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 ◽  
...  

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.

2020 ◽  
Vol 1 (5) ◽  
Author(s):  
Valerio Rosato ◽  
Mario Masarone ◽  
Andrea Aglitti ◽  
Marcello Persico

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver alteration worldwide. It encompasses a spectrum of disorders that range from simple steatosis to a progressive form, defined non-alcoholic steatohepatitis (NASH), that can lead to advanced fibrosis and eventually cirrhosis and hepatocellular carcinoma. On liver histology, NASH is characterized by the concomitant presence of significant fat accumulation and inflammatory reaction with hepatocellular injury. Until now, liver biopsy is still required to differentiate simple steatosis from NASH and evaluate the degree of liver fibrosis. Unfortunately, this technique has well-known limitations, including invasiveness and expensiveness. Moreover, it may be biased by sampling error and intra- or inter-observed variability. Furthermore, due to the increasing prevalence of NAFLD worldwide, to program a systematic screening with liver biopsy is not imaginable. In recent years, different techniques were developed and validated with the aim of non-invasively identifying NASH and assess liver fibrosis degrees. The non-invasive tests range from simple blood-tests analyses to composite scores and complex imaging techniques. Nevertheless, even if they could represent cost-effective strategies for diagnosing NASH, advanced fibrosis and cirrhosis, their accuracy and consequent usefulness are to be discussed. With this aim, in this review the authors summarize the current state of non-invasive assessment of NAFLD. In particular, in addition to the well-established tests, the authors describe the future perspectives in this field, reporting the latest tests based on OMICS, gut-miocrobioma and micro-RNAs. Finally, the authors provide an accurate assessment of how these non-invasive tools perform in clinical practice depending on the clinical context, with the aim of giving the clinicians a useful tool to try to resolve the diagnostic conundrum of NAFLD.


Gut ◽  
2018 ◽  
Vol 68 (10) ◽  
pp. 1884-1892 ◽  
Author(s):  
Cyrielle Caussy ◽  
Veeral H Ajmera ◽  
Puneet Puri ◽  
Cynthia Li-Shin Hsu ◽  
Shirin Bassirian ◽  
...  

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.


2020 ◽  
Vol 26 (32) ◽  
pp. 3928-3938
Author(s):  
Grazia Pennisi ◽  
Ciro Celsa ◽  
Antonina Giammanco ◽  
Federica Spatola ◽  
Salvatore Petta

Non-alcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver diseases worldwide, involving about 25% of people. NAFLD incorporates a large spectrum of pathological conditions, from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and its complications include hepatic decompensation and hepatocellular carcinoma (HCC). This progression occurs, over many years, in an asymptomatic way, until advanced fibrosis appears. Thus, the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis are key issues. To date, the histological assessment of fibrosis with liver biopsy is the gold standard, but obviously, invasiveness is the greater threshold. In addition, rare but potentially life-threatening complications, poor acceptability, sampling variability and cost maybe restrict its use. Furthermore, due to the epidemic of NAFLD worldwide and several limitations of liver biopsy evaluation, noninvasive assessment tools to detect fibrosis in NAFLD patients are needed.


2021 ◽  
Vol 10 (11) ◽  
pp. 2415
Author(s):  
Yasaman Vali ◽  
Jenny Lee ◽  
Jérôme Boursier ◽  
René Spijker ◽  
Joanne Verheij ◽  
...  

(1) Background: FibroTest™ is a multi-marker panel, suggested by guidelines as one of the surrogate markers with acceptable performance for detecting fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). A number of studies evaluating this test have been published after publication of the guidelines. This study aims to produce summary estimates of FibroTest™ diagnostic accuracy. (2) Methods: Five databases were searched for studies that evaluated FibroTest™ against liver biopsy as the reference standard in NAFLD patients. Two authors independently screened the references, extracted data, and assessed the quality of included studies. Meta-analyses of the accuracy in detecting different levels of fibrosis were performed using the bivariate random-effects model and the linear mixed-effects multiple thresholds model. (3) Results: From ten included studies, seven were eligible for inclusion in our meta-analysis. Five studies were included in the meta-analysis of FibroTest™ in detecting advanced fibrosis and five in significant fibrosis, resulting in an AUC of 0.77 for both target conditions. The meta-analysis of three studies resulted in an AUC of 0.69 in detecting any fibrosis, while analysis of three other studies showed higher accuracy in cirrhosis (AUC: 0.92). (4) Conclusions: Our meta-analysis showed acceptable performance (AUC > 0.80) of FibroTest™ only in detecting cirrhosis. We observed more limited performance of the test in detecting significant and advanced fibrosis in NAFLD patients. Further primary studies with high methodological quality are required to validate the reliability of the test for detecting different fibrosis levels and to compare the performance of the test in different settings.


2012 ◽  
Vol 142 (5) ◽  
pp. S-80 ◽  
Author(s):  
Shikha S. Sundaram ◽  
Jillian S. Sullivan ◽  
Ronald J. Sokol ◽  
Kristen N. Robbins ◽  
Kelley Capocelli ◽  
...  

2014 ◽  
Vol 2 (4) ◽  
pp. 276-280 ◽  
Author(s):  
E. B. Tapper ◽  
K. Krajewski ◽  
M. Lai ◽  
T. Challies ◽  
R. Kane ◽  
...  

Author(s):  
N. A. Nosko ◽  
O. M. Rud

Objective — to systematize literature data on the presence of 677C > T and 1298A > C polymorphisms in the MTHFR gene and homocysteine levels in patients with non‑alcoholic fatty liver disease (NAFLD); to calculate the frequencies 677C > T and 1298A > C polymorphisms combinations in the MTHFR gene and their impact on NAFLD development; to compare homocysteine levels in patients with and without NAFLD. Materials and methods. The analysis has been performed for the results of investigation of 49 patients, from them 17 subjects with NAFLD and 32 without it. Clinical, laboratory, statistical and ontological methods were used in the study. The MTHFR 677C > T and MTHFR 1298A > C polymorphisms in the MTHFR gene were investigated with the use of real time polymerase chain reaction (RT‑PCR) technique. Homocysteine levels were determined with chemiluminescent immunoassay with reference values 3.7 — 13.9 µmol/L. Multiple logistic regression method was used to evaluate the effects 677C > T and 1298A > C polymorphisms in the MTHFR gene on NAFLD development. Results. The variant of combination of 667С/С/1298А/А polymorphisms in the MTHFR gene (absence of mutation) was reveled in 6 (12 %) persons, that showed a widespread prevalence of variants with the presence of mutations. The correlation between variants of 677C > T and 1298A > C polymorphism in the MTHFR gene has been established (r = 0.429; p < 0.05). The results of multiple logistic regression demonstrated absence of the significant effects of 677C > T and 1298A > C polymorphisms in the MTHFR gen on NAFLD development (p > 0.05). Comparison of the homocysteine levels in patients with and without NAFLD didn’t reveal significant difference (р > 0.05), as well as comparison in the groups with combinations of 677C > T and 1298А > С polymorphisms in the MTHFR gen (р > 0.05). This can be explained by the fact that NAFLD group consisted of manly young patients without hypertension, type 2 diabetes mellitus and severe liver fibrosis. Conclusions. Ontological systematization of the scientific data on NAFLD revealed that 677C > T and 1298A > C polymorphisms in the MTHFR gen are pathogenetically associated with the significant increase in homocysteine levels as a marker of cardiovascular pathology. Giving the multifactorial nature of hyperhomocysteinemia and wide spread of 677C > T and 1298A > C polymorphisms in the MTHFR gen in population, it seems to be impractical to use genetic investigations for MTHFR gen polymorphism in NAFLD patients routinely, but only for the purpose of differential diagnosis of hyperhomocysteinemia.  


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