Background: Liver ultrasound segmentation is challenging due to low image quality and variability. While deep learning (DL) models have been widely applied for medical segmentation, generic pre-configured models may not meet the specific requirements for targeted areas in liver ultrasound. Quantitative ultrasound (QUS) is emerging as a promising tool for liver fat measurement; however, accurately segmenting regions of interest within liver ultrasound images remains a challenge. Methods: We introduce a generalizable framework using an adaptive evolutionary genetic algorithm to optimize deep learning models, specifically U-Net, for focused liver segmentation. The algorithm simultaneously adjusts the depth (number of layers) and width (neurons per layer) of the network, dropout, and skip connections. Various architecture configurations are evaluated based on segmentation performance to find the optimal model for liver ultrasound images. Results: The model with a depth of 4 and filter sizes of [16, 64, 128, 256] achieved the highest mean adjusted Dice score of 0.921, outperforming the other configurations, using three-fold cross-validation with early stoppage. Conclusions: Adaptive evolutionary optimization enhances the deep learning architecture for liver ultrasound segmentation. Future work may extend this optimization to other imaging modalities and deep learning architectures.

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.

The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)-derived proton density fat fraction (MRIderived PDFF) as the reference standard.

Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness.

AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively).

AC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.

Cross-sectional studies have demonstrated the association of skeletal muscle mass with metabolic-associated fatty liver disease (MAFLD), while longitudinal data are scarce. We aimed to explore the impact of changes in relative skeletal muscle mass on the MAFLD treatment response.

MAFLD patients undergoing magnetic resonance imaging-based proton density fat fraction for liver fat content (LFC) assessments and bioelectrical impedance analysis before and after treatment (orlistat, meal replacement, lifestyle modifications) were enrolled. Appendicular muscle mass (ASM) was adjusted by weight (ASM/W).

Overall, 256 participants were recruited and divided into two groups: with an ASM/W increase (n=166) and without an ASM/W increase (n=90). There was a great reduction in LFC in the group with an ASM/W increase (16.9% versus 8.2%, P < 0.001). However, the change in LFC in the group without an ASM/W increase showed no significant difference (12.5% versus 15.0%, P > 0.05). △ASM/W Follow-up-Baseline [odds ratio (OR)=1.48, 95% confidence interval (CI) 1.05-2.07, P = 0.024] and △total fat mass (OR=1.45, 95% CI 1.12-1.87, P = 0.004) were independent predictors for steatosis improvement (relative reduction of LFC ≥ 30%). The subgroup analysis showed that, despite without weight loss, decrease in HOMA-IR (OR=6.21, 95% CI 1.28-30.13, P=0.023), △total fat mass Baseline -Follow-up (OR=3.48, 95% CI 1.95-6.21, P <0.001 and △ASM/W Follow-up-Baseline (OR=2.13, 95% CI 1.12-4.05, P=0.022) independently predicted steatosis improvement.

ASM/W increase and loss of total fat mass benefit the resolution of liver steatosis, independent of weight loss for MAFLD.

We aimed to evaluate and compare the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) v2018 for hepatocellular carcinoma (HCC) ≤ 3.0 cm on gadoxetic acid-enhanced MRI according to the etiology of cirrhosis.

Thirty-eight patients with alcoholic liver cirrhosis (ALC) and 37 with hepatitis C virus-related cirrhosis (HCV) who underwent preoperative MRI and subsequent surgical resection or transplantation were included. For comparison groups, patients with hepatitis B virus-related cirrhosis (HBV) were included by 1:1 matching with HCV and ALC groups according to age, lesion size, and Child-Pugh classification. The imaging characteristics of background liver and focal lesions were analyzed. The diagnostic performance of LI-RADS was compared between HCV and HBV groups, and between ALC and HBV groups.

ALC group showed significantly higher frequency of hepatic steatosis (25.8 % vs. 6.1 %, p =.04) and lower frequency of nonperipheral washout on portal venous-phase in HCC (63.2 % vs. 97.1 %, p <.001) compared with HBV group. ALC group showed significantly lower sensitivity than HBV group (52.6 % vs. 88.6 %, p<.001). No significant differences in diagnostic performance were found between HCV and HBV groups. In ALC group, hepatobiliary-phase hypointensity provided significantly higher sensitivity (76.3 % vs. 52.6 %, p =.008).

The sensitivity of LI-RADS for diagnosing HCC ≤ 3.0 cm was significantly lower in the ALC group than in the HBV group.

Liver function tests are commonly obtained in symptomatic and asymptomatic patients. Various overlapping lab patterns can be seen due to derangement of hepatocytes and bile ducts function. Imaging tests are pursued to identify underlying etiology and guide management based on the lab results. Liver function tests may reveal mild, moderate, or severe hepatocellular predominance and can be seen in alcoholic and nonalcoholic liver disease, acute hepatitis, and acute liver injury due to other causes. Cholestatic pattern with elevated alkaline phosphatase with or without elevated γ-glutamyl transpeptidase can be seen with various causes of obstructive biliopathy. Acute or subacute cholestasis with conjugated or unconjugated hyperbilirubinemia can be seen due to prehepatic, intrahepatic, or posthepatic causes. We discuss the initial and complementary imaging modalities to be used in clinical scenarios presenting with abnormal liver function tests. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

We aimed to evaluate the effect of hepatic steatosis (HS) on liver volume and to develop a formula to estimate lean liver volume correcting the HS effect.

This retrospective study included healthy adult liver donors who underwent gadoxetic acid-enhanced MRI and proton density fat fraction (PDFF) measurement from 2015 to 2019. The degree of HS was graded at 5% PDFF intervals from grade 0 (no HS; PDFF < 5.5%). Liver volume was measured with hepatobiliary phase MRI using deep learning algorithm, and standard liver volume (SLV) was calculated as the reference lean liver volume. The association between liver volume and SLV ratio with PDFF grades was evaluated using Spearman's correlation (ρ). The effect of PDFF grades on liver volume was evaluated using the multivariable linear regression model.

The study population included 1038 donors (mean age, 31 ± 9 years; 689 men). Mean liver volume to SLV ratio increased according to PDFF grades (ρ = 0.234, p < 0.001). The multivariable analysis indicated that SLV (β = 1.004, p < 0.001) and PDFF grade*SLV (β = 0.044, p < 0.001) independently affected liver volume, suggesting a 4.4% increase in liver volume per one-point increment in the PDFF grade. PDFF-adjusted lean liver volume was estimated using the formula, liver volume/[1.004 + 0.044 × PDFF grade]. The mean estimated lean liver volume to SLV ratio approximated to one for all PDFF grades, with no significant association with PDFF grades (p = 0.851).

HS increases liver volume. The formula to estimate lean liver volume may be useful to adjust for the effect of HS on liver volume.

• Hepatic steatosis increases liver volume. • The presented formula to estimate lean liver volume using MRI-measured proton density fat fraction and liver volume may be useful to adjust for the effect of hepatic steatosis on measured liver volume.

Hepatic steatosis without specific causes (e.g., viral infection, alcohol abuse, etc.) is called non-alcoholic fatty liver disease (NAFLD), which ranges from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), fibrosis, and NASH-related cirrhosis. Despite the usefulness of the standard grading system, liver biopsy has several limitations. In addition, patient acceptability and intra- and inter-observer reproducibility are also concerns. Due to the prevalence of NAFLD and limitations of liver biopsies, non-invasive imaging methods such as ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) that can reliably diagnose hepatic steatosis have developed rapidly. US is widely available and radiation-free but cannot examine the entire liver. CT is readily available and helpful for detection and risk classification, significantly when analyzed using artificial intelligence; however, it exposes users to radiation. Although expensive and time-consuming, MRI can measure liver fat percentage with magnetic resonance imaging proton density fat fraction (MRI-PDFF). Specifically, chemical shift-encoded (CSE)-MRI is the best imaging indicator for early liver fat detection. The purpose of this review is to provide an overview of each imaging modality with an emphasis on the recent progress and current status of liver fat quantification.

To assess interobserver variability in ultrasound-based quantitative liver fat content measurements and to determine how much time these quantitative ultrasound (QUS) techniques require.

One hundred patients with known or suspected of having nonalcoholic fatty liver disease were included in this prospective study. Two observers who were blinded to each other measurements performed tissue attenuation imaging (TAI) and tissue scatter distribution imaging (TSI) techniques independently. Both observers assessed hepatic steatosis visually and obtained 5 measurements for each QUS technique and the median values of the measurements were recorded. Spearman's correlation test was used to assess the correlation between QUS measurements and visual hepatic stetaosis grades. Intraclass correlation coefficient (ICC) test was used to assess interobserver variability in QUS measurements.

The median values of TAI measurements for the observers 1 and 2 were 0.75 and 0.74 dB/cm/MHz, respectively. The median values of TSI measurements for the observers 1 and 2 were 93.53 and 92.58, respectively. The interobserver agreement in TAI (ICC: 0.970) and TSI (ICC: 0.938) measurements were excellent. The mean of the required time period for TAI technique were 55.1 ± 7.8 and 59.9 ± 6.6 seconds for the observers 1 and 2, respectively. The mean of the required time period for TSI technique were 49.1 ± 5.8 and 54.1 ± 5.4 seconds for the observers 1 and 2, respectively.

The current study revealed that both TAI and TSI techniques are highly reproducible and can be implemented into daily practice with little additional time requirement.

Non-alcoholic fatty liver disease is currently the most common chronic liver disease, affecting up to 25% of the global population. Simple fatty liver, in which fat is deposited in the liver without fibrosis, has been regarded as a benign disease in the past, but it is now known to be prognostic. In the future, more emphasis should be placed on the quantification of liver fat. Traditionally, fatty liver has been assessed by histological evaluation, which requires an invasive examination; however, technological innovations have made it possible to evaluate fatty liver by non-invasive imaging methods, such as ultrasonography, computed tomography, and magnetic resonance imaging. In addition, quantitative as well as qualitative measurements for the detection of fatty liver have become available. In this review, we summarize the currently used qualitative evaluations of fatty liver and discuss quantitative evaluations that are expected to further develop in the future.

The recently developed ultrasound-based hepatic fat quantification tools have the potential to be implemented in daily practice with wide acceptance due to inherited advantages of ultrasound technology. Researchers intensively focused on this topic and the accumulated evidences that support clinical usefulness of these tools. However, differences in the researcher-dependent factors of the utilized MRI-PDFF technique, the recommended reference standard, may hinder the better understanding of the diagnostic performances of these tools. Therefore, a standardized approach for MRI-PDFF technique, which is established with international consensus may be considered as important.

In patients with nonalcoholic fatty liver disease, liver fibrosis was associated with a higher risk of cardiovascular events. However, the relationship between liver fibrosis scores and clinical outcomes in patients with cardiovascular disease remains unclear.

Searching from PubMed, EMBASE and Cochrane Library databases yielded cohort studies that reported adjusted effect size between liver fibrosis scores (Fibrosis-4 score [FIB-4] or NAFLD fibrosis score [NFS]) and prognosis in patients with cardiovascular disease. The effect size was computed using a random-effects model.

This meta-analysis included twelve cohort studies involving 25,252 patients with cardiovascular disease. Participants with the highest baseline level of FIB-4 or NFS had a significantly increased risk of cardiovascular events (FIB-4, HR: 1.75, 95% CI: 1.53-2.00, I ²  = 0%; NFS, HR: 1.92, 95% CI: 1.50-2.47, I ²  = 47%). This finding was consistent with the analysis of FIB-4 or NFS as a continuous variable (per 1-unit increment FIB-4, HR: 1.15, 95% CI: 1.06-1.24, I ²  = 72%; NFS, HR: 1.15, 95% CI: 1.07-1.24, I ²  = 71%). Furthermore, participants with the highest levels of FIB-4 or NFS had a greater risk of cardiovascular mortality (FIB-4, HR: 2.07, 95% CI: 1.19-3.61, I ²  = 89%; NFS, HR: 3.72, 95% CI: 2.62-5.29, I ²  = 60%) and all-cause mortality (FIB-4, HR: 1.81, 95% CI: 1.24-2.66, I ²  = 90%; NFS, HR: 3.49, 95% CI: 2.82-4.31, I ²  = 25%). This result was also consistent as a continuous variable.

Higher levels of FIB-4 and NFS are related to an increased risk of cardiovascular events, cardiovascular mortality and all-cause mortality in patients with cardiovascular disease.

Based on the renaissance of dynamic preservation techniques, extended criteria donor (ECD) livers reclaimed a valuable eligibility in the transplantable organ pool. Being more vulnerable to ischemia, ECD livers carry an increased risk of early allograft dysfunction, primary non-function and biliary complications and, hence, unveiled the limitations of static cold storage (SCS). There is growing evidence that dynamic preservation techniques-dissimilar to SCS-mitigate reperfusion injury by reconditioning organs prior transplantation and therefore represent a useful platform to assess viability. Yet, a debate is ongoing about the advantages and disadvantages of different perfusion strategies and their best possible applications for specific categories of marginal livers, including organs from donors after circulatory death (DCD) and brain death (DBD) with extended criteria, split livers and steatotic grafts. This review critically discusses the current clinical spectrum of livers from ECD donors together with the various challenges and posttransplant outcomes in the context of standard cold storage preservation. Based on this, the potential role of machine perfusion techniques is highlighted next. Finally, future perspectives focusing on how to achieve higher utilization rates of the available donor pool are highlighted.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an estimated prevalence of up to 30% in the general population and higher in people with type 2 diabetes. The assessment of liver fat content is essential to help identify patients with or who are at risk for NAFLD and to follow their disease over time. The American Institute of Ultrasound in Medicine-RSNA Quantitative Imaging Biomarkers Alliance Pulse-Echo Quantitative Ultrasound Initiative was formed to help develop and standardize acquisition protocols and to better understand confounding factors of US-based fat quantification. The three quantitative US parameters explored by the initiative are attenuation, backscatter coefficient, and speed of sound. The purpose of this review is to present the current state of attenuation imaging for fat quantification and to provide expert opinion on examination performance and interpretation. US attenuation methods that need further study are outlined.

Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and its prevalence is increasing globally. NAFLD is a multifaceted disorder, and its spectrum includes steatosis to steatohepatitis, which may evolve to advanced fibrosis and cirrhosis. In addition, the presence of NAFLD is independently associated with a higher cardiometabolic risk and increased mortality rates. Considering that the vast majority of individuals with NAFLD are mainly asymptomatic, early diagnosis of non-alcoholic steatohepatitis (NASH) and accurate staging of fibrosis risk is crucial for better stratification, monitoring and targeted management of patients at risk. To date, liver biopsy remains the gold standard procedure for the diagnosis of NASH and staging of NAFLD. However, due to its invasive nature, research on non-invasive tests is rapidly increasing with significant advances having been achieved during the last decades in the diagnostic field. New promising non-invasive biomarkers and techniques have been developed, evaluated and assessed, including biochemical markers, imaging modalities and the most recent multi-omics approaches. Our article provides a comprehensive review of the currently available and emerging non-invasive diagnostic tools used in assessing NAFLD, also highlighting the importance of accurate and validated diagnostic tools.

To assess chronic liver disease (CLD) using multiparametric US in a private practice setting in a cohort of patients with increased skin-to-liver distance.

110 consecutive patients with increased skin-to-liver distance scheduled for US assessment of CLD were reviewed for study completion time, liver stiffness values (LS), attenuation imaging, and shear wave dispersion slope. The ROI was placed 2 cm below the liver capsule. The study included patients with NAFLD/NASH (68), hepatitis C (30), prior Fontan surgery (1), elevated liver function tests (5), alcohol abuse (3), hepatitis B (2), and primary biliary cirrhosis (1). IQR/M values were obtained. Comparison of less experienced sonographers (LES) and more experienced sonographers (MES) were evaluated through Student's t test for independent data. Pearson coefficient r of correlation among quantitative variables was calculated.

The mean time to perform the exam was 129.7 ± 62.1 s. There was a statistically significant difference between LES and MES. The mean IQR/M for LS was 12.3 ± 5.5% m/s. Overall, in a cohort of difficult patients, 4.5% of LS values were not reliable. Fat quantification using attenuation imaging had a mean value of 0.60 ± 0.15 dB/cm/MHz (range 0.35-0.98 cm/dB/MHz) with an IQR/M of 14.7 ± 9.2%. Less reliable measurements of steatosis were obtained in 4.5% of patients. The mean shear wave dispersion slope was 12.74 ± 4.05 (m/s)/kHz (range 7.7-27.5 (m/s)/kHz) with an IQR/M of 38.7 ± 20.2% (range 3-131%). 20.9% of patients had values suggestive of compensated advanced chronic liver disease (cACLD).

Multiparametric US can provide assessment of CLD in less than 3 min in most patients and identify patients at risk for cACLD.

Early detection of fatty-liver disease is important before further aggravations of the disease, such as cirrhosis, can develop. In this study, we developed a low-cost, movable single-sided magnet for in vivo liver fat quantification. A gradient field of 73.5 G/cm and a field strength of 0.0725 T were obtained by structurally optimizing the concave U-shaped magnet, on which the region of interest (ROI) was a curved shape about 0.4 mm thick, 8 cm above the surface of the radiofrequency (RF) coil. We constructed a prototype nuclear magnetic-resonance (NMR) relaxometry system based on this optimized magnet. Subsequent phantom experiments demonstrated the effectiveness of the single-sided magnet in evaluating different proton density fat fraction (PDFF) phantoms. As expected, the results of the six phantoms showed good positive correlation between PDFF and the fitted fat amplitude, which suggested that single-sided NMR relaxometry could be used to quantify liver fat in vivo.

New ultrasound methods that can be used to quantitatively assess liver fat content have recently been developed. These quantitative ultrasound (QUS) methods are based on the analysis of radiofrequency echoes detected by the transducer, allowing calculation of parameters for quantifying the fat in the liver. In this position paper, after a section dedicated to the importance of quantifying liver steatosis in patients with non-alcoholic fatty liver disease and another section dedicated to the assessment of liver fat with magnetic resonance, the current clinical studies performed using QUS are summarized. These new methods include spectral-based techniques and techniques based on envelope statistics. The spectral-based techniques that have been used in clinical studies are those estimating the attenuation coefficient and those estimating the backscatter coefficient. Clinical studies that have used tools based on the envelope statistics of the backscattered ultrasound are those performed by using the acoustic structure quantification or other parameters derived from it, such as the normalized local variance, and that performed by estimating the speed of sound. Experts' opinions are reported.

The World Trade Center (WTC) attack exposed thousands of workers to toxic chemicals that have been linked to liver diseases and cancers. This study examined the relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis in the WTC General Responders Cohort (GRC).

All low-dose computed tomography (CT) scans of the chest performed on the WTC GRC between September 11, 2001 and December 31, 2018, collected as part of the World Trade Center Health Program, were reviewed. WTC dust exposure was categorized into five groups based on WTC arrival time. CT liver density was estimated using an automated algorithm, statistics-based liver density estimation from imaging. The relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis was examined using univariate and multivariable regression analyses.

Of the 1788 WTC responders, 258 (14.4%) had liver attenuation less than 40 Hounsfield units (HU < 40) on their earliest CT. Median time after September 11, 2001 and the earliest available CT was 11.3 years (interquartile range: 8.0-14.9 years). Prevalence of liver attenuation less than 40 HU was 17.0% for arrivals on September 11, 2001, 16.0% for arrivals on (September 12, 2001 or September 13, 2001), 10.9% for arrivals on September 14-30, 2001, and 9.0% for arrivals on January 10, 2001 or later (p = 0.0015). A statistically significant trend of increasing liver steatosis was observed with earlier arrival times (p < 0.0001). WTC arrival time remained a significant independent factor for decreased liver attenuation after controlling for other covariates.

Early arrival at the WTC site was significantly associated with increasing hepatic steatosis.

To investigate the diagnostic performance of attenuation imaging (ATI) for the assessment of low-grade hepatic steatosis using liver biopsy as the reference standard.

The study included 57 potential donor candidates for living liver transplantation who underwent ATI, transient elastography (TE), and liver biopsy for evaluation of hepatic steatosis between February 2020 and April 2020. The attenuation coefficient (AC) from ATI and the controlled attenuation parameter (CAP) from TE were measured for each participant in a random and blind manner. The histologic hepatic fat fraction (HFF) was graded (S0, < 5%; S1, 5-33%; S2, 33-66%; S3, > 66%). The accuracy of ATI for diagnosing hepatic steatosis was compared with that of CAP using ROC analysis. Correlations between AC and HFF were evaluated, and factors affecting AC were determined by linear regression analysis.

The median HFF was 3% (range: 0-35%), with 31 (54.4%), 24 (42.0%), and 2 (3.5%) participants being graded as S0, S1, and S2, respectively. The AUCs for the ROCs of AC and CAP for the detection of hepatic steatosis were 0.808 (95% CI: 0.682-0.900) and 0.829 (95% CI: 0.706-0.916), respectively, with the difference not being statistically significant (p = 0.762). AC showed 61.5% of sensitivity and 90.3% of specificity. AC was positively correlated with HFF (p < 0.001). HFF was the only factor significantly affecting AC.

ATI showed moderate sensitivity and high specificity in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. Only HFF significantly affected AC.

• Attenuation imaging showed moderate sensitivity and high specificity performance in the diagnosis and quantification of hepatic steatosis in low-grade steatosis without fibrosis. • The diagnostic performance of the attenuation coefficient by attenuation imaging did not significantly differ from that of the controlled attenuation parameter by transient elastography in quantifying low-grade steatosis. • The histopathologically determined hepatic fat fraction was the only factor significantly affecting the attenuation coefficient.

The consistency in steatosis grading between magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and controlled attenuation parameter (CAP) before and after treatment remains unclear. This study aimed to compare the diagnostic accuracy of steatosis grading between MRI-PDFF and CAP using liver biopsy as standard and to evaluate the value of monitoring changes in steatosis grading with CAP during follow-up utilizing MRI-PDFF as a reference.

Consecutive patients from a biopsy cohort and a randomized controlled trial were included in this study and classified into 3 groups (the biopsy, orlistat treatment, and routine treatment subgroups). Hepatic steatosis was measured via MRI-PDFF and CAP at baseline and at the 6th month; the accuracy and cutoffs were assessed in the liver biopsy cohort at baseline.

A total of 209 consecutive patients were enrolled. MRI-PDFF and CAP showed comparable diagnostic accuracy for detecting pathological steatosis [⩾S1, area under the receiver operating characteristic curve (AUC) = 0.984 and 0.972, respectively]; in contrast, CAP presented significantly lower AUCs in grades S2-3 and S3 (0.820 and 0.815, respectively). The CAP values correlated well with the MRI-PDFF values at baseline and at the 6th month (r = 0.809 and 0.762, respectively, both p < 0.001), whereas a moderate correlation in their changes (r = 0.612 and 0.524 for moderate-severe and mild steatosis, respectively; both p < 0.001) was observed. The AUC of CAP change was obtained to predict MRI-PDFF changes of ⩾5% and ⩾10% (0.685 and 0.704, p < 0.001 and p = 0.001, respectively). The diagnostic agreement of steatosis grade changes between MRI-PDFF and CAP was weak (κ = 0.181, p = 0.001).

CAP has decreased value for the initial screening of moderate-severe steatosis and is limited in monitoring changes in steatosis during treatment. The confirmation of steatosis grading with MRI-PDFF remains necessary.

The accurate detection and quantification of hepatic steatosis using a noninvasive method are important for the management of nonalcoholic fatty liver disease. We performed a systematic review and meta-analysis of the accuracy of the ultrasound-measured attenuation coefficient (AC) in the evaluation of hepatic steatosis.

The PubMed, Embase, and Cochrane databases were searched for prospective studies reporting the diagnostic accuracy of AC for assessing hepatic steatosis. The meta-analytic pooled sensitivity and specificity of AC for any grade of steatosis (S≥1) and advanced steatosis (S≥2) were estimated using a bivariate random-effects model. Meta-regression analysis was conducted to investigate the causes of heterogeneity among studies.

Thirteen studies including 1,509 patients were identified. The pooled sensitivity and specificity of AC for S≥1 were 76% (95% confidence interval [CI], 73% to 80%; I2=43%) and 84% (95% CI, 77% to 89%; I2=74%), respectively, while for S≥2 they were 87% (95% CI, 83% to 91%; I2=0%) and 79% (95% CI, 75% to 83%; I2=59%), respectively. Study heterogeneity was associated with body mass index (BMI) and the prevalence of steatosis or significant fibrosis.

AC can be clinically useful for assessing hepatic steatosis, with good overall diagnostic performance. The data reported in the published literature differed according to BMI and the prevalence of steatosis or significant fibrosis, and careful interpretation with consideration of these factors might be needed.

The number of individuals suffering from fatty liver is increasing worldwide, leading to interest in the noninvasive study of liver fat. Magnetic resonance spectroscopy (MRS) is a powerful tool that allows direct quantification of metabolites in tissue or areas of interest. MRS has been applied in both research and clinical studies to assess liver fat noninvasively in vivo. MRS has also demonstrated excellent performance in liver fat assessment with high sensitivity and specificity compared to biopsy and other imaging modalities. Because of these qualities, MRS has been generally accepted as the reference standard for the noninvasive measurement of liver steatosis. MRS is an evolving technique with high potential as a diagnostic tool in the clinical setting. This review aims to provide a brief overview of the MRS principle for liver fat assessment and its application, and to summarize the current state of MRS study in comparison to other techniques.

During the past 5 decades, liver transplantation has moved from its pioneering days where success was measured in days to a point where it is viewed as a routine part of medical care. Despite this progress, there are still significant unmet needs and outstanding questions that need addressing in clinical trials to improve outcomes for patients. The traditional endpoint for trials in liver transplantation has been 1-year patient survival, but with rates now approaching 95%, this endpoint now poses a number of significant financial and logistical barriers to conducting trials because of the large numbers of participants required to demonstrate only an incremental improvement. Here, we suggest the following solutions to this challenge: adoption of validated surrogate endpoints; bigger and better collaborative multiarm, multiphase studies; recognition by funders and institutions that work on larger collaborative research projects is potentially more important than smaller, self-led bodies of work; ringfenced areas of research within trial frameworks where individuals can take a lead; and fair funding structures using both industry and public sector money across national and international borders.

Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes. The probe is placed on the surface of the liver and emits red and near infrared light from the tip of the device and measures the amount of backscatter of light from liver tissue via two photodiodes. Measurement of optical backscatter (Mantel-Cox P < 0.0001) and histopathological scoring of macrovesicular steatosis (Mantel-Cox P = 0.046) were predictive of 5-year graft survival. Recipients with early allograft dysfunction defined according to both Olthoff (P = 0.0067) and MEAF score (P = 0.0097) had significantly higher backscatter levels from the donor organ. Backscatter was predictive of graft loss (AUC 0.75, P = 0.0045). This study demonstrates the feasibility of real-time measurement of optical backscatter in donor livers. Early results indicate readings correlate with steatosis and may give insight to graft outcomes such as early allograft dysfunction and graft loss.

The worldwide implementation of a liver graft pool using marginal livers (ie, grafts with a high risk of technical complications and impaired function or with a risk of transmitting infection or malignancy to the recipient) has led to a growing interest in developing methods for accurate evaluation of graft quality. Liver steatosis is associated with a higher risk of primary nonfunction, early graft dysfunction, and poor graft survival rate. The present study aimed to analyze the value of artificial intelligence (AI) in the assessment of liver steatosis during procurement compared with liver biopsy evaluation. A total of 117 consecutive liver grafts from brain-dead donors were included and classified into 2 cohorts: ≥30 versus <30% hepatic steatosis. AI analysis required the presence of an intraoperative smartphone liver picture as well as a graft biopsy and donor data. First, a new algorithm arising from current visual recognition methods was developed, trained, and validated to obtain automatic liver graft segmentation from smartphone images. Second, a fully automated texture analysis and classification of the liver graft was performed by machine-learning algorithms. Automatic liver graft segmentation from smartphone images achieved an accuracy (Acc) of 98%, whereas the analysis of the liver graft features (cropped picture and donor data) showed an Acc of 89% in graft classification (≥30 versus <30%). This study demonstrates that AI has the potential to assess steatosis in a handy and noninvasive way to reliably identify potential nontransplantable liver grafts and to avoid improper graft utilization.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are becoming some of the major health problems in well-developed countries, together with the increasing prevalence of obesity, metabolic syndrome, and all of their systemic complications. As the future prognoses are even more disturbing and point toward further increase in population affected with NAFLD/NASH, there is an urgent need for widely available and reliable diagnostic methods. Consensus on a non-invasive, accurate diagnostic modality for the use in ongoing clinical trials is also required, particularly considering a current lack of any registered drug for the treatment of NAFLD/NASH. The aim of this narrative review was to present current information on methods used to assess liver steatosis and fibrosis. There are several imaging modalities for the assessment of hepatic steatosis ranging from simple density analysis by computed tomography or conventional B-mode ultrasound to magnetic resonance spectroscopy (MRS), magnetic resonance imaging proton density fat fraction (MRI-PDFF) or controlled attenuation parameter (CAP). Fibrosis stage can be assessed by magnetic resonance elastography (MRE) or different ultrasound-based techniques: transient elastography (TE), shear-wave elastography (SWE) and acoustic radiation force impulse (ARFI). Although all of these methods have been validated against liver biopsy as the reference standard and provided good accuracy, the MRS and MRI-PDFF currently outperform other methods in terms of diagnosis of steatosis, and MRE in terms of evaluation of fibrosis.

Background Clinical or biochemical markers that have good correlation with magnetic resonance proton density fat fraction (MR PDFF) can be used as simple tools for the screening for nonalcoholic fatty liver disease (NAFLD) and in determining the degree of fatty infiltration of the liver. The objective of this study was to determine the degree of relationship between MR PDFF and ultrasonography (USG) grades of fatty liver, and clinical and biochemical parameters of adolescents and to determine the sensitivity and specificity of USG for diagnosis of NAFLD. Methods This prospective study included 34 overweight adolescents (mean age, 12.1 ± 1.5 years; range, 10-15.1 years; 10 girls and 24 boys) who underwent both USG and magnetic resonance imaging (MRI). Correlation analysis was performed between MR fat fraction and USG grades of fatty liver, and clinical and biochemical parameters of fatty liver disease. Results MR fat fraction had a moderate positive correlation with serum alanine transaminase (ALT) and aspartate transaminase (AST) (ρ = 0.634, p < 0.001, ρ = 0.516, p = 0.002, respectively) and had a negligible or weak correlation with body mass index (BMI), BMI standard deviation score (SDS), waist circumference (WC), fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), serum triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol levels. The sensitivity and specificity of USG in the diagnosis of NAFLD were 81% (95% confidence interval 54%-95%) and 50% (27%-73%), respectively. The MR fat fraction had a moderate positive correlation with ultrasound grades of fatty liver (ρ = 0.487, p = 0.003). Conclusions Serum ALT and AST are potential biochemical markers to assess the degree of hepatic steatosis in NAFLD, which needs validation in further studies. USG can be used as a screening tool for NAFLD, but the diagnosis should be confirmed by estimating the MR fat fraction.

Fatty liver diseases are highly prevalent in patients with coronary artery disease (CAD) and might progress to irreversible liver fibrosis. Whether baseline liver fibrosis (LF) scores are associated with long-term mortality among patients with CAD requires investigation.

The analysis was conducted based on a prospective cohort study among 3263 patients with CAD in China. Cox models were used to assess the association of baseline levels of LF scores, including non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis 4 score (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), gamma-glutamyltransferase to platelet ratio (GPR), and Forns score, with the risk of all-cause and cardiovascular mortality among CAD patients.

During a median follow-up period of 7.56 (inter-quartile range: 6.86-8.31) years, 538 deaths were identified, 319 of those were due to cardiovascular diseases. Compared with patients with lowest score levels, multivariable-adjusted HRs (95% CI) for those with highest levels of NFS, FIB-4, APRI, GPR and Forns score were 2.89 (2.14-3.91), 2.84 (2.14-3.76), 1.77 (1.33-2.36), 1.47 (1.19-1.83) and 3.10 (1.88-5.11) for all-cause mortality, 3.02 (2.05-4.45), 3.34 (2.29-4.86), 1.99 (1.40-2.83), 1.80 (1.36-2.39) and 2.43 (1.28-4.61) for cardiovascular mortality, respectively. These associations were consistent when we excluded those who died within the first year of follow-up or stratified patients by different sex, age, BMI, diabetes status, metabolic syndrome status, CAD type and hsCRP level.

Higher LF scores are associated with increased risks of all-cause and cardiovascular mortality among CAD patients. LF scores might play a potential role in CAD prognosis prediction.

Machine perfusion is a hot topic in liver transplantation and several new perfusion concepts are currently developed. Prior to introduction into routine clinical practice, however, such perfusion approaches need to demonstrate their impact on liver function, post-transplant complications, utilization rates of high-risk organs, and cost benefits. Therefore, based on results of experimental and clinical studies, the community has to recognize the limitations of this technology. In this review, we summarize current perfusion concepts and differences between protective mechanisms of ex- and in-situ perfusion techniques. Next, we discuss which graft types may benefit most from perfusion techniques, and highlight the current understanding of liver viability testing. Finally, we present results from recent clinical trials involving machine liver perfusion, and analyze the value of different outcome parameters, currently used as endpoints for randomized controlled trials in the field.

The prevalence of elevated intra-hepatic fat (IHF) is increasing in the Western world, either alone as hepatic steatosis (HS) or in conjunction with inflammation (steatohepatitis). These changes to the hepatic parenchyma are an independent risk factor for post-operative morbidity following liver resection for colorectal liver metastases (CRLM). As elevated IHF and colorectal malignancy share similar risk factors for development it is unsurprisingly frequent in this cohort. In patients undergoing resection IHF may be elevated due to excess adiposity or its elevation may be induced by neoadjuvant chemotherapy, termed chemotherapy associated steatosis (CAS). Additionally, chemotherapy is implicated in the development of inflammation termed chemotherapy associated steatohepatitis (CASH). Following cessation of chemotherapy, patients awaiting resection have a 4-6 week washout period prior to resection that is a window for prehabilitation prior to surgery. In patients with NAFLD dietary and pharmacological interventions can reduce IHF within this timeframe but this approach to modifying IHF is untested in this population. In this review, the aetiology of CAS and CASH is reviewed with recommendations to identify those at risk. We also focus on the post-chemotherapy washout period, reviewing dietary interventions applied to the metabolic population and suggest this window may be used as an opportunity to optimise IHF with such a regime as part of a pre-operative prehabilitation programme to produce improved patient outcomes.

In patients with chronic intestinal failure (CIF) and long-term home parenteral nutrition (HPN), liver steatosis is a known late complication, which can progress to intestinal failure-associated liver disease (IFALD). Magnetic resonance imaging (MRI) provides a qualitative and quantitative assessment of liver steatosis. The aim of our study was to assess the prevalence of liver steatosis and find possible new factors that could be connected to liver steatosis in CIF patients on HPN therapy.

Patients diagnosed with CIF and undergoing long-term HPN therapy were enrolled in a prospective cohort study. Clinical, laboratory and body composition data were collected from their medical records between January 2017 and November 2018. Liver steatosis was diagnosed using 3 Tesla Siemens MRI scanner. The associations between various risk factors and liver steatosis were calculated using uni- and multivariate logistic regression.

In our study, we included 63 adult patients with CIF on HPN therapy. The median HPN therapy duration was 70 weeks (IQR 22-203). The prevalence of liver steatosis was 28.6%. Serum cholesterol level, CRP and FFMI were statistically significantly associated with liver steatosis.

The results of our study indicate that CIF patients on HPN therapy experience a low risk of liver disease if they adhere to a well-controlled treatment regime. We found that MRI is an appropriate diagnostic tool for monitoring liver steatosis in patients on long-term PN. With respect to already known risk factors for liver steatosis, we did find a newly described association between FFMI and liver steatosis.

Controlled attenuation parameter (CAP) is a non-invasive method for diagnosing hepatic steatosis. Despite good diagnostic performance, clinical application of CAP is limited due to the influences of covariates. Here, a systematic review on the performance of CAP in the diagnosis and staging of hepatic steatosis in NAFLD patients was performed.

The sensitivity, specificity, diagnostic odds ratio (DOR) and area under receiver operating characteristics (AUROC) curves of the pooled data for CAP in diagnosing and staging the mild (Stage 1), moderate (Stage 2) and severe (Stage 3) steatosis in NAFLD patients were assessed. The clinical utility of CAP was evaluated by Fagan plot. Heterogeneity was explored using subgroup analysis.

Nine studies involving 1297 patients with liver biopsy-proven NAFLD were analyzed. The pooled sensitivity of CAP in detecting mild hepatic steatosis was 87% with a specificity of 91% and a DOR of 84.35. The pooled sensitivity of CAP in detecting moderate hepatic steatosis was 85% with a specificity of 74% and a DOR of 21.28. For severe steatosis, the pooled sensitivity was 76% with a specificity of 58% and a DOR of 4.70. The mean AUROC value for CAP in the diagnosis of mild, moderate, and severe steatosis was 0.96, 0.82 and 0.70, respectively. A subgroup analysis indicated that variation in the geographic regions, cutoffs, age and body mass index (BMI) could be the potential sources of heterogeneity in the diagnosis of moderate to severe steatosis.

CAP should be cautiously considered as a non-invasive substitute for liver biopsy in clinical practice.

The growing number of patients on waiting lists for liver transplantation and the shortage of organs have forced many centers to adopt extended criteria for graft selection, moving the limit of acceptance for marginal livers. Steatotic grafts that were, in the past, considered strictly unacceptable for transplantation because of the high risk of early nonfunction are now considered as a potential resource for organ implementation. Several methods to diagnose, measure, classify, and stage steatosis exist, but none can be considered qualitatively and quantitatively "the ideal method" to date. Clinical, biological, and imaging data can be very helpful to estimate graft steatosis, but histology still remains the gold standard. There is an increasing need for rapid and reliable tools to assess graft steatosis. Herein, we present a comprehensive review of the approaches that are currently used to quantify steatosis in liver grafts.

The purpose of this review is to discuss the current imaging techniques for non-invasive assessment of liver fibrosis (LF).

Elastography-based techniques are the most widely used imaging methods for the evaluation of LF. Currently, MR elastography (MRE) is the most accurate non-invasive method for detection and staging of LF. Ultrasound-based vibration-controlled transient elastography (VCTE) is the most widely used as it can be easily performed at the point of care but has technical limitations especially in the obese. Innovations and technical improvements continue to evolve in elastography for improving accuracy and avoiding misinterpretation from confounding factors. Other imaging methods including diffusion-weighted imaging (DWI), hepatocellular contrast-enhanced (HCE) MRI, T1 relaxometry, T1ρ imaging, textural analysis, liver surface nodularity, susceptibility-weighted imaging, and perfusion imaging are promising but need further evaluation and clinical validation. MRE is the most accurate imaging technique for assessment of LF.

Obesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD).

We aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects.

Forty subjects (60% obese, 40% overweight) with biopsy-confirmed NASH and NAFLD activity score (NAS) ≥4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained.

NASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 ± 6.6 vs control 28.4 ± 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 ± 2.5 vs control 14.1 ± 5.9 mL/kg/min, P < 0.0001). NASH subjects' fitness was comparable to the "least fit" tertile of controls: VO2peak [NASH 16.8 ± 6.6 vs "least fit" 17.3 ± 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 ± 2.5 vs "least fit" 9.3 ± 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT.

Aerobic deconditioning was universally present in NASH subjects. NASH subjects' fitness was similar to our laboratory's "least fit" untrained, sedentary control subjects. Further research investigating NASH patients' ability to improve low baseline aerobic fitness is warranted.

Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis.

To determine how to use CAP in interpreting liver stiffness measurements.

This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP.

Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis.

Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

The article reviews the multimodality (ultrasound, computed tomography, and magnetic resonance [MR]) imaging appearance of nonalcoholic fatty liver disease (NAFLD) and discusses the radiologic diagnostic criteria as well as the sensitivity and specificity of these imaging methods. The authors review the role of both ultrasound and MR elastography for the diagnosis of fibrosis and for the longitudinal evaluation of patients following therapeutic intervention. Lastly, the authors briefly discuss the screening and diagnosis of hepatocellular carcinoma in patients with NAFLD, as there are special considerations in this population.

To evaluate the value of noninvasive tools for diagnosis of hepatic steatosis in patients with chronic hepatitis B (CHB).

Consecutive treatment-naïve patients with CHB with body mass index less than 30kg/m2 who underwent liver biopsy, ultrasound and FibroScan® were enrolled. The diagnostic performance of controlled attenuation parameter (CAP), hepatic steatosis index (HSI) and ultrasound for hepatic steatosis compared with liver biopsy was assessed. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy, with comparisons using the DeLong test.

CAP and HSI accuracies were significantly higher than that of ultrasound to detect patients with biopsy-proven mild steatosis (S1, 65.3%, 56.5%, respectively, vs. 17.7%, χ2=46.305, 31.736, both P<0.05)and moderate-severe (S2-3) steatosis (92.3%, 100%, respectively, vs. 53.8%, χ2=4.887, 7.800, P=0.037, 0.007, respectively). Both CAP and HSI had lower underestimation rates of steatosis grade than ultrasound (12%, 14.8%, respectively, vs. 29.5%, χ2=9.765, 6.452; P<0.05 for both), but they exhibited higher overestimation rates (30.5%, 38.2%, respectively, vs. 12.4%, χ2=39.222, 70.986; both P<0.05). The AUROCs of CAP and HSI were 0.780 (95% confidence intervals [CIs] 0.735-0.822) and 0.655 (95%CI 0.604-0.704) for S ≥1, 0.932 (95%CI 0.902-0.956) and 0.755 (95%CI 0.707-0.799) for S ≥2, 0.990 (95%CI 0.974-0.998) and 0.786 (95% CI 0.740-0.827) for S3, respectively.

CAP might be more accurate for detecting hepatic steatosis than HSI and ultrasound in patients with CHB, but further studies are needed to reduce the overestimation rates.