Hepatocellular carcinoma (HCC), a common consequence of chronic liver disease, ranks among the most prevalent cancers globally and contributes significantly to cancer-related mortality. Liver fibrosis is intimately associated with hepatic function and the likelihood of future HCC occurrence. Despite the fact that liver biopsy continues to be the gold standard for diagnosing fibrosis, its utility is hindered by cost and invasiveness, along with patient unease, procedural rejection, and potential adverse effects. Liver elastography has become a leading noninvasive means of assessing tissue stiffness with considerable diagnostic precision. Malignant tumors generally exhibit higher cellularity in comparison to benign ones, resulting in increased stiffness. Elastography techniques capitalize on alterations in tissue elasticity stemming from specific pathological or physiological processes. Technological innovations, such as advanced ultrasound imaging and artificial intelligence (AI)-integrated systems, are paving the way for enhanced diagnostic accuracy and risk prediction. Recent research underscores the potential of elastography in managing HCC patients, presenting novel clinical applications, including prediction of HCC development, differentiation between malignant and benign liver lesions, evaluating treatment response, and forecasting recurrence post-treatment, though certain findings remain contentious. Therefore, this review aims to sum up the latest advancements in liver elastography for HCC patients, outlining its applications while addressing existing limitations and avenues for future progress.

Metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), is linked to cardiometabolic risk factors such as obesity and type 2 diabetes (T2D). The rising prevalence of MASH and risk of hepatic and extra-hepatic complications emphasize the need for a better understanding of disease progression and associated outcomes. This study aimed to evaluate the incidence of, and demographic and clinical characteristics associated with, progression to MASH-related complications by disease severity in patients with non-cirrhotic MASH or MASH cirrhosis. Alignment between noninvasive tests (NITs) and biopsy-determined fibrosis stage was also assessed.

This analysis used data from the TARGET-NASH cohort that includes adults with MASH across academic and community sites in the United States. Patients with non-cirrhotic MASH or MASH cirrhosis were stratified by disease severity based on fibrosis stage or cirrhosis. Progression to MASH-related outcomes, including all-cause mortality, cirrhosis, and liver transplantation, was assessed.

Among the 2378 patients included in this analysis, 48% had MASH cirrhosis. Incidence of all-cause mortality increased with disease severity from 0.14/100 person-months (100PM) at fibrosis stage 0-1 (F0-F1) to 2.02/100PM with compensated cirrhosis and 4.62/100PM with decompensated cirrhosis. Compared with patients with F0-F1, risk of progression to cirrhosis was higher in patients with F3 [hazard ratio (HR), 95% confidence interval (CI); 18.66, 10.97-31.73] and F2 (HR, 95% CI; 3.74, 2.00-6.98). Among those who progressed to MASH-related outcomes, 67.9% had T2D and 73.9% had hypertension. Vibration-controlled transient elastography showed better alignment with biopsy-determined fibrosis stage than Fibrosis-4 Index (FIB-4).

Progression to all-cause mortality in patients with MASH was significantly associated with the presence of higher fibrosis stage and cirrhosis. Cardiometabolic comorbidities such as T2D and hypertension were prevalent in patients with MASH progression. Early identification and management of MASH may mitigate disease progression and liver-related complications.

Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F).

A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults.

LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease.

We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests.

Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.

Accurate and reliable diagnosis and monitoring of hepatic fibrosis is increasingly important given the variable natural history in chronic liver disease (CLD) and expanding antifibrotic therapeutic options targeting reversibility of early-stage cirrhosis. This highlights the need to develop more refined and effective noninvasive techniques for the dynamic assessment of fibrogenesis and fibrolysis.

We conducted a literature review on PubMed, from 1 December 1970, to 1 November 2024, to evaluate and compare available blood-based and imaging-based noninvasive tools for hepatic fibrosis diagnosis and monitoring. Simple scores such as FIB-4 and NAFLD fibrosis score are suitable for excluding significant or advanced fibrosis, while tertiary centers should adopt complex scores and liver stiffness measurement as part of a secondary diagnostic and more comprehensive evaluation. Moreover, the advent of multiomics for high-resolution molecular profiling, and integration of artificial intelligence for noninvasive diagnostics holds promise for revolutionizing fibrosis monitoring and treatment through novel biomarker discovery and predictive omics-based algorithms.

The increased shift toward noninvasive diagnostics for liver fibrosis needs to align with personalized medicine, enabling more effective, tailored management strategies for patients with liver disease in the future.

There are limited prospective data among overweight and obese individuals on the prevalence of advanced fibrosis, and cirrhosis using advanced MRI-based methods in the USA. The aim of this study was to fill that gap in knowledge by prospectively determining the MRI-based prevalence of steatotic liver disease (SLD) and its subcategories, advanced fibrosis and cirrhosis among overweight and obese individuals residing in the USA.

This is a cross-sectional analysis of prospectively enrolled overweight or obese adults aged 40-75 years from primary care and community-based settings in Southern California. Participants were classified as having SLD if MRI proton density fat fraction ≥5%, and subclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-related liver disease (ALD) consistently with the new nomenclature guidance per AASLD-EASL-ALEH. Advanced fibrosis and cirrhosis were defined as magnetic resonance elastography (MRE) ≥3.63 kPa and MRE ≥4.67 kPa, respectively.

The cohort included 539 participants with mean (±SD) age of 51.5 (±13.1) years and body mass index of 32.6 (±6.2) kg/m2, respectively. The prevalence of SLD, advanced fibrosis and cirrhosis was 75%, 10.8% and 4.5%, respectively. The prevalence of MASLD, MetALD and ALD was 67.3%, 4.8% and 2.6%, respectively. There was no difference in prevalence of advanced fibrosis and cirrhosis among subcategories.

Using advanced MRI methods among community-dwelling overweight and obese adults, the prevalence of cirrhosis was 4.5%. Most common SLD subcategory was MASLD with 67% of individuals, whereas MetALD and ALD were less common. Systematic screening for advanced fibrosis among overweight/obese adults may be considered.

This study aimed to establish the shear wave measurement (SWM) cut-off value for each fibrosis stage using magnetic resonance (MR) elastography values as a reference standard.

We prospectively analyzed 594 patients with chronic liver disease who underwent SWM and MR elastography. Correlation coefficients (were analyzed, and the diagnostic value was evaluated by the area under the receiver operating characteristic curve. Liver stiffness was categorized by MR elastography as F0 (<2.61 kPa), F1 (≥2.61 kPa, <2.97 kPa, any fibrosis), F2 (≥2.97 kPa, <3.62 kPa, significant fibrosis), F3 (≥3.62 kPa, <4.62 kPa, advanced fibrosis), or F4 (≥4.62 kPa, cirrhosis).

The median SWM values increased significantly with increasing fibrosis stage (p < 0.001). The correlation coefficient between SWM and MR elastography values was 0.793 (95% confidence interval 0.761-0.821). The correlation coefficients between SWM and MR elastography values significantly decreased with increasing body mass index and skin-capsular distance; skin-capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. The best cut-off values for any fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis were 6.18, 7.09, 8.05, and 10.89 kPa, respectively.

This multicenter study in a large number of patients established SWM cut-off values for different degrees of fibrosis in chronic liver diseases using MR elastography as a reference standard. It is expected that these cut-off values will be applied to liver diseases in the future.

Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF.

Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated.

A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80-0.86), 0.83 (0.80-0.86), 0.87 (0.84-0.90), and 0.94 (0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86-0.92), 0.92 (0.89-0.94), 0.89 (0.86-0.92), and 0.94 (0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa.

VCTE (7.1-7.9 kPa) and MRE (3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

This research aimed to explore the involvement of interleukins (IL) - IL-6, IL-17, IL-21, and IL-23 - in the evolution and diagnosis of non-alcoholic liver fibrosis and cirrhosis.

The study subjects were selected from the patients who visited the Department of Hepatology of X Hospital in Y City from August 2021 to April 2023. Peripheral blood samples were collected. All participants were divided into liver fibrosis, cirrhosis, hepatitis, and healthy subjects four groups. IL-21, IL-17, IL23, IL-6 were detected by double antibody sandwich.

The results showed that there was a significant difference in the levels of IL-17, IL-21, and IL-23 among the 4 groups (P<0.0001). ROC curve analysis showed that the AUC values of IL-17, IL-21 and liver fiber 4 items were >0.70, suggesting that the diagnostic efficacy of IL-17, IL-21 was similar to that of liver fiber 4 items. Spearman correlation analysis showed that IL-17 had a positive correlation with collagen type III N-peptide, type IV collagen, and Laminin (P < 0.05), and no correlation with Hyaluronic acid (P > 0.05).

IL-17, IL-21, and IL-23 play a pivotal role in the inflammatory pathways associated with liver injuries, establishing themselves as potent auxiliary diagnostic markers in identifying liver fibrosis and cirrhosis.

A prognostic model to predict liver severity in people with metabolic dysfunction-associated steatotic liver disease (MASLD) is very important, but the accuracy of the most commonly used tools is not yet well established.

The meta-analysis aimed to assess the accuracy of different prognostic serological biomarkers in predicting liver fibrosis severity in people with MASLD.

Adults ≥18 years of age with MASLD were included, with the following: liver biopsy and aspartate aminotransferase-to-platelet ratio (APRI), fibrosis index-4 (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD score), FibroMeter, FibroTest, enhanced liver fibrosis (ELF), Forns score, and Hepascore. Meta-analyses were performed using a random effects model based on the DerSimonian and Laird methods. The study's risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2.

In total, 138 articles were included, of which 86 studies with 46,514 participants met the criteria for the meta-analysis. The results for the summary area under the receiver operating characteristic (sAUROC) curve, according to the prognostic models, were as follows: APRI: advanced fibrosis (AF): 0.78, any fibrosis (AnF): 0.76, significant fibrosis (SF): 0.76, cirrhosis: 0.72; FIB-4: cirrhosis: 0.83, AF: 0.81, AnF: 0.77, SF: 0.75; NFS: SF: 0.81, AF: 0.81, AnF: 0.71, cirrhosis: 0.69; BARD score: SF: 0.77, AF: 0.73; FibroMeter: SF: 0.88, AF: 0.84; FibroTest: SF: 0.86, AF: 0.78; and ELF: AF: 0.87.

The results of this meta-analysis suggest that, when comparing the scores of serological biomarkers with liver biopsies, the following models showed better diagnostic accuracy in predicting liver fibrosis severity in people with MASLD: FIB-4 for any fibrosis, FibroMeter for significant fibrosis, ELF for advanced fibrosis, and FIB-4 for cirrhosis.Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD 42020180525].

Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in SERPINA1, which encodes alpha-1 antitrypsin, a protease inhibitor (Pi). Individuals with AATD and the homozygous Pi*ZZ genotype have variable risk of progressive liver disease but the influence of comorbid lung disease is poorly understood.

To characterise patients with AATD Pi*ZZ and liver disease (AATD-LD-Pi*ZZ) with or without lung disease and describe liver disease-related clinical events longitudinally.

This was an observational cohort study of patients in the Mayo Clinic Healthcare System (January 2000-September 2021). Patients were identified using diagnosis codes and natural language processing. Fibrosis stage (F0-F4) was assessed using a hierarchical approach at baseline (90 days before or after the index date) and follow-up. Clinical events associated with liver disease progression were assessed.

AATD-LD-Pi*ZZ patients with lung disease had a longer median time from AATD diagnosis to liver disease diagnosis versus those without lung disease (2.2 vs. 0.2 years, respectively). Compared to those without lung disease, patients with lung disease had a longer time to liver disease-related clinical events (8.5 years and not reached, respectively). AATD-LD-Pi*ZZ patients without lung disease were more likely to undergo liver transplantation compared with those with lung disease.

In patients with AATD and lung disease, there is a delay in the diagnosis of comorbid liver disease. Our findings suggest that liver disease may progress more rapidly in patients without comorbid lung disease.

Liver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy. Recent technological advancements in multiparametric MRI software such as the LiverMultiScanTM offers an attractive non-invasive assay of anatomy and histopathology in the pre-operative setting, especially in the context of CRLM. This narrative review examines the evidence for the LiverMultiScanTM in the assessment of hepatic fibrosis, steatosis/steatohepatitis, and potential applications for chemotherapy-associated hepatic changes. We postulate its future role and the hurdles it must surpass in order to be implemented in the pre-operative management of patients undergoing hepatic resection for colorectal liver metastasis. Such a role likely extends to other hepatic malignancies planned for resection.

Background There is a need for reliable noninvasive methods for diagnosing and monitoring nonalcoholic fatty liver disease (NAFLD). Thus, the multidisciplinary Non-invasive Biomarkers of Metabolic Liver disease (NIMBLE) consortium was formed to identify and advance the regulatory qualification of NAFLD imaging biomarkers. Purpose To determine the different-day same-scanner repeatability coefficient of liver MRI biomarkers in patients with NAFLD at risk for steatohepatitis. Materials and Methods NIMBLE 1.2 is a prospective, observational, single-center short-term cross-sectional study (October 2021 to June 2022) in adults with NAFLD across a spectrum of low, intermediate, and high likelihood of advanced fibrosis as determined according to the fibrosis based on four factors (FIB-4) index. Participants underwent up to seven MRI examinations across two visits less than or equal to 7 days apart. Standardized imaging protocols were implemented with six MRI scanners from three vendors at both 1.5 T and 3 T, with central analysis of the data performed by an independent reading center (University of California, San Diego). Trained analysts, who were blinded to clinical data, measured the MRI proton density fat fraction (PDFF), liver stiffness at MR elastography (MRE), and visceral adipose tissue (VAT) for each participant. Point estimates and CIs were calculated using χ2 distribution and statistical modeling for pooled repeatability measures. Results A total of 17 participants (mean age, 58 years ± 8.5 [SD]; 10 female) were included, of which seven (41.2%), six (35.3%), and four (23.5%) participants had a low, intermediate, or high likelihood of advanced fibrosis, respectively. The different-day same-scanner mean measurements were 13%-14% for PDFF, 6.6 L for VAT, and 3.15 kPa for two-dimensional MRE stiffness. The different-day same-scanner repeatability coefficients were 0.22 L (95% CI: 0.17, 0.29) for VAT, 0.75 kPa (95% CI: 0.6, 0.99) for MRE stiffness, 1.19% (95% CI: 0.96, 1.61) for MRI PDFF using magnitude reconstruction, 1.56% (95% CI: 1.26, 2.07) for MRI PDFF using complex reconstruction, and 19.7% (95% CI: 15.8, 26.2) for three-dimensional MRE shear modulus. Conclusion This preliminary study suggests that thresholds of 1.2%-1.6%, 0.22 L, and 0.75 kPa for MRI PDFF, VAT, and MRE, respectively, should be used to discern measurement error from real change in patients with NAFLD. ClinicalTrials.gov registration no. NCT05081427 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kozaka and Matsui in this issue.

We conducted an individual patient data meta-analysis to establish stiffness cut-off values for magnetic resonance elastography (MRE) in staging liver fibrosis and to assess potential confounding factors.

A systematic review of the literature identified studies reporting MRE data in patients with NAFLD. Data were obtained from the corresponding authors. The pooled diagnostic cut-off value for the various fibrosis stages was determined in a two-stage meta-analysis. Multilevel modelling methods were used to analyse potential confounding factors influencing the diagnostic accuracy of MRE in staging liver fibrosis.

Eight independent cohorts comprising 798 patients were included in the meta-analysis. The area under the receiver operating characteristic curve (AUROC) for MRE in detecting significant fibrosis was 0.92 (sensitivity, 79%; specificity, 89%). For advanced fibrosis, the AUROC was 0.92 (sensitivity, 87%; specificity, 88%). For cirrhosis, the AUROC was 0.94 (sensitivity, 88%, specificity, 89%). Cut-offs were defined to explore concordance between MRE and histopathology: ≥F2, 3.14 kPa (pretest probability, 39.4%); ≥F3, 3.53 kPa (pretest probability, 24.1%); and F4, 4.45 kPa (pretest probability, 8.7%). In generalized linear mixed model analysis, histological steatohepatitis with higher inflammatory activity (odds ratio 2.448, 95% CI 1.180-5.079, p <0.05) and high gamma-glutamyl transferase (GGT) concentration (>120U/L) (odds ratio 3.388, 95% CI 1.577-7.278, p <0.01] were significantly associated with elevated liver stiffness, and thus affecting accuracy in staging early fibrosis (F0-F1). Steatosis, as measured by magnetic resonance imaging proton density fat fraction, and body mass index(BMI) were not confounders.

MRE has excellent diagnostic performance for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Elevated inflammatory activity and GGT level may lead to overestimation of early liver fibrosis, but anthropometric measures such as BMI or the degree of steatosis do not.

This individual patient data meta-analysis of eight international cohorts, including 798 patients, demonstrated that MRE achieves excellent diagnostic accuracy for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Cut-off values (significant fibrosis, 3.14 kPa; advanced fibrosis, 3.53 kPa; and cirrhosis, 4.45 kPa) were established. Elevated inflammatory activity and gamma-glutamyltransferase level may affect the diagnostic accuracy of MRE, leading to overestimation of liver fibrosis in early stages. We observed no impact of diabetes, obesity, or any other metabolic disorder on the diagnostic accuracy of MRE.

Non-alcoholic fatty liver disease (NAFLD) is the world's most prevalent chronic liver disease. In advanced stages, it is associated with significant morbidity and mortality. Magnetic resonance elastography (MRE) and scoring panels Fibrosis-4 (FIB-4) and NAFLD Fibrosis Score (NFS) are useful noninvasive alternatives to liver biopsy for fibrosis staging. Our study aimed to determine how well MRE corresponds with both FIB-4 and NFS at different stages of fibrosis.

We performed a retrospective chart review of patients age ≥18 with NAFLD as their only known liver disease who underwent MRE within six months of a lab draw. MRE stratified patients into fibrosis stages using kPa values. FIB-4 categorized patients as Advanced Fibrosis Excluded, Further Investigation Needed or Advanced Fibrosis Likely. NFS categorized them as F0-2, Indeterminate or F3-4. MRE fibrosis staging was compared to FIB-4 and NFS for both ruling out advanced fibrosis and identifying advanced fibrosis/cirrhosis.

Overall, 193 patients met inclusion criteria. Our statistical analysis included calculating positive predictive values (PPVs) and negative predictive values (NPVs), which are the proportions of positive and negative fibrosis screening results that correspond to positive and negative MRE results respectively. NPV for FIB-4 (0.84) and NFS (0.89) in the 'rule out advanced fibrosis' category signify that 84% and 89% of respective biomarker scores correspond to MRE in early stage disease. The PPV for FIB-4 and NFS in the 'identify advanced fibrosis/cirrhosis' category signify 63% and 72% of respective biomarker scores correspond to MRE in late stage disease.

FIB-4 and NFS scores indicating little to no fibrosis correspond extremely well with MRE, while scores suggesting advanced fibrosis/cirrhosis correspond less convincingly. MRE shows promise as an effective alternative to liver biopsy, however our study suggests FIB-4 and NFS alone may be sufficient for fibrosis staging, particularly in early stage NAFLD.

Fatty liver disease is an important public health problem. Early diagnosis is critical to lower its rate of progression to irreversible/terminal stages. This study aimed to evaluate the accuracy of non-invasive prediction scores for fatty liver disease (NAFLD and NASH) diagnosis in adults.

A search was conducted in 10 databases, a qualitative synthesis of 45 studies, and quantitative analysis of the six most common scores. There were 23 risk scores found for NAFLD diagnosis and 32 for NASH diagnosis. The most used were Fatty Liver Index (FLI), aspartate aminotransferase (AST) to Platelet Ratio Index, Fibrosis-4 Index (FIB-4), AST/alanine aminotransferase (ALT) ratio, BARD score, and NAFLD fibrosis score (NFS).

The results from the meta-analysis for FLI: Area under the curve (AUC) of 0.76 (95% Confidence Interval [CI] 0.73, 0.80), sensitivity 0.67 (CI 95% 0.62, 0.72) and specificity 0.78 (CI 95% 0.74, 0.83). The AST to Platelet Ratio Index: AUC 0.83 (CI 95% 0.80, 0.86), sensitivity 0.45 (95% CI 0.29, 0.62), and specificity of 0.89 (95% CI 0.83, 0.92). The NFS: AUC of 0.82 (CI 95% 0.78, 0.85), sensitivity 0.30 (CI 95% 0.27, 0.33) and specificity 0.96 (CI 95% 0.95,0.96).

The FLI for NAFLD and AST to Platelet Ratio Index for NASH were the risk scores with the highest prognostic value in the included studies. Further research is needed for the application of new diagnostic risk scores for NAFLD and NASH.

Non-alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease that is strongly related to insulin resistance and metabolic syndrome, and it has become the most common liver disorder in developed countries. NAFLD embraces the full pathological process of three conditions: steatosis, non-alcoholic steatohepatitis, and finally, cirrhosis. As NAFLD progresses, symptoms will become increasingly severe as fibrosis develops. Therefore, evaluating the fibrosis stage is crucial for patients with NAFLD. A liver biopsy is currently considered the gold standard for staging fibrosis. However, due to the limitations of liver biopsy, non-invasive alternatives were extensively studied and validated in patients with NAFLD. The advantages of non-invasive methods include their high safety and convenience compared with other invasive approaches. This review introduces the non-invasive methods, summarizes their benefits and limitations, and assesses their diagnostic performance for NAFLD-induced fibrosis.

Metabolic-associated fatty liver disease (MAFLD) is a growing global problem associated with increasing obesity prevalence. Lifestyle modifications are currently recommended, including weight reduction, exercise, and diet control. This study evaluated the short-term effect of lifestyle modifications on transient elastography (TE) values in an obese population with MAFLD. Thirty-two MAFLD patients were recruited for this prospective study and all subjects participated in a 3-month program of lifestyle modification. Sequential demographic parameters and biochemical tests were compared before and after program completion. Liver fat and fibrosis changes were measured using TE with controlled attenuated parameter (CAP) and liver stiffness measurements (LSM). The mean age was 38.7 years old (10 males). The body weight (88.09 kg vs. 80.35 kg), body mass index (32.24 kg/m² vs. 29.4 kg/m² ), waist (103.19 cm vs. 95.75 cm), and hip circumference (111.67 cm vs. 104.75 cm), and blood pressure (128/78 mmHg vs. 119/71 mmHg) significantly improved before and after the intervention, respectively. Aspartate aminotransaminase (24.06 U/L vs. 18.91 U/L), alanine aminotransaminase (33 U/L vs. 23.72 U/L), creatinine (0.75 mg/dl vs. 0.70 mg/dl), cholesterol (176.41 mg/dl vs. 166.22 m/dl), gamma-glutamyl transferase (26.59 IU/L vs. 19.81 IU/L), and low-density lipoprotein cholesterol (115.63 mg/dl vs. 103.19 mg/dl) also improved after the 3-month intervention. The average CAP significantly decreased after intervention (297.5 dB/m vs. 255.0 dB/m), however, no significant difference in LSM was observed (5.24 kPa vs. 4.82 kPa). The current study suggests that short-term lifestyle modification can effectively improve hepatic steatosis, and TE may serve as a monitoring tool for therapeutic intervention.

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD) and is diagnosed by a liver biopsy. Because of the invasiveness of a biopsy, the majority of patients with NASH are undiagnosed. Additionally, the prevalence of NAFLD and NASH creates the need for a simple screening method to differentiate patients with NAFLD versus NASH. Noninvasive strategies for diagnosing NAFLD versus NASH have been developed, typically relying on imaging techniques and endogenous biomarker panels. However, each technique has limitations, and none can accurately predict the associated functional impairment of drug metabolism and disposition. The function of several drug-metabolizing enzymes and drug transporters has been described in NASH that impacts drug pharmacokinetics. The aim of this review is to give an overview of the existing noninvasive strategies to diagnose NASH and to propose a novel strategy based on altered pharmacokinetics using an exogenous biomarker whose disposition and elimination pathways are directly impacted by disease progression. Altered disposition of safe and relatively inert exogenous compounds may provide the sensitivity and specificity needed to differentiate patients with NAFLD and NASH to facilitate a direct indication of hepatic impairment on drug metabolism and prevent subsequent adverse drug reactions. SIGNIFICANCE STATEMENT: This review provides an overview of the main noninvasive techniques (imaging and panels of biomarkers) used to diagnose NAFLD and NASH along with a biopsy. Pharmacokinetic changes have been identified in NASH, and this review proposes a new approach to predict NASH and the related risk of adverse drug reactions based on the assessment of drug elimination disruption using exogenous biomarkers.

Magnetic resonance elastography (MRE) of the liver has emerged as the non-invasive standard for the evaluation of liver fibrosis in chronic liver diseases (CLDs). The utility of MRE in the evaluation of different CLD in both adults and children has been demonstrated in several studies, and MRE has been recommended by several clinical societies. Consequently, the clinical indications for evaluation of CLD with MRE have increased, and MRE is currently used as an add-on test during routine liver MRI studies or as a standalone test. To meet the increasing clinical demand, MRE is being installed in many academic and private practice imaging centers. There is a need for a comprehensive practical guide to help these practices to deliver high-quality liver MRE studies as well as troubleshoot the common issues with MRE to ensure smooth running of the service. This comprehensive clinical practice review summarizes the indications and provides an overview on why to use MRE, technical requirements, system set-up, patient preparation, acquiring the data, and interpretation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new acronym adopted from the consensus of international experts. Given the increasing prevalence of MAFLD in pre-transplant settings, de novo and recurrent graft steatosis/MAFLD are common in post-transplant settings. The impact of graft steatosis on long-term outcomes is unclear. The current knowledge of incidence rate, risk factors, diagnosis, long-term outcomes, and management of graft steatosis (both de novo and recurrent) is discussed in this review.

Patients with non-alcoholic fatty liver disease (NAFLD) with ≥stage 2 fibrosis are at increased risk for liver-related mortality and are candidates for pharmacological therapies for treatment of NAFLD. The aim of this prospective cohort study is to examine the diagnostic accuracy of MR elastography (MRE) combined with fibrosis-4 (FIB-4) in diagnosing ≥stage 2 fibrosis (candidates for pharmacological therapies).

This is a cross-sectional analysis of a prospective cohort (University of California at San Diego (UCSD)-NAFLD) including 238 consecutive patients with contemporaneous MRE and biopsy-proven NAFLD. Non-alcoholic steatohepatitis-Clinical Research Network-Histologic Scoring System was used to assess histology. The radiologist and pathologist were blinded to clinical, pathological and imaging data, respectively. Receiver operating characteristics (ROCs) were determined to examine the diagnostic accuracy of MRE and FIB-4 for diagnosis of ≥stage 2 fibrosis in NAFLD. We then validated these findings in an independent validation cohort derived from Yokohama City University in Japan (Japan-NAFLD Cohort; N=222 patients).

In the UCSD-NAFLD (training) Cohort, MRE demonstrated a clinically significant diagnostic accuracy for the detection of ≥stage 2 fibrosis with an area under the ROC curve (AUROC) of 0.93 (95% CI 0.90 to 0.97) vs FIB-4 with an AUROC of 0.78 (95% CI 0.71 to 0.85), which was both clinically and statistically significant (p<0.0001). We then combined MRE with FIB-4 (MRE ≥3.3 kPa and FIB-4 ≥1.6) to develop a clinical prediction rule to rule in ≥stage 2 fibrosis patients which had positive predictive value (PPV) of 97.1% (p<0.02) in the UCSD-NAFLD cohort (AUROC of 0.90 (95% CI 0.85 to 0.95)) which remained significant at PPV of 91.0% (p<0.003) in the Japan-NAFLD Cohort (AUROC of 0.84 (95% CI 0.78 to 0.89)).

MRE combined with FIB-4 (MEFIB) index may be used for non-invasive identification of candidates for (≥stage 2 fibrosis) pharmacological therapy among patients with NAFLD with a high PPV.

Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).

PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model.

We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs.

When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking.

Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.

In subjects with nonalcoholic fatty liver disease (NAFLD), advanced fibrosis (AF) carries the highest risk of adverse liver-related events. To reduce the number of unnecessary biopsies, several noninvasive tools (NITs) for the risk stratification of fibrosis have been developed. We conducted this meta-analysis to assess the performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis scores (NFS), the 2 most common NITs, for the appropriate selection of subjects with AF for biopsy.

Four databases were searched until December 2020 (CRD42021224766). Original articles reporting data on the performance of FIB-4 and NFS, interpreted according to standard cutoffs in subjects with biopsy-proven NAFLD, were included. Separate data extractions were performed according to the lower cutoff, the higher cutoff, and the dual threshold approach. The numbers of subjects classified as true-negative, true-positive, false-negative, and false-positive were extracted. Summary operating points were estimated using a random-effects model.

Eighteen studies evaluating 12,604 subjects were included. Participants were adult outpatients with biopsy-proven NAFLD or nonalcoholic steatohepatitis. Overall, a weak-to-moderate performance was found for both scores. The head-to-head comparison showed FIB-4 to be associated with a higher performance in ruling in and NFS in ruling out AF in the single threshold approach, whereas, with the dual threshold approach, a lower prevalence of indeterminate findings was found for FIB-4.

This meta-analysis suggested that currently available NITs have a limited performance in identifying AF among subjects with NAFLD. Further studies are needed to optimize existing thresholds or develop new NITs.

Magnetic resonance elastography (MRE) is the most accurate method of liver stiffness measurement (LSM) in nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the role of MRE in the prediction of hard outcomes in NAFLD.

Adults with NAFLD who underwent MRE between 2007 and 2019 at Mayo Clinic, Rochester were identified. Cox regression analyses were used to explore the predictive role of baseline LSM for 1) development of cirrhosis in noncirrhotic NAFLD and 2) development of liver decompensation or death in those with compensated cirrhosis. A total of 829 NAFLD subjects (54% women, median age 58 years) were identified. Of 639 subjects without cirrhosis, 20 developed cirrhosis after a median follow-up of 4 years. Baseline LSM was predictive of future cirrhosis development: age-adjusted HR = 2.93 (95% CI, 1.86-4.62, p <.0001) per 1 kPa increment (C-statistic = 0.86). Baseline LSM by MRE can be used to guide timing of longitudinal noninvasive monitoring: 5, 3 and 1 years for LSM of 2, 3 and 4-5 kPa, respectively. Of 194 subjects with compensated cirrhosis, 81 developed decompensation or death after a median follow-up of 5 years. Baseline LSM was predictive of future decompensation or death: HR = 1.32 (95% CI, 1.13-1.56, p = .0007) per 1 kPa increment after adjusting for age, sex and MELD-Na. The 1-year probability of future decompensation or death in cirrhosis with baseline LSM of 5 kPa vs 8 kPa is 9% vs 20%, respectively.

In NAFLD, LSM by MRE is a significant predictor of future development of cirrhosis. These data expand the role of MRE in clinical practice beyond the estimation of liver fibrosis and provide important evidence that improves individualized disease monitoring and patient counseling.

The change in tissue stiffness caused by pathological changes in the tissue's structure could be detected earlier, prior to the manifestation of their clinical features. Magnetic resonance elastography (MRE) is a noninvasive imaging technique that uses low-frequency vibrations to quantitatively measure the elasticity or stiffness of tissues. In tumor tissue, stiffness is directly related to tumor development, invasion, metastasis, and chemoradiotherapy resistance. It also dictates the choice of surgical method. At present, MRE is widely used in assessing different human organs, such as the liver, brain, breast, prostate, uterus, gallbladder, and colon stiffness. In the field of oncology, MRE's value lies in tumor diagnosis (especially early diagnosis), selection of treatment method, and prognosis evaluation. This article summarizes the principle of MRE and its research and application progress in tumor diagnosis and treatment.

The increased prevalence of non-alcoholic fatty liver disease (NAFLD) requires special attention in pediatric patients, as it manifests in them in a more severe and progressive way compared to adults. The implementation of the appropriate therapeutic interventions is determinant of the attempts to treat it. For that purpose, early diagnosis and staging of the disease is essential. The purpose of this review was to find and reveal the most appropriate diagnostic strategies and tools for diagnosis and staging of pediatric NAFLD/NASH based on their accuracy, safety and effectiveness. The methodology followed was that of the literature review. Particular emphasis was put on the recent bibliography. A comparative study of published articles about the diagnosis and management of pediatric NAFLD/NASH was also performed. In terms of diagnosis, the findings converged on the use of classical ultrasound. Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children. Even though liver biopsy is the gold standard, especially for NASH, it should be avoided for pediatric patients. Biochemical tests are less specific and less sensitive for the diagnosis of NAFLD, and some of them are of high cost. It seems that diagnostic imaging should be a first-line tool for the staging and monitoring pediatric NAFLD/NASH in order for appropriate interventions to be implanted in a timely way.

This review summarizes the current state of non-invasive diagnosis of non-alcoholic fatty liver disease (NAFLD). This begins with a brief discussion of blood-based analysis (serum biomarkers) then progresses through various imaging modalities (imaging biomarkers) including magnetic resonance (MR), computed tomography (CT), and ultrasound-based imaging methods. The review concludes with comment on the advantages, disadvantages, and prospects of commercially available modalities and the impact they may have on diagnosis and management of patients with NAFLD.

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.

Non-alcoholic fatty liver disease (NAFLD), one of the most common liver diseases, is associated with liver-related complications and metabolic comorbidities. The phenotype is wide, ranging from simple steatosis to non-alcoholic steatohepatitis with advanced fibrosis. In this analysis of a phase 1 trial, clinical characteristics of screened subjects with NAFLD were studied according to the extent of fibrosis assessed using magnetic resonance elastography (MRE).

One hundred ninety-four subjects with body mass index (BMI) of 25-40 kg/m2 and suspected NAFLD were assessed by MRE and grouped by MRE thresholds as a proxy for fibrosis staging (groups 0-4). Data were summarized by group levels, and correlation analyses between MRE values and clinical parameters (including magnetic resonance imaging-proton density fat fraction) were performed.

Most subjects had MRE values in the lower range (groups 0-1; N = 148). Type 2 diabetes (T2D) and BMI > 35 kg/m2 were more frequent in groups with higher than lower MRE values. Subjects in the highest MRE groups also tended to be older and have higher liver enzyme concentrations compared with lower MRE groups. No, or weak, correlations were found between MRE values and clinical parameters (all r values ≤ 0.45).

There was considerable variation and overlap in clinical characteristics across the spectrum of liver stiffness. Although groups with high MRE values generally included more subjects with T2D and obesity, and had higher age and concentrations of liver enzymes, the clinical characteristics did not strongly correlate with MRE scores in this population.

Registered on Clinicaltrials.gov on November 29, 2017 (NCT03357380).

Dysregulation of the gut microbiome has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, we compared stool microbiomes across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients, and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles by using the random forest machine learning algorithm and differential abundance analysis identified discrete metagenomic and metabolomic signatures that were similarly effective in detecting cirrhosis (diagnostic accuracy 0.91, area under curve [AUC]). Combining the metagenomic signature with age and serum albumin levels accurately distinguished cirrhosis in etiologically and genetically distinct cohorts from geographically separated regions. Additional inclusion of serum aspartate aminotransferase levels, which are increased in cirrhosis patients, enabled discrimination of cirrhosis from earlier stages of fibrosis. These findings demonstrate that a core set of gut microbiome species might offer universal utility as a non-invasive diagnostic test for cirrhosis.

Non-invasive evaluation of liver fibrosis has evolved over the last couple of decades. Currently, elastography techniques are the most widely used non-invasive methods for clinical evaluation of chronic liver disease (CLD). MR elastography (MRE) of the liver has been used in the clinical practice for nearly a decade and continues to be widely accepted for detection and staging of liver fibrosis. With MRE, one can directly visualize propagating shear waves through the liver and an inversion algorithm in the scanner automatically converts the shear wave properties into an elastogram (stiffness map) on which liver stiffness can be calculated. The commonly used MRE method, two-dimensional gradient recalled echo (2D-GRE) sequence has produced excellent results in the evaluation of liver fibrosis in CLD from various etiologies and newer clinical indications continue to emerge. Advances in MRE technique, including 3D MRE, automated liver elasticity calculation, improvements in shear wave delivery and patient experience, are promising to provide a faster and more reliable MRE of liver. Innovations, including evaluation of mechanical parameters, such as loss modulus, displacement, and volumetric strain, are promising for comprehensive evaluation of CLD as well as understanding pathophysiology, and in differentiating various etiologies of CLD. In this review, the current status of the MRE of liver in CLD are outlined and followed by a brief description of advanced techniques and innovations in MRE of liver.

Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression. To properly detect fibrosis, it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores, followed by a complementary imaging study (transient elastography, magnetic resonance elastography or acoustic radiation force impulse) and finally a liver biopsy, when needed. To help with the selection of the most appropriate method a Fagan's nomogram analysis is provided in this review, describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis. Finally, treatment should always include diet and exercise, as well as controlling the components of the metabolic syndrome, +/- vitamin E, considering the presence of sleep apnea, and when available, allocate those patients with advanced fibrosis or high risk of progression into clinical trials. The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD, aiming to decrease/stop its progression and improve their prognosis.

Nonalcoholic fatty liver disease is a growing epidemic affecting 30% of the adult population in the Western world. Its progressive form, nonalcoholic steatohepatitis (NASH), is associated with an increased risk of advanced fibrosis, cirrhosis and liver-related mortality. Therefore, the detection of NAFLD and risk stratification according to the severity of the disease is crucial for the management of patients with NAFLD. Liver biopsy for such risk stratification strategies is limited by its cost and risks; therefore, noninvasive alternatives have been developed. Among noninvasive biomarkers developed in NAFLD, magnetic resonance (MR)-based biomarkers have emerged as key noninvasive biomarkers in NAFLD with the ability to accurately detect hepatic steatosis and liver fibrosis. The potential utility of MRI for the detection of NASH and functional liver assessment has also recently emerged. In the current review, we will discuss the data supporting the utility of MR-based biomarker for the detection of features of NAFLD and its potential use in clinical practice and clinical research in NAFLD.

Worldwide, nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents, but also as a real public health issue. Over the last decades, the increase in the rates of obesity and overweight in children has led to the increase in the worldwide prevalence of pediatric NAFLD. Detection of a hyperechoic appearance of the liver at ultrasounds or elevated levels of transaminases, identified during a routine control in children, suggests NAFLD. The disorder can be diagnosed with either non-invasive strategies or through liver biopsy, which further allows the identification of specific histological aspects, distinct from those found in adults. Since NAFLD is a clinically heterogeneous disease, there is an imperative need to identify noninvasive biomarkers and screening techniques for early diagnosis in children, in order to prevent metabolic and cardiovascular complications later in adulthood. This review emphasizes the main diagnosis tools in pediatric NAFLD, a systemic disorder with multifactorial pathogenesis and varying clinical manifestations.

Fatty liver syndrome is an emerging health problem in the world, due to the high prevalence of obesity and alcohol use disorder. Given the nature of the disease's advancement to cirrhosis and liver-related complications, it is important to assess the severity of the disease, which is typically done via a liver biopsy. Due to the limitations and risks of liver biopsy, the role of noninvasive tests is essential and evolving to stratify the stage of the liver disease, predict the outcomes, and/or monitor the treatment response. This review is focused on noninvasive tests, including the use of serum-based biomarkers, ultrasound-based shear wave elastography, transient elastography, and magnetic resonance elastography in both clinical and research settings.

Liver fibrosis assessed by liver biopsy is predictive of clinical liver events in patients with nonalcoholic fatty liver disease (NAFLD). Magnetic resonance elastography (MRE) correlates with liver biopsy in assessing liver fibrosis. However, data assessing the relationship between MRE and clinical liver events are lacking. We investigated the association between MRE and clinical liver events/death and identified the cut-off to predict clinical liver events in NAFLD patients.

We conducted a multicenter retrospective study of NAFLD patients who underwent MRE between 2016 and 2019. Clinical liver events were defined as decompensation events and death. We categorized patients into noncirrhosis, compensated cirrhosis and decompensated cirrhosis. Fisher's exact test was used to test association strength. Receiver operative curve methods were used to determine the optimal cut-off of MRE liver stiffness and to maximize the accuracy for classifying noncirrhosis, compensated cirrhosis and decompensated cirrhosis. Logistic regression modelling was used to predict decompensation.

The study included 320 NAFLD patients who underwent MRE. The best threshold for distinguishing cirrhosis from noncirrhosis was 4.39 kPa (AUROC 0.92) and from decompensated cirrhosis was 6.48 kPa (AUROC 0.71). Odds of decompensation increased as liver stiffness increased (OR 3.28) (P < .001). Increased liver stiffness was associated with ascites, hepatic encephalopathy, oesophageal variceal bleeding and mortality (median 7.10, 10.15 and 10.15 kPa respectively).

In NAFLD patients, liver stiffness measured by MRE with a cut-off of ≥6.48 kPa is associated with decompensation and mortality, and specific MRE cut-offs are predictive of individual clinical liver events.

Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more 'complex' serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.