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.

Early allograft dysfunction (EAD) affects outcomes in liver transplantation (LT). Existing risk models developed for deceased-donor LT depend on posttransplant factors and fall short in living-donor LT (LDLT), where pretransplant evaluations are crucial for preventing EAD and justifying the donor's risks.

This retrospective study analyzed data from 2944 adult patients who underwent LDLT at 17 centers between 2016 and 2020. We developed a logistic regression model to predict EAD based on this development cohort. We used data from 1020 patients at the King Faisal Transplant Center for external validation.

In the development cohort, 321 patients (10.9%) experienced EAD. These patients had poorer health status, more liver decompensation, and higher requirements of hospitalization than those without EAD. Multivariable logistic regression identified independent pretransplant predictors of EAD: laboratory Model for End-Stage Liver Disease score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.09), the necessity for hospitalization at the time of transplant (OR, 2.58; 95% CI, 2.00-3.30), and graft weight in kilogram (OR, 0.27; 95% CI, 0.17-0.45). Using these predictors, we developed the model for EAD after LDLT, which demonstrated strong discriminative ability in the development cohort with an area under the curve (AUC) of 0.71 (95% CI, 0.68-0.74). The model maintained high discrimination during internal validation (AUC, 0.70; 95% CI, 0.67-0.73) and showed a modest reduction in discriminative power in external validation (AUC, 0.65; 95% CI, 0.61-0.68).

EAD post-LDLT is influenced by the recipient's pretransplant health condition and the graft weight. Integrating the model for EAD after LDLT into the pretransplant process of pairing donors and recipients can enhance the safety and efficacy of LDLT.

Diffuse liver disease is a substantial world-wide problem. With the combination of conventional ultrasound of the abdomen, fat quantification and elastography, appropriate staging of the patient can be assessed. This information allows for the diagnosis of steatosis and detection of fibrosis as well as prognosis, surveillance, and prioritization for treatment. With the potential for reversibility with appropriate treatment accurate assessment for the stage of chronic liver disease is critical.

Hepatic steatosis (HS), particularly macrovesicular steatosis (MaS), influences transplant outcomes. Accurate assessment of MaS is crucial for graft selection. While traditional assessment methods have limitations, non-invasive spectroscopic techniques like Raman and reflectance spectroscopy offer promise. This study aimed to evaluate the efficacy of a portable ambient light-compatible spectroscopic system in assessing global HS and MaS in human liver specimens.

A two-stage approach was employed on thawed snap-frozen human liver specimens under ambient room light: biochemical validation involving a comparison of fat content from Raman and reflectance intensities with triglyceride (TG) quantifications and histopathological validation, contrasting Raman-derived fat content with evaluations by an expert pathologist and a "Positive Pixel Count" algorithm. Raman and reflectance intensities were combined to discern significant (≥ 10%) discrepancies in global HS and MaS.

The initial set of 16 specimens showed a positive correlation between Raman and reflectance-derived fat content and TG quantifications. The Raman system effectively differentiated minimum-to-severe global and macrovesicular steatosis in the subsequent 66 specimens. A dual-variable prediction algorithm was developed, effectively classifying significant discrepancies (> 10%) between algorithm-estimated global HS and pathologist-estimated MaS.

Our study established the viability and reliability of a portable spectroscopic system for non-invasive HS and MaS assessment in human liver specimens. The compatibility with ambient light conditions and the ability to address limitations of previous methods marks a significant advancement in this field. By offering promising differentiation between global HS and MaS, our system introduces an innovative approach to real-time and quantitative donor HS assessments. The proposed method holds the promise of refining donor liver assessment during liver recovery and ultimately enhancing transplantation outcomes.

Severe macrovesicular steatosis in donor livers is associated with primary graft dysfunction. The Banff Working Group on Liver Allograft Pathology has proposed recommendations for steatosis assessment of donor liver biopsy specimens with a consensus for defining "large droplet fat" (LDF) and a 3-step algorithmic approach.

We retrieved slides and initial pathology reports from potential liver donor biopsy specimens from 2010 to 2021. Following the Banff approach, we reevaluated LDF steatosis and employed a computer-assisted manual quantification protocol and artificial intelligence (AI) model for analysis.

In a total of 113 slides from 88 donors, no to mild (<33%) macrovesicular steatosis was reported in 88.5% (100/113) of slides; 8.8% (10/113) was reported as at least moderate steatosis (≥33%) initially. Subsequent pathology evaluation, following the Banff recommendation, revealed that all slides had LDF below 33%, a finding confirmed through computer-assisted manual quantification and an AI model. Correlation coefficients between pathologist and computer-assisted manual quantification, between computer-assisted manual quantification and the AI model, and between the AI model and pathologist were 0.94, 0.88, and 0.81, respectively (P < .0001 for all).

The 3-step approach proposed by the Banff Working Group on Liver Allograft Pathology may be followed when evaluating steatosis in donor livers. The AI model can provide a rapid and objective assessment of liver steatosis.

Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss.

In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020. Overall, 1040 right-lobe donors were included, with 150 and 890 donors in the weight loss and control (non-steatosis) groups, respectively.

We performed 1:1 individual matching using the greedy matching method, by which 124 patients were included in each group. The median period from the date of the first visit to donation was 113 (interquartile range: 78-184) days in the weight loss group. As body weight changed from 82.8 ± 13.7 kg to 70.8 ± 11.8 kg (p < 0.0001), body mass index also improved from 27.8 ± 3.9 kg/m2 to 23.8 ± 3.1 kg/m2 (p < 0.0001). No significant between-group differences existed in the postoperative laboratory data for living donors and recipients. The incidence of postoperative complications in donors was comparable between the groups (control group, 9.7%; weight loss group, 13.7%; p = 0.3185). The graft and recipient survival rates were comparable between the groups (p = 1.000).

Weight loss through diet and exercise significantly could improve hepatic steatosis in living donor candidates for liver transplantation, with the surgical outcomes in recipients and donors being equivalent to those in recipients and non-steatotic donors.

Podocyte degenerative changes are common in various kidney diseases, and their accurate identification is crucial for pathologists to diagnose and treat such conditions. However, this can be a difficult task, and previous attempts to automate the identification of podocytes have not been entirely successful. To address this issue, this study proposes a novel approach that combines pathologists' expertise with an automated classifier to enhance the identification of podocytopathies. The study involved building a new dataset of renal glomeruli images, some with and others without podocyte degenerative changes, and developing a convolutional neural network (CNN) based classifier. The results showed that our automated classifier achieved an impressive 90.9% f-score. When the pathologists used as an auxiliary tool to classify a second set of images, the medical group's average performance increased significantly, from [Formula: see text]% to [Formula: see text]% of f-score. Fleiss' kappa agreement among the pathologists also increased from 0.59 to 0.83. Conclusion: These findings suggest that automating this task can bring benefits for pathologists to correctly identify images of glomeruli with podocyte degeneration, leading to improved individual accuracy while raising agreement in diagnosing podocytopathies. This approach could have significant implications for the diagnosis and treatment of kidney diseases. Clinical impact: The approach presented in this study has the potential to enhance the accuracy of medical diagnoses for detecting podocyte abnormalities in glomeruli, which serve as biomarkers for various glomerular diseases.

The effect of donor body mass index (BMI) on liver transplantation (LT) outcomes remains unclear.

A systematic search of the MEDLINE, CENTRAL, Web of Science, and bibliographic reference lists was conducted. All comparative studies evaluating the outcomes of LT in obese (BMI > 30 kg/m2) and nonobese donors (BMI < 30 kg/m2) were included, and their risk of bias was assessed using the ROBINS-I assessment tool. Patient and graft survival, acute rejection, and graft failure requiring retransplantation were evaluated as outcome parameters. A random-effects model was used for outcome synthesis.

We included 6 comparative studies reporting a total of 5071 liver transplant recipients from 708 obese and 4363 nonobese donors. There was no significant difference in 1-y (89.1% versus 84.0%, odds ratio [OR] 1.58; 95% CI 0.63-3.94, P = 0.33), 5-y (74.2%% versus 73.5%, OR 1.12; 95% CI 0.45-2.80, P = 0.81) graft survival, and 1-y (87.1% versus 90.3%, OR 0.71; 95% CI 0.43-1.15, P = 0.17) and 5-y (64.5% versus 71.6%, OR 0.71; 95% CI 0.49-1.05, P = 0.08) patient survival between 2 groups. Furthermore, recipients from obese and nonobese donors had a comparable risk of graft failure requiring retransplantation (OR 0.92; 95% CI 0.33-2.60, P = 0.88) or acute graft rejection (OR 0.70; 95% CI 0.45-1.11, P = 0.13).

A meta-analysis of the best available evidence (level 2a) demonstrates that donor obesity does not seem to have a negative impact on graft or patient outcomes. The available studies might be subject to selection bias as the grafts from obese donors are usually subject to biopsy to exclude steatosis and the recipients usually belong to the low-risk group. Future research is needed to evaluate the impact of donors subgrouped by various higher BMI on graft and patient-related outcomes as well as to capture data of the discarded grafts from obese donors; hence, selection criteria for the grafts that could be used for transplantation from obese donors is identified.

Liver transplantation (LT) is a major treatment for patients with end-stage liver diseases. Steatosis is a significant risk factor for primary graft nonfunction and associated with poor long-term graft outcomes. Traditionally, the evaluation of steatosis is based on frozen section examination to estimate the percentage of hepatocytes containing lipid vesicles. However, this visual evaluation correlates poorly with the true lipid content. This study aimed to address the potential of infrared (IR) microspectroscopy for rapidly estimating lipid content in the context of LT and assessing its impact on survival. Clinical data were collected for >20 months from 58 patients who underwent transplantation. For each liver graft, macrovacuolar steatosis and microvesicular steatosis were evaluated through histologic examination of frozen tissue section. Triglycerides (TG) were further quantified using gas phase chromatography coupled with a flame ionization detector (GC-FID) and estimated by IR microspectroscopy. A linear relationship and significant correlation were observed between the TG measured by GC-FID and those estimated using IR microspectroscopy (R2 = 0.86). In some cases, microvesicular steatosis was related to high lipid content despite low levels of macrovacuolar steatosis. Seven patients experienced posttransplantation liver failure, including 5 deceased patients. All patients underwent transplantation with grafts containing significantly high TG levels. A concentration of 250 nmol/mg was identified as the threshold above which the risk of failure after LT significantly increased, affecting 35% of patients. Our study established a strong correlation between LT outcomes and lipid content. IR microspectroscopy proved to be a rapid and reliable approach for assessing the lipid content in clinical settings.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.

This study aimed to evaluate the diagnostic performance of attenuation measurement (ATT; dual-frequency method) and improved algorithm of ATT (iATT; reference method) for the assessment of hepatic steatosis using magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) as the reference standard.

We prospectively analyzed 427 patients with chronic liver disease who underwent ATT, iATT, or MRI-derived PDFF. Correlation coefficients were analyzed, and diagnostic values were evaluated by area under the receiver operating characteristic curve (AUROC). The steatosis grade was categorized as S0 (<5.2%), S1 (≥5.2%, <11.3%), S2 (≥11.3%, <17.1%), and S3 (≥17.1%) according to MRI-derived PDFF values.

The median ATT and iATT values were 0.61 dB/cm/MHz (interquartile range 0.55-0.67 dB/cm/MHz) and 0.66 dB/cm/MHz (interquartile range 0.57-0.77 dB/cm/MHz). ATT and iATT values increased significantly as the steatosis grade increased in the order S0, S1, S2, and S3 (p < 0.001). The correlation coefficients between ATT or iATT values and MRI-derived PDFF values were 0.533 (95% confidence interval [CI] 0.477-0.610) and 0.803 (95% CI 0.766-0.834), with a significant difference between them (p < 0.001). For the detection of hepatic steatosis of ≥S1, ≥S2, and ≥S3, iATT yielded AUROCs of 0.926 (95% CI 0.901-0.951), 0.913 (95% CI 0.885-0.941), and 0.902 (95% CI 0.869-0.935), with significantly higher AUROC values than for ATT (p < 0.001, p < 0.001, p = 0.001).

iATT showed excellent diagnostic performance for hepatic steatosis, and was strongly correlated with MRI-derived PDFF, with AUROCs of ≥0.900.

Nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated steatotic liver disease (MASLD), is an escalating health concern linked to obesity and type 2 diabetes. Despite liver biopsy being the gold standard, its invasiveness underscores the need for noninvasive diagnostic methods.

A cross-sectional study was performed to assess MASLD using the noninvasive OWLiver® serum lipidomics test in a cohort of 117 patients with severe obesity undergoing bariatric surgery, comparing outcomes with liver biopsy. Exclusions (n = 24) included insufficient data, liver disease etiology other than MASLD, corticosteroid treatment, excessive alcohol consumption, low glomerular filtration rate, and declination to participate. Comprehensive laboratory tests, demographic assessments, and liver biopsies were performed. Serum metabolites were analyzed using OWLiver®, a serum lipidomic test that discriminates between healthy liver, steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and MASH with fibrosis ≥2 by means of three algorithms run sequentially.

Liver biopsy revealed a MASLD prevalence of 95.7%, with MASH present in 28.2% of cases. OWLiver® demonstrated a tendency to diagnose more severe cases. Body mass index (BMI), rather than the presence of type 2 diabetes, emerged as the sole independent factor linked to the probability of concordance. Therefore, the all-population concordance of 63.2% between OWLiver® and liver biopsy notably raised to 77.1% in patients with a BMI <40 kg/m2. These findings suggest a potential correlation between lower BMI and enhanced concordance between OWLiver® and biopsy.

This study yields valuable insights into the concordance between liver biopsy and the noninvasive serum lipidomic test, OWLiver®, in severe obesity. OWLiver® demonstrated a tendency to amplify MASLD severity, with BMI values influencing concordance. Patients with BMI <40 kg/m2 may derive optimal benefits from this noninvasive diagnostic approach.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a leading cause of chronic liver disease, has increased worldwide along with the epidemics of obesity and related dysmetabolic conditions characterized by impaired glucose metabolism and insulin signaling, such as type 2 diabetes mellitus (T2D). MASLD can be defined as an excessive accumulation of lipid droplets in hepatocytes that occurs when the hepatic lipid metabolism is totally surpassed. This metabolic lipid inflexibility constitutes a central node in the pathogenesis of MASLD and is frequently linked to the overproduction of lipotoxic species, increased cellular stress, and mitochondrial dysfunction. A compelling body of evidence suggests that the accumulation of lipid species derived from sphingolipid metabolism, such as ceramides, contributes significantly to the structural and functional tissue damage observed in more severe grades of MASLD by triggering inflammatory and fibrogenic mechanisms. In this context, MASLD can further progress to metabolic dysfunction-associated steatohepatitis (MASH), which represents the advanced form of MASLD, and hepatic fibrosis. In this review, we discuss the role of sphingolipid species as drivers of MASH and the mechanisms involved in the disease. In addition, given the absence of approved therapies and the limited options for treating MASH, we discuss the feasibility of therapeutic strategies to protect against MASH and other severe manifestations by modulating sphingolipid metabolism.

Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool.

Non-alcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction-associated fatty liver disease (MAFLD), is a growing health concern associated with obesity and type 2 diabetes. Bariatric surgery offers potential benefits, but its impact on MAFLD remains incompletely understood, with scarce long-term follow-up prospective studies. Moreover, being liver biopsy the gold standard for liver condition measurement, the need for non-invasive techniques that allow the assessment of MAFLD development after bariatric surgery is imperative. OWLiver® Care and OWLiver® represent two serum lipidomic tests, featuring panels comprising 11 and 20 triglycerides, respectively.

We conducted a prospective study involving 80 Caucasians to assess the effects of bariatric surgery on MAFLD using non-invasive diagnostics and to identify baseline predictors of MAFLD remission. Serum samples were collected before surgery and at a 3-year follow-up.

After 3 years, the proportion of patients exhibiting a healthy liver escalated from 5.0% at baseline to 26.3%. Conversely, the percentage of steatohepatitis declined from 35.1% to a mere 7.6%. Younger age, female gender, and the absence of type 2 diabetes were associated with MAFLD remission. However, age stood as the only independent variable associated with this favorable liver evolution (R2 = 0.112).

Bariatric surgery demonstrates mid-term benefits in improving MAFLD, with younger age as a baseline predictor of remission. Non-invasive diagnostic methods, like OWLiver®, are valuable tools for monitoring MAFLD evolution. Further research with larger populations and longer follow-up periods is warranted to refine personalized treatment approaches.

Metabolic dysfunction-associated steatotic liver disease (MASLD), or non-alcoholic fatty liver disease (NAFLD), is a common disease that is diagnosed through manual evaluation of liver biopsies, an assessment that is subject to high interobserver variability (IBV). IBV can be reduced using automated methods.

Many existing computer-based methods do not accurately reflect what pathologists evaluate in practice. The goal is to demonstrate how these differences impact the prediction of hepatic steatosis. Additionally, IBV complicates algorithm validation.

Forty tissue sections were analyzed to detect steatosis, nuclei, and fibrosis. Data generated from automated image processing were used to predict steatosis grades. To investigate IBV, 18 liver biopsies were evaluated by multiple observers.

Area-based approaches yielded more strongly correlated results than nucleus-based methods (⌀ Spearman rho [ρ] = 0.92 vs. 0.79). The inclusion of information regarding tissue composition reduced the average absolute error for both area- and nucleus-based predictions by 0.5% and 2.2%, respectively. Our final area-based algorithm, incorporating tissue structure information, achieved a high accuracy (80%) and strong correlation (⌀ Spearman ρ = 0.94) with manual evaluation.

The automatic and deterministic evaluation of steatosis can be improved by integrating information about tissue composition and can serve to reduce the influence of IBV.

Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20-30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations.

There is great variability in the assessment and reporting of fat in frozen sections of donor liver biopsies. The Banff Working Group has proposed a novel method and definition for scoring large droplet fat (LDF) in donor liver biopsies. This study compares the Banff method with a simpler Average of Fields (AF) method and evaluates the impact of different LDF definitions.

Three pathologists assessed percentage of LDF (LDF%) in 10 donor liver biopsies using Banff and AF methods, applying the Banff LDF definition (cell distention with a single droplet larger than adjacent hepatocytes). Additionally, LDF% by the AF method was compared using two LDF definitions: Banff definition versus LDF definition 2 (single fat droplet occupying greater than half of a hepatocyte with nuclear displacement).

Intraobserver concordance between the Banff and AF methods was similar for all three pathologists (kappa 0.76-1). Both methods exhibited 70% interobserver concordance, and there was substantial agreement (kappa 0.68) in the LDF% among the three pathologists for both methods. Comparing the two LDF definitions, results were significantly lower with the Banff definition; LDF >50% was observed in four cases with LDF definition 2 but none of the cases with the Banff definition.

There is high interobserver and intraobserver concordance of LDF% between the Banff and AF methods. LDF% determined by the Banff definition was lower than with LDF definition 2, and needs to be validated based on graft outcome before it can be recommended for clinical use.

The study aimed to evaluate the correlation and diagnostic value of liver fat quantification in unenhanced dual-energy CT (DECT) using quantitative magnetic resonance imaging (MRI) mDIXON-Quant sequence as reference standard in patients with breast cancer.

Patients with breast cancer were prospectively recruited between June 2018 and April 2020. Each patient underwent liver DECT and MRI mDIXON-Quant examination. The DECT-fat volume fraction (FVF) and liver-spleen attenuation differences were compared with the MRI-proton density fat fraction using scatterplots, Bland-Altman plots, and concordance correlation coefficient. Receiver operating characteristic curves were established to determine the diagnostic accuracy of hepatic steatosis by DECT.

A total of 216 patients with breast cancer (mean age, 50.08 ± 9.33 years) were evaluated. The DECT-FVF correlated well with MRI-proton density fat fraction ( r2 = 0.902; P < 0.001), which was higher than the difference in liver-spleen attenuation ( r2 = 0.728; P < 0.001). Bland-Altman analysis revealed slight positive bias; the mean difference was 3.986. The DECT-FVF yielded an average concordance correlation coefficient of 0.677, which was higher than the difference of liver-spleen attenuation (-0.544). The DECT-FVF and the difference in liver-spleen attenuation both lead to mild overestimation of hepatic steatosis. The areas under the curve of DECT-FVF (0.956) were higher than the difference in liver-spleen attenuation (0.807) in identifying hepatic steatosis ( P < 0.001).

Dual-energy CT-FVF may serve as a reliable screening and quantitative tool for hepatic steatosis in patients with breast cancer.

Pathologists quantify liver steatosis as the fraction of lipid droplet-containing hepatocytes out of all hepatocytes, whereas the magnetic resonance-determined proton density fat fraction (PDFF) reflects the tissue triacylglycerol concentration. We investigated the linearity, agreement, and correspondence thresholds between histological steatosis and PDFF across the full clinical spectrum of liver fat content associated with non-alcoholic fatty liver disease.

Using individual patient-level measurements, we conducted a systematic review and meta-analysis of studies comparing histological steatosis with PDFF determined by magnetic resonance spectroscopy or imaging in adults with suspected non-alcoholic fatty liver disease. Linearity was assessed by meta-analysis of correlation coefficients and by linear mixed modelling of pooled data, agreement by Bland-Altman analysis, and thresholds by receiver operating characteristic analysis. To explain observed differences between the methods, we used RNA-seq to determine the fraction of hepatocytes in human liver biopsies.

Eligible studies numbered 9 (N = 597). The relationship between PDFF and histology was predominantly linear (r = 0.85 [95% CI, 0.80-0.89]), and their values approximately coincided at 5% steatosis. Above 5% and towards higher levels of steatosis, absolute values of the methods diverged markedly, with histology exceeding PDFF by up to 3.4-fold. On average, 100% histological steatosis corresponded to a PDFF of 33.0% (29.5-36.7%). Targeting at a specificity of 90%, optimal PDFF thresholds to predict histological steatosis grades were ≥5.75% for ≥S1, ≥15.50% for ≥S2, and ≥21.35% for S3. Hepatocytes comprised 58 ± 5% of liver cells, which may partly explain the lower values of PDFF vs. histology.

Histological steatosis and PDFF have non-perfect linearity and fundamentally different scales of measurement. Liver fat values obtained using these methods may be rendered comparable by conversion equations or threshold values.

Magnetic resonance-proton density fat fraction (PDFF) is increasingly being used to measure liver fat in place of the invasive liver biopsy. Understanding the relationship between PDFF and histological steatosis fraction is important for preventing misjudgement of clinical status or treatment effects in patient care. Our analysis revealed that histological steatosis fraction is often significantly higher than PDFF, and their association varies across the spectrum of fatty liver severity. These findings are particularly important for physicians and clinical researchers, who may use these data to interpret PDFF measurements in the context of histologically evaluated liver fat content.

To validate the proton density fat fraction (PDFF) obtained by the MRQuantif software from 2D chemical shift encoded MR (CSE-MR) data in comparison with the histological steatosis data.

This study, pooling data from 3 prospective studies spread over time between January 2007 and July 2020, analyzed 445 patients who underwent 2D CSE-MR and liver biopsy. MR derived liver iron concentration (MR-LIC) and PDFF was calculated using the MRQuantif software. The histological standard steatosis score (SS) served as reference. In order to get a value more comparable to PDFF, histomorphometry fat fraction (HFF) were centrally determined for 281 patients. Spearman correlation and the Bland and Altman method were used for comparison.

Strong correlations were found between PDFF and SS (rs = 0.84, p < 0.001) or HFF (rs = 0.87, p < 0.001). Spearman's coefficients increased to 0.88 (n = 324) and 0.94 (n = 202) when selecting only the patients without liver iron overload. The Bland and Altman analysis between PDFF and HFF found a mean bias of 5.4% ± 5.7 [95% CI 4.7, 6.1]. The mean bias was 4.7% ± 3.7 [95% CI 4.2, 5.3] and 7.1% ± 8.8 [95% CI 5.2, 9.0] for the patients without and with liver iron overload, respectively.

The PDFF obtained by MRQuantif from a 2D CSE-MR sequence is highly correlated with the steatosis score and very close to the fat fraction estimated by histomorphometry. Liver iron overload reduced the performance of steatosis quantification and joint quantification is recommended. This device-independent method can be particularly useful for multicenter studies.

The quantification of liver steatosis using a vendor-neutral 2D chemical-shift MR sequence, processed by MRQuantif, is well correlated to steatosis score and histomorphometric fat fraction obtained from biopsy, whatever the magnetic field and the MR device used.

• The PDFF measured by MRQuantif from 2D CSE-MR sequence data is highly correlated to hepatic steatosis. • Steatosis quantification performance is reduced in case of significant hepatic iron overload. • This vendor-neutral method may allow consistent estimation of PDFF in multicenter studies.

Nonalcoholic fatty liver disease (NAFLD) is a primary cause of parenchymal liver disease globally. There are currently several methods available to test the degree of steatosis in NAFLD patients, but all have drawbacks that limit their use.The objective of this study is to determine if a new technique, ultrasound (US) attenuation imaging (ATI), correlates with magnetic resonance proton density fat fraction imaging and hepatic echogenicity as seen on gray scale US imaging.Fifty-four patients were recruited at the University of Washington Medical Center from individuals who had already been scheduled for hepatic US or magnetic resonance imaging (MRI). All participants then underwent both hepatic MRI proton density fat fraction and US. Ultrasound images were then evaluated using ATI with 2 observers who individually determined relative grayscale echogenicity.Analysis showed positive correlation between ATI- and MRI-determined fat percentage in the case group (Spearman correlation: 0.50; P = 0.015). Furthermore, participants with NAFLD tended to have a higher ATI than controls (median: 0.70 vs 0.54 dB/cm/MHz; P < 0.001).This study demonstrates that US ATI combined with grayscale imaging is an effective way of assessing the degree of steatosis in patients with moderate to severe NAFLD.

Image-based detection of intralesional fat in focal liver lesions has been established in diagnostic guidelines as a feature indicative of hepatocellular carcinoma (HCC) and associated with a favorable prognosis. Given recent advances in MRI-based fat quantification techniques, we investigated a possible relationship between intralesional fat content and histologic tumor grade in steatotic HCCs.

Patients with histopathologically confirmed HCC and prior MRI with proton density fat fraction (PDFF) mapping were retrospectively identified. Intralesional fat of HCCs was assessed using an ROI-based analysis and the median fat fraction of steatotic HCCs was compared between tumor grades G1-3 with non-parametric testing. ROC analysis was performed in case of statistically significant differences (p < 0.05). Subgroup analyses were conducted for patients with/without liver steatosis and with/without liver cirrhosis.

A total of 57 patients with steatotic HCCs (62 lesions) were eligible for analysis. The median fat fraction was significantly higher for G1 lesions (median [interquartile range], 7.9% [6.0─10.7%]) than for G2 (4.4% [3.2─6.6%]; p = .001) and G3 lesions (4.7% [2.8─7.8%]; p = .036). PDFF was a good discriminator between G1 and G2/3 lesions (AUC .81; cut-off 5.8%, sensitivity 83%, specificity 68%) with comparable results in patients with liver cirrhosis. In patients with liver steatosis, intralesional fat content was higher than in the overall sample, with PDFF performing better in distinguishing between G1 and G2/3 lesions (AUC .92; cut-off 8.8%, sensitivity 83%, specificity 91%).

Quantification of intralesional fat using MRI PDFF mapping allows distinction between well- and less-differentiated steatotic HCCs.

PDFF mapping may help optimize precision medicine as a tool for tumor grade assessment in steatotic HCCs. Further investigation of intratumoral fat content as a potential prognostic indicator of treatment response is encouraged.

• MRI proton density fat fraction mapping enables distinction between well- (G1) and less- (G2 and G3) differentiated steatotic hepatocellular carcinomas. • In a retrospective single-center study with 62 histologically proven steatotic hepatocellular carcinomas, G1 tumors showed a higher intralesional fat content than G2 and G3 tumors (7.9% vs. 4.4% and 4.7%; p = .004). • In liver steatosis, MRI proton density fat fraction mapping was an even better discriminator between G1 and G2/G3 steatotic hepatocellular carcinomas.

An accurate estimation of liver fat content is necessary to predict how a donated liver will function after transplantation. Currently, a pathologist needs to be available at all hours of the day, even at remote hospitals, when an organ donor is procured. Even among expert pathologists, the estimation of liver fat content is operator-dependent. Here we describe the development of a low-cost, end-to-end artificial intelligence platform to evaluate liver fat content on a donor liver biopsy slide in real-time. The hardware includes a high-resolution camera, display, and GPU to acquire and process donor liver biopsy slides. A deep learning model was trained to label and quantify fat globules in liver tissue. The algorithm was deployed on the device to enable real-time quantification and characterization of fat content for transplant decision-making. This information is displayed on the device and can also be sent to a cloud platform for further analysis.

Liver allograft steatosis is a significant risk factor for postoperative graft dysfunction and has been associated with inferior patient and graft survival, particularly in the case of moderate or severe macrovesicular steatosis. In recent years, the increasing incidence of obesity and fatty liver disease in the population has led to a higher proportion of steatotic liver grafts being used for transplantation, making the optimization of their preservation an urgent necessity. This review discusses the mechanisms behind the increased susceptibility of fatty livers to ischemia-reperfusion injury and provides an overview of the available strategies to improve their utilization for transplantation, with a focus on preclinical and clinical evidence supporting donor interventions, novel preservation solutions, and machine perfusion techniques.

End-ischemic viability testing by normothermic machine perfusion (NMP) represents an effective strategy to recover liver grafts having initially been discarded for liver transplantation (LT). However, its results in the setting of significant (≥30%) macrovesicular steatosis (MaS) have not been specifically assessed. Prospectively maintained databases at two high-volume LT centers in Northern Italy were searched to identify cases of end-ischemic NMP performed to test the viability of livers with MaS ≥ 30% in the period from January 2019 to January 2022. A total of 14 cases were retrieved, representing 57.9% of NMP and 5.7% of all machine perfusion procedures. Of those patients, 10 (71%) received transplants. Two patients developed primary nonfunction (PNF) and required urgent re-LT, and both were characterized by incomplete or suboptimal lactate clearance during NMP. PNF cases were also characterized by higher perfusate transaminases, lower hepatic artery and portal vein flows at 2 h, and a lack of glucose metabolism in one case. The remaining eight patients showed good liver function (Liver Graft Assessment Following Transplantation risk score, -1.9 [risk, 13.6%]; Early Allograft Failure Simplified Estimation score, -3.7 [risk, 2.6%]) and had a favorable postoperative course. Overall, NMP allowed successful transplantation of 57% of livers with moderate-to-severe MaS. Our findings suggest that prolonged observation (≥6 h) might be required for steatotic livers and that stable lactate clearance is a fundamental prerequisite for their use.

Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.

Background Accumulation of lipid in the liver (ie, hepatic steatosis) is the basis of nonalcoholic fatty liver disease (NAFLD). Asymptomatic steatosis can lead to nonalcoholic steatohepatitis and downstream complications. Purpose To assess the diagnostic performance of calibrated US (CAUS) as a method for detection and staging of hepatic steatosis in comparison with liver biopsy. Materials and Methods Two-dimensional US images in 223 consecutive patients who underwent US-guided liver biopsy from May 2012 to February 2016 were retrospectively analyzed by two observers using CAUS. CAUS semiautomatically estimates echo-level and texture parameters, with particular interest in the residual attenuation coefficient (RAC), which is the remaining steatosis-driven attenuation obtained after correction of the beam profile. Data were correlated with patient characteristics and histologically determined steatosis grades and fibrosis stages. The data were equally divided into training and test sets to independently train and test logistic regression models for detection (>5% fat) and staging (>33% and >66% fat) of hepatic steatosis by using area under the receiver operating characteristic curve (AUC) analysis. Results A total of 195 patients (mean age, 50 years ± 13 [SD]; 110 men) were included and divided into a training set (n = 97 [50%]) and a test set (n = 98 [50%]). The average CAUS interobserver correlation coefficient was 0.95 (R range, 0.87-0.99). The best correlation with steatosis was found for the RAC parameter (R = 0.78, P < .01), while no correlation was found for fibrosis (R = 0.14, P = .054). Steatosis detection using RAC showed an AUC of 0.97 (95% CI: 0.94, 1.00), and the multivariable AUC was found to be 0.97 (95% CI: 0.95, 1.00). The predictive performance for moderate and severe hepatic steatosis using RAC was 0.93 (95% CI: 0.88, 0.98) and 0.93 (95% CI: 0.87, 0.98), respectively. Conclusion The calibrated US parameter residual attenuation coefficient detects and stages steatosis accurately with limited interobserver variability, and performance is not hampered by the presence of fibrosis. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Grant in this issue.

The Scientific Registry of Transplant Recipients (SRTR) had not traditionally considered biopsy results in risk-adjustment models, yet biopsy results may influence outcomes and thus decisions regarding organ acceptance.

Using SRTR data, which includes data on all donors, waitlisted candidates, and transplant recipients in the United States, we assessed (1) the impact of macrovesicular steatosis on deceased donor yield (defined as number of livers transplanted per donor) and 1-y posttransplant graft failure and (2) the effect of incorporating this variable into existing SRTR risk-adjustment models.

There were 21 559 donors with any recovered organ and 17 801 liver transplant recipients included for analysis. Increasing levels of macrovesicular steatosis on donor liver biopsy predicted lower organ yield: ≥31% macrovesicular steatosis on liver biopsy was associated with 87% to 95% lower odds of utilization, with 55% of these livers being discarded. The hazard ratio for graft failure with these livers was 1.53, compared with those with no pretransplant liver biopsy and 0% to 10% steatosis. There was minimal change on organ procurement organization-specific deceased donor yield or program-specific posttransplant outcome assessments when macrovesicular steatosis was added to the risk-adjustment models.

Donor livers with macrovesicular steatosis are disproportionately not transplanted relative to their risk for graft failure. To avoid undue risk aversion, SRTR now accounts for macrovesicular steatosis in the SRTR risk-adjustment models to help facilitate use of these higher-risk organs. Increased recognition of this variable may also encourage further efforts to standardize the reporting of liver biopsy results.

Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets. However, compiling such datasets is challenging and specific recommendations are missing. A committee of various stakeholders, including commercial AI developers, pathologists, and researchers, discussed key aspects and conducted extensive literature reviews on test datasets in pathology. Here, we summarize the results and derive general recommendations on compiling test datasets. We address several questions: Which and how many images are needed? How to deal with low-prevalence subsets? How can potential bias be detected? How should datasets be reported? What are the regulatory requirements in different countries? The recommendations are intended to help AI developers demonstrate the utility of their products and to help pathologists and regulatory agencies verify reported performance measures. Further research is needed to formulate criteria for sufficiently representative test datasets so that AI solutions can operate with less user intervention and better support diagnostic workflows in the future.

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.

Hepatic steatosis (HS) can be comprehensively assessed by visually comparing the hepatic and vessel attenuation on unenhanced computed tomography (CT). We aimed to evaluate the reliability and reproducibility of a CT-based visual grading system (VGS) for comprehensive assessment of HS.

In this retrospective study, a four-point VGS based on the visual comparison of liver and hepatic vessels was validated by six reviewers with diverse clinical experience using the unenhanced CT images of 717 potential liver donors. The diagnostic performance of VGS and quantitative indices (difference and ratio of the hepatic and splenic attenuation) to diagnose HS were evaluated using multi-reader multi-case receiver operating characteristics (ROC) analysis (reference: pathology). The interobserver agreement was assessed using Fleiss κ statistics.

Using the VGS, all six reviewers showed areas under the ROC curves (AUROCs) higher than 0.9 for diagnosing total steatosis (TS) ≥ 30%, macrovesicular steatosis (MaS) ≥ 30%, and MaS ≥ 10%. No difference was noted between the AUROCs of the VGS and quantitative indices (p ≥ 0.1). The reviewers showed substantial agreement (Fleiss κ, 0.61). Most discrepancies occurred between the two lowest grades of VGS (81.5%; 233/283), in which most subjects (97.0%; 226/233) had a MaS < 10%. The average-reader sensitivity and specificity of the VGS were 0.80 and 0.94 to detect TS ≥ 30% and 0.93 and 0.81 to detect MaS ≥ 10%.

VGS was reliable and reproducible in assessing HS. It may be useful as a non-invasive and simple tool for comprehensive HS assessment.

Hepatic steatosis is a major cause of chronic liver disease. Two-dimensional (2D) ultrasound is the most widely used non-invasive tool for screening and monitoring, but associated diagnoses are highly subjective.

To develop a scalable deep learning (DL) algorithm for quantitative scoring of liver steatosis from 2D ultrasound images.

Using multi-view ultrasound data from 3310 patients, 19513 studies, and 228075 images from a retrospective cohort of patients received elastography, we trained a DL algorithm to diagnose steatosis stages (healthy, mild, moderate, or severe) from clinical ultrasound diagnoses. Performance was validated on two multi-scanner unblinded and blinded (initially to DL developer) histology-proven cohorts (147 and 112 patients) with histopathology fatty cell percentage diagnoses and a subset with FibroScan diagnoses. We also quantified reliability across scanners and viewpoints. Results were evaluated using Bland-Altman and receiver operating characteristic (ROC) analysis.

The DL algorithm demonstrated repeatable measurements with a moderate number of images (three for each viewpoint) and high agreement across three premium ultrasound scanners. High diagnostic performance was observed across all viewpoints: Areas under the curve of the ROC to classify mild, moderate, and severe steatosis grades were 0.85, 0.91, and 0.93, respectively. The DL algorithm outperformed or performed at least comparably to FibroScan control attenuation parameter (CAP) with statistically significant improvements for all levels on the unblinded histology-proven cohort and for "= severe" steatosis on the blinded histology-proven cohort.

The DL algorithm provides a reliable quantitative steatosis assessment across view and scanners on two multi-scanner cohorts. Diagnostic performance was high with comparable or better performance than the CAP.

In liver transplantation (LT), steatosis is commonly judged to be a risk factor for graft dysfunction, and quantitative assessment of hepatic steatosis remains crucial. Liver biopsy as the gold standard for evaluation of hepatic steatosis has certain drawbacks, i.e. invasiveness, and intra- and inter-observer variability. A non-invasive, quantitative modality could replace liver biopsy and eliminate these disadvantages, but has not yet been evaluated in human LT.

We performed a pilot study to evaluate the feasibility and accuracy of hyperspectral imaging (HSI) in the assessment of hepatic steatosis of human liver allografts for transplantation. Thirteen deceased donor liver allografts were included in the study. The degree of steatosis was assessed by means of conventional liver biopsy as well as HSI, performed at the end of backtable preparation, during normothermic machine perfusion (NMP), and after reperfusion in the recipient.

Organ donors were 51 [30-83] years old, and 61.5% were male. Donor body mass index was 24.2 [16.5-38.0] kg/m2. The tissue lipid index (TLI) generated by HSI at the end of back-table preparation correlated significantly with the histopathologically assessed degree of overall hepatic steatosis (R2 = 0.9085, p<0.0001); this was based on a correlation of TLI and microvesicular steatosis (R2 = 0.8120; p<0.0001). There is also a linear relationship between the histopathologically assessed degree of overall steatosis and TLI during NMP (R2 = 0.5646; p = 0.0031) as well as TLI after reperfusion (R2 = 0.6562; p = 0.0008).

HSI may safely be applied for accurate assessment of hepatic steatosis in human liver grafts. Certainly, TLI needs further assessment and validation in larger sample sizes. This article is protected by copyright. All rights reserved.