Metabolic dysfunction and alcohol-associated liver disease (MetALD) may increase liver fibrosis progression, but data on screening are scarce. We aimed to assess the performance of noninvasive tests (NITs) for detecting significant fibrosis in individuals with suspected MetALD.

This is a cross-sectional study of prospectively enrolled adults identified as overweight or obese. We included adults with suspected MetALD defined by ≥1 of 5 cardiometabolic criteria and self-reported alcohol use within MetALD ranges or lower self-reported alcohol use but with phosphatidylethanol (PEth) levels ≥25 ng/mL. Clinical assessment included contemporaneous magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE). Significant fibrosis was defined as MRE ≥3.14 kPa (or VCTE ≥7.6 kPa if MRE was missing). Analyses included AUROCs.

Among 617 individuals screened, we identified 97 (15.7%) with suspected MetALD. The mean age was 50.6±12.8 years, 67% were men, the mean body mass index was 31.4±6.5 kg/m2, 12.4% had diabetes, and 8% had significant fibrosis. Fibrosis-4 ≥1.3 demonstrated good performance for significant fibrosis (AUROC: 0.78, 95% CI: 0.58-0.98, sensitivity 80%, specificity 76%, positive predictive value 17%, and negative predictive value 98%). VCTE ≥8 kPa also had good performance (AUROC: 0.85, 95% CI: 0.66-1.00, sensitivity 80%, specificity 91%, positive predictive value 36%, and negative predictive value 99%). A stepwise approach using fibrosis-4 followed by VCTE yielded a low false negative rate (2% misclassified as low risk).

A clinical care algorithm utilizing a stepwise approach with fibrosis-4 and VCTE shows adequate performance in detecting significant fibrosis in individuals with suspected MetALD.

Non-alcoholic fatty liver disease (NAFLD) has become an increasing public health concern. We examined the association between serum high-sensitivity C-reactive protein(hs-CRP)to high-density lipoprotein cholesterol (HDL-C) ratio (HCHR) and the prevalence of NAFLD, extent of hepatic steatosis and fibrosis in the general US population. This cross-sectional analysis included 4039 adult participants from the 2017 to 2018 National Health and Nutrition Examination Survey. Multivariable logistic regression and multivariable linear regression analyses were used to assess the association between HCHR levels and NAFLD, fatty liver degree, and liver fibrosis. Generalized additive models examined the nonlinear relationship between the HCHR and NAFLD. In the three models, HCHR was positively associated with NAFLD, model 1 (OR  1.315, 95% CI 1.273, 1.359), model 2 (OR 1.364, 95% CI 1.317, 1.412) and model 3 (OR  1.120, 95% CI 1.074, 1.168). Stratified analyses showed that the association was more prominent in women, those younger than 40 years, Mexican-Americans, and those with a 25-30 kg/m2 BMI. Nonlinear association analysis revealed a threshold effect between HCHR and NAFLD, with a threshold inflection point of 2.598. We also found a significant link between HCHR and liver steatosis and the risk of liver fibrosis. In the US adult population, the increased risk of NAFLD, liver fibrosis, and severity of hepatic steatosis are independently associated with increased HCHR, and the HCHR may serve as a potential marker for NAFLD and liver fibrosis.

On-site conservative estimations of steatosis could result in the unnecessary discard of donor livers. This study applied the body mass index as an independent statistical indicator to determine the extent of this problem. We aimed to quantitatively evaluate if decisions based nonbiopsy donor liver assessments are more conservative (inclined to reject marginal fatty livers) than biopsy-based evaluations.

The study processed intradatabase comparisons using 177 081 datasets from Organ Procurement and Transplantation Network spanning 2004 to 2022 September in the United States. Postmatching body mass index was applied as an independent indicator of statistical risk of hepatic steatosis (HS).

A total of 7420, 4990, 5994, and 7523 pair of donors with/without biopsy records were matched in 2004-2010, 2011-2014, 2015-2018, and 2019-2022 September, respectively. Consistent with our hypothesis, absent biopsies and evaluations before and during organ procurement were observed to be more conservative, leading to the discard of 16.4% (2004-2010), 16.9% (2011-2014), 10.6% (2015-2018), and 10.3% (2019-2022 September) of potential donor livers.

The study concludes that there was a significant (10.3%-16.9%) disparity caused by on-site nonbiopsy assessments of HS, leading to the unnecessary discard of potential donor livers. The findings emphasize the need to develop more accurate intraoperative techniques for assessing HS to optimize donor liver procurement.

Limited data have prevented routine genetic testing from being integrated into clinical practice in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to quantify the effect of genetic variants on changes in fibrosis severity per decade in MASLD.

This cross-sectional study included prospectively recruited adults with MASLD aged 18-70 who underwent magnetic resonance elastography (MRE) and genotyping for PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13. A genetic risk score (GRS) was calculated as the sum of established risk alleles in PNPLA3 minus protective variants in HSD17B13 (0=low risk, 1=high risk). We also estimated the polygenic risk score-hepatic fat content (PRS-HFC) and the adjusted version (PRS-5). The primary endpoint was the age-related change in liver stiffness measurement (LSM) on MRE by GRS. Findings were validated using an external cohort from Latin America.

Among 570 participants, the median age was 57 [49-64] years, 56.8% were women, and 34.2% were Hispanic. Median MRE was 2.4 [2.1-3.0] kPa, and 51% had high GRS. High GRS was independently associated with increased LSM (β=0.28 kPa, 95%CI:0.12-0.44, p=0.001) per 10-year age increase, while the low GRS group showed no significant difference. Similar findings were observed using PRS-HFC and PRS-5. PNPLA3 genotype alone also predicted higher LSM (C/G: β=0.32 kPa, 95%CI:0.02-0.61, p=0.034; G/G: β=0.87 kPa, 95%CI:0.52-1.22, p<0.0001) and G/G genotype was associated with significantly higher LSM by age 44, which was consistent in the validation population.

GRS, PRS-HFC, PRS-5, and PNPLA3 genotypes alone are associated with greater fibrosis per decade, resulting in divergent disease trajectories starting in midlife. Assessing genetic risk in MASLD will identify high-risk patients who require more frequent monitoring.

This study provides granular evidence that genetic predisposition, particularly the PNPLA3 G/G genotype, significantly influences the trajectory of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), with a more pronounced impact emerging after the fourth decade of life. These findings highlight the importance of incorporating genetic risk assessment into MASLD management, as it allows for the early identification of high-risk individuals who may benefit from more frequent monitoring and targeted interventions. Given the rising global burden of MASLD, clinicians, researchers, and policymakers should consider integrating genetic stratification into existing risk assessment frameworks to refine screening and surveillance strategies. By optimizing patient selection for non-invasive fibrosis assessment and potential therapeutic interventions, this approach could enhance precision medicine efforts and may improve long-term outcomes.

With the increasing need for accurate liver disease diagnostics, non-invasive imaging techniques with rapid and precise quantitative measurements need to be established. This study introduced and validated the application of simultaneous multi-relaxation-time imaging (TXI) for the quantitative assessment of liver tissue by simultaneously acquiring proton density fat fraction (PDFF), lateral relaxation rate (R2*), and longitudinal relaxation time (T1) maps. It aimed to compare the accuracy and consistency of TXI with established quantitative magnetic resonance imaging (MRI) techniques, such as three-dimensional variable flip angle (VFA) T1 mapping, and multi-point quantitative Dixon (qDixon), in healthy volunteers and patients diagnosed with non-alcoholic fatty liver disease (NAFLD).

A prospective cohort of 35 healthy volunteers (mean age: 52±13 years, 21 women) and nine NAFLD patients (mean age: 48±13 years, 6 women) underwent liver MRI using TXI, VFA T1 mapping, and qDixon sequences. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess inter-observer agreement and measurement consistency. Paired T-tests and Pearson correlation coefficients were used to compare the TXI measurements with those from conventional MRI techniques. Differences between the healthy volunteers and NAFLD patients were evaluated using the independent sample T-test.

The ICCs for the TXI-derived T1, R2*, and PDFF in healthy volunteers were 0.985 [95% confidence interval (CI): 0.971-0.993], 0.999 (95% CI: 0.998-1.000), and 0.995 (95% CI: 0.990-0.997), respectively, indicating excellent agreement. The regression analysis revealed strong correlations between the TXI and reference MRI measurements for the T1 (R2=0.895), R2* (R2=0.984), and PDFF (R2=0.894) values with no significant differences (P=0.713, 0.090, and 0.072, respectively). Statistically significant differences were observed in the R2* (P=0.045) and PDFF (P<0.001) values between the NAFLD patients and healthy volunteers, but no significant difference was observed in the T1 values (P=0.965). Multiparametric imaging showed that TXI provides comprehensive liver tissue characterization, consistent with conventional MRI techniques.

TXI offers a rapid and reliable method for the simultaneous acquisition of T1, R2*, and PDFF maps, and has high consistency with established quantitative MRI techniques. This approach has significant potential for non-invasive liver tissue characterization in clinical settings, particularly in the diagnosis and monitoring of conditions such as NAFLD.

Liver imaging and transient elastography (TE) are both tools used to assess liver fibrosis and steatosis among people with hepatitis C virus (HCV) infection. However, the diagnostic accuracy of conventional imaging in detecting fibrosis and steatosis in this patient population remains unclear.

To investigate the correlation between steatosis and fibrosis and abnormal findings on liver imaging in patients with HCV.

We conducted a retrospective cross-sectional analysis of patients with HCV at Grady Liver Clinic who had TE exams between 2018-2019. We analyzed the correlation of controlled attenuation parameter and liver stiffness measurement on TE and abnormal findings on liver imaging. Liver imaging findings (hepatic steatosis, increased echogenicity, cirrhosis, and chronic liver disease) were further evaluated for their diagnostic performance in detecting fibrosis (≥ F2, ≥ F3, ≥ F4) and steatosis (≥ S1, ≥ S2, ≥ S3).

Of 959 HCV patients who underwent TE, 651 had liver imaging. Higher controlled attenuation parameter scores were observed in patients with abnormal liver findings (P = 0.0050), hepatic steatosis (P < 0.0001), and increased echogenicity (P < 0.0001). Higher liver stiffness measurement values were also noted in those with abnormal liver (P < 0.0001) and increased echogenicity (P = 0.0026). Steatosis severity correlated with hepatic steatosis (r = 0.195, P < 0.001) and increased echogenicity (r = 0.209, P < 0.001). For fibrosis detection, abnormal liver imaging had moderate sensitivity (81.7%) and specificity (70.4%) for cirrhosis (≥ F4), while cirrhosis on imaging had high specificity (99.2%) but low sensitivity (18.3%). Increased echogenicity showed high specificity (92.8%) but low sensitivity (20.9%) for steatosis detection.

Liver imaging detects advanced fibrosis and steatosis but lacks early-stage sensitivity. Integrating TE with imaging may improve evaluation in patients with HCV.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has a high global incidence and associated with increased lipid accumulation in hepatocytes, elevated hepatic enzyme levels, liver fibrosis, and hepatic carcinoma. Despite decades of research and significant advancements, the treatment of MASLD still faces formidable challenges. Nanoprobes for diagnostics and nanomedicine for targeted drug delivery to the liver present promising options for MASLD diagnosis and treatment, enhancing both imaging contrast and bioavailability. Here, we review recent advances in nanotechnology applied to MASLD diagnosis and treatment, specifically focusing on drug delivery systems targeting hepatocytes, hepatic stellate cells, Kupffer cells, and liver sinusoidal endothelial cells. This review aims to provide an overview of nanomedicine's potential in early MASLD diagnosis and therapeutic interventions, addressing related complications.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.

Amidst the global rise of metabolic dysfunction-associated steatotic liver disease (MASLD), driven by increasing obesity rates, there is a pressing need for precise, non-invasive diagnostic tools. Our research aims to validate MRI Proton Density Fat Fraction (MRI-PDFF) utility, compared to liver biopsy, in grading hepatic steatosis in MASLD.

A systematic search was conducted across Embase, PubMed/Medline, Scopus, and Web of Science until January 13, 2024, selecting studies that compare MRI-PDFF with liver biopsy for hepatic steatosis grading, defined as grades 0 (< 5% steatosis), 1 (5-33% steatosis), 2 (34-66% steatosis), and 3 (> 66% steatosis).

Twenty-two studies with 2844 patients were included. The analysis showed high accuracy of MRI-PDFF with AUCs of 0.97 (95% CI = 0.96-0.98) for grade 0 vs ≥ 1, 0.91 (95% CI = 0.88-0.93) for ≤ 1 vs ≥ 2, and 0.91 (95% CI = 0.88-0.93) for ≤ 2 vs 3, diagnostic odds ratio (DOR) from 98.74 (95% CI = 58.61-166.33) to 23.36 (95% CI = 13.76-39.68), sensitivity and specificity from 0.93 (95% CI = 0.88-0.96) to 0.76 (95% CI = 0.63-0.85) and 0.93 (95% CI = 0.88-0.96) to 0.89 (95% CI = 0.84-0.93), respectively. Likelihood ratio (LR) + ranged from 13.3 (95% CI = 7.4-24.0) to 7.2 (95% CI = 4.9-10.5), and LR - from 0.08 (95% CI = 0.05-0.13) to 0.27 (95% CI = 0.17-0.42). The proposed MRI-PDFF threshold of 5.7% for liver fat content emerges as a potential cut-off for the discrimination between grade 0 vs ≥ 1 (p = 0.075).

MRI-PDFF is a precise non-invasive technique for diagnosing and grading hepatic steatosis, warranting further studies to establish its diagnostic thresholds.

This study underscores the high diagnostic accuracy of MRI-PDFF for distinguishing between various grades of hepatic steatosis for early detection and management of MASLD, though further research is necessary for broader application.

MRI-PDFF offers precision in diagnosing and monitoring hepatic steatosis. The diagnostic accuracy of MRI-PDFF decreases as the grade of hepatic steatosis advances. A 5.7% MRI-PDFF threshold differentiates steatotic from non-steatotic livers.

MRI proton density fat fraction (MRI-PDFF), controlled attenuation parameters (CAP), and attenuation coefficients (AC) are capable of steatosis characterization and may be useful as noninvasive alternatives for diagnosing hepatic steatosis.

This meta-analysis aimed to evaluate the performance of MRI-PDFF, CAP, and AC in grading hepatic steatosis, using histology as the reference standard.

We conducted a comprehensive search of the PubMed, Cochrane Library, Embase, and Web of Science databases until June 2024. The quality of eligible studies was assessed. Pooled sensitivity, specificity, and area under receiver operating characteristic (AUC) curves were calculated using a bivariate random-effects model. Meta-regression analysis, subgroup analysis, and Deeks' test were performed to explore heterogeneity and assess publication bias.

This meta-analysis included 38 studies with 5056 patients with metabolic dysfunction-associated steatotic liver disease. The AUC values for grading steatosis ≥S1, ≥S2, and ≥S3 were 0.99, 0.89, and 0.90 for MRI-PDFF, 0.95, 0.84, and 0.77 for CAP, and 0.97, 0.90, and 0.89 for AC, respectively. CAP demonstrated lower accuracy for detecting steatosis grades ≥S2 and ≥S3 compared to MRI-PDFF (0.89 vs. 0.84, p<0.001; 0.90 vs. 0.77, p<0.001) and AC (0.90 vs. 0.84, p<0.001; 0.89 vs. 0.77, p<0.001). Subgroup analyses revealed that MRI-PDFF and CAP exhibited superior diagnostic performance in diagnosing ≥S2 and ≥S3 steatosis among individuals in Asia, with a body mass index ≤30 kg/m2, and age <51 years.

A direct comparison with CAP showed greater accuracy for MRI-PDFF and AC in diagnosing moderate and severe steatosis, and similar diagnostic performance for MRI-PDFF and AC. For patients with steatosis, AC should be incorporated into routine ultrasound screening.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the umbrella term that comprises metabolic dysfunction-associated steatotic liver, or isolated hepatic steatosis, through to metabolic dysfunction-associated steatohepatitis, the progressive necroinflammatory disease form that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. MASLD is estimated to affect more than one-third of adults worldwide. MASLD is closely associated with insulin resistance, obesity, gut microbial dysbiosis and genetic risk factors. The obesity epidemic and the growing prevalence of type 2 diabetes mellitus greatly contribute to the increasing burden of MASLD. The treatment and prevention of major metabolic comorbidities such as type 2 diabetes mellitus and obesity will probably slow the growth of MASLD. In 2023, the field decided on a new nomenclature and agreed on a set of research and action priorities, and in 2024, the US FDA approved the first drug, resmetirom, for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis with moderate to advanced fibrosis. Reliable, validated biomarkers that can replace histology for patient selection and primary end points in MASH trials will greatly accelerate the drug development process. Additionally, noninvasive tests that can reliably determine treatment response or predict response to therapy are warranted. Sustained efforts are required to combat the burden of MASLD by tackling metabolic risk factors, improving risk stratification and linkage to care, and increasing access to therapeutic agents and non-pharmaceutical interventions.

Background Steatosis is a critical health problem, creating a growing need for opportunistic screening. Early detection may allow for effective treatment and prevention of further liver complications. Purpose To evaluate photon-counting CT (PCCT) fat quantification on contrast-enhanced scans and validate the results against fat quantification via histopathologic assessment, controlled attenuation parameter (CAP) from transient elastography, and MRI proton density fat fraction (PDFF). Materials and Methods In this prospective, observational clinical study, PCCT-derived fat fraction quantification was assessed in participants with known or suspected liver disease. Participants underwent PCCT between February 2022 and January 2024. Participants also underwent biopsy, US with CAP measurement, or MRI with a PDFF sequence for hepatic fat fraction quantification. Liver fat fraction was measured on virtual noncontrast PCCT images using spectral processing software with a three-material decomposition algorithm for fat, liver tissue, and iodine. Steatosis was graded for each modality. Correlation between PCCT-based steatosis grades and biopsy- and CAP-based grades was assessed with the Spearman correlation coefficient. Agreement between PCCT and MRI PDFF measurements was assessed with the intraclass correlation coefficient. Receiver operating characteristic curve analysis was conducted to determine the optimal PCCT fat fraction threshold for distinguishing between participants with and those without steatosis. Results The study included 178 participants, of whom 27 (mean age, 60.7 years ± 15.2 [SD]; 18 male participants) underwent liver biopsy, 26 (mean age, 60.0 years ± 18.3; 15 male participants) underwent CAP measurement, and 125 (mean age, 61.2 years ± 13.1; 70 male participants) underwent MRI PDFF measurement. There was excellent agreement between PCCT and MRI PDFF assessment of liver fat fraction (intraclass correlation coefficient, 0.91 [95% CI: 0.87, 0.94]). In stratified analysis, the intraclass correlation coefficient was 0.84 (95% CI: 0.63, 0.93) in participants with known fibrosis and 0.92 (95% CI: 0.88, 0.94) in participants without fibrosis. There was moderate correlation of PCCT-based steatosis grade with histologic (ρ = 0.65) and CAP-based (ρ = 0.45) steatosis grade. Based on the Youden index, the PCCT fat fraction threshold that best discriminated between participants with and those without steatosis was 4.8%, with a maximum achievable sensitivity of 81% (38 of 47) and a specificity of 71% (55 of 78). Conclusion PCCT in a standard clinical setting allowed for accurate estimation of liver fat fraction compared with MRI PDFF-based reference standard measurements. © RSNA, 2025 See also the editorial by Kartalis and Grigoriadis in this issue.

The Hep-Net position paper comes at a significant time in the history of Metabolically Associated Fatty Liver Disease (MAFLD) due to the rapid rise in this disease entity in the past decade. Metabolically Associated Fatty Liver Disease, by its very name, encompasses several common metabolic disease entities, top among those being diabetes and obesity. For Pakistan, the situation is serious as it is among the top 10 countries globally regarding the prevalence of obesity and number one in terms of diabetes, with over a quarter of adults affected. There remains slight ambiguity as regards the nomenclature of MAFLD, with western societies preferring to remove the word "fatty" and substitute with `'steatotic" i.e. MASLD. Regardless of names/titles the metabolic nature of the disease and its management remains the same and fortunately, that is something where universal consensus is present. Under the umbrella of Hep-Net, eminent hepatologists from all over Pakistan have pooled their efforts to formulate guidelines that are specifically tailored to the Pakistani population, its specific lifestyle and relevant interventions that are needed to treat fatty/steatotic liver disease. By virtue of its multi-systemic consequences, metabolic fatty liver disease represents the most significant and expensive disease entity, globally. Prevention, through public education and timely intervention in diagnosed cases will serve to avert a healthcare storm that will far outweigh viral hepatitis.

Endoscopic ultrasound shear wave elastography (EUS-SWE) is a novel modality for liver stiffness measurement. The aims of this study are to evaluate the performance and reliability of EUS-SWE for detecting advanced liver disease in a prospective cohort.

EUS-SWE measurements were prospectively obtained from patients undergoing EUS between August 2020 and March 2023. Liver stiffness measurements were compared between patients with and without advanced liver disease (ALD), defined as stage ≥3, to determine diagnostic accuracy for advanced fibrosis and portal hypertension. Logistic regression was performed to identify variables that impact the reliability of EUS-SWE readings. Select patients underwent paired magnetic resonance elastography (MRE) for liver fibrosis correlation.

Patients with ALD demonstrated higher liver stiffness compared to healthy controls (left lobe: 17.6 vs. 12.7 kPa, P <0.001; median right lobe: 24.8 vs. 11.0 kPa, P <0.001). The area under the receiver operator characteristic (AUROC) for the detection of ALD was 0.73 and 0.80 for left and right lobe measurements, respectively. General anesthesia was associated with reliable EUS-SWE liver readings (odds ratio: 2.73, 95% CI: 1.07-7.39, P =0.040). Left lobe measurements correlated significantly with MRE with an increase of 0.11 kPa (95% CI: 0.05-0.17 kPA) for every 1 kPa increase on EUS-SWE. D.

SWE is a promising technology that can readily be incorporated into standard EUS examinations for the assessment of ALD.

Hepatic steatosis (HS) criteria for living donor liver transplantation (LDLT) donor eligibility should be based on large droplet fat as per Banff consensus recommendations. We aimed to establish magnetic resonance imaging proton density fat fraction cutoffs for HS assessment in potential LDLT donors. This retrospective study included consecutive potential LDLT donors who underwent MRI and liver biopsy between 2013 and 2023 at 2 tertiary institutions, each as development (n = 3062; 2015 men; median [IQR] age of 32 [25-38] y) and external validation (n = 472; 287 men; 35 [26-44] y) data sets. Proton density fat fraction (PDFF) was measured using dedicated MRI sequences. Histologic HS, defined as a large droplet fat fraction, was used as the reference standard. Dual PDFF cutoffs aimed at 95% sensitivity or 95% specificity, for diagnosing histologic HS of ≥10%, ≥20%, ≥30%, and ≥40%, were determined in the development data set using 10-fold cross-validation. The cutoffs were then validated in the external validation data set. The equation for estimating histologic HS from PDFF was also derived using linear regression. The PDFF cutoffs for histologic HS of ≥10%, ≥20%, ≥30%, and ≥40%, targeting 95% sensitivity, were 3.7%, 5.5%, 8.0%, and 10.0%, respectively. External validation demonstrated high sensitivities ≥97.9% with specificities ranging from 60.9% to 95.1%. The PDFF cutoffs targeting 95% specificity were 6.3%, 8.0%, 9.1%, and 10.1%, respectively. External validation rendered high specificities ranging from 88.5% to 95.3%, with sensitivities ranging from 76.6% to 100%. For diagnosing histologic HS ≥30%, which is the most prevalently used threshold for LDLT donor eligibility assessment, the PDFF cutoffs achieved sensitivities and specificities of over 90%. The equation of (Histologic HS = -2.95 + 1.93 × PDFF) was derived.

MR elastography (MRE) at 60 Hz is widely used for staging liver fibrosis. MRE with lower frequencies may provide inflammation biomarkers.

To establish a practical simultaneous dual-frequency liver MRE protocol at both 30 Hz and 60 Hz during a single examination and validate the occurrence of second harmonic waves at 30 Hz.

Retrospective.

One hundred six patients (48 females, age: 50.0 ± 13.4 years) were divided as follows: Cohort One (15 patients with chronic liver disease [CLD] and 25 healthy volunteers) with simultaneous dual-frequency MRE. Cohort Two (66 patients with CLD) with second harmonic MRE.

3-T, single- or dual-frequency MRE at 30 Hz and 60 Hz.

Liver stiffness (LS) in both cohorts was evaluated with manually placed volumetric ROIs by two independent analyzers. Image quality was assessed by three independent readers on a 4-point scale (0-3: none/failed, fair, moderate, excellent) based on the depth of wave propagation with 1/3 incremental penetration. The success rate was derived from the percentage of nonzero quality scores.

Measurement agreement, bias, and repeatability of LS were assessed using intraclass correlation coefficients (ICCs), Bland-Altman plots, and repeatability coefficient (RC). Mann-Whitney U tests were used to evaluate the differences in image quality between different methods. A P-value <0.05 was considered statistically significant.

Success rate was 97.5% in Cohort One and 91% success rate for the second harmonic MRE in Cohort Two. The second harmonic and conventional MRE showed excellent agreement in LS (all ICCs >0.90). The quality scores for the second harmonic wave images were lower than those from the conventional MRE (Z = -4.523).

Compared with conventional and second harmonic methods, simultaneous dual-frequency had better image quality, high success rate and the advantage of intrinsic co-registration, while the second harmonic method can be an alternative if custom waveform is not available.

3 TECHNICAL EFFICACY: Stage 1.

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.

Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain-such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease-technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation.

We aimed to elucidate the value of ultrasound-based biomarkers for predicting the major life-threatening events in metabolic dysfunction-associated steatotic liver disease (MASLD). We established a prospective cohort of 279 patients who underwent two-dimensional shear wave elastography (2D-SWE), ultrasound-guided attenuation parameter (UGAP). An area under the curve analysis was performed to determine the cutoff values of liver stiffness measurements (LSM) by 2D-SWE and attenuation coefficient (AC) by UGAP for a moderate fibrosis and a moderate steatosis. We then classified the cohort into Groups A (low LSM and low AC), B (low LSM and high AC), C (high LSM and high AC), and D (high LSM and low AC). We compared the incidence of events between the groups, and estimated the hazard ratios (HRs) with 95% confidence intervals (CIs). The LSM and AC cut off values were 8.37 kPa and 0.62 dB/cm/MHz, respectively. The cumulative incidence rate in Groups A, B, C, and D were 11.2%, 12.2%, 29.5%, and 31.0%/5years, respectively (p < 0.05). LSM (HRs = 1.20, 95%CIs: 1.09-1.32, p < 0.01), and AC (HRs = 1.62, 95%CIs: 1.04-2.51, p = 0.03) were associated with life-threatening events. A combination of 2D-SWE and UGAP may help identify patients with MASLD at high risk for subsequent life-threatening events.

In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

Many studies have shown a link between physical activity (PA) and nonalcoholic fatty liver disease (NAFLD). However, more research is needed to investigate the relationship between different types of PA and NAFLD. This study aimed to explore the potential link between different types of PA, hepatic steatosis, and liver fibrosis.

A cross-sectional study was conducted using the data set from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. A multiple linear regression model was used to examine the linear relationship between different types of PA, the controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). In addition, smoothing curve fitting and threshold effect analysis were used to depict their nonlinear relationship.

This study involved 5933 adults. Multiple linear regression analysis revealed a significantly negative correlation between leisure-time PA and CAP, while the relationship between occupation-related PA, transportation-related PA, and CAP was not significant. Subgroup analysis further revealed that leisure-time PA was significantly negatively correlated with CAP in women and younger age groups (under 60 y old), while the relationship was not significant in men and older age groups. In addition, there was a significant negative correlation between leisure-time PA and liver fibrosis in men.

Leisure-time PA can prevent hepatic steatosis, and women and young people benefit more. Occupation-related PA is not associated with hepatic steatosis and cannot replace leisure-time PA. In men, increasing leisure-time PA is more effective in preventing liver fibrosis.

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.

Context: Previous studies have reported that pregnant women with non-alcoholic fatty liver disease (NAFLD) face an increased risk of gestational hypertension (GH) and preeclampsia (PE). However, no study has assessed the relationship between the Hepatic Steatosis Index (HSI), a biomarker for NAFLD, in early pregnancy and the subsequent risk of GH and PE. Objective: We aimed to investigate the relationship between HSI in early pregnancy and the risks of GH and PE in Chinese women. Methods: Based on the China Birth Cohort Study conducted from February 2018 to December 2022, this prospective cohort study collected liver enzyme and body mass index data from pregnant participants during 6-13+6 gestational weeks. The incidences of GH and PE were monitored until delivery. Results: This study included 39,114 pregnant women, and GH and PE incidences were 4.2% and 4.1%, respectively. After multivariable adjustment, the risks of GH (Q2: OR = 1.35, 95% CI = 1.13-1.62; Q3: OR = 1.86, 95% CI = 1.57-2.20; Q4: OR = 3.81, 95% CI = 3.25-4.46) and PE (Q2: OR = 1.22, 95% CI = 1.01-1.47; Q3: OR = 1.96, 95% CI = 1.65-2.32; Q4: OR = 3.60, 95% CI = 3.07-4.22) significantly increased with higher HSI quartiles. Further analysis indicated that compared to women aged 35 years or older, HSI in pregnant women under 35 years had relatively stronger predictive value for GH (OR ≥ 35 = 4.527, 95% CI = 3.762-5.446 vs. OR < 35 = 2.325, 95% CI = 1.729-3.128) and PE (OR ≥ 35 = 4.13, 95% CI = 3.433-4.983 vs. OR < 35 = 2.348, 95% CI = 1.736-3.176). Conclusion: Elevated HSI may be associated with an increased risk of GH and PE.

The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has led to an increased occurrence of steatotic liver grafts (SLG) in liver transplantation (LT). However, the implications of SLG on post-transplant de novo hepatic steatosis (PTHS) and advanced fibrosis (≥F3) remain uncertain. This study aimed to characterize PTHS and ≥ F3 using magnetic resonance imaging (MRI) in patients who underwent LT for non-MASLD indications and to examine their relationship with SLG.

Post-LT patients with implant biopsy fat content data were recruited for MRI assessments. MRI-proton density fat fraction (MRI-PDFF) and MR elastography (MRE) were performed using a 1.5 Tesla Optima 450 W MR scanner with a 3D volumetric sequence. PTHS and ≥ F3 were defined as MRI-PDFF ≥5% and MRE ≥3.64 kPa, respectively. SLG was defined as implant biopsy fat content ≥5%.

A total of 292 patients (70.5% men, median age at LT: 51.9 years, 22.6% with SLG) were recruited. The majority (73.6%) were transplanted for hepatitis B virus (HBV)-related complications. MRI performed at a median of 12.2 years post-LT identified PTHS in 27.4 and 10.6% of patients. PTHS was independently associated with SLG (OR 2.067, 95% CI 1.082-3.951), central obesity (OR 3.952, 95% CI 1.768-8.832), and hypertension (OR 2.510, 95% CI 1.268-4.966). In contrast, ≥F3 was associated with sex, change in BMI, and abnormal liver biochemistry but not with PTHS or SLG.

MRI identified a high prevalence of PTHS, which was associated with SLG and metabolic risk factors among Chinese patients transplanted for non-MASLD indications. Advanced graft fibrosis was not associated with PTHS or SLG.

To explore the connection between metabolic parameters and the severity of hepatic steatosis determined through ultrasound in elderly individuals with metabolic dysfunction-associated fatty liver disease (MAFLD).

4,663 senior individuals who were 65 years of age or older were included in this research. They were examined physically at the Ninghai Street Community Health Service Center in Yantai City between June 7, 2021, and October 15, 2021. There were two categories of individuals identified: the MAFLD group (n = 2,985) and the non-MAFLD group (n = 1,678). Based on liver ultrasonography results, individuals in the MAFLD group were further separated into three groups: mild (n = 2,104), moderate (n = 766), and severe (n = 115). To identify indicators of risk for the severity of hepatic steatosis, metabolic data was contrasted between the groups employing logistic regression.

In comparison to the non-MAFLD group, the MAFLD group showed significantly elevated levels of body mass index (BMI), blood pressure, gender, age, lipid profile, alanine transaminase (ALT), and fasting blood glucose (FBG; p < 0.05). Among individuals with MAFLD, there was a positive correlation between BMI, FBG, ALT, and aspartate transaminase (AST) levels and the severity of hepatic steatosis (p < 0.05). Logistic regression analysis indicated that BMI, female gender, FBG, ALT, triglycerides (TG), and serum uric acid (SUA) constituted risk factors for increased severity of hepatic steatosis in MAFLD.

The severity of hepatic steatosis in elderly MAFLD patients is significantly correlated with female gender, BMI, ALT, FBG, TG, and SUA.

Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system.

A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references.

ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is a broad condition characterized by lipid accumulation in the liver tissue, which can progress to fibrosis and cirrhosis if left untreated. Traditionally, liver biopsy is the gold standard for evaluating fibrosis. However, non-invasive biomarkers of liver fibrosis are developed to assess the fibrosis without the risk of biopsy complications. Novel serum biomarkers have emerged as a promising tool for non-invasive assessment of liver fibrosis in MAFLD patients. Several studies have shown that elevated levels of Mac-2 binding protein glycosylation isomer (M2BPGi) are associated with increased liver fibrosis severity in MAFLD patients. This suggests that M2BPGi could serve as a reliable marker for identifying individuals at higher risk of disease progression. Furthermore, the use of M2BPGi offers a non-invasive alternative to liver biopsy, which is invasive and prone to sampling errors. Overall, the usage of M2BPGi in assessing liver fibrosis in MAFLD holds great promise for improving risk stratification and monitoring disease progression in affected individuals. Further research is needed to validate its utility in clinical practice and establish standardized protocols for its implementation.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in the United States. It is characterized by steatosis in the liver and is potentially reversible. Risk factors include obesity, type 2 mellitus, and other metabolic disorders. Metabolic dysfunction-associated steatohepatitis (MASH), a more severe form of MASLD, puts patients at risk for cirrhosis, liver decompensation, and liver cancer. Diet, exercise, and weight loss are the cornerstones of management. Although only 1 medication has been approved for treatment of MASH, other pharmacotherapies and surgeries that aid weight loss and optimize metabolic risk factors can be used. Early diagnosis and intervention are important to prevent progression to cirrhosis and its complications, including cancer.

The fatty liver disease represents a complex, multifaceted challenge, requiring a multidisciplinary approach for effective management and research. This article uses conventional and advanced imaging techniques to explore the etiology, imaging patterns, and quantification methods of hepatic steatosis. Particular emphasis is placed on the challenges and advancements in the imaging diagnostics of fatty liver disease. Techniques such as ultrasound, CT, MRI, and elastography are indispensable for providing deep insights into the liver's fat content. These modalities not only distinguish between diffuse and focal steatosis but also help identify accompanying conditions, such as inflammation and fibrosis, which are critical for accurate diagnosis and management.

It is not clear if conventional liver fat cutoff of 5.56% weight which has been used for identifying fatty liver in western populations is also applicable for Asians. In Asian women of reproductive age, we evaluate the optimum metabolic syndrome (MetS)-linked liver fat cutoff, the specific metabolomic alterations apparent at this cutoff, as well as prospective associations of preconception liver fat levels with gestational dysglycemia.

Liver fat (measured by magnetic resonance spectroscopy), MetS, and nuclear magnetic resonance (NMR)-based plasma metabolomic profiles were assessed in 382 Asian women, who were planning to conceive. Ninety-eight women went on to become pregnant and received an oral glucose tolerance test at week 26 of gestation.

The optimum liver fat cutoff for diagnosing MetS was 2.07%weight. Preconception liver fat was categorized into Low (liver fat < 2.07%), Moderate (2.07% ≤ liver fat < 5.56%), and High (liver fat ≥ 5.56%) groups. Individual MetS traits showed worsening trends, going from Low to Moderate to High groups. Multiple plasma metabolomic alterations, previously linked to incident type 2 diabetes (T2D), were already evident in the Moderate group (adjusted for ethnicity, age, parity, educational attainment, and BMI). Both a cross-sectional multi-metabolite score for incident T2D and mid-gestational glucose area under the curve showed increasing trends, going from Low to Moderate to High groups (p < 0.001 for both). Gestational diabetes incidence was 2-fold (p = 0.23) and 7-fold (p < 0.001) higher in the Moderate and High groups relative to the Low group.

In Asian women of reproductive age, moderate liver fat accumulation below the conventional fatty liver cutoff was not metabolically benign and was linked to gestational dysglycemia. The newly derived cutoff can aid in screening individuals before adverse metabolic phenotypes have consolidated, which provides a longer window for preventive strategies.

Liver fibrosis, a critical predictor of the prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD), is traditionally diagnosed via biopsy. Nevertheless, non-invasive alternatives, such as serum biomarkers, vibration-controlled transient elastography, and magnetic resonance elastography, have become prominent because of the limitations of biopsies. Serum biomarkers, such as fibrosis-4 index and NFS Score, are also used widely, offering reliable diagnostic performance for advanced fibrosis. Vibration-controlled transient elastography and shear wave elastography provide further non-invasive evaluations with high diagnostic accuracy, particularly for advanced fibrosis, but the results may be affected by factors such as obesity. Magnetic resonance elastography, with superior diagnostic accuracy and operator independence, is a promising method, but its high cost and limited availability restrict its widespread use. Emerging algorithms, such as NIS4, FAST, or MAST score, have strong potential in identifying high-risk metabolic dysfunction-associated steatohepatitis patients. The integration of multiple non-invasive methods can optimize diagnostic accuracy, reducing the need for invasive biopsies while identifying patients at risk of liver-related complications. Further research is needed to refine these diagnostic tools and improve accessibility.

Liver fibrosis is a common pathway shared by all forms of progressive chronic liver disease. There is an unmet clinical need for noninvasive imaging tools to diagnose and stage fibrosis, which presently relies heavily on percutaneous liver biopsy. Here we explored the feasibility of using a novel type I collagen-targeted manganese (Mn)-based MRI probe, Mn-CBP20, for liver fibrosis imaging. In vitro characterization of Mn-CBP20 demonstrated its high binding affinity for human collagen (K d = 9.6 μM), high T1-relaxivity (48.9 mM-1s-1 at 1.4T and 27°C), and kinetic inertness to Mn release under forcing conditions. We demonstrated MRI using Mn-CBP20 performs comparably to previously reported gadolinium-based type I collagen-targeted probe EP-3533 in a mouse model of carbon tetrachloride-induced liver fibrosis, and further demonstrate efficacy to detect fibrosis in a diet-induced mouse model of metabolically-associated steatohepatitis. Biodistribution studies using the Mn-CBP20 radio-labeled with the positron-emitting 52Mn isotope demonstrate efficient clearance of Mn-CBP20 primarily via renal excretion. Mn-CBP20 represents a promising candidate that merits further evaluation and development for molecular imaging of liver fibrosis.