Article

Design and validation of a histological scoring system for nonalcoholic fatty liver disease

Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA.
Hepatology (Impact Factor: 11.19). 06/2005; 41(6):1313-21. DOI: 10.1002/hep.20701
Source: PubMed

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."

1 Follower
 · 
352 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background It is widely known that salt is an accelerating factor for the progression of metabolic syndrome and causes cardiovascular diseases, most likely due to its pro-oxidant properties. We hypothesized that excessive salt intake also facilitates the development of nonalcoholic steatohepatitis (NASH), which is frequently associated with metabolic syndrome. Methods We examined the exacerbating effect of high-salt diet on high-fat diet-induced liver injury in a susceptible model to oxidative stress, apoE knockout and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transgenic mice. Results High-salt diet led to NASH in high-fat diet-fed LOX-1 transgenic/apoE knockout mice without affecting high-fat diet-induced dyslipidemia or hepatic triglyceride accumulation. Additionally, a high-salt and high-fat diet stimulated oxidative stress production and inflammatory reaction to a greater extent than did a high-fat diet in the liver of LOX-1 transgenic/apoE knockout mice. Conclusions We demonstrated that high-salt diet exacerbated NASH in high-fat diet-fed LOX-1 transgenic /apoE knockout mice and that this effect was associated with the stimulation of oxidative and inflammatory processes; this is the first study to suggest the important role of excessive salt intake in the development of NASH. Electronic supplementary material The online version of this article (doi:10.1186/s12944-015-0002-9) contains supplementary material, which is available to authorized users.
    Lipids in Health and Disease 02/2015; 14. DOI:10.1186/s12944-015-0002-9 · 2.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthetase. Elevated ADMA reduces NO formation and is associated with endothelial dysfunction. The aims of this study were to evaluate endothelial function and the cardiovascular risk (CVR) profile in patients with non-alcoholic fatty liver disease (NAFLD), and to determine whether or not an association with metabolic syndrome (MS) increases these parameters. A total of 100 consecutive patients with NAFLD, who were seen in Liver Disease Outpatient clinic and 45 age- and sex-matched controls were included. Endothelial function was evaluated based on the serum ADMA level measured using a validated ELISA kit (DLD Diagnostika GMBH, Hamburg, Germany) and flow-mediated vasodilatation (FMV) measured via high-resolution external ultrasonography. The CVR profile was calculated according to the Framingham equation. At baseline there weren't any significant differences in brachial artery diameter between the NAFLD and control groups (3.7 ± 0.6 mm vs. 3.6 ± 0.6 mm, respectively). FMV and flow-independent vasodilatation in response to sublingual nitroglycerin did not differ between the NAFLD and control groups (mean: 16% ± 9.4% vs. 17.9% ± 12.4%, and 21.4% ± 14% vs. 17.8% ± 11.3%, respectively, p > 0.05). No significant difference in the serum ADMA concentration between the NAFLD and control groups was observed (mean: 0.8 ± 0.07 μmol L(-1) vs. 0.74 ± 0.2 μmol L(-1), respectively). The CVR profile was significantly higher in the NAFLD group than in the control group (mean: 9% ± 6.9% vs. 4.6% ± 3.8%, P = 0.000). MS associated with NAFLD significantly increased the CVR profile (mean: 11.2% ± 7.4%, P = 0.000). An abnormal serum alanine aminotransferase level (>37 IU L(-1)) and the presence of fibrosis did not increase the CVR profile (p > 0.05). The risk of cardiovascular events is increased in patients with NAFLD. The association with MS is further increased such risk.
    Diabetology and Metabolic Syndrome 10/2014; 6. DOI:10.1186/1758-5996-6-109 · 2.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Relationship between adipose tissue and fatty liver, and its possible evolution in fibrosis, is supported by clinical and research experience. Given the multifactorial pathogenesis of non-alcoholic fatty liver disease (NAFLD), treatments for various contributory risk factors have been proposed; however, there is no single validated therapy or drug association recommended for all cases which can stand alone. Mechanisms, diagnostics, prevention and treatment of obesity, fatty liver and insulin resistance are displayed along with recommendations and position points. Evidences and practice can get sustainable and cost-benefit valuable outcomes by participatory interventions. These recommendations can be enhanced by comprehensive research projects, addressed to societal issues and innovation, market appeal and industry development, cultural acceptance and sustainability. The basis of participatory medicine is a greater widespread awareness of a condition which is both a disease and an easy documented and inclusive clue for associated diseases and unhealthy lifestyle. This model is suitable for addressing prevention and useful for monitoring improvement, worsening and adherence with non-invasive imaging tools which allow targeted approaches. The latter include health psychology and nutritional and physical exercise prescription expertise disseminated by continuous medical education but, more important, by concrete curricula for training undergraduate and postgraduate students. It is possible and recommended to do it by early formal teaching of ultrasound imaging procedures and of practical lifestyle intervention strategies, including approaches aimed to healthier fashion suggestions. Guidelines and requirements of research project funding calls should be addressed also to NAFLD and allied conditions and should encompass the goal of training by research and the inclusion of participatory medicine topics. A deeper awareness of ethics of competences in health professionals and the articulation of knowledge, expertise and skills of medical doctors, dieticians, health psychologists and sport and physical exercise graduates are the necessary strategy for detectin a suboptimal health status and achieving realistically beneficial lifestyle changes. "The devil has put a penalty on all things we enjoy in life. Either we suffer in health or we suffer in soul or we get fat" (Albert Einstein); the task of medical research and intervention is to make possible to enjoy life also without things that make sufferance in health and souls and which excessively increase body fat.
    12/2014; 5(1):21. DOI:10.1186/1878-5085-5-21

Full-text (2 Sources)

Download
1,595 Downloads
Available from
May 20, 2014