Diagnostic and interventional circulating biomarkers in nonalcoholic steatohepatitis

IntroductionIn the setting of the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent forms of chronic liver disease worldwide. Approximately 25% of adults globally have NAFLD which includes those with NAFL, or simple steatosis, and individuals with nonalcoholic steatohepatitis (NASH) where inflammation, hepatocyte injury and potentially hepatic fibrosis are found in conjunction with steatosis. Individuals with NASH, particularly those with hepatic fibrosis, have higher rates of liver‐related and overall mortality, making this distinction of significant clinical importance. One of the core challenges in current clinical practice is identifying this subset of individuals with NASH without the use of liver biopsy, the gold standard for both diagnostics and staging disease severity. Identifying noninvasive biomarkers, an accurately measured and reproducible parameter, would aide in identifying patients eligible for NASH pharmacotherapy clinical trials and to help tailor intensity of monitoring required.Methods, Results and ConclusionsIn this review, we highlight both the currently available and novel diagnostic and interventional circulating biomarkers under investigation for NASH, underscoring their accuracy and limitations relevant to our patient population and current clinical practice.One of the core challenges in NASH is the ability to accurately diagnose and stage individuals using non‐invasive methods. In this review, we highlight both the currently available and novel diagnostic and interventional circulating biomarkers under investigation for NASH, underscoring their accuracy and limitations relevant to our patient population and current clinical practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163493/2/edm2177.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163493/1/edm2177_am.pd

Cost-effectiveness of NASH screening

La stéatose hépatique non alcoolique (NAFLD) est la cause d’hépatopathie chronique la plus fréquente dans les pays occidentaux. Aucune étude n’a vérifié le rapport coûtefficacité du dépistage pour la stéatohépatite non-alcoolique (NASH), le stade avancé de la maladie. Nous avons réalisé une analyse coût-utilité des stratégies annuelles non invasives de dépistage, utilisant une perspective d’un système de soins canadien, dans la population générale et l’avons comparé à une population à haut risque composée de patients obèses et diabétiques. Les algorithmes de dépistage incluent des techniques bien étudiées notamment le «NAFLD fibrosis score», la technique «transient elastography» (TE), et l’imagerie «acoustic radiation force impulse» (ARFI) pour la détection de la fibrose avancée (≥ F3); et le test «plasma cytokeratin-18» (CK-18) pour la détection de la NASH. La biopsie du foie et l’élastographie par résonance magnétique (MRE) ont été comparées comme méthodes de confirmation. Les coûts en dollars canadiens furent corrigés en fonction de l’inflation et actualisés à un taux d'actualisation de 5%. Un rapport coût-efficacité différentiel (ICER) de ≤$C50,000 / année de vie pondérée par la qualité (QALY) a été considéré comme coûtefficace. Nous avons trouvé que par rapport à la stratégie sans dépistage annuel, le dépistage annuel avec l’algorithme NAFLD fibrosis score/TE/CK-18 et avec MRE comme méthode de confirmation pour la fibrose avancée, a donné un ICER de$C26,143 par année de vie pondérée par la qualité (QALY) gagnée. Le dépistage annuel dans les populations à haut risque obèses et diabétiques était encore plus coût-efficace, avec un ICER de $C9,051 et$C7,991 par QALY gagnée respectivement. La confirmation avec la biopsie du foie n’était pas coût-efficace. Notre modèle indique que le dépistage annuel pour la NASH peut être coût-efficace, particulièrement dans les populations obèses et diabétiques à haut risque.Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. No studies have examined the cost-effectiveness of screening for nonalcoholic steatohepatitis (NASH), its advanced form. We performed a cost-utility analysis of annual non-invasive screening strategies using third-party payer perspective in a general population and compared it to screening in a highrisk obese or diabetic population. Screening algorithms involved well-studied techniques including NAFLD fibrosis score, transient elastography (TE), and acoustic radiation force impulse (ARFI) imaging for detecting advanced fibrosis (≥ F3); and plasma cytokeratin-18 for NASH detection. Liver biopsy and magnetic resonance elastography (MRE) were compared as confirmation methods. Canadian dollar costs were adjusted for inflation and discounted at a 5% rate. Incremental cost-effectiveness ratio (ICER) of ≤$C50,000 / quality adjusted life year (QALY) was considered cost-effective. Compared with no screening, screening with NAFLD fibrosis score/TE/CK-18 algorithm with MRE as confirmation for advanced fibrosis had an ICER of$C26,143 per quality-adjusted life year (QALY) gained. Screening in high-risk obese or diabetic populations was more cost-effective, with an ICER of $C9,051 and$C7,991 per QALY gained respectively. Liver biopsy confirmation was not found to be cost-effective. Our model suggests that annual NASH screening can be cost-effective, particularly in high-risk obese or diabetic populations

Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy. NAFLD covers a spectrum that ranges from simple steatosis, nonalcoholic steatohepatitis (NASH) with varying degrees of fibrosis, to cirrhosis, which is a major risk factor for hepatocellular carcinoma. Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity, type 2 diabetes mellitus and dyslipidemia, with a global prevalence of 25%. NAFLD arises when the uptake of fatty acids (FA) and triglycerides (TG) from circulation and de novo lipogenesis saturate the rate of FA β-oxidation and very-low density lipoprotein (VLDL)-TG export. Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH, and therefore, alterations in liver and serum lipidomic signatures are good indicators of the disease's development and progression. This review focuses on the importance of the classification of NAFLD patients into different subtypes, corresponding to the main alteration(s) in the major pathways that regulate FA homeostasis leading, in each case, to the initiation and progression of NASH. This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments

Imaging biomarkers for steatohepatitis and fibrosis detection in non-alcoholic fatty liver disease

There is a need, in NAFLD management, to develop non-invasive methods to detect steatohepatitis (NASH) and to predict advanced fibrosis stages. We evaluated a tool based on optical analysis of liver magnetic resonance images (MRI) as biomarkers for NASH and fibrosis detection by investigating patients with biopsy-proven NAFLD who underwent magnetic resonance (MR) protocols using 1.5T General Electric (GE) or Philips devices. Two imaging biomarkers (NASHMRI and FibroMRI) were developed, standardised and validated using area under the receiver operating characteristic curve (AUROC) analysis. The results indicated NASHMRI diagnostic accuracy for steatohepatitis detection was 0.83 (95% CI: 0.73–0.93) and FibroMRI diagnostic accuracy for significant fibrosis determination was 0.85 (95% CI: 0.77–0.94). These findings were independent of the MR system used. We conclude that optical analysis of MRI has high potential to define non-invasive imaging biomarkers for the detection of steatohepatitis (NASHMRI) and the prediction of significant fibrosis (FibroMRI) in NAFLD patients.Comisión Europea, 7º Programa Marco FP7/2007–2013 HEALTH-F2-2009-241762 Project Fatty Liver Inhibition of Progression (FLIP)Junta de Andalucía, Consejería de Salud PI-0488-2012/201

The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases

This guidance provides a data-supported approach to the diagnostic, therapeutic, and preventive aspects of NAFLD care. A “Guidance” document is different from a “Guideline.” Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation (GRADE) system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence