLD, although hepatic de novo lipogenesis and dietary fat supply contribute to the pathogenesis of NAFLD. Approximately 10–25% NAFLD patients develop NASH, the evolutive form of hepatic steatosis. Presumably in a genetically predisposed environment, this increased lipid overload overwhelms the oxidative capacity and reactive oxygen species are generated, leading to lipid peroxidation, cytokine induction, chemoattraction of inflammatory cells, hepatic stellate cell activation and finally fibrogenesis with extracellular matrix deposition. No currently available therapies for NAFLD and NASH exist. Recently nuclear receptors have emerged as key regulators of lipid and carbohydrate metabolism for which specific pharmacological ligands are available, making them attractive therapeutic targets for NAFLD and NASH.     

The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance

Non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH) represent a spectrum of diseases involving hepatic fat accumulation and histological features essentially identical to alcoholic liver disease; however, they occur in the absence of excessive alcohol intake. They typically arise in conjunction with one or more features of the metabolic syndrome. Lifestyle mediated weight loss remains the primary mode of therapy for NAFLD and NASH, but this is often ineffective and adjunctive medical and surgical treatments are presently lacking. Prebiotic fibres are a group of non-digestible carbohydrates that modulate the human microbiota in a manner that is advantageous to host health. Rodent studies suggest that dietary supplementation with prebiotic fibres positively impacts NAFLD by modifying the gut microbiota, reducing body fat, and improving glucoregulation. Future research should focus on placebo-controlled, human, clinical trials using histological endpoints to address the effects of prebiotics on NAFLD and NASH. The aim of this review is to summarize current knowledge about prebiotics as an emerging therapeutic target for NAFLD.     

Lipid-lowering agents in nonalcoholic fatty liver disease and steatohepatitis: human studies

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers to the presence of hepatic steatosis without significant intake of alcohol. NAFLD is an asymptomatic disease that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD is currently the most common cause of incidental abnormal liver tests and elevated serum liver enzyme activities in the developed world. Obesity, diabetes, and other components of the metabolic syndrome are frequently associated with the NAFLD. The treatment of NAFLD focuses on life-style modifications. Statins, fibrates, and other lipid-lowering agents have been proposed as effective lipid-lowering treatments in patients with NAFLD/NASH. However, clinicians are concerned that hyperlipidemic patients with NAFLD/NASH who are treated with statins could develop transaminitis. We assessed the efficacy and safety of lipid-lowering agents for NAFLD/NASH by reviewing reports of human studies including pilot, prospective, preliminary, and post hoc analysis studies on online databases during the period of 1980 to December 2012. The results of studies provide compelling evidence that lipid-lowering agents are safe and efficacious in patients with NAFLD/NASH and that some of these agents can induce a reduction in the extent of the hepatic steatosis. Well-designed randomized controlled studies of adequate size and duration with histological endpoints are needed in order to establish a suitable lipid-lowering treatment for hyperlipidemic patients with NAFLD/NASH, and for nonhyperlipidemic patients with NAFLD/NASH with a high risk for cardiovascular disease.