Noninvasive tests (NITs), such as platelet-based indices and ultrasound/MRI elastography, are widely used to assess liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, platelet counts are not routinely included in Japanese health check-ups, limiting their utility in large-scale screenings. Additionally, elastography, while effective, is costly and less accessible in routine practice. Most existing AI-based models incorporate these markers, restricting their applicability. This study aimed to develop a simple yet accurate AI model for liver fibrosis staging using only routine demographic and biochemical markers.

This retrospective study analyzed biopsy-proven data from 463 Japanese MASLD patients. Patients were randomly assigned to training (N = 370, 80%) and test (N = 93, 20%) cohorts. The AI model incorporated age, sex, BMI, diabetes, hypertension, hyperlipidemia, and routine blood markers (AST, ALT, γ-GTP, HbA1c, glucose, triglycerides, cholesterol).

The Support Vector Machine model demonstrated high diagnostic performance, with an area under the curve (AUC) of 0.886 for detecting significant fibrosis (≥ F2). The AUCs for advanced fibrosis (≥ F3) and cirrhosis (F4) were 0.882 and 0.916, respectively. Compared to FIB-4, APRI, and FAST score (0.80-0.96), SVM achieved comparable accuracy while eliminating the need for platelet count or elastography.

This AI model accurately assesses liver fibrosis in MASLD patients without requiring platelet count or elastography. Its simplicity, cost-effectiveness, and strong diagnostic performance make it well-suited for large-scale health screenings and routine clinical use.

Advanced liver fibrosis in cases of metabolic dysfunction-associated steatotic liver disease (MASLD) leads to cirrhosis and hepatocellular carcinoma. The current gold standard for liver fibrosis is invasive liver biopsy. Therefore, a less invasive biomarker that accurately reflects the stage of liver fibrosis is highly desirable.

This study enrolled 269 patients with liver biopsy-proven MASLD. Patients were divided into three groups (F0/1 (n = 41/85), F2 (n = 47), and F3/4 (n = 72/24)) according to fibrosis stage. We performed serum N-glycomics and identified glycan biomarker for fibrosis stage. Moreover, we explored the carrier proteins and developed a sandwich ELISA to measure N-glycosylation changes of carrier protein.

Comprehensive N-glycomic analysis revealed significant changes in the expression of A2F bisect and its precursors as fibrosis progressed. The sum of neutral N-glycans carrying bisecting GlcNAc and core Fuc (neutral sum) had a better diagnostic performance to evaluate advanced liver fibrosis (AUC = 0.804) than conventional parameters (FIB4 index, aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), and serum level of Mac-2-binding protein glycol isomer (M2BPGi). The combination of the neutral sum and FIB4 index enhanced diagnostic performance (AUC = 0.840). IgM, IgA, and complement C3 were identified as carrier proteins with A2F bisect N-glycan. A sandwich ELISA based on N-glycans carrying bisecting GlcNAc and IgA showed similar diagnostic performance than the neutral sum.

A2F bisect N-glycan and its precursors are promising candidate biomarkers for advanced fibrosis in MASLD patients. Analysis of these glycan alterations on IgA may have the potential to serve as a novel ELISA diagnostic tool for MASLD in routine clinical practice.

UMIN000030720.

A novel noninvasive score, Agile-4 score, combining liver stiffness measurements, aspartate aminotransferase/alanine aminotransferase, platelet count, diabetes status and sex has been developed for the identification of cirrhosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We assessed the performance of Agile-4 for ruling-in/out liver cirrhosis in MASLD patients.

We searched Medline, Cochrane library, Web of science, Scopus and Echosens website up to May 2024. Eligible studies assessed the accuracy of Agile-4 for ruling-in (≥0.565) and ruling-out (<0.251) liver cirrhosis, using biopsy as the reference standard, at predefined thresholds. We calculated pooled sensitivity and specificity estimates for both Agile-4 thresholds alongside 95% confidence intervals following bivariate random-effect models. We assessed the risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2 tool.

We included seven studies with 6037 participants. An Agile-4 score ≥0.565 yielded a pooled specificity of 0.93 (95% CI, 0.86-0.97). Similarly, an Agile-4 score <0.251 excluded cirrhosis with a summary sensitivity of 0.90 (0.80-0.95). Assuming a cirrhosis prevalence of 30%, the positive predictive value (PPV) for ruling-in cirrhosis was 80%, while the negative predictive value for ruling-out cirrhosis was 95%. Most studies were at high or unclear risk for bias due to concerns regarding patient selection and the blinding status of Agile-4 score interpretation in relation to biopsy results.

Agile-4 score performs well for ruling-in/out liver cirrhosis in MASLD patients. Owing to the relatively low PPV, sequential application of the Agile-4 after fibrosis-4 index (FIB-4) testing might further enhance its performance.

Noninvasive tests (NITs) are used in all aspects of liver disease management. Their most prominent break-through since the millennium has been in advancing early detection of liver fibrosis, but their use is not limited to this. In contrast to the symptom-driven assessment of decompensation in patients with cirrhosis, NITs provide not only opportunities for earlier diagnoses but also accurate prognostication, targeted treatment decisions, and a means of monitoring disease. NITs can inform disease management and decision-making based on validated cutoffs and standardized interpretations as a valuable supplement to clinical acumen. The Baveno VI and VII consensus meetings resulted in tangible improvements to pathways of care for patients with compensated and decompensated advanced chronic liver disease, including the combination of platelet count and transient elastography to diagnose clinically significant portal hypertension. Furthermore, circulating NITs will play increasingly important roles in assessing the response to interventions against ascites, variceal bleeding, HE, acute kidney injury, and infections. However, due to NITs' wide availability, there is a risk of inaccurate use, leading to a waste of resources and flawed decisions. In this review, we describe the uses and pitfalls of NITs for hepatic decompensation, from risk stratification in primary care to treatment decisions in outpatient clinics, as well as for the in-hospital management of patients with acute-on-chronic liver failure. We summarize which NITs to use when, for what indications, and how to maximize the potential of NITs for improved patient management.

In response to the growing health crisis of liver-related morbidity and mortality, screening for liver cirrhosis has emerged as a promising strategy for early detection and timely intervention. By identifying individuals with severe fibrosis or compensated cirrhosis, screening holds the promise of enhancing treatment outcomes, delaying disease progression, and ultimately improving the quality of life of affected individuals. Clinical practice guidelines from international scientific societies currently recommend targeted screening strategies, investigating high-risk populations with known risk factors of liver disease. While there is good evidence that screening increases case finding in the population, and a growing number of studies indicate that screening may motivate beneficial lifestyle changes in patients with steatotic liver disease, there are major gaps in knowledge in need of clarification before screening programs of cirrhosis are implemented. Foremost, randomized trials are needed to ensure that screening leads to improved liver-related morbidity and mortality. If not, screening for cirrhosis could be unethical due to overdiagnosis, overtreatment, increased health care costs, negative psychological consequences of screening, and futile invasive investigations. Moreover, the tests used for screening need to be optimized toward lower false positive rates than the currently used FIB-4 while retaining few false negatives. Finally, barriers to adherence to screening and implementation of screening programs need to be elucidated. This review provides a comprehensive overview of the current landscape of screening strategies for liver cirrhosis and the promises and pitfalls of current methods for early cirrhosis detection.

Risk of disease progression and clinical outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with fibrosis stage and presence of "at-risk metabolic dysfunction-associated steatohepatitis (MASH)." Although liver biopsy is considered the gold standard to diagnose MASH and stage of fibrosis, biopsy is infrequently performed in clinical practice and has associated sampling error, lack of interrater reliability, and risk for procedural complications. Noninvasive tests (NITs) are routinely used in clinical practice for risk stratification of patients with MASLD. Several NITs are being developed for detecting "at-risk MASH" and cirrhosis. Clinical care guidelines apply NITs to identify patients needing subspecialty referral. With recently approved Food and Drug Administration treatment for MASH and additional emerging pharmacotherapy, NITs will identify patients who will most benefit from treatment, monitor treatment response, and assess risk for long-term clinical outcomes. In this review, we examine the performance of NITs to detect "at-risk MASH," fibrosis stage, response to treatment, and risk of clinical outcomes in MASLD and MASH.

Background and aims: The enhanced liver fibrosis (ELF) score is a blood test that combines three markers linked to liver fibrosis. The utility of the ELF score has been demonstrated primarily in Western countries, but whether it is useful in areas with a high number of elderly people suffering from chronic liver disease has yet to be determined. Methods: This is a prospective study that included 373 consecutive patients who underwent a liver biopsy and had their ELF score measured on the same day. The diagnostic accuracy of the ELF score for liver fibrosis and the effect of age on the ELF score were investigated. Results: The median (interquartile) ELF scores in F0, F1, F2, F3, and F4 are 8.7 (8.2-9.2), 9.3 (8.8-10.0), 10.1 (9.4-10.7), 10.7 (9.9-11.2), and 12.0 (11.2-12.7), respectively. ELF scores increased with increasing liver fibrosis stage (p < 0.001). The diagnostic accuracy of the ELF score and FIB-4 for significant fibrosis (F2-4) and advanced fibrosis (F3-4) was comparable, but the ELF score had a higher diagnostic accuracy for cirrhosis (F4) than FIB-4. When patients were stratified by age of 60 years, the median ELF score did not differ by age in F2, F3, and F4. However, the median FIB-4 increased in patients with ≥60 years compared to those with <60 years in all fibrosis stages. Conclusions: ELF score has high diagnostic accuracy for liver fibrosis, regardless of age, and it could be used as a primary screening method.

Recently, the American Gastroenterological Association and the American Association for the Study of Liver Diseases developed clinical pathways to evaluate populations at high risk for NAFLD. We assessed the diagnostic performance of the new guidance in a well-phenotyped cohort of patients with Type 2 diabetes mellitus (T2DM).

This prospective study enrolled patients age ≥50 years with T2DM. Participants underwent a standardized clinical research visit with MRI and ultrasound-based assessment of liver fat and stiffness and Enhanced Liver Fibrosis (ELF) testing. Of 417 participants (36% men) with T2DM with FIB-4 and MRE data, the prevalence of NAFLD was 64% and 12% had advanced fibrosis (MRE≥3.63 kPa). Applying the American Gastroenterological Association pathway of FIB-4 and vibration-controlled transient elastography, the false negative rate was 3.3% and 18% would qualify for specialty referral. Applying the FIB-4 + ELF American Association for the Study of Liver Diseases pathway, the false negative rate was 4.5%, but 50% would qualify for specialty referral. Applying higher ELF cut points improved the pathway, yielding a similar false negative rate of 4.9% but decreased specialty referral to 27%.

Validation of the American Gastroenterological Association clinical pathway in a prospectively recruited cohort with T2DM revealed a low false negative rate and avoided specialty referral in a large percentage of patients. The American Association for the Study of Liver Diseases pathway with FIB-4 + ELF resulted in a high rate of specialty referral, which improved with the utilization of higher ELF cut points and may serve as an alternative for primary care and endocrinology clinics without access to vibration-controlled transient elastography.

In patients with chronic hepatitis C, 8 weeks of glecaprevir and pibrentasvir (GLE/PIB) treatment for chronic hepatitis (non-cirrhosis) and 12 weeks for cirrhosis have been approved in Japan. However, whether 8 weeks of treatment for cirrhosis may reduce treatment efficacy has not been adequately investigated.

This prospective, nationwide, multicenter cohort study enrolled 1275 patients with chronic hepatitis C who received GLE/PIB therapy. The effect of liver fibrosis and treatment periods on the efficiency of GLE/PIB therapy was investigated. The primary endpoint was the sustained virological response (SVR) rate in patients with chronic hepatitis (non-cirrhosis) and cirrhosis. The association between treatment periods and liver fibrosis on the SVR after 12 weeks of treatment rate was investigated.

The SVR rates in patients with chronic hepatitis with 8 weeks of treatment, chronic hepatitis with 12 weeks of treatment, cirrhosis with 8 weeks of treatment, and cirrhosis with 12 weeks of treatment were 98.9% (800/809), 100% (87/87), 100% (166/166), and 99.1% (211/213), respectively, and were was not different among these groups (P = 0.4).

GLE/PIB therapy for chronic hepatitis C had high efficacy regardless of liver fibrosis status and treatment periods. Periods of GLE/PIB therapy could be chosen with available modalities, and high SVR rates could be achieved regardless of the decision.

Magnetic resonance elastography (MRE) is used for the evaluation of liver fibrosis; however, it remains unclear whether MRE-based liver stiffness is associated with hepatocellular carcinoma (HCC) development, particularly in patients with chronic hepatitis B.

A total of 504 patients with chronic hepatitis B receiving MRE were enrolled. The primary endpoint was the association between MRE-based liver stiffness and HCC.

In a cross-sectional analysis at the time of MRE measurement, the median (interquartile range) liver stiffness values in patients with presence or history of HCC and those without HCC were 3.68 (2.89-4.96) and 2.60 (2.22-3.45) kPa, respectively, and liver stiffness was significantly higher in patients with presence or history of HCC than in those without HCC (P < 0.001). In a longitudinal analysis of patients without HCC, the 1-, 3-, and 5-year cumulative incidence of HCC in patients with liver stiffness ≥3.6 kPa and those with liver stiffness <3.6 kPa were 3.8%, 7.0%, and 22.9%, and 0%, 0.9%, and 1.5%, respectively (P < 0.001). In the multivariable analysis, MRE-based liver stiffness (per 1 kPa) or liver stiffness ≥3.6 kPa was an independent factor for HCC development with an adjusted hazard ratio (aHR) of 1.61 (95% confidence interval [CI], 1.3-2.0) or aHR of 8.22 (95% CI, 2.1-31).

MRE-based liver stiffness is associated with HCC risk in patients with chronic hepatitis B and may be used for the early prediction of HCC development and determination of indications for treatment.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities. A US-based DL network (FIB-Net) was trained on US images to predict whether the shear-wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis-4 Index (FIB-4) followed by FIB-Net and a three-step algorithm (Three-step#1) using FIB-4 followed by FIB-Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB-4, SWE, FIB-Net, and European Association for the Study of the Liver guidelines (ie, FIB-4 followed by SWE), along with sequential algorithms. Results The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB-Net obtained a noninferior specificity with a margin of 5% (P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB-4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion A sequential algorithm combining FIB-4 and a US DL model showed higher diagnostic accuracy and improved referral management for all-cause advanced liver fibrosis compared with FIB-4 or the DL model alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ghosh in this issue.

Background and Objectives: The prevalence of NAFLD (non-alcoholic fatty liver disease) is increasing, and up to 64% of Asian patients with NAFLD are obese. Non-invasive tests (NITs) for the assessment of liver fibrosis are increasingly being used, but data on their performance in obese Asian patients are lacking. In this pilot cross-sectional study, we aim to compare the distribution of serum and radiological markers of fibrosis between obese Asian biopsy-proven NAFLD patients with and without fibrosis and estimate the diagnostic accuracies of these indices. Materials and Methods: Obese Asian patients with NAFLD and who had undergone a liver biopsy showing histological evidence of NAFLD were invited to participate. Liver fibrosis was assessed using laboratory (APRI, AAR, BARD, FIB4, NFS, and Asia-Pacific NAFLD advanced fibrosis score) and imaging modalities (TE: transient elastography, MRE: magnetic resonance elastography, and SWU: shear wave ultrasonography). Results: A total of 16 patients were included in the final analysis. On liver biopsy, nine patients (56.3%) had significant fibrosis (F2 or higher), and six of these patients had advanced fibrosis (F3 or higher). F4 fibrosis was present in one patient (6.3%). For the laboratory markers, we found that the BARD score correctly identified five out of six patients with advanced fibrosis (83.4%, p value 0.045). Among all the NITs studied, liver stiffness measured by TE had the highest accuracy of 87.5% in its established threshold of 8.5 kPa for the detection of advanced fibrosis. MRE also performed well (81.2% in 3.64 kPa). Conclusions: In conclusion, TE has performed well in the detection of advanced fibrosis in obese Asian patients with biopsy-proven NAFLD in our pilot study. Further large-scale definitive studies are needed to validate the results of our findings.

Metabolic dysfunction-associated Fatty Liver Disease (MAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver and hepatic steatosis, which can progress to critical conditions, including Metabolic dysfunction-associated Steatohepatitis (MASH), liver fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Galectin-3, a member of the galectin family of proteins, has been involved in cascades that are responsible for the pathogenesis and progression of liver fibrosis in MAFLD. This review summarizes the present understanding of the role of galectin-3 in the severity of MAFLD and its associated liver fibrosis. The article assesses the underlying role of galectin-3-mediated fibrogenesis, including the triggering of hepatic stellate cells, the regulation of extracellular degradation, and the modulation of immune reactions and responses. It also highlights the assessments of the potential diagnostic and therapeutic implications of galectin-3 in liver fibrosis during MAFLD. Overall, this review provides insights into the multifaceted interaction between galectin-3 and liver fibrosis in MAFLD, which could lead to the development of novel strategies for diagnosis and treatment of this prevalent liver disease.

Liver disease is a major health concern globally, with high morbidity and mor-tality rates. Precise diagnosis and assessment are vital for guiding treatment approaches, predicting outcomes, and improving patient prognosis. Magnetic resonance imaging (MRI) is a non-invasive diagnostic technique that has been widely used for detecting liver disease. Recent advancements in MRI technology, such as diffusion weighted imaging, intravoxel incoherent motion, magnetic resonance elastography, chemical exchange saturation transfer, magnetic resonance spectroscopy, hyperpolarized MR, contrast-enhanced MRI, and ra-diomics, have significantly improved the accuracy and effectiveness of liver disease diagnosis. This review aims to discuss the progress in new MRI technologies for liver diagnosis. By summarizing current research findings, we aim to provide a comprehensive reference for researchers and clinicians to optimize the use of MRI in liver disease diagnosis and improve patient prognosis.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent form of chronic liver disease that poses challenges in diagnosis and risk stratification. Non-alcoholic steatohepatitis (NASH), the more progressive form of NAFLD, is particularly challenging to diagnose in the absence of histology. Liver biopsy is infrequently performed due to its invasive nature, potential for sampling error, and lack of inter-rater reliability. Non-invasive tests that can accurately identify patients with at-risk NASH (ie, individuals with biopsy-proven NASH with NAFLD activity score [NAS] ≥4 and fibrosis stage ≥2) are key tools to identify candidates for pharmacologic therapy in registrational trials for the treatment of NASH-related fibrosis. With emerging pharmacotherapy, non-invasive tests are required to track treatment response. Lastly, there is an unmet need for non-invasive tests to assess risk for clinical outcomes including progression to cirrhosis, hepatic decompensation, liver-related mortality, and overall mortality. In this Review we examine advances in non-invasive tests to diagnose and monitor NAFLD and NASH.

While nonalcoholic fatty liver disease is a leading cause of end-stage liver disease, most patients with nonalcoholic fatty liver disease do not develop cirrhosis and its complications. Therefore, risk stratification using inexpensive, noninvasive screening modalities is critical to avoid overdiagnosis and overtreatment of a large proportion of the population. In this review, we discuss the data supporting screening and current professional society recommendations on this topic. Screening for at-risk nonalcoholic fatty liver disease is recommended in patients with risk factors including diabetes, the metabolic syndrome, hepatic steatosis, and elevated aminotransferases. Screening typically consists of noninvasive testing using serum biomarkers followed by elastography using specialized imaging modalities. This sequential screening approach accurately identifies both high- and low-risk patients and is cost-effective when applied to at-risk populations. In conclusion, screening for advanced nonalcoholic fatty liver disease in the primary care setting is a crucial part of identifying high-risk patients who may benefit from aggressive intervention while avoiding overtreatment of patients at low risk of liver-related complications.

Patients with nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) or other components of metabolic syndrome are at high risk for disease progression. We proposed an algorithm to identify high-risk NAFLD patients in clinical practice using noninvasive tests (NITs).

Evidence about risk stratification of NAFLD using validated NITs was reviewed by a panel of NASH Experts. Using the most recent evidence regarding the performance of NITs and their application in clinical practice were used to develop an easy-to-use algorithm for risk stratification of NAFLD patients seen in primary care, endocrinology and gastroenterology practices.

The proposed algorithm uses a three-step process to identify NAFLD patients who are potentially at high risk for adverse outcomes. The first step is to use clinical data to identify most patients who are at risk for having potentially progressive NAFLD (e.g. having T2D or multiple components of metabolic syndrome). The second step is to calculate the FIB-4 score as a NIT that can further risk stratifying individuals who are at low risk for progressive liver disease and can be managed by their primary healthcare providers to manage their cardiometabolic comorbidities. The third step is to use second-line NITs (transient elastography or enhanced liver fibrosis tests) to identify those who at high risk for progressive liver disease and should be considered for specially care by providers with NASH expertise.

The use of this simple clinical algorithm can identify and assist in managing patients with NAFLD at high risk for adverse outcomes.

Patients with non-alcoholic fatty liver disease (NAFLD) and significant fibrosis (fibrosis stage ≥2) are candidates for pharmacological trials. The aim of this study was to perform a head-to-head comparison of the diagnostic test characteristics of three non-invasive stiffness-based models including MEFIB (magnetic resonance elastography [MRE] plus FIB-4), MAST (magnetic resonance imaging [MRI]-aspartate aminotransferase [AST]), and FAST (FibroScan-AST) for detecting significant fibrosis.

This prospective study included 563 patients with biopsy-proven NAFLD undergoing contemporaneous MRE, MRI proton density fat fraction (MRI-PDFF) and FibroScan from two prospective cohorts derived from Southern California and Japan. Diagnostic performances of models were evaluated by area under the receiver-operating characteristic curve (AUC).

The mean age of the cohort was 56.5 years (51% were women). Significant fibrosis was observed in 51.2%. To detect significant fibrosis, MEFIB outperformed both MAST and FAST (both p <0.001); AUCs for MEFIB, MAST, and FAST were 0.901 (95% CI 0.875-0.928), 0.770 (95% CI 0.730-0.810), and 0.725 (95% CI 0.683-0.767), respectively. Using rule-in criteria, the positive predictive value of MEFIB (95.3%) was significantly higher than that of FAST (83.5%, p = 0.001) and numerically but not statistically greater than that of MAST (90.0%, p = 0.056). Notably, MEFIB's rule-in criteria covered more of the study population than MAST (34.1% vs. 26.6%; p = 0.006). Using rule-out criteria, the negative predictive value of MEFIB (90.1%) was significantly higher than that of either MAST (69.6%) or FAST (71.8%) (both p <0.001). Furthermore, to diagnose "at risk" non-alcoholic steatohepatitis defined as NAFLD activity score ≥4 and fibrosis stage ≥2, MEFIB outperformed both MAST and FAST (both p <0.05); AUCs for MEFIB, MAST, and FAST were 0.768 (95% CI 0.728-0.808), 0.719 (95% CI 0.671-0.766), and 0.687 (95% CI 0.640-0.733), respectively.

MEFIB was better than MAST and FAST for detection of significant fibrosis as well as "at risk" NASH. All three models provide utility for the risk stratification of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) affects over 25% of the general population worldwide and is one of the main causes of chronic liver disease. Because so many individuals have NAFLD, it is not practical to perform liver biopsies to identify those with more severe disease who may require pharmacological interventions. Therefore, accurate non-invasive tests are crucial. Herein, we compared three such tests and found that a test called MEFIB was the best at detecting patients who might require treatment.

Liver fibrosis is the most important prognostic factor in patients with nonalcoholic fatty liver disease (NAFLD). Several noninvasive markers for fibrosis, including blood-based markers and imaging based-markers have been developed. Indirect fibrosis markers (e.g., fibrosis-4 index and NAFLD fibrosis score) consist of standard laboratory data and clinical parameters. Given its availability and high negative predictive value for advanced fibrosis, these markers are suitable for screening at primary care. Blood-based fibrogenesis markers (enhanced liver fibrosis and N-terminal propeptide of type 3 collagen), ultrasound-based modalities (vibration-controlled transient elastography, point shear wave elastography [SWE], and two-dimensional SWE), and magnetic resonance elastography have high diagnostic accuracy for liver fibrosis and are suitable for diagnosing liver fibrosis at secondary care centers. Sequential use of these markers can increase diagnostic accuracy and reduce health care costs. Furthermore, combining noninvasive makers may assist in identifying candidates for pharmacological trials and reducing screening failure. Emerging data suggest that these noninvasive markers are associated with liver-related events (hepatocellular carcinoma and decompensation) and mortality. Furthermore, delta change in noninvasive markers over time is also associated with time-course change in fibrosis, liver-related event risk, and mortality risk. However, the association between liver fibrosis and cardiovascular disease (CVD) risk is still controversial. CVD risk may decrease in patients with decompensated liver disease and noninvasive markers may be useful for assessing CVD risk in these patients. Therefore, noninvasive markers may be utilized as measures of fibrosis as well as real-time prognostic tools, in place of liver biopsy.

Over the last two decades, there have been tremendous advances in the non-invasive diagnosis and risk stratification of chronic liver diseases (CLDs). Non-invasive approaches are based on the quantification of biomarkers in serum samples or on the measurement of liver stiffness, using either ultrasound- or magnetic resonance-based elastography techniques. The fibrosis-4 index (non-patented) and enhanced liver fibrosis test (patented) are the most widely adopted serum markers, whereas vibration-controlled transient elastography is the most widely adopted elastography technique. In this review, we discuss the role of non-invasive tests in the current era, as well as their accuracy and how their use in clinical practice has changed the practice of hepatology, including identification of early cirrhosis in patients with risk factors for CLD, diagnosis of portal hypertension, establishing prognosis in compensated cirrhosis, guiding antiviral treatment, and screening for fibrosis and cirrhosis in primary care.