Search

The most common chronic liver illness worldwide is metabolic dysfunction linked to fatty liver disease (MAFLD), which is poorly understood by doctors and patients. Many people with this disease develop steatohepatitis, cirrhosis and its consequences, as well as extrahepatic manifestations; these conditions are particularly common if they are linked to diabetes mellitus or obesity. A breakthrough with numerous benefits is the switch from NAFLD to MAFLD in terms of terminology and methodology. The diagnosis of MAFLD is based on affirmative criteria; unlike NAFLD, it is no longer based on exclusion. The diagnosis of MAFLD and the evaluation of steatosis and fibrosis is achieved using liver biopsy and non-invasive laboratory or radiographic techniques. We briefly address the most recent developments in MAFLD epidemiology and diagnosis. [ABSTRACT FROM AUTHOR]

Aims: To examine whether an extended lifestyle metrics incorporating sleep quality improves risk stratification for metabolic dysfunction-associated fatty liver disease (MAFLD), at-risk metabolic dysfunction-associated steatohepatitis (MASH) and significant fibrosis. Methods: A total of 5011 participants with abdominal ultrasound from Imaging sub-cohort of South China Cohort (ISSCC) and 3672 participants underwent vibration controlled transient elastography from US National Health and Nutrition Examination Survey (US NHANES) were included. Liver Essential 5 was constructed by incorporating sleep quality into traditional healthy lifestyles (HLS). Results: A total of 4.66–17.72% of the association between traditional HLS and MAFLD was mediated by sleep quality regardless of the detection techniques, and their joint associations on MAFLD were significant in both cohorts. ORs for individuals with poor sleep and unfavorable HLS were 1.72 (1.29–2.30) in ISSCC and 2.25 (1.55–3.26) in US NHANES, respectively. Around half of the participants previously considered as following a favorable HLS were re-classified by Liver Essential 5 with significantly higher prevalences of MAFLD in both cohorts (P < 0.001). Similar results were also found on at-risk MASH and significant fibrosis in US NHANES. ORs of participants with per one increment increase in Liver Essential 5 were 0.82 (0.77–0.89) and 0.79 (0.70–0.88) for MAFLD in ISSCC and US NHANES, 0.62 (0.48–0.78) for at-risk MASH and 0.78 (0.65–0.93) for significant fibrosis. Conclusions: Liver Essential 5, which incorporates sleep quality and traditional lifestyle factors, provides additional risk stratification for MAFLD-related outcomes. [ABSTRACT FROM AUTHOR]

Background and aims: Diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) have been proposed but not yet validated. This study aimed to compare the diagnostic accuracy of the MASLD definition with the existing criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) in identifying patients with significant fibrosis. Methods: The analysis included a total of 8317 individuals who had complete biochemical and liver ultrasonography data from the National Health and Nutrition Examination Survey (2017–2020). In this study, significant fibrosis (≥ F2) was determined by a median liver stiffness of ≥ 8.0 kPa. To identify independent factors associated with significant fibrosis, multivariable logistic regression analyses were applied. Results: MAFLD (OR 3.44; 95% CI 2.88–4.12; P < 0.0001) has a trend for stronger and independent association with significant fibrosis compared to MASLD (OR 2.63; 95% CI 2.22–3.11; P < 0.0001). Non-MASLD MAFLD is independently associated with a 14.28-fold higher odds of significant fibrosis compared to non-MAFLD MASLD. The sensitivity for detecting significant fibrosis for MAFLD and MASLD was 76.23% vs 69.94%, respectively. The performance of MAFLD remains consistent in a sub-analysis of patients with no or mild alcohol intake. Conclusions: The definition of MAFLD provides a more precise identification of individuals who have both fatty liver and significant fibrosis, assessed by non-invasive tests. [ABSTRACT FROM AUTHOR]

With high prevalence and substantial mortality, metabolic dysfunction-associated steatotic liver disease and chronic obstructive pulmonary disease (COPD) are significant public health concerns. Utilizing a large, population-based dataset from the National Health and Nutrition Examination Survey, our study probes the relationship between COPD prevalence and hepatic steatosis and fibrosis, as measured by Vibration-Controlled Transient Elastography. We analyzed data from 693 individuals with COPD and 7229 without. Through weighted multivariate logistic regression analysis, a restricted cubic spline curve, and threshold effect analysis, we investigated the correlation between the severity of hepatic steatosis and fibrosis and the presence of COPD. Our findings revealed a positive correlation between the controlled attenuation parameter (CAP) and COPD prevalence [OR = 1.03 (95% CI 1.01, 1.05)], even after multivariate adjustment. Furthermore, we observed a U-shaped association between CAP and COPD, where the inflection point, CAP value of 264.85 dB/m, corresponded to the lowest COPD prevalence. Our study emphasizes a substantial and complex link between hepatic steatosis and COPD. These findings urge healthcare professionals to factor liver health into COPD management and prompt further exploration into the underlying mechanisms. This could pave the way for the development of improved prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the inter-platform reproducibility of ultrasound-based fat fraction examination in nonalcoholic fatty liver disease (NAFLD). Methods: Patients suspected of having NAFLD were prospectively enrolled from January 2023. Ultrasound-based fat fraction examinations were performed using two different platforms (ultrasound-derived fat fraction [UDFF] and quantitative ultrasound-derived estimated fat fraction [USFF]) on the same day. The correlation between UDFF and USFF was assessed using Pearson correlation coefficient. Intraclass correlation coefficient (ICC), Bland–Altman analysis with 95% limits of agreement (LOAs), and the coefficient of variation (CV) were used to assess inter-platform reproducibility. Results: A total of 41 patients (21 men and 20 women; mean age, 53.9 ± 12.6 years) were analyzed. Moderate correlation was observed between UDFF and USFF (Pearson's r = 0.748; 95% confidence interval [CI]: 0.572–0.858). On Bland–Altman analysis, the mean difference between UDFF and USFF values was 1.3% with 95% LOAs ranging from -8.0 to 10.6%. The ICC between UDFF and USFF was 0.842 (95% CI: 0.703–0.916), with a CV of 29.9%. Conclusion: Substantial inter-platform variability was observed among different ultrasound-based fat fraction examinations. Therefore, it is not appropriate to use ultrasound-based fat fraction values obtained from different vendors interchangeably. Critical relevance statement: Considering the substantial inter-platform variability in ultrasound-based fat fraction assessments, caution is imperative when interpreting and comparing fat fraction values obtained from different ultrasound platforms in clinical practice. Key points: • Inter-platform reproducibility of ultrasound-based fat fraction examinations is important for its clinical application. • Significant variability across different ultrasound-based fat fraction examinations was observed. • Using ultrasound-based fat fraction values from different vendors interchangeably is not advisable. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between different ultrasound attenuation-based techniques and to compare their diagnostic performances using proton magnetic resonance spectroscopy (1H-MRS) as a reference standard. Methods: Participants who had clinical suspicion of nonalcoholic fatty liver disease (NAFLD) were prospectively recruited. Each subject had ultrasound with attenuation imaging (ATI) or quantitative ultrasound including tissue attenuation imaging (TAI) and tissue scatter-distribution imaging (TSI), and controlled-attenuation parameter (CAP) and 1H-MRS if available. The technical success rates, intra-observer repeatabilities of attenuation and backscattering coefficient were evaluated. ATI, TAI and CAP were three attenuation-based techniques. Spearman coefficient was used to test correlations among them and 1H-MRS. In addition, the diagnostic performances of these parameters for detecting ≥ 5% or 10% hepatic steatosis were evaluated. Results: 130 participants had ultrasound scanning. Among them, 67 had CAP and 48 had 1H-MRS. The technical success rates were all 100%. The intra-observer repeatabilities of them were also excellent (ICCs > 0.90) and AC-ATI correlated well with AC-TAI (r = 0.752). AC-ATI, AC-TAI showed moderate correlation with CAP, (rATI = 0.623, 95% CI 0.446–0.752, P < 0.001; rTAI = 0.573, 95% CI 0.377–0.720, P < 0.001). For correlation with 1H-MRS, ATI and TAI performed better than CAP(rATI = 0.587; rTAI = 0.712; r CAP = 0.485). The AUCs of ATI, TAI, TSI and CAP for detecting ≥ 5% hepatic steatosis were 0.883, 0.862, 0.870 and 0.868, respectively. The AUC improved to 0.907 when TAI and TSI were combined (P < 0.05). When detecting ≥ 10% hepatic steatosis, the AUCs were 0.855, 0.702, 0.822 and 0.838, respectively. Conclusion: Different ultrasound attenuation-based techniques were well correlated and exhibited good diagnostic performances in quantitative diagnosis of hepatic steatosis, however, the threshold values were different. Combinations of multiple parameters may improve the diagnostic performance in detecting hepatic steatosis. Trial registration : The study has been registered online (https://www.chictr.org.cn; unique identifier: ChiCTR2300069459). [ABSTRACT FROM AUTHOR]

Introduction: Non-alcoholic fatty liver disease (NAFLD) is part of a disease spectrum ranging from steatosis to steatohepatitis (NASH), fibrosis, and cirrhosis, and when associated with metabolic syndrome (MS), and overt diabetes is defined as metabolic NAFLD (MAFLD). Some easily available, inexpensive biomarkers have been validated based on common anthropometric and laboratory parameters, including the Fatty Liver Index (FLI), the Fibrosis (FIB)-4 Score (FIB-4), and the NAFLD Fibrosis Score (NFS). In people with overweight/obesity, MS, and diabetes, the pathogenesis of fatty liver involves parameters known to be positively affected by Policaptil Gel Retard (PGR), a phytocomplex already successfully used in adolescents and adults with MS and type 2 diabetes mellitus (T2DM). This study's primary outcome was to assess PGR's ability to improve indirect validated signs of liver steatosis and fibrosis, i.e., FLI, FIB-4, and NFS Scores; as the secondary outcome, we aimed to confirm PGR's positive effects on anthropometric parameters and lipid levels and to assess any eventually occurring cytolysis liver marker changes in patients with MS/T2DM and MAFLD/NASH. Methods: In this spontaneous, longitudinal, single-blind, randomized clinical study, 245 outpatients with MS/T2DM were enrolled and randomized to PGR or placebo for 24 weeks. All underwent a low-calorie diet (20–25% less than the calories required to maintain current weight) and were encouraged to intensify physical activity. Fat distribution, liver fat content/fibrosis, and biochemical parameters were evaluated at baseline and after 24 weeks. Results: Our data show for the first time in adults with MAFLD that, when added to lifestyle changes including a hypocaloric diet and intensified physical activity, PGR improves lipid and glucose metabolism-related parameters, including insulin-resistance, and significantly reduces not only visceral fat but also liver fat content and related liver fibrosis severity. The prevalence of subjects with severe steatosis (FLI > 60) significantly decreased from 95.08 to 47.53% (p < 0.001) only in the treatment group, which also displayed a significantly decreased prevalence of medium-severe cases (F3–F4) from 83.62% to 52.35% (p < 0.001) and a markedly increased prevalence of low degree cases (F0–F1) from 9.01 to 42.15% (p < 0.001). Conclusions: The effect of PGR is related to a reduction in the post-meal blood glucose and insulin peaks. As glucose absorption (GA) directly regulates pancreatic insulin release, the attenuated insulin response is likely due to delayed GA with decreased body weight, visceral fat, and cardiovascular risk. Also, an effect on the intestinal microbiota, already documented in the animal model, cannot be excluded, especially considering the reported PGR-related shift from the Firmicutes, notoriously responsible for increased lipid gut absorption, to the Bacteroides phylum. [ABSTRACT FROM AUTHOR]

Background: Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. Methods: Biopsy-proven 641 NAFLD patients (55.2% males, median age 42 years) were included from three different centers of Asia. AF (≥ F3) was identified as per histological staging (24.8%). Results: TE had the highest area under the receiver operating characteristic curve (AUROC) 0.82 (0.79–0.86), and all other biomarker-based NITs had low AUROC (< 0.7). NITs performed poorly at established thresholds. The combination of NITs utilizing liver stiffness measurement (LSM) and biomarkers, Agile 3+ and FAST, demonstrated acceptable diagnostic accuracy (AUROC 0.82 and 0.78, respectively), but none were superior to LSM alone. LSM measured using appropriate M and XL probes remained accurate regardless of body mass index (BMI); NFS and APRI scores were less accurate at higher BMI ranges. A two-step approach using NFS rule-out criteria (< − 2.97 to rule out) followed by LSM (< 7.3 kPa to rule out and ≥ 12.7 kPa to rule in) correctly classified 62.4% of patients, with only 10.2% of patients incorrectly classified. Conclusion: NITs have not been validated to identify AF in the Asian NAFLD population, and internationally accepted thresholds yield high false-negative rates. LSM and LSM-based combination tests remain the most accurate. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusion: 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. Clinical relevance statement: 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. Key Points: • 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. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD), previously called metabolic nonalcoholic fatty liver disease, is the most prevalent chronic liver disease worldwide. The multi-factorial nature of MAFLD severity is delineated through an intricate composite analysis of the grade of activity in concert with the stage of fibrosis. Despite the preeminence of liver biopsy as the diagnostic and staging reference standard, its invasive nature, pronounced interobserver variability, and potential for deleterious effects (encompassing pain, infection, and even fatality) underscore the need for viable alternatives. We reviewed computed tomography (CT)-based methods for hepatic steatosis quantification (liver-to-spleen ratio; single-energy "quantitative" CT; dual-energy CT; deep learning-based methods; photon-counting CT) and hepatic fibrosis staging (morphology-based CT methods; contrast-enhanced CT biomarkers; dedicated postprocessing methods including liver surface nodularity, liver segmental volume ratio, texture analysis, deep learning methods, and radiomics). For dual-energy and photon-counting CT, the role of virtual non-contrast images and material decomposition is illustrated. For contrast-enhanced CT, normalized iodine concentration and extracellular volume fraction are explained. The applicability and salience of these approaches for clinical diagnosis and quantification of MAFLD are discussed. Relevance statement CT offers a variety of methods for the assessment of metabolic dysfunction-associated fatty liver disease by quantifying steatosis and staging fibrosis. Key points • MAFLD is the most prevalent chronic liver disease worldwide and is rapidly increasing. • Both hardware and software CT advances with high potential for MAFLD assessment have been observed in the last two decades. • Effective estimate of liver steatosis and staging of liver fibrosis can be possible through CT. [ABSTRACT FROM AUTHOR]

Our aim was to explore the correlation between ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) based on FibroTouch (China) and clinical features in patients with non-alcoholic fatty liver disease (NAFLD), so as to provide a certain basis for the clinical application of FibroTouch in NAFLD. Hepatic steatosis and fibrosis in patients with NAFLD were graded according to FibroTouch, and the relationship between steatosis and fibrosis levels and clinical characteristics was retrospectively analyzed. Hepatic steatosis was positively related with weight, BMI, waist, hyperlipidemia, hyperuricemia, FBG, UA, TG, ALT, AST, GGT, LSM and hepatic fibrosis grading, and was negatively related with gender (male), age and AST/ALT ratio. Hepatic fibrosis was positively related with age, BMI, waist, hypertension, FBG, ALT, AST, GGT, NFS, APRI, FIB-4, UAP and hepatic steatosis grading, and was negatively related with blood platelet (PLT) counts. Moreover, BMI, waist, TG, ALT and LSM were independent risk factors of hepatic steatosis, while decreased PLT counts, AST and UAP were independent risk factors of hepatic fibrosis. Body mass parameters, metabolic risk factors and liver function indicators increase the risk of hepatic steatosis and fibrosis in patients with NAFLD, and UAP and LSM can interact with each other. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of attenuation imaging (ATI) with an ultrasound scanner (US) in the detection of paediatric hepatic steatosis. Methods: Ninety-four prospectively enrolled children were classified into normal weight and overweight/obese (OW/OB) groups according to body mass index (BMI). US findings, including hepatic steatosis grade and ATI value, were examined by two radiologists. Anthropometric and biochemical parameters were obtained, and nonalcoholic fatty liver disease (NAFLD) scores, including the Framingham steatosis index (FSI) and hepatic steatosis index (HSI), were calculated. Results: After screening, 49 OW/OB and 40 normal weight children aged 10–18 years old (55 males and 34 females) participated in this study. The ATI value was significantly higher in the OW/OB group than in the normal weight group and showed a significant positive correlation with BMI, serum alanine transferase (ALT), uric acid, and NAFLD scores (p < 0.05). In the multiple linear regression adjusted for age, sex, BMI, ALT, uric acid, and HSI, ATI showed a significant positive association with BMI and ALT (p < 0.05). The receiver operating characteristic analysis showed a very good ability of ATI to predict hepatic steatosis. The intraclass correlation coefficient (ICC) of interobserver variability was 0.92, and the ICCs of intraobserver variability were 0.96 and 0.93 (p < 0.05). According to the two-level Bayesian latent class model analysis, the diagnostic performance of ATI showed the best performance for predicting hepatic steatosis among other known noninvasive NAFLD predictors. Conclusions: This study suggests that ATI is an objective and possible surrogate screening test for detecting hepatic steatosis in paediatric patients with obesity. Clinical relevance statement: Using ATI as a quantitative tool in hepatic steatosis allows clinicians to estimate the extent of the condition and track changes over time. This is helpful for monitoring disease progression and guiding treatment decisions, especially in paediatric practice. Key Points: • Attenuation imaging is a noninvasive US-based method for the quantification of hepatic steatosis. • Attenuation imaging values were significantly higher in the OW/OB and steatosis groups than in the normal weight and no steatosis groups, respectively, with a meaningful correlation with known clinical indicators of nonalcoholic fatty liver disease. • Attenuation imaging performs better than other noninvasive predictive models used to diagnose hepatic steatosis. [ABSTRACT FROM AUTHOR]

This is the first meta-analysis of the available literature about the efficacy of metformin exclusively in pediatric patients with non-alcoholic fatty liver disease (NAFLD). We conducted a systematic literature search through major electronic databases till March 12, 2023, investigating the efficacy and safety of metformin in pediatric NAFLD. Weighted mean difference (WD) and standard deviation (SD) were used for continuous outcomes. In total, 4 randomized controlled trials (RCTs) with 309 pediatric patients with NAFLD were included in the meta-analysis. Metformin could not reach a statistically significant improvement in alanine aminotransferase (ALT) levels [(ALT: WMD = − 1.55 IU/L, 95% CI: − 5.38 to 2.28, I2 = 16%, p = 0.43), but had a statistically significant impact (p < 0.05) in insulin and HOMA-IR regulation, triglycerides, and high-density lipoprotein level improvement. Conclusion: According to the data of this meta-analysis, treatment with metformin failed to statistically improve liver enzymes but may be beneficial in the improvement of lipid parameters and insulin metabolism regulation in pediatric patients with NAFLD. As there are not enough available studies in the literature, the influence of metformin on liver ultrasonography or histology in pediatric NAFLD should be further analyzed in future studies. What is Known: • Lifestyle modification with weight loss through physical activity and dietary modification is the recommended treatment option for pediatric NAFLD. • Metformin may reduce steatosis on ultrasound and may have a beneficial role in liver histology collated with insulin resistance improvement. What is New: • Metformin may improve insulin sensitivity and lipid parameters in children with obesity and NAFLD. • Metformin does not have a significant effect on transaminase levels in children with obesity and NAFLD. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disorders that will be started from more than or equal to 5% of fats deposited into the liver hepatocyte cells and progressively leads to steatosis, further increment in fat deposition, and signature of inflammatory markers which cause the non-alcoholic steatohepatitis (NASH) condition. Due to a lack of diagnosis and effective treatment, NASH is converted into liver cirrhosis or hepatocarcinoma, which indicates the irreversible stage of the disease and finally recommends liver transplantation for patient survival. However, nowadays, several clinical biomarkers are identified, and most of the new biomarkers are in the developmental stage, but still the diagnosis of each stage of fatty liver is unaccomplished. So, in this review article, we try to present all current mechanistic perspectives to find the non-invasive biomarkers which could be the best approach in the future to diagnose fatty liver disease in each stage. Main text: NAFLD is a growing phase disease if properly not taken care of by the patient. There are certain factors that can make fast progress in the disease stage like NAFLD to advance liver fibrosis or hepatocarcinoma. We describe to the best extent how different types of disease stages in the case of the fatty liver could be diagnosed using non-invasive biomarkers. A certain type of mechanistic pathophysiology approach is used to differentiate each stage of fatty liver disease like serum biomarkers (inflammatory cytokines), lipoproteins, micro-RNAs, gut microbiome-associated biomarkers, lipid droplet-associated perilipins, apolipoprotein E, the role of dihydroceramide, and gene expression studies. Conclusions: Recent advancements in diagnostic biomarkers research focused on non-invasive methods, but the diagnosis of different stages of fatty liver disease is still inconclusive. We tried to cover all the potential non-invasive biomarkers in our manuscript. This review helps the researchers to develop possible diagnostic biomarkers for each stage of liver disease. [ABSTRACT FROM AUTHOR]

Our aim was to explore the correlation between ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) based on FibroTouch (China) and clinical features in patients with non-alcoholic fatty liver disease (NAFLD), so as to provide a certain basis for the clinical application of FibroTouch in NAFLD. Hepatic steatosis and fibrosis in patients with NAFLD were graded according to FibroTouch, and the relationship between steatosis and fibrosis levels and clinical characteristics was retrospectively analyzed. Hepatic steatosis was positively related with weight, BMI, waist, hyperlipidemia, hyperuricemia, FBG, UA, TG, ALT, AST, GGT, LSM and hepatic fibrosis grading, and was negatively related with gender (male), age and AST/ALT ratio. Hepatic fibrosis was positively related with age, BMI, waist, hypertension, FBG, ALT, AST, GGT, NFS, APRI, FIB-4, UAP and hepatic steatosis grading, and was negatively related with blood platelet (PLT) counts. Moreover, BMI, waist, TG, ALT and LSM were independent risk factors of hepatic steatosis, while decreased PLT counts, AST and UAP were independent risk factors of hepatic fibrosis. Body mass parameters, metabolic risk factors and liver function indicators increase the risk of hepatic steatosis and fibrosis in patients with NAFLD, and UAP and LSM can interact with each other. [ABSTRACT FROM AUTHOR]

Aim: Nonalcoholic fatty liver disease (NAFLD) is a silent epidemy that has become the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is an advanced stage of NAFLD, which is linked to a high risk of cirrhosis and hepatocellular carcinoma. The aim of this study is to develop a predictive model to identify the main risk factors associated with the progression of hepatic fibrosis in patients with NASH. Methods: A database from a multicenter retrospective cross-sectional study was analyzed. A total of 215 patients with NASH biopsy-proven diagnosed were collected. NAFLD Activity Score and Kleiner scoring system were used to diagnose and staging these patients. Noninvasive tests (NITs) scores were added to identify which one were more reliable for follow-up and to avoid biopsy. For analysis, different Machine Learning methods were implemented, being the eXtreme Gradient Booster (XGB) system the proposed algorithm to develop the predictive model. Results: The most important variable in this predictive model was High-density lipoprotein (HDL) cholesterol, followed by systemic arterial hypertension and triglycerides (TG). NAFLD Fibrosis Score (NFS) was the most reliable NIT. As for the proposed method, XGB obtained higher results than the second method, K-Nearest Neighbors, in terms of accuracy (95.05 vs. 90.42) and Area Under the Curve (0.95 vs. 0.91). Conclusions: HDL cholesterol, systemic arterial hypertension, and TG were the most important risk factors for liver fibrosis progression in NASH patients. NFS is recommended for monitoring and decision making. [ABSTRACT FROM AUTHOR]

Objectives: 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. Methods: 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. Results: 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). Conclusion: HS increases liver volume. The formula to estimate lean liver volume may be useful to adjust for the effect of HS on liver volume. Key Points: • 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. [ABSTRACT FROM AUTHOR]

Objective: Magnetic resonance spectroscopy (MRS) provides a powerful method of measuring fat fraction. However, previous studies have shown that MRS results give lower values compared with visual estimates from biopsies in fibrotic livers. This study investigated these discrepancies and considered whether a tissue water content correction, as assessed by MRI relaxometry, could provide better agreement. Materials and methods: 110 patients were scanned in a 1.5 T Philips scanner and biopsies were obtained. Multiple echo MRS (30 × 30 × 30 mm volume) was used to determine Proton Density Fat Fraction (PDFF). Biopsies were assessed by visual assessment for fibrosis and steatosis grading. Digital image analysis (DIA) was also used to quantify fat fraction within tissue samples. T1 relaxation times were then used to estimate tissue water content to correct PDFF for confounding factors. Results: PDFF values across the four visually assessed steatosis grades were significantly less in the higher fibrosis group (F3–F4) compared to the lower fibrosis group (F0–F2). The slope of the linear regression of PDFF vs DIA fat fraction was ~ 1 in the low fibrosis group and 0.77 in the high fibrosis group. Correcting for water content based on T1 increased the gradient but it did not reach unity. Discussion: In fibrotic livers, PDFF underestimated fat fraction compared to DIA methods. Values were improved by applying a water content correction, but fat fractions were still underestimated. [ABSTRACT FROM AUTHOR]

Background: As recommendations for non-invasive fibrosis risk assessment in nonalcoholic fatty liver disease (NAFLD) emerge, it is not known how often they are performed in primary care. Aims: We investigated the completion of confirmatory fibrosis risk assessment in primary care patients with NAFLD and indeterminate-risk or greater Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Scores (NFS). Methods: This retrospective cohort study of electronic health record data from a primary care clinic identified patients with diagnoses of NAFLD from 2012 through 2021. Patients with a diagnosis of a severe liver disease outcome during the study period were excluded. The most recent FIB-4 and NFS scores were calculated and categorized by advanced fibrosis risk. Charts were reviewed to identify the outcome of a confirmatory fibrosis risk assessment by liver elastography or liver biopsy for all patients with indeterminate-risk or higher FIB-4 (≥ 1.3) and NFS (≥ − 1.455) scores. Results: The cohort included 604 patients diagnosed with NAFLD. Two-thirds of included patients (399) had a FIB-4 or NFS score greater than low-risk, 19% (113) had a high-risk FIB-4 (≥ 2.67) or NFS (≥ 0.676) score, and 7% (44) had high-risk FIB-4 and NFS values. Of these 399 patients with an indication for a confirmatory fibrosis test, 10% (41) underwent liver elastography (24) or liver biopsy (18) or both (1). Conclusions: Advanced fibrosis is a key indicator of future poor health outcomes in patients with NAFLD and a critical signal for referral to hepatology. Significant opportunities exist to improve confirmatory fibrosis risk assessment in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Background: Non-invasive tests are widely used to diagnose fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), however, the optimal method remains unclear. We compared the accuracy of simple serum models, a serum model incorporating direct measures of fibrogenesis (Hepascore), and Fibroscan®, for detecting fibrosis in NAFLD. Methods: NAFLD patients undergoing liver biopsy were evaluated with Hepascore, NAFLD Fibrosis Score (NFS), FIB-4 and AST-platelet ratio index (APRI), with a subset (n = 131) undergoing Fibroscan®. Fibrosis on liver biopsy was categorized as advanced (F3–4) or cirrhosis (F4). Accuracy was determined by area under receiving operating characteristic curves (AUC). Indeterminate ranges were calculated using published cut-offs. Results: In 271 NAFLD patients, 83 (31%) had F3–4 and 47 (17%) cirrhosis. 6/131 (4%) had an unreliable Fibroscan®. For the detection of advanced fibrosis, the accuracy of Hepascore (AUC 0.88) was higher than FIB-4 (0.73), NFS (0.72) and APRI (0.69) (p < 0.001 for all). Hepascore had similar accuracy to Fibroscan® (0.80) overall, but higher accuracy in obese individuals (0.91 vs 0.80, p = 0.001). Hepascore more accurately identified patients with cirrhosis than APRI (AUC 0.85 vs 0.71, p = 0.01) and NFS (AUC 0.73, p = 0.01) but performed similar to FIB-4 and Fibroscan®. For the determination of F3-4, the proportion of patients in indeterminate area was lower for Hepascore (4.8%), compared to FIB-4 (42%), NFS (36%) and APRI (44%) (p < 0.001 for all). Conclusions: Hepascore has greater accuracy and a lower indeterminate range than simple serum fibrosis tests for advanced fibrosis in NAFLD, and greater accuracy than Fibroscan® in obese individuals. [ABSTRACT FROM AUTHOR]

Background & Aims: Cardiorespiratory fitness and liver fibrosis are independently associated with poor outcomes in patients with nonalcoholic steatohepatitis (NASH), however, conflicting reports exist about their relationship. We aimed to better characterize the relationship between cardiorespiratory fitness and liver histology in a cross-sectional study of patients with biopsy-proven NASH. Methods: Participants aged 18–75 years completed VO2peak fitness assessment using symptom-limited graded exercise testing. Participants were compared by liver fibrosis stage and NAFLD Activity Score (NAS). Multivariable models were constructed to assess factors related to relative VO2peak, including liver fibrosis and NAS. Results: Thirty-five participants with mean age 48 ± 12 years and body mass index 33.5 ± 7.6 kg/m2 were enrolled. Seventy-four percent of participants were female and 49% had diabetes. A dose-dependent relationship was found between relative VO2peak and liver fibrosis. Relative VO2peak was significantly lower in participants with advanced fibrosis (F3 disease- 15.7 ± 5.3 vs. ≤ F2 disease- 20.7 ± 5.9 mL/kg/min, p = 0.027). NAS > 5 was also associated with lower relative VO2peak (22.6 ± 5.7 vs. 16.5 ± 5.1 mL/kg/min, p = 0.012) compared to NAS ≤ 5. With multivariable modeling, advanced fibrosis remained independently predictive of relative VO2peak while NAS trended towards significance. Discussion and Conclusions: Advanced liver fibrosis is independently associated with cardiorespiratory fitness in patients with NASH. This may explain the incremental increase in mortality as liver fibrosis stage increases. Further research is needed to determine if exercise training can improve cardiorespiratory fitness across multiple stages of liver fibrosis and directly reduce morbidity and mortality in patients with NASH. [ABSTRACT FROM AUTHOR]

Purpose: We explore the use of intravenously delivered perfluorocarbon (PFC) nanoemulsion and 19F MRI for detecting inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD). Correlative studies of 1H-based liver proton density fat fraction (PDFF) and T1 measurements and histology are also evaluated. Procedures: C57BL/6 mice were fed standard or high-fat diet (HFD) for 6 weeks to induce NAFLD. 1H MRI measurements of PDFF and T1 relaxation time were performed at baseline to assess NAFLD onset prior to administration of a PFC nanoemulsion to enable 19F MRI of liver PFC uptake. 1H and 19F MRI biomarkers were acquired at 2, 21, and 42 days post-PFC to assess changes. Histopathology of liver tissue was performed at experimental endpoint. Results: Significant increases in liver volume, PDFF, and total PFC uptake were noted in HFD mice compared to Std diet mice. Liver fluorine density and T1 relaxation time were significantly reduced in HFD mice. Conclusions: We demonstrated longitudinal quantification of multiple MRI biomarkers of disease in NAFLD mice. The changes in liver PFC uptake in HFD mice were compared with healthy mice that suggests that 19F MRI may be a viable biomarker of liver pathology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Fatty liver disease is a growing public health burden. We estimated prepandemic fatty liver disease prevalence determined by transient elastography-assessed hepatic steatosis and fibrosis, and examined associations with lifestyle and other factors in a United States population sample. Methods: Liver stiffness and controlled attenuation parameter (CAP) were assessed on 7923 non-Hispanic white, non-Hispanic black, non-Hispanic Asian, and Hispanic men and women aged 20 years and over in the National Health and Nutrition Examination Survey (NHANES) 2017–March 2020 prepandemic data. Results: The prevalence of fatty liver disease (CAP > 300 dB/m) was 28.8% and of fibrosis (liver stiffness > 8 kPa) was 10.4%. Only 7.2% of participants with fatty liver disease and 10.9% with fibrosis reported being told by a health care provider that they had liver disease. In addition to known risk factors such as metabolic factors and ALT, persons with fatty liver disease were less likely to meet physical activity guidelines, more likely to be sedentary for ≥ 12 h a day, and reported a less healthy diet. Persons with fibrosis were less likely to have a college degree and reported a less healthy diet. Conclusions: In the U.S. population, most persons with fatty liver disease are unaware of their condition. Physical activity and dietary modifications might reduce the fatty liver disease burden. There is an urgent need for fatty liver disease management in high-risk individuals using transient elastography or other noninvasive methods to intervene in disease progression. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, which can progress from simple steatosis to advanced cirrhosis and hepatocellular carcinoma. Clinical diagnosis of NAFLD is crucial in the early stages of the disease. The main aim of this study was to apply machine learning (ML) methods to identify significant classifiers of NAFLD using body composition and anthropometric variables. A cross-sectional study was carried out among 513 individuals aged 13 years old or above in Iran. Anthropometric and body composition measurements were performed manually using body composition analyzer InBody 270. Hepatic steatosis and fibrosis were determined using a Fibroscan. ML methods including k-Nearest Neighbor (kNN), Support Vector Machine (SVM), Radial Basis Function (RBF) SVM, Gaussian Process (GP), Random Forest (RF), Neural Network (NN), Adaboost and Naïve Bayes were examined for model performance and to identify anthropometric and body composition predictors of fatty liver disease. RF generated the most accurate model for fatty liver (presence of any stage), steatosis stages and fibrosis stages with 82%, 52% and 57% accuracy, respectively. Abdomen circumference, waist circumference, chest circumference, trunk fat and body mass index were among the most important variables contributing to fatty liver disease. ML-based prediction of NAFLD using anthropometric and body composition data can assist clinicians in decision making. ML-based systems provide opportunities for NAFLD screening and early diagnosis, especially in population-level and remote areas. [ABSTRACT FROM AUTHOR]

Background: Advanced fibrosis and cirrhosis (compensated advanced chronic liver disease [cACLD]) are clinically indistinguishable and increase risk of developing clinically significant portal hypertension. Baveno VII recommends using elastography to rule out and diagnose cACLD with liver stiffness measurement (LSM) cut-offs of 10/15 kPa. Methods: In a retrospective analysis of 330 nonalcoholic fatty liver disease (NAFLD) patients, performance of the Baveno VII cut-offs for diagnosing cACLD was compared with newly suggested lower cut-offs (8/12 kPa). A model for detecting cACLD among those with LSM between 8 and 12 kPa was developed and compared with recently published models. Results: Seventy (21.2%) of the 330 NAFLD patients had biopsy-proven cACLD. The Baveno VII cut-offs (10/15 kPa) had a lower sensitivity of 72.8% (60.9–82.8%) and a specificity of 93.4% (89.7–96.1%). Sensitivity and specificity of lower cut-offs (8/12 kPa) were 91.4% (82.3–96.8%) and 88.5% (83.9–92.1%), respectively. Modeling based on the presence of diabetes (odds ratio [OR] 3.625[1.161–11.320], p = 0.027) and serum aspartate aminotransferase (AST) levels (OR 1.636[1.098–2.436], p = 0.015) correctly identified 75.7% of patients with LSM between 8 and 12 kPa. Our model performed best with an area under receiver operator curve (AUROC) of 0.725 (95%CI 0.609–0.822), compared to Papatheodoridi (AUROC 0.626, CI 0.506–.736) and Zhou (AUROC 0.523, CI 0.403–0.640) models. A two-step strategy comprising application of lower LSM cut-offs followed by the predictive model correctly identified the presence of cACLD in 83% of the patients as compared to 75% by the Baveno VII cut-offs. Conclusion: A two-step strategy employing lower LSM cut-offs and modeling based on diabetes and AST levels outperforms Baveno VII cut-offs for identifying cACLD in NAFLD patients. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation in IBD is postulated to drive NAFLD progression from steatosis to fibrosis. Aims: To study the histopathological spectrum of NAFLD in Crohn disease (CD) and Ulcerative colitis (UC). Methods: Patients with biopsy proven NAFLD at a quaternary center from 2008 to 2018 were included in this retrospective analysis. Inflammatory bowel disease (IBD) diagnosed either clinically and/or endoscopically at the time of liver biopsy. Multivariable regression and propensity score (PS) weighted analysis were conducted. Statistical analysis were performed using SAS statistical software. Results: Among 1009 patients with NAFLD a diagnosis of IBD was identified in 50 cases (34 CD and 16 UC). On multivariable analysis; CD was independently associated with significantly higher odds of advanced fibrosis (AF) on liver biopsy (adjusted OR = 4.09, 95% CI = 1.40–11.94) compared to NAFLD patients without IBD. Similar results were obtained with both the overlap PS weighted model (OR = 3.17, 95% CI = 1.55–6.49) and the PS matched model (OR = 3.49, 95% CI = 1.50–8.13). Conclusion: In a large cohort of patients with histologically well characterized NAFLD, AF was more common in CD patients than NAFLD patients without IBD. These findings must be confirmed in a larger cohort, but suggest CD patients with NAFLD could be at greater risk for liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: Bariatric-metabolic surgery (BS) decreases the grade of steatosis, hepatic inflammation, and fibrosis in patients with severe obesity and non-alcoholic fatty liver disease (NAFLD). Mechanisms include substantial weight loss, but also simultaneous effects on glucose homeostasis. Therefore, we aimed to investigate the association between NAFLD and remission of type 2 diabetes (T2D) up to 8 years following different types of BS. Methods: In a retrospective cohort study including 107 patients with obesity and T2D at baseline, the association between biopsy-proven NAFLD defined as steatosis in > 5% of hepatocytes at the time of surgery and T2D remission up to 8 years following different surgical procedures was investigated. Univariate regression analysis was used to examine the association between NAFLD and remission of T2D. Results: Long-term remission of T2D was present in 56% of patients (n = 60). The presence of low-grade liver steatosis (grade 1) was associated with remission of T2D. Patients with a liver steatosis score ≥ 2 showed higher HbA1c levels at baseline. There were no significant differences in preoperative presence of lobular inflammation, hepatocyte ballooning, or fibrosis between patients who achieved T2D remission compared with those with no remission. Type of surgery did not affect remission of T2D. Conclusion: Our results suggest that the presence of low-grade liver steatosis is associated with remission of T2D following sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Therefore, BS should be considered at an early NAFLD stage in patients with T2D. [ABSTRACT FROM AUTHOR]

Background: Lower whole body bone mineral density (BMD) has been reported in children with nonalcoholic fatty liver disease (NAFLD), but potential mediators remain uncertain. Aims: To assess BMD at multiple skeletal sites in children with confirmed NAFLD and controls with obesity, adjusting for known determinants of BMD, and examine potential mediators. Methods: We assessed age-, sex-, and race-specific, and height-adjusted BMD z-scores of whole body, lumbar spine, hip, femoral neck and forearm by dual-energy-x-ray absorptiometry in 79 children, 8–19 years old: 46 with biopsy-confirmed NAFLD [29 steatohepatitis (NASH)/17 fatty liver (NAFL)] and 33 controls without liver disease. We compared BMD z-scores by multivariable regression, adjusting for known BMD determinants and potential mediators (inflammatory and insulin resistance measures). Results: Unadjusted mean BMD z-scores in NAFLD were similar to controls, but significantly lower in NASH vs. NAFL at all sites. After covariate adjustment, mean forearm BMD z-score was higher in NAFL (β 0.60 ± SE 0.30, p < 0.05) and lower in NASH (β – 0.49 ± SE 0.26, p = 0.06) vs. controls (p = 0.002 for group), with similar trends at whole body and total hip; hs-CRP negatively associated with whole body and forearm BMD z-scores (p < 0.05), while visceral fat area negatively associated with femoral neck (p < 0.05). Only three children had clinically low whole body BMD z-scores (< – 2), one per group (control, NAFL and NASH). Conclusions: NASH, but not NAFL, may be associated with increased risk of reduced BMD in children. Systemic inflammation, independent of body composition and load bearing, may mediate reduction in BMD in NASH. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a major environmental pollutant and food contaminant with endocrine-disrupting effects on human and animal health. Perinatal and developmental exposure to BPA has been known to cause hepatotoxicity in adulthood. However, its intergenerational effects in a metabolically challenged population have been scarcely investigated. Our study was designed to assess the intergenerational effect of an environmentally relevant dose of BPA and diet-induced parental obesity on the hepatic health outcome of F1 offspring. Wistar rats were given a high-fat diet to induce obesity, followed by chronic low dosages of BPA (10 ppm × 180 days) in drinking water. Post-treatment, rats were crossed within groups to obtain the F1 generation. Weanling pups were observed for weight gain, levels of hepatic antioxidants, liver function enzymes, cholesterol, C-reactive protein, and triglyceride in the serum. Histological changes in the liver tissue were also investigated. mRNA expression of energy homeostasis genes (FTO and MCR-4) in the liver was analyzed alongside blood biomarkers. We observed higher birth weight and rapid weight gain in the test group in comparison with controls, which was consistent with the changes in mRNA and protein expression of FTO and MCR-4. BPA caused a significant, treatment-related change in the inflammatory marker C-reactive protein, lipid peroxidation, antioxidants, and lipid profile. These findings were accompanied by histological changes in the liver tissue characteristic of hepatic steatosis indicating the onset of the non-alcoholic fatty liver disease (NAFLD). Our study offers a link between exposure to BPA in parents and onset of NAFLD in their offspring. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Metformin is increasingly used to treat gestational diabetes (GDM) and pregnancies complicated by pregestational type 2 diabetes or polycystic ovary syndrome but data regarding long-term offspring outcome are lacking in both human studies and animal models. Using a mouse model, this study investigated the effects of maternal metformin intervention during obese glucose-intolerant pregnancy on adiposity, hepatic steatosis and markers of metabolic health of male and female offspring up to the age of 12 months. Methods: C57BL/6J female mice were weaned onto either a control diet (Con) or, to induce pre-conception obesity, an obesogenic diet (Ob). The respective diets were maintained throughout pregnancy and lactation. These obese dams were then randomised to the untreated group or to receive 300 mg/kg oral metformin hydrochloride treatment (Ob-Met) daily during pregnancy. In male and female offspring, body weights and body composition were measured from 1 month until 12 months of age, when serum and tissues were collected for investigation of adipocyte cellularity (histology), adipose tissue inflammation (histology and quantitative RT-PCR), and hepatic steatosis and fibrosis (histochemistry and modified Folch assay). Results: At 12 months of age, male Ob and Ob-Met offspring showed increased adiposity, adipocyte hypertrophy, elevated expression of proinflammatory genes, hyperleptinaemia and hepatic lipid accumulation compared with Con offspring. Male Ob-Met offspring failed to show hyperplasia between 8 weeks and 12 months, indicative of restricted adipose tissue expansion, resulting in increased immune cell infiltration and ectopic lipid deposition. Female Ob offspring were relatively protected from these phenotypes but Ob-Met female offspring showed increased adiposity, adipose tissue inflammation, hepatic lipid accumulation, hyperleptinaemia and hyperinsulinaemia compared with Con female offspring. Conclusions/interpretation: Maternal metformin treatment of obese dams increased offspring metabolic risk factors in a sex- and age-dependent manner. These observations highlight the importance of following up offspring of both sexes beyond early adulthood after interventions during pregnancy. Our findings illustrate the complexity of balancing short-term benefits to mother and child vs any potential long-term metabolic effects on the offspring when prescribing therapeutic agents that cross the placenta. [ABSTRACT FROM AUTHOR]

Background: Endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as a viable mean to obtain core tissue, but the optimal tools and techniques are still an area of active investigation. Aims: (1) To compare tissue adequacy using "wet saline" (WS) vs. "wet heparin" (WH) technique (2) To compare post-procedure pain between EUS-LB and percutaneous liver biopsy (PLB). Methods: Retrospective review of consecutive patients who underwent EUS-LB and PLB for benign parenchymal liver disease between May 2017 to October 2019 at a single tertiary veterans affairs medical center. Results: About 257 biopsies from 217 patients were included. Among the 102 EUS-LB specimens, 53 were obtained using WS technique and 49 were obtained using WH technique. Specimen adequacy was similar in both groups. Median Aggregate Specimen Length (ASL) and length of longest piece did not differ significantly between WS and WH groups. Clots were present more frequently in the WS group. Among patients who underwent EUS-LB of both right and left liver lobes, an adequate biopsy was obtained in 85% of patients in the WS group and 96% of patients in the WH group. The percentage of patients experiencing immediate post-procedure pain was higher with PLB compared to EUS-LB, but these results were not statistically significant. Conclusions: Both WS and WH EUS-LB techniques can offer high rates of specimen adequacy with low rates of pain and other post-procedure complications. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH), a common clinical disease, is becoming a leading cause of hepatocellular carcinoma (HCC). Dual specificity phosphatase 22 (DUSP22, also known as JKAP or JSP-1) expressed in numerous tissues plays essential biological functions in immune responses and tumor growth. However, the effects of DUSP22 on NASH still remain unknown. Here, we find a significant decrease of DUSP22 expression in human and murine fatty liver, which is mediated by reactive oxygen species (ROS) generation. Hepatic-specific DUSP22 deletion particularly exacerbates lipid deposition, inflammatory response and fibrosis in liver, facilitating NASH and non-alcoholic fatty liver disease (NAFLD)-associated HCC progression. In contrast, transgenic over-expression, lentivirus or adeno-associated virus (AAV)-mediated DUSP22 gene therapy substantially inhibit NASH-related phenotypes and HCC development in mice. We provide mechanistic evidence that DUSP22 directly interacts with focal adhesion kinase (FAK) and restrains its phosphorylation at Tyr397 (Y397) and Y576 + Y577 residues, subsequently prohibiting downstream activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) cascades. The binding of DUSP22 to FAK and the dephosphorylation of FAK are indispensable for DUSP22-meliorated NASH progression. Collectively, our findings identify DUSP22 as a key suppressor of NASH-HCC, and underscore the DUSP22-FAK axis as a promising therapeutic target for treatment of the disease. Mechanisms underlying the pathogenesis of nonalcoholic steatohepatitis are unclear. Here, the authors show that ROS-mediated DUSP22 degradation participates in the progression of fatty liver, contributing to the development of NASH and associated HCC via regulating FAK and its downstream ERK1/2 and NF-κB signaling cascade. [ABSTRACT FROM AUTHOR]

Increased incidence of liver diseases emphasizes greater caution in prescribing antirheumatic drugs due to their hepatotoxicity. A transient elevation of transaminases to autoimmune hepatitis and acute liver failure has been described. For every 10 cases of alanine aminotransferase (ALT) elevation in a clinical trial, it is estimated that one case of more severe liver injury will develop once the investigated drug is widely available. Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (tsDMARDs) are less likely to cause liver damage. However, various manifestations, from a transient elevation of transaminases to autoimmune hepatitis and acute liver failure, have been described. Research on non-alcoholic fatty liver disease (NAFLD) has provided insight into a pre-existing liver disease that may be worsen by medication. Diabetes and obesity could be an additional burden in drug-induced liver injury (DILI). In the intertwining of the inflammatory and metabolic pathways, the most important cytokines are IL-6 and TNF alpha, which are also the cornerstone of biological treatment for rheumatoid arthritis. This narrative review evaluates the complexity and prevention of DILI in RA and treatment options involving biological therapy and tsDMARDs. [ABSTRACT FROM AUTHOR]

Background: In patients with clinically severe obesity, metabolic associated fatty liver disease (MAFLD) and steatohepatitis are highly prevalent. There is a lack of prospective studies evaluating the impact of bariatric surgery (BS) on MAFLD using both noninvasive and histological criteria. The present study aims to assess the impact of BS on MAFLD using histological and biochemical criteria. Methods: This is a prospective study of 52 patients subjected to BS. Noninvasive fibrosis risk scores (NIFRS) along with anthropometric, clinical, and biochemical parameters were recorded pre- and 12 months post-BS. Liver biopsy was obtained in all individuals at baseline (wedge biopsy) and was repeated at 12 months (percutaneous Tru-cut) in those diagnosed with steatohepatitis. The primary outcome was the change in the degree of steatohepatitis and fibrosis. The secondary outcome was the change in scores for hepatocellular ballooning, lobular inflammation, steatosis, and fibrosis. Results: One year after BS, steatohepatitis resolved in core biopsies with no worsening of fibrosis in 95.7% of individuals (n = 21, 95% CI: 87.3–100), and 13 (56.5%) exhibited complete resolution. Of 15 patients with fibrosis at baseline, 13 (86.7%) showed improvement and 12 exhibited fibrosis resolution. The values of transaminases improved, but only gamma glutamyl transferase (GGT) showed statistical significance. Among the NIFRS, NAFLD fibrosis score (NFS) and Hepamet fibrosis score (HFS) showed significant improvement. Conclusions: In the setting it was studied, BS improved or resolved steatohepatitis and fibrosis in patients with obesity. NIFRS, especially NFS and HFS, and levels of GGT could be used as markers of recovery of liver function after BS. [ABSTRACT FROM AUTHOR]

Purpose: The effect of hepatic steatosis on the development of colorectal liver metastases (CRLM) remains unknown. This study evaluated the usefulness of fat signal fraction assessed with magnetic resonance imaging (MRI) and the effect of hepatic steatosis on hepatic recurrences following initial hepatectomy for CRLM. Methods: Between January 2013 and December 2019, 64 patients underwent initial hepatectomy for CRLM. The medical records of these patients were reviewed to evaluate the recurrence and survival outcomes. Results: The fat signal fraction was positively correlated with the nonalcoholic fatty liver disease activity score and liver-spleen ratio. Recurrence following the initial hepatectomy was observed in 48/64 patients, and hepatic recurrence was observed in 30/64 patients. The fat signal fraction was significantly higher in patients with hepatic recurrence after initial hepatectomy. The hepatic recurrence rate was 69.2% in patients with fat signal fraction ≥ 0.0258, which was significantly higher than that in patients with fat signal fraction < 0.0258. Hepatic recurrence-free survival rate was significantly higher in patients with fat signal fraction < 0.0258 than in those with fat signal fraction ≥ 0.0258. Multivariate analyses revealed that fat signal fraction ≥ 0.0258 was an independent risk factor for hepatic recurrence. Conclusion: The fat signal fraction assessed with MRI was significantly associated with hepatic recurrence following initial hepatectomy for CRLM. [ABSTRACT FROM AUTHOR]

Background: Deregulation of immune response and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Resistin is a physiological modulator of inflammation and redox homeostasis of different cell types. Increased resistin serum concentration and the direct association between resistin hepatic expression and NAFLD severity suggest that resistin participates in NAFLD pathogenesis. Aims: To evaluate resistin-induced regulation of redox homeostasis in mononuclear leukocytes from NAFLD patients and controls. Methods: We evaluated basal and resistin-mediated modulation of reactive oxygen species (ROS) and glutathione content by flow cytometry, and antioxidant enzyme activities by spectrophotometry. Results: Peripheral blood mononuclear cells (PBMC) from NAFLD patients showed higher ROS content and glutathione peroxidase activity and lower glutathione content, superoxide dismutase and glutathione reductase activities than control PBMC. Resistin decreased ROS levels and superoxide dismutase activity and increased glutathione reductase and catalase activities in PBMC from controls but not from patients. Resistin decreased glutathione content in PBMC from control and NAFLD patients, with greater effect on patient cells. Basal and resistin-modulated ROS levels were directly associated with obesity-related risk factors for NAFLD. Hepatic myeloid cells and T-lymphocytes from NAFLD patients showed higher basal ROS content than cells from controls. Resistin decreased ROS levels in hepatic T-lymphocytes from controls but not from patients. Conclusions: Resistin regulates redox homeostasis in mononuclear leukocytes. A decreased response to resistin in leukocytes from NAFLD patients is associated with an impaired redox homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: Untreated nonalcoholic fatty liver may progress to nonalcoholic steatohepatitis (NASH) and cirrhosis and induce hepatocellular carcinoma and liver failure. Type 2 diabetes mellitus (T2DM), often complicated with nonalcoholic fatty liver disease (NAFLD), is a driver of NAFLD progression. Thus, efficacious treatment strategies for patients with coexisting NAFLD and T2DM are important for preventing NAFLD progression. Although previous studies have demonstrated that either sodium-glucose transporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1 RAs) benefit NASH patients with T2DM, the rate of NASH resolution has not sufficiently improved. Therefore, we developed a protocol for a randomized controlled trial to examine whether the addition of an SGLT2i to the treatment regimen of patients receving a GLP-1 RA (combination therapy), within the therapeutic dose range for T2DM, increases the rate of NASH resolution in patients with coexisting NASH and T2DM. Methods: This open-label, randomized, parallel-group study commenced in June 2021, will conclude recruitment in May 2023, and will end by March 2025. Sixty patients with NASH complicated by T2DM are enrolled at the Ehime University Hospital in Toon, Japan. Participants will be randomized into: (1) an intervention group receiving combination therapy with the SGLT2i luseogliflozin 2.5 mg, once daily (Taisho Pharmaceutical, Tokyo, Japan) and the GLP-1 RA semaglutide 0.5 mg, once per week (Novonordisk, Copenhagen, Denmark); and (2) a control group receiving monotherapy with the GLP-1 analog semaglutide. The primary endpoints, which will be ascertained by liver biopsy, are: (1) NASH resolution rate from baseline without worsening of liver fibrosis after 52 weeks of intervention; (2) rate of improvement from baseline of at least 1 point in the NAFLD activity score without worsening of liver fibrosis after 52 weeks of intervention; and (3) rate of improvement from baseline of at least one fibrosis stage without worsening of NASH after 52 weeks of intervention. Trial Registration: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) number: UMIN000045003. Japan Registry of Clinical Trials registration number: jRCTs061210009. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic dysfunction–associated fatty liver disease–related cirrhosis is possible at the time of bariatric surgery, complicated by further liver decompensation. Hepatic decompensation can also occur in the absence of cirrhosis but the presentation is less clear. Methods: We analyze the clinical characteristics, histological findings, and management of patients without cirrhosis who developed hepatic decompensation after bariatric surgery in our single tertiary-care hospital. Results: From 2014 to 2019, 6 patients underwent a transvenous liver biopsy for liver decompensation after bariatric surgery. Mean age at diagnosis was 44 years. The time between bariatric surgery and the onset of symptoms varied widely (min. 8 months, max. 17 years). Mean % of weight loss was high at 43%. The clinical presentation was as follows: fatigue and jaundice (5/6), leg edema (3/6), and ascites (1/6). Blood test showed increased transaminases (mean ALT 53 UI/L, mean AST 130 UI/L), bilirubin (mean 6 mg/dL), and INR (mean 1.5) with a low albumin level (mean 27 mg/dL). The hepatic venous pressure gradient was high (mean 10 mmHg). Histology revealed steatosis, hepatocyte ballooning but also portal inflammation with polymorphonuclear cells, and bile duct alterations. Mean fibrosis score was 2. The clinical course was favorable with nutritional support with a mean follow-up of 36 months. Conclusion: Liver decompensation in the absence of cirrhosis can occur after bariatric surgery with a highly variable delay. A special histological signature is present with the coexistence of steatosis, bile duct alterations, and portal inflammation. Substantial clinical improvement with appropriate nutritional support seems to be effective. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) can progress to advanced fibrosis, especially in patients with type 2 diabetes. Small studies have shown that fibrosis can also regress. Aim: We aimed to provide large-scale data on progression and regression of fibrosis in diabetics with NAFLD. Methods: Adult diabetic patients with the diagnosis of NAFLD based on ICD-9 codes were identified. We used scores from noninvasive tests to identify patients with advanced fibrosis, calculated at first assessment and last follow-up visit. Cutoff values for advanced fibrosis were AST: ALT ratio > 1.4, AST to platelet ratio index > 1.5, FIB-4 score > 2.67, and NAFLD fibrosis score > 0.676. Results: Our cohort included 50,695 diabetics with NAFLD (55.3% female; 71% Caucasian; mean age, 51.2 ± 11.6 y). During median follow-up of 84.4 months, 25.8% transitioned from no advanced fibrosis to advanced fibrosis (progression), 6.4% transitioned from advanced fibrosis to no advanced fibrosis (regression), and the rest remained stable. Factors associated with transition to advanced fibrosis were female sex, older age at first evaluation, African-American race, obesity, chronic kidney disease, or coronary artery disease. Use of insulin increased the risk of progression to advanced fibrosis (odds ratio,1.36; p <.001), whereas use of oral hypoglycemic agents, angiotensin 2 receptor blockers, and fibrates was associated with reduced risk (odds ratios, 0.92, 0.94 and 0.90, respectively; all p <.05). Conclusions: In a large cohort of patients with type 2 diabetes and NAFLD, more than a quarter progressed to advanced fibrosis. These findings indicate the need for early detection and staging of NAFLD in diabetics. [ABSTRACT FROM AUTHOR]

Background and aims: As the prevalence of nonalcoholic fatty liver disease (NAFLD) is approximately 30% in the general population, it is important to develop a non-invasive biomarker for the diagnosis of nonalcoholic steatohepatitis (NASH). This prospective cross-sectional study aimed to develop a scoring system for NASH diagnosis through multiparametric magnetic resonance (MR) and clinical indicators. Methods: Medical history, laboratory tests, and MR parameters of patients with NAFLD were assessed. A scoring system was developed using a logistic regression model. In total, 127 patients (58 with nonalcoholic fatty liver [NAFL] and 69 with NASH) were enrolled. After evaluating 23 clinical characteristics of the patients (4 categorical and 19 numeric variables) for the NASH diagnostic model, an equation for MR elastography (MRE)-based NASH score was obtained using 3 demographic factors, 2 laboratory variables, and MRE. Results: The MRE-based NASH score showed a satisfactory accuracy for NASH diagnosis (c-statistics, 0.841; 95% CI 0.772–0.910). At a cut-off MRE-based NASH score of 0.68 for NASH diagnosis, its sensitivity was 0.68 and specificity was 0.91. When an MRE-based NASH score of 0.37 was used as a cut-off for NASH exclusion, the sensitivity was 0.91 and specificity was 0.55. Overall, 35% (44/127) of patients were in the gray zone (between 0.37 and 0.68). Internal validation via bootstrapping also indicated the satisfactory accuracy of NASH diagnosis (optimism-corrected statistics, 0.811). Conclusion: MRE-based NASH score is a useful and accurate non-invasive biomarker for diagnosis of NASH in patients with NAFLD. [ABSTRACT FROM AUTHOR]

The accuracy of attenuation coefficients and B-mode ultrasound for distinguishing between S0 (healthy, < 5% fat) and S1–3 (steatosis ≥ 5%) livers compared to a controlled attenuation parameter is unclear. This meta-analysis aimed to comprehensively assess the diagnostic performance of B-mode ultrasound imaging for evaluating steatosis of ≥ 5%. We searched the PubMed, Embase, and Web of Science databases for studies on the accuracy of B-mode ultrasound for differentiating S0 from S1–3 in adults with chronic liver disease. A bivariate random-effects model was performed to estimate the pooled sensitivity, specificity, positive (PLR) and negative likelihood ratios (NLR), and diagnostic odds ratios (DORs). Subgroup analyses by attenuation coefficient, conventional B-mode ultrasound findings, and B-mode ultrasound findings without semi-quantification methods were performed. Liver steatosis was scored as follows: S0, < 5%; S1, 5–33%; S2, 33–66%; and S3, > 66%. Nineteen studies involving 3240 patients were analyzed. The pooled sensitivity and specificity of B-mode ultrasound for detecting S1 were 0.70 (95% confidence interval [CI], 0.63–0.77) and 0.86 (95% CI 0.82–0.89), respectively. The pooled PLR, NLR, and DOR were 4.90 (95% CI 3.69–6.51), 0.35 (95% CI 0.27– 0.44), and 14.1 (95% CI 8.7–23.0), respectively. The diagnostic accuracy was better in patients with attenuation coefficients (area under the curve [AUC], 0.89; sensitivity, 0.75; specificity, 0.86) than in those with conventional B-mode findings (AUC, 0.80; sensitivity, 0.59; specificity, 0.83). In particular, the diagnostic value was better when the attenuation coefficient guided by B-mode ultrasound was utilized. To screen patients with steatosis of ≥ 5%, attenuation coefficient should be used. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the diagnostic performance of attenuation imaging (ATI) for the assessment of low-grade hepatic steatosis using liver biopsy as the reference standard. Methods: 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. Results: 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. Conclusions: 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. Key Points: • 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. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of liver surface nodularity (LSN) for the assessment of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods: We retrospectively analysed patients with pathologically proven NAFLD who underwent liver MRI. Demographic, clinical, and laboratory data (including FIB-4 scores) were gathered. The SAF score was used to assess NAFLD. MRI-proton density fat fraction (PDFF) and LSN were determined on pre-contrast MR sequences. ROC curve analysis was performed to evaluate the diagnostic performance of MRI-LSN for the diagnosis of advanced (F3-F4) liver fibrosis. Results: The final population included 142 patients. Sixty-seven (47%) patients had non-alcoholic steatohepatitis (NASH), and 52 (37%) had advanced fibrosis. The median MRI-PDFF increased with the grades of steatosis: 8.1%, 18.1%, and 31% in S1, S2, and S3 patients, respectively (p < 0.001). The area under the ROC curve (AUC) of MRI-LSN ≥ 2.50 was 0.838 (95%CI 0.767–0.894, sensitivity 67.3%, specificity 88.9%, positive and negative predictive values 77.8% and 82.5%, respectively) for the diagnosis of advanced fibrosis. Combining FIB-4 and MRI-LSN correctly classified 103/142 (73%) patients. This was validated in an external cohort of 75 patients. Conclusions: MRI-LSN has good diagnostic performance in diagnosis of advanced fibrosis in NAFLD patients. A combination of FIB-4 and MRI-LSN derived from pre-contrast MRI could be helpful to detect advanced fibrosis. Key Points: • MRI-LSN ≥ 2.5 was accurate for the diagnosis of advanced hepatic fibrosis in NAFLD patients. • The combination of FIB-4 and MRI-LSN improved the detection of advanced fibrosis. • MRI-LSN can be easily derived by unenhanced MRI sequences that are routinely acquired. [ABSTRACT FROM AUTHOR]

Background: There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection. Aims: To evaluate the diagnostic performance of noninvasive serum-based scores to detect steatosis using two distinct chronic HBV cohorts with liver histology evaluation. Methods: Chronic HBV cohorts with untreated HBV mono-infection (N = 302) and with treated HBV–HIV (N = 92) were included. Liver histology was scored centrally. Four serum-based scores were calculated: hepatic steatosis index (HSI), nonalcoholic fatty liver disease Liver Fat Score (NAFLD-LFS), visceral adiposity index (VAI), and triglyceride glucose (TyG) index. Optimal cutoffs (highest sensitivity + specificity) to detect ≥ 5% HS, stratified by cohort, were evaluated. Results: HBV–HIV (vs. HBV mono-infected) patients were older (median 50 vs. 43 years), and a higher proportion were male (92% vs. 60%), were black (51% vs. 8%), had the metabolic syndrome (41% vs. 25%), and suppressed HBV DNA (< 1000 IU/mL; 82% vs. 9%). Applying optimal cutoffs, the area under the receiver operator curve for detecting ≥ 5% steatosis in HBV-only and HBV–HIV, respectively, was 0.69 and 0.61 for HSI, 0.70 and 0.76 for NAFLD-LFS, 0.68 and 0.64 for TyG, and 0.68 and 0.69 for VAI. The accuracy of optimal cutoffs ranged from 61% (NAFLD-LFS) to 67% (TyG) among HBV-only and 56% (HSI) to 76% (NAFLD-LFS) among HBV–HIV. Negative predictive values were higher than positive predictive values for all scores in both groups. Conclusion: The relative utility of scores to identify steatosis in chronic HBV differs by co-infection/anti-HBV medication status. However, even with population-specific cutoffs, several common serum-based scores have only moderate utility. ClinicalTrials.gov NCT01924455. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the relationship between biopsy-assessed hepatic steatosis, magnetic resonance imaging (MRI)–assessed proton density fat fraction (PDFF), and magnetic resonance elastography (MRE)–assessed liver stiffness measurement (LSM), in patients with or at risk for nonalcoholic fatty liver disease (NAFLD). Methods: A retrospective study was performed, encompassing 256 patients who had a liver biopsy and MRI/MRE examination performed within 1 year. Clinical and laboratory data were retrieved from the electronic medical record. Hepatic steatosis and fibrosis were assessed by histopathological grading/staging. First, we analyzed the diagnostic performance of PDFF for distinguishing hepatic steatosis with the receiver operating characteristic analyses. Second, variables influencing LSM were screened with univariant analyses, then identified with multivariable linear regression. Finally, the potential relationship between PDFF and LSM was assessed with linear regression after adjustment for other influencing factors, in patients with diagnosed steatosis (PDFF ≥ 5%). Results: The diagnostic accuracy of PDFF in distinguishing steatosis grades (S0-3) was above 0.82. No significant difference in LSM was found between patients with S1, S2, and S3 steatosis and between all steatosis grades after patients were grouped according to fibrosis stage. No statistically significant relationship was found between the LSM and PDFF (estimate = − 0.02, p = 0.065) after adjustment for fibrosis stage and age in patients with diagnosed steatosis (PDFF ≥ 5%). Conclusions: In patients with NAFLD, the severity of hepatic steatosis has no significant influence on the liver stiffness measurement with magnetic resonance elastography. Key Points: • The MRI-based proton density fat fraction provides a quantitative assessment of hepatic steatosis with high accuracy. • No significant effect of hepatic steatosis on MRE-based liver stiffness measurement was found in patients with S1, S2, and S3 steatosis and between all steatosis grades after patients were grouped according to fibrosis stage. • After adjusting for fibrosis stage and age, there was no statistically significant relationship between liver stiffness and proton density fat fraction in patients with hepatic steatosis (p = 0.065). [ABSTRACT FROM AUTHOR]

Vitamin D is reported to have anti-inflammatory and insulin-sensitizing effects, yet vitamin D effects on hepatic fat content in children with nonalcoholic fatty liver disease (NAFLD) are not studied sufficiently. We aimed to evaluate the role of vitamin D supplementation on the hepatic fat content and NAFLD progression in children. This randomized controlled clinical trial was performed on 109 children with biopsy-proven NAFLD; only 100 patients completed the study. Patients were randomly assigned into two groups: the treatment group who received 2000 IU/day vitamin D for 6 months and the control group who received a placebo. Anthropometric measurements, vitamin D levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), serum triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting blood glucose (FBG), fasting blood insulin level (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), and serum calcium level were measured at the beginning and the end of the study. Liver biopsy was taken before and at the end of the study for all included children. There was a significant improvement of the hepatic steatosis and lobular inflammation by liver biopsy in the treatment group after treatment. However, there was no significant effect on the hepatocyte ballooning or hepatic fibrosis. There were significant decrease of AST, ALT, TG, LDL, FBG, FBI, and HOMA-IR and significant increase of vitamin D levels and HDL in the treatment group compared to the placebo group (P < 0.05). Conclusion: Vitamin D supplementation was found to be beneficial in the treatment of NAFLD in children. Trial registration: www.pactr.org, PACTR201710002634203. What is Known: • Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in pediatrics. • Several studies reported a negative association between low serum vitamin D level and grades of NAFLD. What is New: • Vitamin D supplementation has significantly decreased hepatic steatosis and lobular inflammation and improved the grades of NAFLD in children, confirmed by liver biopsy, but no effect on hepatocyte ballooning or fibrosis was observed. • Adjuvant vitamin D supplementation is recommended in children with NAFLD. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the diagnostic performance of novel ultrasound technology normalized local variance (NLV) and the standard deviation of NLV (NLV-SD) using different ROIs for hepatic steatosis in patients with metabolic-associated fatty liver disease (MAFLD) and to identify the factors that influence the NLV value and NLV-SD value, using pathology results as the gold standard. Methods: We prospectively enrolled 34 consecutive patients with suspected MAFLD who underwent percutaneous liver biopsy for evaluation of hepatic steatosis from June 2020 to December 2020. All patients underwent ultrasound and NLV examinations. NLV values and NLV-SD values were measured using different ROIs just before the liver biopsy procedure. Results: The distribution of hepatic steatosis grade on histopathology was 4/19/6/5 for none (< 5%)/ mild (5–33%)/ moderate (> 33–66%)/ and severe steatosis (> 66%), respectively. The NLV value with 50-mm-diameter ROI and NLV-SD value with 50-mm-diameter ROI showed a significant negative correlation with hepatic steatosis (spearman correlation coefficient: − 0.449, p = 0.008; − 0.471, p = 0.005). The AUROC of NLV (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.875, 0.735, and 0.583, respectively. The AUROC of NLV-SD (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.900, 0.745, and 0.603, respectively. NLV (50 mm) values and NLV-SD (50 mm) values between two readers showed excellent repeatability and the intraclass correlation coefficient (ICC) was 0.930 (p < 0.001) and 0.899 (p < 0.001). Hepatic steatosis was the only determinant factor for NLV value and NLV-SD value (p = 0.012, p = 0.038). Conclusion: The NLV (50 mm) and NLV-SD (50 mm) provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with great reproducibility. This study showed that the degree of steatosis was the only significant factor affecting the NLV value and NLV-SD value. [ABSTRACT FROM AUTHOR]

Purpose: Paediatric obesity is a well-known risk factor for metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on the levels of total homocysteine (tHcy) and total glutathione (tGSH) plasma levels in children with MAFLD. Material and Methods: Twenty-four children with severe obesity who underwent LSG were included in the study. The metabolic parameters, systemic inflammatory markers, one-carbon metabolism products, ultrasound and histological improvement were evaluated at baseline (T0M) and after 12 months from LSG (T12M). Results: The patients exhibited a significant amelioration of several metabolic parameters at T12M. A significant reduction of steatosis was observed at ultrasound (from 72.7% of moderate-severe grade to 0% severe steatosis), accompanied by a statistically significant improvement of ballooning, portal and lobular inflammation and fibrosis. A statistically significant decrease of tumour necrosis factor circulating levels was also observed (T0M median = 290.3, IQR = 281.0–317.0 pg/mL; T12M median = 260.4, IQR = 240.0–279.0 pg/mL; p < 0.0001). After 12 months from LSG, a significant increase of mean plasma levels of tHcy(T0M mean = 15.7 ± 4.1 μmol/L; T12M mean = 21.1 ± 9.3 μmol/L; p = 0.0146) was also observed. The increase of tHcy showed no causal link with the improvement of MAFLD-related inflammatory, metabolic and histological pattern. Conclusion: LSG in children with obesity induces an improvement of MAFLD-related metabolic derangement and liver damage, but also a mild hyperhomocysteinemia that should be avoided to prevent cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with chronic hepatitis B (CHB) are at an increased risk of disease progression. The influence of hepatic steatosis (HS) to liver fibrosis was controversial. We aim to investigate the association between HS and liver fibrosis and explore the predicting factors for advanced fibrosis. Methods: CHB patients undergoing liver biopsy with complete assessments of HS, necroinflammation grade [histological activity index (HAI) score], and fibrosis stage were retrospectively recruited. Logistic regression analysis was performed to determine the factors associated with advanced liver fibrosis. Results: In this cohort of 672 patients, 342 (50.9%) had HS and 267 (39.4%) were of advanced liver fibrosis. Age [odds ratio (OR) 1.026, 95% confidence interval (CI) 1.007–1.046, p = 0.008], body mass index (BMI, OR 1.091, 95% CI 1.026–1.159, p = 0.005), genotype (C vs. B) (OR 2.790, 95% CI 1.847–4.214, p < 0.001), platelet (OR 0.986, 95% CI 0.982–0.991, p < 0.001), and HAI score (OR 1.197, 95% CI 1.114–1.285, p < 0.001) were independent factors for advanced liver fibrosis in multivariate logistic regression analysis. HAI score was also a significantly associated factor for significant liver fibrosis in non-cirrhotic subpopulation (OR 1.578, 95% CI 1.375–1.810, p < 0.001). HS was not related to advanced/significant liver fibrosis in overall/non-cirrhotic population (p > 0.05). Conclusions: Significant or advanced liver fibrosis is associated with grade of necroinflammation but not with HS in CHB patients. [ABSTRACT FROM AUTHOR]