Systematic Review with Meta-Analysis: Diagnostic Accuracy of Pro-C3 for Hepatic Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.
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SUBMITTER: Mak AL
PROVIDER: S-EPMC8698886 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:This study aimed to assess the accuracy of staging liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) usingpoint shear wave elastography (pSWE) and transient elastography (TE). SETTING:Relevant records on NAFLD were retrieved from PubMed, Embase, Web of Science and the China National Knowledge Infrastructure databases up to 20 December 2017. A bivariate mixed-effects model was conducted to combine sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the summary receiver operating characteristic curve (AUC) between pSWE and TE. A sensitivity analysis was implemented to explore the source of heterogeneity. PARTICIPANTS:Patients with NAFLD who had a liver stiffness measurement using pSWE and TE before liver biopsy were enrolled according to the following criteria: 2×2?contingency tables can be calculated via the reported number of cases; sensitivity and specificity were excluded according to the following criteria: history of other hepatic damage, such as chronic hepatitis C, concurrent active hepatitis B infection, autoimmune hepatitis, suspicious drug usage and alcohol abuse. RESULTS:Nine pSWE studies comprising a total of 982 patients and 11 TE studies comprising a total of 1753 patients were included. For detection of significant fibrosis, advanced fibrosis and cirrhosis, the summary AUC was 0.86 (95% CI 0.83 to 0.89), 0.94 (95% CI 0.91 to 0.95) and 0.95 (95% CI 0.93 to 0.97) for pSWE, and the summary AUC was 0.85 (95% CI 0.82 to 0.88), 0.92 (95% CI 0.89 to 0.94) and 0.94 (95% CI 0.93 to 0.97) for TE, respectively. The proportion of failure measurement was over tenfold as common with TE using an M probe compared with pSWE. CONCLUSION:pSWE and TE, providing precise non-invasive staging of liver fibrosis in NAFLD, are promising techniques, particularly for advanced fibrosis and cirrhosis.
| S-EPMC6112406 | biostudies-literature
Project description:Background & aimsNon-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. Even at young age, it can progress to liver fibrosis. Given the drawbacks of liver biopsy, there is a need for non-invasive methods to accurately stage liver fibrosis in this age group. In this systematic review, we evaluate the diagnostic accuracy of non-invasive methods for staging liver fibrosis in children with NAFLD.MethodsWe searched MEDLINE, Embase, Web of Science and the Cochrane Library, for studies that evaluated the performance of a blood-based biomarker, prediction score or imaging technique in staging liver fibrosis in children with NAFLD, using liver biopsy as the reference standard.ResultsTwenty studies with a total of 1787 NAFLD subjects were included, which evaluated three prediction scores, five simple biomarkers, two combined biomarkers and six imaging techniques. Most studies lacked validation. Substantial heterogeneity of studies and limited available study data precluded a meta-analysis of the few fibrosis tests evaluated in more than one study. The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis.ConclusionDue to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.
| S-EPMC8453517 | biostudies-literature
Project description:BACKGROUND:This study was performed to systematically evaluate the accuracy of magnetic resonance elastography (MRE) in staging of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). METHODS:PUBMED, EMBASE, Web of Science, CNKI, Cochrane Library database were searched from January 2008 to December 2018 for studies related to MRE in the diagnosis of NAFLD liver fibrosis. The quality of the included literature was assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The pooled sensitivity, the pooled specificity, and area under the receiver operating characteristic curve (AUROC) value was performed by STATA 14.0 software. RESULTS:A total of 12 studies were included, involving 910 patients. The pooled sensitivity and specificity of each group were 0.77 (95%CI 0.69-0.83) and 0.90 (95%CI 0.83-0.94) for F???1 (mild liver fibrosis), 0.87 (95%CI 0.74-0.94) and 0.86 (95%CI 0.71-0.94) for F???2 (significant liver fibrosis), 0.89 (95%CI 0.81-0.94) and 0.84 (95%CI 0.63-0.94) for F???3(severe liver fibrosis), 0.94 (95%CI 0.85-0.98) and 0.75 (95%CI 0.35-0.94) for F???4 (early cirrhosis), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.89, 0.93, 0.93, and 0.95, respectively. CONCLUSIONS:MRE has high accuracy in the diagnosis of hepatic fibrosis staging in patients with NAFLD.
| S-EPMC7137512 | biostudies-literature
Project description:There is an unmet need for non-invasive biomarkers in non-alcoholic fatty liver disease (NAFLD) that can diagnose advanced disease and identify patients suitable for clinical trials. The PRO-C3 collagen neo-epitope is a putative direct marker of fibrogenesis. We assessed the performance of PRO-C3 in a large, well-characterised international NAFLD cohort and report the development and validation of 2 novel panels for the diagnosis of advanced fibrosis (F≥3) in NAFLD, including a simplified clinical score which eliminates the need for online calculators.MethodsPlasma PRO-C3 levels were determined in a prospectively recruited international cohort of 449 patients with biopsy diagnosed NAFLD across the full disease spectrum (F0: n = 90; F1: 100; F2: 92; F3: 101; F4: 66). The cohort was divided into a discovery group (n = 151) and a validation group (n = 298). Logistic regression was performed to establish complex (FIBC3) and simplified (ABC3D) diagnostic scores that accurately identify advanced fibrosis. Performance for each was compared to established non-invasive fibrosis scoring systems.ResultsPlasma PRO-C3 levels correlated with grade of histological steatohepatitis (rs = 0.367, p ≪0.0001) and stage of fibrosis (rs = 0.462, p ≪0.0001), exhibiting similar performance to current fibrosis scores such as FIB4 for the detection of F≥3 fibrosis. FIBC3 exhibited substantially improved accuracy (AUROC 0.89 and 0.83 in the discovery and validation sets, respectively) and outperformed FIB4 and other similar diagnostic panels. The simplified version, ABC3D, was concurrently developed and had comparable diagnostic accuracy (AUROC 0.88 and 0.81 in the discovery and validation sets, respectively).ConclusionPlasma PRO-C3 levels correlate with severity of steatohepatitis and fibrosis stage. The FIBC3 panel is an accurate tool with a single threshold value that maintains both sensitivity and specificity for the identification of F≥3 fibrosis in NAFLD, eliminating indeterminate results and outperforming commonly used non-invasive tools. A greatly simplified version (ABC3D) that is readily amenable to use in the clinic has been validated and shown to perform with similar accuracy, and may prove a useful tool in routine clinical practice.Lay summaryWe performed a comprehensive, independent evaluation of a collagen biomarker (PRO-C3) to detect and quantify liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We report the development of 2 diagnostic panels using PRO-C3 to identify patients with advanced fibrosis, one optimal but more complex to calculate (FIBC3), the other easier to use (ABC3D) whilst still performing well.
| S-EPMC7001575 | biostudies-literature
Project description:Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F ≥ 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58-0.94); specificity: 91.1% (95%CI 0.89-0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73-0.90); specificity: 84.4% (95%CI 0.62-0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63-0.79); specificity: 82.8% (95%CI 0.71-0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains.
| S-EPMC8269151 | biostudies-literature
Project description:Telomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p < 0.001) with age, regardless of NAFLD status. Therefore, telomere length was corrected for age. Age-adjusted telomere length than decreased gradually with an increasing severity of fibrosis in patients with NAFLD (p < 0.028). In multivariate analysis, age-adjusted telomere length (odds ratio [OR] 0.59; 95% CI 0.37-0.92; p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80-0.99; p = 0.039) were independently associated with significant fibrosis. The age-adjusted telomere length tends to decrease along with the fibrosis stage of NAFLD. In particular, among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver.
| S-EPMC8429461 | biostudies-literature
Project description:OBJECTIVES:We conducted an individual participant data (IPD) pooled analysis on diagnostic accuracy of MRE to detect fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). METHODS:Through a systematic literature search, we identified studies of MRE (at 60-62.5 Hz) for staging fibrosis in patients with NAFLD, using liver biopsy as gold standard, and contacted study authors for IPD. Through pooled analysis, we calculated the cluster-adjusted AUROC, sensitivity and specificity of MRE for any (?stage 1), significant (?stage 2) and advanced (?stage 3) fibrosis and cirrhosis (stage 4). RESULTS:We included nine studies with 232 patients with NAFLD (mean age, 51?±?13 years; 37.5% males; mean BMI, 33.5?±?6.7 kg/m(2); interval between MRE and biopsy <1 year, 98.3%). Fibrosis stage distribution (stage 0/1/2/3/4) was 33.6, 32.3, 10.8, 12.9 and 10.4%, respectively. Mean AUROC (and 95% CIs) for diagnosis of any, significant or advanced fibrosis and cirrhosis was 0.86 (0.82-0.90), 0.87 (0.82-0.93), 0.90 (0.84-0.94) and 0.91 (0.76-0.95), respectively. Similar diagnostic performance was observed in stratified analysis based on sex, obesity and degree of inflammation. CONCLUSIONS:MRE has high diagnostic accuracy for detection of fibrosis in NAFLD, independent of BMI and degree of inflammation. KEY POINTS:• MRE has high diagnostic accuracy for detection of fibrosis in NAFLD. • BMI does not significantly affect accuracy of MRE in NAFLD. • Inflammation had no significant influence on MRE performance in NAFLD for fibrosis.
| S-EPMC5051267 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterized cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD.
| S-EPMC4279183 | biostudies-literature
Project description:Background: The hepatic lipidome of patients with early stages of non-alcoholic fatty liver disease (NAFLD) has been fairly well-explored. However, studies on more progressive forms of NAFLD, i.e., liver fibrosis, are limited. Materials and methods: Liver fatty acids were determined in cholesteryl esters (CE), phospholipids (PL), and triacylglycerols (TAG) by gas chromatography. Cross-sectional associations between fatty acids and biopsy-proven NAFLD fibrosis (n = 60) were assessed using multivariable logistic regression models. Stages of fibrosis were dichotomized into none-mild (F0-1) or significant fibrosis (F2-4). Models were adjusted for body-mass index (BMI), age and patatin-like phospholipase domain-containing protein 3 (PNPLA3 rs738409) (I148M) genotype. A secondary analysis examined whether associations from the primary analysis could be confirmed in the corresponding plasma lipid fractions. Results: PL behenic acid (22:0) was directly associated [OR (95% CI): 1.86 (1.00, 3.45)] whereas PL docosahexaenoic acid (22:6n-3) [OR (95% CI): 0.45 (0.23, 0.89)], TAG oleic acid (18:1n-9) [OR (95% CI): 0.52 (0.28, 0.95)] and 18:1n-9 and vaccenic acid (18:1n-7) (18:1) [OR (95% CI): 0.52 (0.28, 0.96)] were inversely associated with liver fibrosis. In plasma, TAG 18:1n-9 [OR (95% CI): 0.55 (0.31, 0.99)], TAG 18:1 [OR (95% CI): 0.54 (0.30, 0.97)] and PL 22:0 [OR (95% CI): 0.46 (0.25, 0.86)] were inversely associated with liver fibrosis. Conclusion: Higher TAG 18:1n-9 levels were linked to lower fibrosis in both liver and plasma, possibly reflecting an altered fatty acid metabolism. Whether PL 22:6n-3 has a protective role, together with a potentially adverse effect of hepatic 22:0, on liver fibrosis warrants large-scale studies.
| S-EPMC8784562 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) has become a progressive metabolic disease that is emerging as a global epidemic. Considering that the complex pathogenesis has not been fully elucidated, barely specific pharmacological therapy is recommended in current guidelines. Gentiana scabra (GS) is a commonly used herb in Tibetan medicine, which has received much attention in recent years due to its diverse pharmacological properties, including anti-inflammation, anti-oxidation, and anti-fibrosis. However, the therapeutic mechanisms are still unclear. Our investigation demonstrated a regulatory effect of GS on pro-inflammatory macrophages, which was extensively investigated in NAFLD that revealed intimate participation in the disease evolution, and the non-canonical IKK family member TANK-binding kinase 1 (TBK1) was involved in this process. Plasmid vectors for shTBK1 and amlexanox (AML), an inhibitor of TBK1, were used in this study to verify the mechanisms of TBK1 both in vitro and in vivo, while a co-culture system for hepatocytes and BMDMs was constructed to confirm the critical role of macrophages for inflammatory cascade. The results revealed that metabolic burden up-regulated the phosphorylation of TBK1, resulting in activation of NF-κB signaling pathway, and consequently caused an elevated expression of MCP1 to induce the macrophage recruitment and accelerate the inflammatory cascade. In contrast, GS could inhibit the TBK1 phosphorylation and the MCP1 expression to restrain the recruitment of pro-inflammatory macrophages, so as to provide curative effects on metabolic dysfunction and inflammation. Considering that GS is non-toxic and can be used as a kind of tea for long-term drinking, we propose it may be an effective option for the prevention and treatment of NAFLD, which deserves further exploration and application, and may provide new insights to improve the current standardized intervention strategy.
| S-EPMC8803634 | biostudies-literature