Socioeconomic status and health disparities drive differences in accelerometer-derived physical activity in fatty liver disease and significant fibrosis.

BACKGROUND AND AIMS: The cornerstone of clinical management of patients with nonalcoholic fatty liver disease (NAFLD) are lifestyle changes such as increasing physical activity (PA) aimed at improving cardiometabolic risk. To inform NAFLD prevention and treatment guidelines we aimed to: (i) quantify the role of PA on lowering the risk for NAFLD and fibrosis; (ii) characterize NAFLD and fibrosis association with PA in the context of socioeconomic environment. METHODS: A sample of 2648 participants from the NHANES 2003-2006 was selected to develop survey weighted multivariable logistic regression models for predicting NAFLD and significant fibrosis, diagnosed non-invasively via fatty liver index (FLI) and fibrosis-4 (FIB-4) index. The PA measures were obtained from a hip-worn accelerometer. RESULTS: The predictive model for NAFLD showed AUC of 0.687 and a decrease of 43% in NAFLD risk with moderate vigorous PA (MVPA) (OR = 0.569, p < 0.001). The predictive model for fibrosis had AUC of 0.755 and there was a 48% and a 70% decrease in significant fibrosis risk with MVPA (OR = 0.518, p = 0.022) and total log activity count (TLAC) (OR = 0.296, p = 0.017), respectively. Participants with NAFLD and NAFLD with fibrosis engage in declining PA. Despite having jobs with higher level of PA and participating in more moderate-to-vigorous PA, a larger proportion of Hispanics participants had NAFLD and significant fibrosis. CONCLUSIONS: These findings demonstrate the role of PA as a protective factor against the presence of NAFLD and significant fibrosis. Protective levels of PA in NAFLD differ by races.

7 Tesla MRI Liver Fat Quantification in Mice: Data Quality Assessment.

PURPOSE: The objective of this study was to evaluate the robustness of proton density fat fraction (PDFF) data determined by magnetic resonance imaging (MRI) and spectroscopy (MRS) via spatially resolved error estimation. MATERIALS AND METHODS: Using standard T2* relaxation time measurement protocols, in-vivo and ex-vivo MRI data with water and fat nominally in phase or out of phase relative to each other were acquired on a 7 T small animal scanner. Based on a total of 24 different echo times, PDFF maps were calculated in a magnitude-based approach. After identification of the decisive error-prone variables, pixel-wise error estimation was performed by simple propagation of uncertainty. The method was then used to evaluate PDFF data acquired for an explanted mouse liver and an in vivo mouse liver measurement. RESULTS: The determined error maps helped excluding measurement errors as cause of unexpected local PDFF variations in the explanted liver. For in vivo measurements, severe error maps gave rise to doubts in the acquired PDFF maps and triggered an in-depth analysis of possible causes, yielding abdominal movement or bladder filling as in vivo occurring reasons for the increased errors. CONCLUSION: The combination of pixel-wise acquisition of PDFF data and the corresponding error maps allows for a more specific, spatially resolved evaluation of the PDFF value reliability.

LipidSIM: Inferring mechanistic lipid biosynthesis perturbations from lipidomics with a flexible, low-parameter, Markov modeling framework.

Lipid metabolism is a complex and dynamic system involving numerous enzymes at the junction of multiple metabolic pathways. Disruption of these pathways leads to systematic dyslipidemia, a hallmark of many pathological developments, such as nonalcoholic steatohepatitis and diabetes. Recent advances in computational tools can provide insights into the dysregulation of lipid biosynthesis, but limitations remain due to the complexity of lipidomic data, limited knowledge of interactions among involved enzymes, and technical challenges in standardizing across different lipid types. Here, we present a low-parameter, biologically interpretable framework named Lipid Synthesis Investigative Markov model (LipidSIM), which models and predicts the source of perturbations in lipid biosynthesis from lipidomic data. LipidSIM achieves this by accounting for the interdependency between the lipid species via the lipid biosynthesis network and generates testable hypotheses regarding changes in lipid biosynthetic reactions. This feature allows the integration of lipidomics with other omics types, such as transcriptomics, to elucidate the direct driving mechanisms of altered lipidomes due to treatments or disease progression. To demonstrate the value of LipidSIM, we first applied it to hepatic lipidomics following Keap1 knockdown and found that changes in mRNA expression of the lipid pathways were consistent with the LipidSIM-predicted fluxes. Second, we used it to study lipidomic changes following intraperitoneal injection of CCl4 to induce fast NAFLD/NASH development and the progression of fibrosis and hepatic cancer. Finally, to show the power of LipidSIM for classifying samples with dyslipidemia, we used a Dgat2-knockdown study dataset. Thus, we show that as it demands no a priori knowledge of enzyme kinetics, LipidSIM is a valuable and intuitive framework for extracting biological insights from complex lipidomic data.

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.

Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods.

Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in Collinsella sp. and Oscillospiraceae for the control samples and enrichment in Lachnospiraceae (and in particular Dorea sp.) and Veillonellaceae in NAFLD. The families, Bifidobacteriaceae, Lactobacillaceae, and Enterococcaceae (particularly Enterococcus faecium and Enterococcus faecalis), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in Candida krusei and a decrease in Bacteroides uniformis for NAFLD patients were detected using MALDI-TOF-MS. An increase in Gracilibacteraceae, Chitinophagaceae, Pirellulaceae, Erysipelatoclostridiaceae, Muribaculaceae, and Comamonadaceae, and a decrease in Acidaminococcaceae in NAFLD were observed with 16S NGS, and enrichment in Fusobacterium nucleatum was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.

Multimodal assessment of non-alcoholic fatty liver disease with transmission-reflection optoacoustic ultrasound.

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term referring to a group of conditions associated to fat deposition and damage of liver tissue. Early detection of fat accumulation is essential to avoid progression of NAFLD to serious pathological stages such as liver cirrhosis and hepatocellular carcinoma. Methods: We exploited the unique capabilities of transmission-reflection optoacoustic ultrasound (TROPUS), which combines the advantages of optical and acoustic contrasts, for an early-stage multi-parametric assessment of NAFLD in mice. Results: The multispectral optoacoustic imaging allowed for spectroscopic differentiation of lipid content, as well as the bio-distributions of oxygenated and deoxygenated hemoglobin in liver tissues in vivo. The pulse-echo (reflection) ultrasound (US) imaging further provided a valuable anatomical reference whilst transmission US facilitated the mapping of speed of sound changes in lipid-rich regions, which was consistent with the presence of macrovesicular hepatic steatosis in the NAFLD livers examined with ex vivo histological staining. Conclusion: The proposed multimodal approach facilitates quantification of liver abnormalities at early stages using a variety of optical and acoustic contrasts, laying the ground for translating the TROPUS approach toward diagnosis and monitoring NAFLD in patients.

Quantitative Assessment of Hepatic Steatosis Using Label-Free Multiphoton Imaging and Customized Image Processing Program.

Nonalcoholic fatty liver disease is rapidly becoming one of the most common causes of chronic liver disease worldwide and is the leading cause of liver-related morbidity and mortality. A quantitative assessment of the degree of steatosis would be more advantageous for diagnostic evaluation and exploring the patterns of disease progression. Here, multiphoton microscopy, based on the second harmonic generation and 2-photon excited fluorescence, was used to label-free image the samples of nonalcoholic fatty liver. Imaging results confirm that multiphoton microscopy is capable of directly visualizing important pathologic features such as normal hepatocytes, hepatic steatosis, Mallory bodies, necrosis, inflammation, collagen deposition, microvessel, and so on and is a reliable auxiliary tool for the diagnosis of nonalcoholic fatty liver disease. Furthermore, we developed an image segmentation algorithm to simultaneously assess hepatic steatosis and fibrotic changes, and quantitative results reveal that there is a correlation between the degree of steatosis and collagen content. We also developed a feature extraction program to precisely display the spatial distribution of hepatocyte steatosis in tissues. These studies may be beneficial for a better clinical understanding of the process of steatosis as well as for exploring possible therapeutic targets.

Factors associated with discordance in the assessment of fibrosis stage between transient elastography and liver biopsy in NAFLD patients.

BACKGROUND AND AIMS: Few studies focus on the concordance of fibrosis stage assessment between transient elastography (TE) and liver biopsy (LB) in non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the rate of discordance and factors associated with discordance in the fibrosis stage assessment between TE and LB. METHODS: LB-proven NAFLD patients were enrolled retrospectively. Liver fibrosis was assessed via TE and LB based on Steatosis-Activity-Fibrosis (SAF) criteria. Cohen's kappa was used to estimate the discordance between the fibrosis stage assessment by TE and LB. Logistic regression was utilized to determine the factors associated with discordance. RESULTS: A total of 172 eligible patients were included. The concordance of fibrosis staging between TE and LB was moderate (kappa = 0.446, p < 0.001). The overall rate of discordance was 52.90% (91/172) and highest in the F2 stage (66.28%) and F3 stage (60.42%), moderate in the F1 stage (23.81%), and lowest in the F4 stage (0.00%). The rate of overestimation and underestimation was 23.66% and 38.71% in patients detected by M-probe, while the rate of overestimation and underestimation was 33.87% and 19.35% in patients detected by XL-probe, respectively. BMI [OR=1.494, p = 0.017] and type 2 diabetes mellitus (T2DM) (OR=4.678, p = 0.008) were significantly associated with the overestimation in fibrosis stage assessment when the M-probe was applied. CONCLUSIONS: The discordance between TE and LB in fibrosis stage assessment was unexpectedly high and mainly observed in F1-F3 patients. BMI and T2DM were the factors associated with overestimation using the M-probe.

Simultaneous imaging of ultrasonic relative backscatter and attenuation coefficients for quantitative liver steatosis assessment.

Prevalence of liver disease is continuously increasing and nonalcoholic fatty liver disease (NAFLD) is the most common etiology. We present an approach to detect the progression of liver steatosis based on quantitative ultrasound (QUS) imaging. This study was performed on a group of 55 rats that were subjected to a control or methionine and choline deficient (MCD) diet known to induce NAFLD. Ultrasound (US) measurements were performed at 2 and 6 weeks. Thereafter, animals were humanely euthanized and livers excised for histological analysis. Relative backscatter and attenuation coefficients were simultaneously estimated from the US data and envelope signal-to-noise ratio was calculated to train a regression model for: (1) fat fraction percentage estimation and (2) performing classification according to Brunt's criteria in grades (0 <5%; 1, 5-33%; 2, >33-66%; 3, >66%) of liver steatosis. The trained regression model achieved an [Formula: see text] of 0.97 (p-value < 0.01) and a RMSE of 3.64. Moreover, the classification task reached an accuracy of 94.55%. Our results suggest that in vivo QUS is a promising noninvasive imaging modality for the early assessment of NAFLD.

Usefulness of two-dimensional shear wave elastography in the assessment of non-alcoholic fatty liver disease in children and adolescents.

Two-dimensional shear wave elastography (2D-SWE) evaluates liver stiffness using a non-invasive method, but studies in the paediatric population are rare. This study evaluated the role of 2D-SWE in the diagnosis and severity of paediatric non-alcoholic fatty liver disease (NAFLD). In total, 131 patients with NAFLD and 25 healthy controls were enrolled in this study. The diagnosis and severity of NAFLD were initially assessed using the ultrasound fatty liver index (US-FLI), and all participants underwent 2D-SWE. US-FLI semi-quantitatively measures the severity of NAFLD on a scale of 2-8. The assessment of liver stiffness measurement (LSM) by 2D-SWE is presented in kilopascals (kPa). The NAFLD group was characterised by significantly higher LSM (4.40 ± 0.90 kPa) than the control group (3.76 ± 0.28 kPa) (P < 0.001). 2D-SWE significantly correlated with age, height, weight, body mass index, glucose, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein cholesterol, US-FLI, and triglyceride-glucose index (P < 0.001). In the receiver operating characteristic curve analysis, the area under the curve of LSM for predicting US-FLI ≥ 2 and ≥ 6 was 0.784 (P < 0.001) and 0.819 (P < 0.001), respectively. In conclusion, we suggest that 2D-SWE can be used as a non-invasive diagnostic tool for diagnosing and assessing the severity of paediatric NAFLD.

Multiparametric MR assessment of liver fat, iron, and fibrosis: a concise overview of the liver "Triple Screen".

Chronic liver disease (CLD) is a common source of morbidity and mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) serves as a major cause of CLD with a rising annual prevalence. Additionally, iron overload can be both a cause and effect of CLD with a negative synergistic effect when combined with NAFLD. The development of state-of-the-art multiparametric MR solutions has led to a change in the diagnostic paradigm in CLD, shifting from traditional liver biopsy to innovative non-invasive methods for providing accurate and reliable detection and quantification of the disease burden. Novel imaging biomarkers such as MRI-PDFF for fat, R2 and R2* for iron, and liver stiffness for fibrosis provide important information for diagnosis, surveillance, risk stratification, and treatment. In this article, we provide a concise overview of the MR concepts and techniques involved in the detection and quantification of liver fat, iron, and fibrosis including their relative strengths and limitations and discuss a practical abbreviated MR protocol for clinical use that integrates these three MR biomarkers into a single simplified MR assessment. Multiparametric MR techniques provide accurate and reliable non-invasive detection and quantification of liver fat, iron, and fibrosis. These techniques can be combined in a single abbreviated MR "Triple Screen" assessment to offer a more complete metabolic imaging profile of CLD.

Monte Carlo modeling of hepatic steatosis based on stereology and spatial distribution of fat droplets.

BACKGROUND AND OBJECTIVE: To model hepatic steatosis in adult humans with non-alcoholic fatty liver disease based on stereology and spatial distribution of fat droplets from liver biopsy specimens. METHODS: Histological analysis was performed on 30 adult human liver biopsy specimens with varying degrees of steatosis. Morphological features of fat droplets were characterized by gamma distribution function (GDF) in both two-dimensional (2D) and three-dimensional (3D) spaces from three aspects: 1) size distribution indicating non-uniformity of fat droplets in radius; 2) nearest neighbor distance distribution indicating heterogeneous accumulation (i.e., clustering) of fat droplets; 3) regional anisotropy indicating inter-regional variability in fat fraction (FF). To generalize the morphological description of hepatic steatosis to different FFs, correlation analysis was performed among the estimated GDF parameters and FFs for all specimens. Finally, Monte Carlo modeling of hepatic steatosis was developed to simulate fat droplet distribution in tissue. RESULTS: Morphological features, including size and nearest neighbor distance in 2D and 3D spaces as well as regional anisotropy, statistically captured the distribution of fat droplets by the GDF fit (R2 > 0.54). The estimated GDF parameters (i.e., scale and shape parameters) and FFs were well correlated, with R2 > 0.55. In addition, simulated 3D liver morphological models demonstrated similar sections to real histological samples both visually and quantitatively. CONCLUSIONS: The morphology of hepatic steatosis is well characterized by stereology and spatial distribution of fat droplets. Simulated models demonstrate similar appearances to real histological samples. Furthermore, the model may help understand MRI signal behavior in the presence of liver steatosis.

Liver Assessment in Patients with Ataxia-Telangiectasia: Transient Elastography Detects Early Stages of Steatosis and Fibrosis.

Background: Ataxia-telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition, and altered body composition. Liver diseases with steatosis, fibrosis, and hepatocellular carcinoma are frequent findings in older patients but sensitive noninvasive diagnostic tools are lacking. Objectives: To determine the sensitivity of transient elastography (TE) as a screening tool for early hepatic tissue changes and serum biomarkers for liver disease. Methods: Thirty-one A-T patients aged 2 to 25 years were examined prospectively from 2016-2018 by TE. In addition, we evaluated the diagnostic performance of liver biomarkers for steatosis and necroinflammatory activity (SteatoTest and ActiTest, Biopredictive, Paris) compared to TE. For calculation and comparison, patients were divided into two groups (<12, >12 years of age). Results: TE revealed steatosis in 2/21 (10%) younger patients compared to 9/10 (90%) older patients. Fibrosis was present in 3/10 (30%) older patients as assessed by TE. We found a significant correlation of steatosis with SteatoTest, alpha-fetoprotein (AFP), HbA1c, and triglycerides. Liver stiffness correlated significantly with SteatoTest, ActiTest, HbA1c, and triglycerides. Conclusion: Liver disease is a common finding in older A-T patients. TE is an objective measure to detect early stages of steatosis and fibrosis. SteatoTest and ActiTest are a good diagnostic assessment for steatosis and necroinflammatory activity in patients with A-T and confirmed the TE results.

The Non-Invasive Assessment of Circulating D-Loop and mt-ccf Levels Opens an Intriguing Spyhole into Novel Approaches for the Tricky Diagnosis of NASH.

Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease worldwide affecting both adults and children. Nowadays, no therapeutic strategies have been approved for NAFLD management, and hepatic biopsy remains the gold standard procedure for its diagnosis. NAFLD is a multifactorial disease whose pathogenesis is affected by environmental and genetic factors, and it covers a spectrum of conditions ranging from simple steatosis up to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Several studies underlined the urgent need to develop an NAFLD risk prediction model based on genetics, biochemical indicators, and metabolic disorders. The loss of mitochondrial dynamics represents a typical feature of progressive NAFLD. The imbalance of mitochondrial lifecycle together with the impairment of mitochondrial biomass and function trigger oxidative stress, which in turn damages mitochondrial DNA (mtDNA). We recently demonstrated that the main genetic predictors of NAFLD led to mitochondrial dysfunction. Moreover, emerging evidence shows that variations in the displacement loop (D-loop) region impair mtDNA replication, and they have been associated with advanced NAFLD. Finally, lower levels of mitophagy foster the overload of damaged mitochondria, resulting in the release of cell-free circulating mitochondrial DNA (mt-ccf) that exacerbates liver injury. Thus, in this review we summarized what is known about D-loop region alterations and mt-ccf content during NAFLD to propose them as novel non-invasive biomarkers.

Costs of a structured early detection program for advanced liver fibrosis and cirrhosis: insights on the "plus" of Check-up 35.

BACKGROUND: The implementation of an early detection program for liver cirrhosis in a general population has been discussed for some time. Recently, the effectiveness of a structured screening procedure, called SEAL (Structured Early detection of Asymptomatic Liver cirrhosis), using liver function tests (AST and ALT) and APRI to early detect advanced fibrosis and cirrhosis in participants of the German "Check-up 35" was investigated. METHODS: This study identifies the expected diagnostic costs of SEAL in routine care and their drivers and reports on prevailing CLD etiologies in this check-up population. The analysis is based on theoretical unit costs, as well as on the empirical billing and diagnostic data of SEAL participants. RESULTS: Screening costs are mainly driven by liver biopsies, which are performed in a final step in some patients. Depending on the assumed biopsy rates and the diagnostic procedure, the average diagnostic costs are between EUR 5.99 and 13.74 per Check-up 35 participant and between EUR 1,577.06 and 3,620.52 per patient diagnosed with fibrosis/cirrhosis (F3/F4). The prevailing underlying etiology in 60% of cases is non-alcoholic fatty liver disease. DISCUSSION: A liver screening following the SEAL algorithm could be performed at moderate costs. Screening costs in routine care depend on actual biopsy rates and procedures, attendance rates at liver specialists, and the prevalence of fibrosis in the Check-up 35 population. The test for viral hepatitis newly introduced to Check-up 35 as once-in-a-lifetime part of Check-up 35 is no alternative to SEAL.

Triglyceride-Glucose Index and Hepatic Steatosis Index for the assessment of liver steatosis in HCV patients.

BACKGROUND: Liver steatosis in patients with chronic infection of hepatitis C virus (HCV) is important from multiple standpoints: faster disease progression, more frequent hepatocellular carcinoma and cirrhosis development or worse therapy response. Liver biopsy as diagnostic method, is in recent years more and more challenged due to its well-known flaws. Hepatic steatosis index (HSI) and triglyceride-glucose (TyG) Index, are surrogate scores developed in the first place for noninvasive assessment of steatosis in patients with nonalcoholic fatty liver disease (NAFLD). However, their use in the context of chronic hepatitis C (CHC) virus infection is still unclear. Aim of our study was to assess the accuracy of both HSI and TyG index in patients with CHC. METHODS: The cohort included 814 patients with CHC infection in whom liver biopsy was performed. After implementing strict criteria for sample adequacy and necessary data, 424 patients were finally enrolled in our study. Histological findings were used as a reference point, and surrogate scores HSI and TyG index were expressed through receiver operating characteristic (ROC) curves in order to assess their ability in determining patients without (<5%) or with steatosis (>5%), but also to address their ability in assessing between different degrees of steatosis. RESULTS: The average age of study population was 37.09 years and the majority of patients were men (67%). Liver steatosis was detected in approximately half of the liver biopsy samples (50.4%). About 5% of them had severe steatosis. The area under the ROC curve values for HSI and TyG index when detecting liver steatosis were 0.76 and 0.629, respectively. Similar values were obtained comparing between absence of steatosis and mild steatosis (5-30%). CONCLUSIONS: Non-invasive surrogate scores HSI and TyG index in CHC patients, have good performance to detect the presence of steatosis. In this context, these tools are cheap, widely available and could be valuable asset in liver steatosis assessment outside liver biopsy.

Liver biopsy for assessment of chronic liver diseases: a synopsis.

The world-wide increase in chronic liver disease (CLD) calls for refinement of diagnostic and prognostic measures for early and accurate disease detection and management. Regardless of the aetiology, liver biopsy allows direct visualisation of specimen under the microscope. It facilitates histological evaluation of disease-specific morphological alterations. Thereby, it aids in disease diagnosis, prognosis, and assessment of treatment compliance/response. Indeed, with the advent of non-invasive methods, liver biopsy is used less frequently than before, but it is still considered as a gold standard for staging and grading several CLDs. This short review revisits liver biopsy. It highlights the significance of liver biopsy in evaluating CLDs and explains the commonly used Ishak, METAVIR and Batts-Ludwig scoring systems for grading and staging CLDs. The utility of liver biopsy in examining alcohol-related liver disease and non-alcoholic fatty liver disease (NAFLD) is discussed along with the disease-specific alcoholic hepatitis histology score (AHHS) and non-alcoholic fatty liver disease activity score (NAS). Additionally, the review elaborates on the role of liver biopsy in evaluating viral hepatitis, haemochromatosis, and hepatocellular carcinoma. Contextual explanation on the diagnosis of metabolic dysfunction-associated liver disease (MAFLD) is provided. The significance and clinical indications of repeat biopsy are also explained. Lastly, caveats and limitations associated with liver biopsy are reviewed. Essentially, this review collates the application of liver biopsy in assessing various CLDs and provides succinct explanations of the core scoring systems, all under one roof. It is clinically relevant and provides a useful synopsis to budding scientists and hepato-pathologists.

Reliability of Non-invasive Liver Fibrosis Assessment Tools Versus Biopsy in Pre- and Post-bariatric Surgery Patients with Non-alcoholic Fatty Liver Disease.

PURPOSE: Liver biopsy (LBx) remains the gold standard to assess fibrosis in non-alcoholic fatty liver disease (NAFLD). Biochemical markers are also useful, but their reliability is not clear in patients with morbid obesity. We assessed the performance of six non-invasive fibrosis assessment tools before and after bariatric surgery (BSx) using LBx. MATERIALS AND METHODS: This is a cross-sectional and prospective cohort study. LBx was performed at the time of BSx and 12-month post-operatively and assessed using the Brunt system. Clinical and biochemical measurements were collected at the same time points and six non-invasive fibrosis assessment tools were calculated. RESULTS: One hundred seventy patients had BSx; 79.4% female; age was 46.6 ± 9.8 years, and BMI was 48.6 ± 7.5 kg/m2. From liver histology, 88% had F0-F2 and 11.2% F3-F4. At BSx, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 had better accuracy (0.86 and 0.88) with specificity of 96.6% and 94.0% and negative predictive values (NPV) of 88.9% and 93.7%. However, sensitivity (6.7% and 40.0%) and positive predictive values (PPV) (20.0% and 46.2%) were low. Twelve months post-surgery (n = 54), 88.9% of patients had F0-F2 and 11.1% had F3-F4. Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) had the best accuracy (0.79 and 0.77) with specificity of 83.7% and 86.9% and NPV of 92.3% and 86.9%. However, sensitivity (25% and 0%) and PPV (12.5% and 0%) were low. CONCLUSION: Overall, FIB-4, APRI, and NFS showed similar performances with higher accuracy, specificity, and NPV. Sensitivity and PPV were low. These tests are more useful at excluding advanced fibrosis.

Three segments sampling strategy for the assessment of liver steatosis using magnetic resonance imaging proton density fat fraction.

PURPOSE: This research aims to determine the best liver segments representing the whole-liver fat fraction (FF) in magnetic resonance imaging (MRI)-based measurement of the proton density fat fraction (PDFF). METHOD: This retrospective study included 989 adult subjects who underwent MRI-PDFF from March 2018 to January 2021. Three regions of interest (ROI) were measured and averaged for each hepatic segment and the volume-weighted hepatic FF was calculated. Intrahepatic fat variability was assessed by standard deviation between all ROIs. Univariate and multivariate linear regression analyses were done for the factors associated with intrahepatic fat variability among clinical characteristics, blood parameters and the volume-weighted FF. The arithmetic means of specific hepatic segments that were the closest to the volume-weighted FF were identified in all subjects and those with moderate or severe fatty liver. RESULTS: The volume-weighted FF was 8.18% and variability was 1.33%. Volume-weighted FF was the only associated factor with intrahepatic variability. The arithmetic mean of segments V, VI, and IV was closest to the volume-weighted FF in all subjects and in subjects with moderate or severe fatty liver. CONCLUSIONS: There was considerable heterogeneity in hepatic steatosis between each segment of the liver, and the variability was significantly affected by the volume-weighted FF. The mean hepatic FF from segments V, VI, and IV could be used to estimate the volume-weighted FF of the whole liver, not only in the general population but also in patients with moderate or severe fatty liver.