Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease

AIM:To investigate a simple noninvasive scoring system for predicting liver cirrhosis in nonalcoholic fatty liver disease(NAFLD)patients.METHODS:A total of 1048 patients with liver-biopsyconfirmed NAFLD were enrolled from nine hepatology centers in Japan(stage 0,216;stage 1,334;stage 2,270;stage 3,190;stage 4,38).The weight and height of the patients were measured using a calibrated scale after requesting the patients to remove their shoes and any heavy clothing.Venous blood samples were obtained in the morning after the patients had fasted overnight for 12 h.Laboratory evaluation was performed in all patients.Statistical analysis was conducted using SPSS version 12.0.Continuous variables were expressed as mean±SD.RESULTS:The optimal cutoff value of platelet count,serum albumin,and aminotransferase/alanine aminotransferase ratio(AAR)was set at<15.3 104/μL,<4.0g/dL,and>0.9,respectively,by the receiver operating characteristic curve.These three variables were combined in an unweighted sum(platelet count=1 point,serum albumin=1 point,AAR=1 point)to form an easily calculated composite score for predicting cirrhosis in NAFLD patients,called the PLALA(platelet,albumin,AAR)score.The diagnosis of PLALA≥2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients.CONCLUSION:The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.     

Proposal for a histological scoring and grading system for non-alcoholic fatty liver disease.

AIM/BACKGROUND: The spectrum of histopathological features in non-alcoholic fatty liver disease (NAFLD) has been well described. At least two scoring systems have been established. We propose here a system in which numerical scores are obtained using the different features. METHODS: Twenty-five cases of well-defined NAFLD were identified. Two pathologists blinded to identifiers and clinical data independently scored the liver biopsies twice for portal fibrosis (PF: 0-6), lobular inflammation and necrosis (LIN: 0-3), Mallory bodies (MB: 0-3), hepatocyte ballooning (HB: 0-3), perisinusoidal fibrosis (PSF: 0-3) and fatty change (FC: 1-4). The kappa statistic tested observer concordance. Non-parametric measures of correlation and hierarchical cluster analysis were used to elaborate a grading system. RESULTS: A broad spectrum of NAFLD was observed. Intra- and interobserver concordance was satisfactory. An activity score was created (AS: 0-12) as the sum of LIN, MB, HB and PSF, but not FC. A system for severity of NAFLD was developed: Grade 1 (PF: 0-2 and AS: 0-4), Grade 2 (PF: 3 or AS: 5-7) and Grade 3 (PF: 4-6 or AS: 8-12). Diabetes, elevated alkaline phosphatase and decreased platelets were associated with advanced grade. CONCLUSIONS: This simple, reproducible NAFLD score produces a three-tier severity grade. This numerical system may prove useful in assessing disease severity and interval changes.     

内源性大麻系统与非酒精性脂肪肝

非酒精性脂肪肝（NAFLD）是一种以肝脏脂肪浸润、肝细胞炎症坏死为特征的慢性疾病。Nayak等、报道大约2／3的隐匿性肝硬化患者是由非酒精性脂肪肝所致。随着我国大众营养条件改善,生活习惯改变,NAFLD发病率逐年上升。     

Association between endotoxemia and histological features of nonalcoholic fatty liver disease

AIM To assess whether surrogate biomarkers of endotoxemia were correlated with the histological features ofnonalcoholic fatty liver disease(NAFLD).METHODS One hundred twenty-six NAFLD patients who had undergone percutaneous liver biopsy were enrolled. Serum lipopolysaccharide(LPS)-binding protein(LBP) and anti-endotoxin core immunoglobulin G(Endo Cab Ig G) antibody concentrations at the time of liver biopsy were measured using the enzyme-linked immunosorbent assays to examine for relationships between biomarker levels and histological scores. RESULTS Serum LBP concentration was significantly increased in nonalcoholic steatohepatitis(NASH) patients as compared with nonalcoholic fatty liver(NAFL) subjects and was correlated with steatosis(r = 0.38, P 0.0001) and ballooning scores(r = 0.23, P = 0.01), but not with the severity of lobular inflammation or fibrosis. Multivariate linear regression analysis revealed that LBP was associated with steatosis score and circulating C-reactive protein, aspartate aminotransferase, and fibrinogen levels. Serum Endo Cab Ig G concentration was comparable between NASH and NAFL patients. No meaningful correlations were detected between Endo Cab Ig G and histological findings. CONCLUSION LBP/Endo Cab Ig G were not correlated with lobular inflammation or fibrosis. More accurate LPS biomarkers are required to stringently assess the contribution of endotoxemia to conventional NASH.     

Development and validation of machine learning models for nonalcoholic fatty liver disease

Background: Nonalcoholic fatty liver disease(NAFLD) had become the most prevalent liver disease worldwide. Early diagnosis could effectively reduce NAFLD-related morbidity and mortality. This study aimed to combine the risk factors to develop and validate a novel model for predicting NAFLD. Methods: We enrolled 578 participants completing abdominal ultrasound into the training set. The least absolute shrinkage and selection operator(LASSO) regression combined with random forest(RF) was conducted...     

The clinical utility of biomarkers and the nonalcoholic steatohepatitis CRN liver biopsy scoring system in patients with nonalcoholic fatty liver disease

Background and Aims:  We identified patients with nonalcoholic fatty liver disease (NAFLD) to determine the predictive value of serum markers to diagnose histological steatohepatitis (NASH).
Methods:  Demographic, serological, radiological and histological variables on 95 consecutive patients with NAFLD were recorded. The serum markers studied were CK18, Hyaluronic acid, TIMP 1 and YKL 40. The NAS score and the metavir score were the histological scoring systems used.
Results:  CK18 levels were higher in the NASH group compared to the simple steatosis group (394 ± 53 µ/L vs 194 ± 26 µ/L; P  < 0.05). In assessing clinical effectiveness, CK18 yielded an AUC of 0.8 for NASH (cut-off value 300 µ/L gives PPV 81% and NPV 85%).The fibrosis markers showed no differences between groups. We stratified the same cohort according to liver fibrosis (F0 vs F1–F4). Fibrosis was associated with advanced age, high body mass index and type 2 diabetes. The biomarkers performed relatively poorly at identifying liver fibrosis (F1–F4), with HA performing the best (AUC 0.73); performance improved for advanced fibrosis (F3/F4) - (HA: AUC 0.77). The NAS score performed the best overall at identifying liver fibrosis (AUC 0.79).
Discussion:  CK18 is the only biomarker studied that can identify NASH. Additionally, liver biopsy should be performed in all high risk patients to determine the standardised NAS score to identify patients at high risk of disease progression.     

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.     

非酒精性脂肪性肝病的药物治疗

非酒精性脂肪性肝病(以下简称脂肪肝)的病因和发病机制较复杂,迄今尚未完全明了,因此,目前临床上缺乏针对脂肪肝治疗的有效药物。脂肪肝的治疗,多数学者认为重点在于去除病因,治疗原发疾病;调整饮食,修整不良行为,合理运动,辅以一定的药物治疗。根据脂肪肝发生发展的不同阶段,相关的发病机制以及突出的临床表现和异常的实验室结果酌情进行药物选择。 胰岛素抵抗、游离脂肪酸增加引发的糖脂代谢紊乱是脂肪肝形成的第一次打击。改善胰岛素抵抗,糖脂代谢异常,可望阻止肝细胞从脂肪变性向脂肪性肝炎发展。二氯醋酸二异丙胺     

Genes and nonalcoholic fatty liver disease

Whereas most individuals with nonalcoholic fatty liver disease (NAFLD) will have steatosis, only a minority will ever develop progressive disease. Family studies and interethnic variations in susceptibility suggest that genetic factors may be important in determining disease risk. Although no genetic associations with advanced NAFLD have been replicated in large studies, preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, tumor necrosis factor-α, transforming growth factor-β, and angiotensinogen may be associated with steatohepatitis and/or fibrosis. With the advent of high-throughput gene analyses and the reduced cost of whole genomewide scans, it seems likely that genes contributing to inherited susceptibility to this common disease will be identified in the near future.     

炎症与非酒精性脂肪性肝病

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是代谢综合征的肝脏组分.代谢综合征代表慢性炎症状态,代谢综合征患者会呈现不同的免疫异常.脂肪组织的天然免疫功能紊乱导致机体产生异常的脂肪源性因子.某些因子抑制肝脏脂质清除,促进其在肝细胞内蓄积,产生脂肪变性.后者在肝脏先天性免疫系统发生Th-1极化的基础上诱导肝脏产生更多的致炎细胞因子,促进了非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)的形成.但由于Th-2等其他细胞因子减少,尽管肝脏持续暴露于这些可以促进多种促纤维生成因子产生的致炎因子,NASH发展成肝硬化的现象却相对少见.     

Ethnicity and nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in the United States; however, few data are available about racial and ethnic variation. We investigated relationships between ethnicity, NAFLD severity, metabolic derangements, and sociodemographic characteristics in a well-characterized cohort of adults with biopsy-proven NAFLD. Data were analyzed from 1,026 adults (≥18 years) in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) from 2004 to 2008, for whom liver histology data were available within 6 months of enrollment. Associations between ethnicity (i.e., Latino versus non-Latino white) and NAFLD severity (i.e., NASH versus non-NASH histology and mild versus advanced fibrosis) were explored with multiple logistic regression analysis. We also investigated effect modification of ethnicity on metabolic derangements for NAFLD severity. Within the NASH CRN, 77% (N = 785) were non-Latino white and 12% (N = 118) were Latino. Sixty-one percent (N = 628) had NASH histology and 28% (N = 291) had advanced fibrosis. Latinos with NASH were younger, performed less physical activity, and had higher carbohydrate intake, compared to non-Latino whites with NASH. Gender, diabetes, hypertension, hypertriglyceridemia, aspartate aminotransferase (AST), platelets, and the homeostasis model assessment of insulin resistance (HOMA-IR) were significantly associated with NASH. Age, gender, AST, alanine aminotransferase, alkaline phosphatase, platelets, total cholesterol, hypertension, and HOMA-IR, but not ethnicity, were significantly associated with advanced fibrosis. The effect of HOMA-IR on the risk of NASH was modified by ethnicity: HOMA-IR was not a significant risk factor for NASH among Latinos (odds ratio [OR] = 0.93; 95% confidence interval [CI]: 0.85-1.02), but was significant among non-Latino whites (OR, 1.06; 95% CI: 1.01-1.11). CONCLUSION: Metabolic risk factors and sociodemographic characteristics associated with NASH differ by ethnicity. Additional insights into NASH pathogenesis may come from further studies focused on understanding ethnic differences in this disease.     

罗格列酮与非酒精性脂肪性肝病

脂肪性肝病(FLD)是遗传-环境-代谢应激相关因素所致的以肝细胞脂肪变性为主的临床病理综合征.FLD包括酒精性肝病(ALD)和非酒精性脂肪性肝病(NAFLD).随着社会经济的发展,生活水平的提高,NAFLD已成为健康体格检查肝功能异常的主要原因.     

Sirtuins and nonalcoholic fatty liver disease

Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class Ⅲ histone/protein deacetylases. Sirtuins(SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function. Sirtuins have been shown to play a key role in the development and rescue of various metabolic diseases including non-alcoholic fatty liver disease(NAFLD). NAFLD is currently the most chronic liver disease due mainly to high-calorie consumption and lower physical activity. No pharmacological approach is available to treat NAFLD, the current recommended treatment are lifestyle modification such as weight loss through calorie restriction and exercise. Recent studies have shown downregulation of sirtuins in human as well as animal models of NAFLD indicating an important role of sirtuins in the dynamic pathophysiology of NAFLD. In this review, we highlight the recent knowledge on sirtuins, their role in NAFLD and their unique potential role as novel therapeutic target for NAFLD treatment.     

New treatments for nonalcoholic fatty liver disease

The majority of patients with nonalcoholic fatty liver disease are overweight and obese, lead relatively sedentary lifestyles, and have underlying insulin resistance. Treatment aimed at improving body weight and activity should be the cornerstone of our therapeutic armamentarium in combating this disease. Evidence suggests that diets low in processed carbohydrates and saturated fats with a goal to achieve a 500-to 1000-calorie/day deficit improve insulin sensitivity, reduce serum aminotransferases, and decrease hepatic steatosis. Encouragingly, improvements are seen with as little as a 5% reduction in body weight. Histopathologic parameters of steatohepatitis also appear to improve with weight loss. Antioxidant supplementation, specifically with vitamin E, may be considered as adjunctive therapy. Other antioxidants and the thiazolidinediones (pioglitazone and rosiglitazone) appear to be efficacious, but larger confirmatory studies are needed to ensure they are safe and beneficial in patients with nonalcoholic steatohepatitis. Novel agents such as renin-angiotensin system inhibitors may eventually prove to be efficacious as well. Future treatment for patients failing to achieve weight loss goals is likely to consist of combination therapy targeting insulin resistance, oxidative stress, and fibrogenesis.     

非酒精性脂肪肝的药物治疗

非酒精性脂肪肝目前尚无疗效理想的治疗药物，希望能够做到的仅仅是改善胰岛素抵抗，维护机体内环境脂质代谢、能量代谢和抗氧化物的平衡，促使机体保持在适应性反应阶段，延缓、阻止脂肪性肝病的病情进展。     

非酒精性脂肪性肝病的治疗策略

非酒精性脂肪性肝病(NAFLD)不仅可导致肝病相关残疾和死亡,而且与动脉粥佯硬化性心脑血管事件的高发密切相关。为此,必须重视NAFLD的防治,遗憾的是至今尚乏治疗NAFLD的特效药物,现主要根据患者的具体病情采取个体化的三阶梯疗法。 第一阶梯为基础治疗,适用于各种类型的NAFLD病例,具体包括:①改变生活方式,如节食、运动、禁酒、戒烟;②去除病因和诱因,停用肝毒药物和避免接触肝毒物质,以及纠正肠道菌群紊乱;③控制原发基础疾病或伴随疾病,旨在通过上     

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.     

Current treatment options for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.