Diagnosis of Non-alcoholic Fatty Liver Disease (NAFLD): Current Concepts

2019 ◽  
Vol 24 (38) ◽  
pp. 4574-4586 ◽  
Author(s):  
Margarita Papatheodoridi ◽  
Evangelos Cholongitas
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Diagnostic Tools ◽  
Routine Practice ◽  
Advanced Fibrosis ◽  
Disease Etiology ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Nafld Fibrosis Score

Nonalcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The majority of NAFLD patients do not progress to NASH and their morbidity risk is low. However, clinical and economic burden of the disease is considerable since the prevalence of the disease is estimated as high as 25% of the general population. Liver biopsy remains the current gold standard for diagnosis, despite limitations regarding sampling variability, invasive nature, and high cost. However, numerous non-invasive biomarkers, including mainly serum markers or imaging modalities, intend to detect the presence of steatosis, NASH or advanced fibrosis. To date, ultrasound is suggested as first-line screening tool for defining steatosis in a selected population, while diagnosis of NAFLD requires exclusion of other chronic liver disease etiology or other steatosis causes. A crucial step in the management of NAFLD patients is the identification of advanced fibrosis, which may be reliably excluded by using NAFLD-Fibrosis score or FIB-4 score or by performing transient elastography. The most robust modalities implement Magnetic Resonance technology and manage to accurately quantify steatosis or identify fibrosis stage, but are not yet applicable in routine practice. The most challenging endpoint has proved to be a non-invasive diagnosis of NASH since no reliable biomarkers have been found to detect or predict inflammation in NAFLD. Lately, research focuses on validating existing markers as robust diagnostic tools for clinical use and investigating novel experimental markers of disease. Current strategies concepts aim to safely diagnose NAFLD patients, aid drug development and finally, guide personalised treatment.

scholarly journals Serum metabolites detect the presence of advanced fibrosis in derivation and validation cohorts of patients with non-alcoholic fatty liver disease

Gut ◽  
2018 ◽  
Vol 68 (10) ◽  
pp. 1884-1892 ◽  
Author(s):  
Cyrielle Caussy ◽  
Veeral H Ajmera ◽  
Puneet Puri ◽  
Cynthia Li-Shin Hsu ◽  
Shirin Bassirian ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Unmet Need ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Serum Metabolites ◽  
Non Invasive ◽  
Nafld Fibrosis Score ◽  
Alcoholic Fatty Liver Disease

ObjectiveNon-invasive and accurate diagnostic tests for the screening of disease severity in non-alcoholic fatty liver disease (NAFLD) remain a major unmet need. Therefore, we aimed to examine if a combination of serum metabolites can accurately predict the presence of advanced fibrosis.DesignThis is a cross-sectional analysis of a prospective derivation cohort including 156 well-characterised patients with biopsy-proven NAFLD and two validation cohorts, including (1) 142 patients assessed using MRI elastography (MRE) and(2) 59 patients with biopsy-proven NAFLD with untargeted serum metabolome profiling.ResultsIn the derivation cohort, 23 participants (15%) had advanced fibrosis and 32 of 652 analysed metabolites were significantly associated with advanced fibrosis after false-discovery rate adjustment. Among the top 10 metabolites, 8 lipids (5alpha-androstan-3beta monosulfate, pregnanediol-3-glucuronide, androsterone sulfate, epiandrosterone sulfate, palmitoleate, dehydroisoandrosterone sulfate, 5alpha-androstan-3beta disulfate, glycocholate), one amino acid (taurine) and one carbohydrate (fucose) were identified. The combined area under the receiver operating characteristic curve (AUROC) of the top 10 metabolite panel was higher than FIB--4 and NAFLD Fibrosis Score (NFS) for the detection of advanced fibrosis: 0.94 (95% CI 0.897 to 0.982) versus 0.78 (95% CI0.674 to 0.891), p=0.002 and versus 0.84 (95% CI 0.724 to 0.929), p=0.017, respectively. The AUROC of the top 10 metabolite panel remained excellent in the independent validation cohorts assessed by MRE or liver biopsy: c-statistic of 0.94 and 0.84, respectively.ConclusionA combination of 10 serum metabolites demonstrated excellent discriminatory ability for the detection of advanced fibrosis in an derivation and two independent validation cohorts with greater diagnostic accuracy than the FIB-4-index and NFS. This proof-of-concept study demonstrates that a non-invasive blood-based diagnostic test can provide excellent performance characteristics for the detection of advanced fibrosis.

scholarly journals Step layered combination of noninvasive fibrosis models improves diagnostic accuracy of advanced fibrosis in nonalcoholic fatty liver disease

2019 ◽  
Vol 28 (3) ◽  
pp. 289-296 ◽  
Author(s):  
Mei Yang ◽  
Lina Jiang ◽  
Yijin Wang ◽  
Xi Li ◽  
Zhengsheng Zou ◽  
...  
Keyword(s):  
Liver Disease ◽  
Diagnostic Accuracy ◽  
Fatty Liver ◽  
Predictive Value ◽  
Fatty Liver Disease ◽  
Validation Cohort ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Nafld Fibrosis Score

Background and Aims: Liver fibrosis is stage-dependently associated with non-alcoholic fatty liver disease (NAFLD) progression. The increased awareness of non-invasive diagnosis has led to the establishment of many fibrosis diagnosis models with various accuracies. We aimed to evaluate the diagnostic performance of nine clinical non-invasive fibrosis models in NAFLD and provide an optimal diagnostic method for advanced fibrosis by step layered combination of non-invasive models. Methods: 453 consecutive patients with biopsy-proven NAFLD were enrolled from three centers and were divided into study cohort and validation cohort randomly. Aspartate aminotransferase-to-platelet ratio index (APRI), BARD, FiB-4, FibroMeter NAFLD, Forns’ Index, Hui model, non-invasive Koeln-Essen- index (NIKEI), S Index and NAFLD fibrosis score (NFS) were calculated. The high area under the receiver operating characteristic curve (AUROC) models were stepwise combined for further diagnosing NAFLD advanced fibrosis. Results: All models had good performance with high negative predictive value (NPV) and specificity for diagnosing fibrosis, while positive predictive value (PPV) and sensitivity were low. APRI, BARD, FibroMeter NAFLD and NIKEI had higher AUROCs and their step layered combination for diagnosing advanced fibrosis showed high specificity, sensitivity, NPV and PPV up to 89.13%, 72.50%, 74.36%, and 88.17%, which also performed well in the validation cohort. Conclusions: APRI, BARD, FibroMeter NAFLD and NIKEI had better diagnostic accuracy, and could be preferred for diagnosing NAFLD fibrosis. The step layered combination of these models performed much better than each single scoring system for diagnosing advanced fibrosis, provides valuable reference for clinical practice and might be a potential substitution of liver biopsy.

scholarly journals Simple non-invasive biomarkers of advanced fibrosis in the evaluation of non-alcoholic fatty liver disease

2014 ◽  
Vol 2 (4) ◽  
pp. 276-280 ◽  
Author(s):  
E. B. Tapper ◽  
K. Krajewski ◽  
M. Lai ◽  
T. Challies ◽  
R. Kane ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

scholarly journals The Validation of Conventional Non-Invasive Fibrosis Scoring Systems in Patients with Metabolic Associated Fatty Liver Disease

2020 ◽  
Author(s):  
Yinlian Wu ◽  
Rahul Kumar ◽  
Mingfang Wang ◽  
Medha Singh ◽  
Jiaofeng Huang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Characteristic Curve ◽  
Scoring Systems ◽  
Advanced Fibrosis ◽  
Discrimination Ability ◽  
Non Invasive ◽  
Nafld Fibrosis Score ◽  
The Difference

Abstract Background：Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease (MAFLD). This study evaluated the diagnostic performance of four non-invasive scores including AST to platelet ratio index (APRI), fibrosis-4 index (FIB-4), BMI, AST/ALT ratio, and diabetes score (BARD), and NAFLD fibrosis score(NFS) in patients with MAFLD.Methods: Consecutive patients with histologically-confirmed MAFLD were included. The discrimination ability of different non-invasive scores was compared.Results: A total of 417 patients were included, 156 (37.4%) of them had advanced fibrosis (METAVIR ≥F3). The area under receiver operating characteristic curve (AUROC) of FIB-4, NFS, APRI and BARD for predicting advanced fibrosis were 0.736, 0.724, 0.671 and 0.609 respectively. The AUROC between FIB-4 and NFS were similar (P=0.523), while the difference between FIB-4 and APRI (P=0.001) and FIB-4 and BARD (P<0.001) was statistically significant. The best thresholds of FIB-4，NFS，APRI and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05, -2.1, 0.42 and 2. A subgroup analysis showed that FIB-4, APRI and NFS performed worse in pure MAFLD than HBV-MAFLD group.Conclusions: APRI and BARD score do not perform well in MAFLD. The FIB-4 and NFS could be more useful but new threshold is needed. Novel non-invasive scoring system for fibrosis is required for MAFLD.

scholarly journals Diagnosis of Fibrosis Using Blood Markers and Logistic Regression in Southeast Asian Patients With Non-alcoholic Fatty Liver Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Sang ◽  
Hongmei Yan ◽  
Wah Kheong Chan ◽  
Xiaopeng Zhu ◽  
Tao Sun ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Nafld Fibrosis Score ◽  
Glutamyl Transferase ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of fibrosis. Liver biopsy remains the gold standard for the confirmation of fibrosis in NAFLD patients. Effective and non-invasive diagnosis of advanced fibrosis is essential to disease surveillance and treatment decisions. Herein we used routine medical test markers and logistic regression to differentiate early and advanced fibrosis in NAFLD patients from China, Malaysia, and India (n1 = 540, n2 = 147, and n3 = 97) who were confirmed by liver biopsy. Nine parameters, including age, body mass index, fasting blood glucose, presence of diabetes or impaired fasting glycemia, alanine aminotransferase, γ-glutamyl transferase, triglyceride, and aspartate transaminase/platelet count ratio, were selected by stepwise logistic regression, receiver operating characteristic curve (ROC), and hypothesis testing and were used for model construction. The area under the ROC curve (auROC) of the model was 0.82 for differentiating early and advanced fibrosis (sensitivity = 0.69, when specificity = 0.80) in the discovery set. Its diagnostic ability remained good in the two independent validation sets (auROC = 0.89 and 0.71) and was consistently superior to existing panels such as the FIB-4 and NAFLD fibrosis score. A web-based tool, LiveFbr, was developed for fast access to our model. The new model may serve as an attractive tool for fibrosis classification in NAFLD patients.

Evaluation of MicroRNA-122 as A Non-invasive Diagnostic Biomarker For Non-Alcoholic Fatty Liver Disease and NASH related Cirrhosis

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nevine Ibrahim Musa ◽  
Sara Hassan Agwa ◽  
Heba Ahmed Faheem ◽  
Ahmed Mohamed Gharib Alam El-din
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Invasive Technique ◽  
University Hospitals ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Nafld Fibrosis Score ◽  
Normal Controls

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. NAFLD is considered to represent the hepatic manifestation of metabolic syndrome. NAFLD was traditionally considered as a relatively benign liver disease. However, some patients with NAFLD progress to liver fibrosis, cirrhosis and hepatocellular carcinoma 8-13. Therefore, the precise diagnosis and staging of NAFLD patients is clinically important. Liver biopsy is the gold standard for the evaluation of NAFLD patients in terms of staging. However, liver biopsy is an invasive technique, and the identification of noninvasive biomarkers is required. Objective To assess the value of MicroRNA-122 as a non-invasive biomarker for diagnosis of NAFLD and NASH related Cirrhosis. Patients and Methods In the present study, we assess the value of MicroRNA-122 as a noninvasive biomarker for diagnosis of NAFLD and NASH related Cirrhosis. Gastroenterology and Hepatology outpatient clinic at: Ain Shams University Hospitals, Shebin El-Kom Teaching Hospital, Kafr Elsheikh University Hospitals. Clinical Pathology department at Faculty of Medicine, Ain Shams University. Results Patients with NASH had higher NAFLD score than patients with NAFLD than normal control. Patients with NASH had significantly higher frequency of upregulated miRNA-22. Patients with NASH had higher miRNA 122 expression than normal controls and patients with NAFLD. Likewise, patients with NAFLD had higher miRNA 122 expression than normal controls. The miRNA 122 was a significant discriminator of NAFLD and NASH with a sensitivity of 75% and specificity of 82% for NAFLD and a sensitivity of 91% and specificity of 86% for the NASH. Conclusion miRNA-122 is a sensitive and specific biomarker in the early detection of NAFLD and NASH as they are linked to the lipid metabolism reducing the need for liver biopsy. NAFLD fibrosis score had high sensitivity in differentiating the NAFLD groups from the control group and in differentiating the steatosis group from the NASH group. Serum levels of miRNA-122 were positively correlated with BMI, ALT and AST.

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