Abdominal ultrasound for diagnosis of nonalcoholic fatty liver disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. The progressive subtype of NAFLD or nonalcoholic steatohepatitits (NASH), may progress to cirrhosis and its complications. Unfortunately, accurate noninvasive modalities for diagnosing NASH and monitoring its progression are unavailable, necessitating a liver biopsy. Abdominal ultrasound (US) is widely used for screening asymptomatic patients with an incidental elevation of liver enzymes. However, US cannot detect small amounts of hepatic steatosis and cannot establish the diagnosis of NASH or stage of hepatic fibrosis. In this issue of AJG, a new radiologic scoring system has been reported to have excellent performance in diagnosing NAFLD and visceral obesity. However, the utility of this scoring system in establishing the diagnosis of NASH and hepatic fibrosis, has not been shown. Additionally, validity of this scoring system to other populations (i.e. obese) and in the setting of private practice must be proven. In summary, this study provides some valuable data regarding the utility of radiologic modalities in detecting hepatic steatosis and abdominal fat but still falls short in answering some important diagnostic and prognostic questions in NAFLD. The evolving field of diagnostic imaging for NAFLD holds promise. A combination of serum biomarkers and radiologic modalities may one day provide the best diagnostic approach for patients with NAFLD, and potentially replace the necessity for liver biopsy in most patients.     

The efficacy of ezetimibe on nonalcoholic fatty liver disease (NAFLD)

The usefulness of ezetimibe was examined in 297 patients with dyslipidemia who did not achieve LDL-C target levels set in JAS 2007 Guidelines by lifestyle modification. The mean period of administration was 178.2±295.4 days. Ezetimibe significantly improved serum lipid levels in the patients with and without non-alcoholic fatty liver disease (NAFLD) (p<0.01). Significant improvement of AST, ALT and γ GTP levels were also observed in the patients with NAFLD (p<0.01, p<0.05, and p<0.01, respectively). Seventy of the patients with NAFLD who underwent abdominal ultrasound before and after administration of ezetimibe were followed. Of those, 38.6% of the patients showed disappearance of steatosis, indicating that administration of ezetimibe is useful in patients with NAFLD.     

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.     

Biopsy rate and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD)

Abstract

Background: Licensed therapies for nonalcoholic fatty liver disease (NAFLD) do not yet exist, but clinical trials are testing treatment options. Inclusion criteria often require liver biopsy showing fibrosis (F2/3) or cirrhosis (F4) and nonalcoholic steatohepatitis (NASH). However, histological criteria pose a serious obstacle for recruitment.

Aims: Characterize the relevance of liver biopsies in the selection of patients with NAFLD.

Methods: Patients between 2013 and 2018 with the ICD-10 code K76.0 were analyzed. Fibrosis was defined by the NASH clinical research network (CRN) fibrosis staging system, NASH by a NAFLD activity score (NAS) ≥4. Predictive factors were determined by logistic regression.

Results: Liver biopsy was performed in 87/638 (13.6%) patients (49% female, age 52.5?±?14.0, BMI 30.4?±?5.9?kg/m²). Fibrosis stage F0/F1/F2/F3/F4 was observed in N?=?7/47/7/17/9, an NAS ≥4 in N?=?27. Fibrosis stage F2/F3 and F4 along with NAS ≥4 was found in 1.7% and 0.5% of cases. Liver stiffness measurement, LSM (OR 2.3 per doubling of value; CI 1.3–4.4, p?=?.005) and FIB-4 (OR 2.3 per doubling of value; CI 1.2–4.4, p?=?.012) were significant predictors for fibrosis?≥?F2. Predictive factors for NASH were not identified.

Conclusion: The biopsy rate in NAFLD patients is low and fibrosis?≥?F2 along with NAS ≥4 only present in a few cases. Transient elastography and FIB-4 are useful to select patients at risk for fibrosis for liver biopsy.     

Epidemiology and risk factors of nonalcoholic fatty liver disease (NAFLD)

The nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic steatosis, determined by either imaging or histology, in the absence of secondary causes of hepatic fat accumulation. Nonalcoholic fatty liver is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes or fibrosis. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. Although initial epidemiological studies have focused on its prevalence in the Western countries, it is becoming increasingly clear that NAFLD is highly prevalent in the Asia Pacific region, and there may be important distinctions in its phenotype between Asia Pacific and Western countries. Of particular interest are “lean NAFLD” and the “urban-rural divide,” which will be discussed in this review article. Obesity, dyslipidemia, type 2 diabetes and metabolic syndrome are established risk factors for developing NAFLD. Many other risk factors (e.g., hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea, hypopituitarism and hypogonadism) for NAFLD have been described in the Western countries, but these associations are yet to be investigated adequately in the Asia Pacific region.     

线粒体功能不全与非酒精性脂肪性肝病

非酒精性脂肪性肝病（NAFLD）是遗传、环境、代谢、应激相关因素所致的一种慢性肝脏疾病,包括单纯性脂肪肝、脂肪性肝炎和脂肪性肝硬化三种类型。NAFLD的发病机制复杂,     

重视非酒精性脂肪性肝病进展的遗传危险因素

尽管动物模型(鼠)可以复制促进甘油三酯(TG)在肝脏沉积和从脂肪变性到非酒精性脂肪性肝炎(NASH)、肝硬化及肝细胞肝癌这个连续的过程,提供可能的病理机制,但在人类复制这个过程依然没有得到明确的界定[1].最近,从人类基因识别序列的研究中得到了一些新的见解,可能为非酒精性脂肪性肝病(NAFLD)发病机制提供新的分子线索[2-4].     

Development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: proposal of a postoperative NAFLD scoring system

Background

The main etiology of NAFLD and NASH after pancreatic resection is still unclear, and the therapeutic strategy has yet to be established. The focus of this review is how predict and prevent NAFLD/NASH after pancreaticoduodenectomy.

Methods

From April 2005 to October 2008, 54 patients who underwent pancreaticoduodenectomy in our institution were enrolled in this study. From the pre-, intra- and postoperative risk factors, we identified the most influential risk factors of postoperative NAFLD by uni- and multivariate analyses. Moreover, a postoperative NAFLD scoring system was proposed based on these risk factors.

Results

The incidence of postoperative NAFLD was 37.0% (20/54). Of these, 10% (2/20) of patients were diagnosed as having NASH by percutaneous liver biopsy. By multivariate analysis, pancreatic adenocarcinoma (p < 0.05), pancreatic resection line (p < 0.01) and postoperative diarrhea (p < 0.01) were identified as the most influential factors concerning postoperative NAFLD. Based on these results, we proposed a postoperative NAFLD scoring system (0–10) and evaluated the correlation between the score and decreasing rates of CT values, revealing a significant correlation (r = 0.829 p < 0.001). The prevalence of postoperative NAFLD in the patients with our scores of 0–3, 4–6 and 7–10 points was 0 (0/22), 35 (6/17) and 93% (14/15), respectively.

Conclusions

In conclusion, NAFLD develops frequently in patients who undergo PD, and some patients even progress to NASH. A postoperative NAFLD scoring system makes it possible to predict the occurrence of NAFLD after PD, and aggressive nutrition support is needed for patients with high scores.     

Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD)

BACKGROUND: One of the major pathogenic mechanisms for progression of nonalcoholic fatty liver disease (NAFLD) is oxidative stress. Recently, many studies have demonstrated the role of oxidative stress in NAFLD however, studies describing the antioxidant status in these patients are lacking. AIM: To study the levels of oxidative stress and antioxidant status among patients with NAFLD. PATIENTS AND METHODS: It was a prospective study in which 29 patients with NAFLD, 25 diseased controls with chronic viral hepatitis, and 23 healthy controls were enrolled. Apart from standard biochemical parameters, lipid peroxidation products were measured as thiobarbituric acid reactive substances. As measures of antioxidant capacity, superoxide dismutase, vitamin C levels and ferric reducing ability of plasma were measured. RESULTS: Level of thiobarbituric acid reactive substances was significantly higher among NAFLD patients as compared with diseased [4.7 nmol/mL (1.0 to 10.2) vs. 2.4 nmol/mL (0.8 to 10.7); P=0.02] or healthy controls [4.7 nmol/mL (1.0 to 10.2) vs. 1.8 nmol/mL (0.5 to 4.1); P=0.0001]. FRAP was found to be significantly higher in patients with NAFLD as compared with healthy controls [450.3 (197.6 to 733.3) vs. 340.8 (141.6 to 697.5) mumol Fe liberated; P=0.04], even though it was similar between NAFLD and diseased controls. Among NAFLD patients, there was no significant correlation between histological grading or staging and levels of pro and antioxidants. CONCLUSIONS: Products of lipid peroxidation are significantly increased among patients with NAFLD as compared with chronic viral hepatitis or healthy controls. Larger studies and newer markers of oxidative stress are required to clarify the association between oxidative stress and histological severity in NAFLD.     

AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions

This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic “hits”.The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (primary liver cancers and extra-hepatic cancers).Moreover, we critically report on the diagnostic role of non-invasive biomarkers, imaging techniques and liver biopsy, which remains the reference standard for diagnosing the disease, but cannot be proposed to all patients with suspected NAFLD.Finally, the management of NAFLD is also reviewed, by highlighting the lifestyle changes and the pharmacological options, with a focus on the innovative drugs.We conclude that the results of ongoing studies are eagerly expected to lead to introduce into the clinical arena new diagnostic and prognostic biomarkers, prevention and surveillance strategies as well as to new drugs for a tailored approach to the management of NAFLD in the individual patient.     

Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD)

Background  

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver diseases, ranging from pure steatosis to nonalcoholic steatohepatitis (NASH), and eventually to liver cirrhosis with its complications. Identifying advanced fibrosis in patients is crucial to evaluating prognosis and possible therapeutic intervention. A novel, simple, and highly accurate scoring system called BARD, which identifies patients with NAFLD and without significant fibrosis, has been recently introduced and validated in North America..The aim of this study is to validate the BARD scoring system in a Polish cohort with NAFLD.     

Correlation of adipose tissue with liver histology in Asian Indian patients with nonalcoholic fatty liver disease (NAFLD)

Background. There is sparse literature on the association of adipose tissue with liver histology in patients with nonalcoholic fatty liver disease (NAFLD).Aim. To study the correlation of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) with liver histology in Indian patients with NAFLD.Material and methods. A single slice CT scan at the level of L4-L5 vertebrae was done to assess the abdominal VAT and SAT volumes in 21 patients with histological diagnosis of NAFLD. Adult treatment panel III criteria with modified abnormal waist were used to define metabolic syndrome (MS). Histological grading was done according to the NAFLD activity score (NAS).Results. Twenty-one patients with NAFLD [13 males, median age: 35 years, median BMI: 25.97 kg/m²] were included prospectively. Even though overweight/obese patients had severe liver disease, there was no difference in the volume of VAT adjusted for BMI between 6 (28.5%) lean and 15 (71.5%) overweight/obese patients. Patients with NASH and borderline NASH were older, obese with higher VAT and SAT volumes than no-NASH group. SAT volume (SATV) correlated significantly with hepatic steatosis but none of the adipose tissue volumes had any correlation with other histological variables. Both SATV and TAT volume (TATV) correlated significantly with severity of liver disease as determined by NAS score whereas presence of MS or insulin resistance had no correlation with histological severity.Conclusion. Both subcutaneous and total adipose tissue volume are related to the disease severity as determined by NAFLD activity score in Indian patients with NAFLD.     

Disease severity predicts higher healthcare costs among hospitalized nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) patients in Spain

The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) presents many public health challenges, including a substantial impact on healthcare resource utilization and costs. There are important regional differences in the burden of NAFLD/NASH, and Spain-specific data are lacking. This retrospective, observational study examined the impact of liver disease severity, comorbidities, and demographics on healthcare resource utilization and costs in Spain.NAFLD/NASH patients in the Spanish National Health System''s Hospital Discharge Records Database (1/1/2006 to 4/30/2017) were categorized into disease severity cohorts as NAFLD/NASH overall, NAFLD/NASH non-progressors, compensated cirrhosis (CC), decompensated cirrhosis (DCC), liver transplant (LT), or hepatocellular carcinoma (HCC). Patients were followed from index date until the earliest of 6 months, disease progression, end of coverage, death, or end of study. Within each cohort, pre- and post-index healthcare resource utilization and costs per patient per month (PPPM) were calculated.A total of 8,205 patients (mean age 58.4; 54% male) were identified; 5,984 (72.9%) were non-progressors, 139 (1.7%) progressed to CC, 2,028 (24.7%) to DCC, 115 (1.4%) to LT, and 61 (0.7%) to HCC. Pre-index comorbidity burden was high across disease cohorts, and the frequency of comorbidities increased with disease severity. From pre- to post-index, average length of stay (LOS) increased significantly (23%–41%) as did all-cause PPPM costs (44%–46%), with significantly longer LOS and costs in patients with increasing disease severity.Progression of NAFLD/NASH was associated with significantly higher costs and longer LOS. A coordinated approach is needed to manage resources and costs in Spain.     

Serum vitamin-E levels and its relation to clinical features in nonalcoholic fatty liver disease with elevated ALT levels

BACKGROUND: Oxidative stress and free oxygen radicals play an important role in the progression from simple fatty liver to steatohepatitis. Deficiency of antioxidants like vitamin-E has been reported to trigger this progression. The main aims of our study were to measure plasma vitamin-E levels in nonalcoholic fatty liver disease (NAFLD), to explain its relationship with biochemical parameters and to examine the possible therapeutic and prophylactic role of vitamin-E. METHODS: 52 patients with NAFLD and elevated liver function tests were enrolled. After 6 months of follow-up with a standard low-fat, low-calorie diet, changes in liver enzymes were evaluated. RESULTS: Deficiency of vitamin-E was detected in 16 patients with NAFLD. Homogenous echo pattern of the liver and attenuation was found to be significantly higher in the low vitamin-E group (p = 0.03). The low vitamin-E group had significantly higher levels of triglyceride (p = 0.02). After 6 months, patients in the low vitamin-E group did not respond to the diet and no decrease in ALT levels was detected (p = 0.04). CONCLUSION: This is the first study measuring the serum vitamin-E levels in nonalcoholic fatty liver disease. A correlation was found between low vitamin-E levels, high triglyceride levels, as well as sonographic findings, both of which are negative prognostic factors causing progression of fatty liver to steatohepatitis. Patients with low vitamin-E levels did not respond to a classical diet for fatty liver disease. Based on the data, we suggest that diet alone is not adequate for patients with fatty liver, and vitamin-E supplementation should be added.     

Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD)

BACKGROUND: Liver fibrosis is the main predictor of the progression of nonalcoholic fatty liver disease. Transient elastography (FibroScan), which measures liver stiffness, is a novel, noninvasive method to assess liver fibrosis. AIM: We investigated the usefulness of liver stiffness measurement in the evaluation of liver fibrosis in nonalcoholic fatty liver disease patients. STUDY POPULATION: A total of 97 nonalcoholic fatty liver disease patients. METHODS: Transient elastography was performed for liver stiffness measurement in 97 nonalcoholic fatty liver disease patients. And the relationship between histological parameters and liver stiffness measurement was studied by multivariate analysis. Moreover, we investigated the relationship between liver stiffness measurement and the serum levels of hyaluronic acid and type IV collagen 7s domain. RESULTS: The liver stiffness was well correlated with the stage of liver fibrosis (Kruskal-Wallis test p < 0.0001). The areas under the receiver-operating characteristic curves were 0.927 for > or = F1, 0.865 for > or = F2, 0.904 for > or = F3, 0.991 for > or = F4. Only fibrosis stage was correlated significantly with liver stiffness measurement by multiple regression analysis. Liver stiffness was also strongly correlated with the serum levels of type IV collagen 7s domain (r = 0.525, p < 0.0001) and hyaluronic acid (r = 0.457, p < 0.0001). CONCLUSIONS: Our results show a significant correlation between liver stiffness measurement and fibrosis stage in nonalcoholic fatty liver disease patients, as confirmed by the results of liver biopsy, which remains the gold standard for evaluation of the severity of liver fibrosis in patients with nonalcoholic steatohepatitis.     

Other disease associations with non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is usually seen in middle-aged women with obesity, non-insulin-dependent diabetes mellitus and/or hyperlipidaemia. NAFLD has also been associated with other conditions. Surgical procedures to treat obesity such as jejunoileal bypass and gastroplasty as well as massive small bowel resection have been associated with NAFLD. Mechanisms such as rapid weight loss, certain nutritional deficiencies and bacterial overgrowth have been proposed. Other nutritional conditions such as extreme malnutrition and total parenteral nutrition can also cause NASH. This can be due to abnormal glucose and fat metabolism, deficiencies like carnitine, essential fatty acid and choline or, in the case of parenteral nutrition, excess of calories, glucose or lipids. Several drugs have also been implicated as well as some inborn errors of metabolism and, more rarely, other diseases.     

亚太地区非酒精性脂肪性肝病诊断与治疗共识简介

NAFLD是指除外过量饮酒和其他明确的损肝因素所致的，以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征。大量流行病学研究表明，NAFLD已成为一种呈现全球化趋势的常见慢性肝病。随着肥胖及其相关代谢紊乱的增多，近10余年来亚太地区NAFLD患病率增长迅速。有限的研究资料显示，