Association Between Triglyceride-Glucose Index and Homeostasis Model Assessment for Insulin Resistance with Estimated Glucose Disposal Rate.

This cross-sectional study was aimed to compare insulin resistance, Triglyceride- Glucose (TyG) index, fatty liver index (FLI) and hepatic steatosis index (HSI), glycaemic and lipids among groups/quartiles based upon estimated Glucose Disposal Rate (eGDR) from August 2022 to December 2022 among 249 male participants. The eGDR results in (mg/kg/min) were divided into four quartiles as: Group-I: {<6.88, n = 62}, Group-II: {<6.88-9.45, n = 63}, Group-III: {9.46-10.39, n = 62}, and Group-IV: {>10.39, n = 62}. Fasting plasma glucose (FPG), HbA1c, low density lipoprotein (LDL), homeostasis model assessment for insulin-resistance (HOMAIR), and TyG index demonstrated significant worsening increase from high to low eGDR groups. Receiver operating curve (ROC) analysis to calculate area under curve (AUC) for diagnostic efficiency candidate indices for eGDR demonstrated highest AUC for FLI as AUC: 0.736 (95% CI: 0.669-0.803), p < 0.001, followed by FPG: AUC: 0.682 (95% CI: 0.606-0.757), HOMAIR: AUC: 0.670 (95% CI: 0.602-0.739), HSI: AUC: 0.660 (95% CI: 0.589-0.731), TyG index: 0.658 (95% CI: 0.583-0.732), and HbA1c: 0.639 (95% CI: 0.583-0.732). Glycaemic measures, lipid indices, insulin resistance and TyG index deteriorated with declining eGDR. Diagnostic performance as evaluated by AUC for eGDR was highest for FLI, followed by FPG, HOMAIR, HSI, TyG index, HbA1c, and triglycerides. Key Words: Triglyceride, Insulin, Glucose, Diabetes.

Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol-Liver-Intestine Axis Health.

Excessive alcohol intake will aggravate the health risk between the liver and intestine and affect the multi-directional information exchange of metabolites between host cells and microbial communities. Because of the side effects of clinical drugs, people tend to explore the intervention value of natural drugs on diseases. As a flavor substance, spices have been proven to have medicinal value, but they are still rare in treating hepatointestinal diseases caused by alcohol. This paper summarized the metabolic transformation of alcohol in the liver and intestine and summarized the potential value of various perfume active substances in improving liver and intestine diseases caused by alcohol. It is also found that bioactive substances in spices can exert antioxidant activity in the liver and intestine environment and reduce the oxidative stress caused by diseases. These substances can interfere with fatty acid synthesis, promote sugar and lipid metabolism, and reduce liver injury caused by steatosis. They can effectively regulate the balance of intestinal flora, promote the production of SCFAs, and restore the intestinal microenvironment.

Multiparametric ultrasound as a new concept of assessment of liver tissue damage.

Liver disease accounts for approximately 2 million deaths per year worldwide. All chronic liver diseases (CLDs), whether of toxic, genetic, autoimmune, or infectious origin, undergo typical histological changes in the structure of the tissue. These changes may include the accumulation of extracellular matrix material, fats, triglycerides, or tissue scarring. Noninvasive methods for diagnosing CLD, such as conventional B-mode ultrasound (US), play a significant role in diagnosis. Doppler US, when coupled with B-mode US, can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic decompensation. US elastography can assess liver stiffness, serving as a surrogate marker for liver fibrosis. It is important to note that interpreting these values should not rely solely on a histological classification. Contrast-enhanced US (CEUS) provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver lesions. Clinical evaluation, the etiology of liver disease, and the patient current comorbidities all influence the interpretation of liver stiffness measurements. These measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD. B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild steatosis. The controlled attenuation parameter requires a dedicated device, and cutoff values are not clearly defined. Quan-titative US parameters for liver fat estimation include the attenuation coefficient, backscatter coefficient, and speed of sound. These parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US parameters. Multiparametric US (MPUS) of the liver introduces a new concept for complete noninvasive diagnosis. It encourages examiners to utilize the latest features of an US machine, including conventional B-mode, liver stiffness evaluation, fat quantification, dispersion imaging, Doppler US, and CEUS for focal liver lesion characterization. This comprehensive approach allows for diagnosis in a single examination, providing clinicians worldwide with a broader perspective and becoming a cornerstone in their diagnostic arsenal. MPUS, in the hands of skilled clinicians, becomes an invaluable predictive tool for diagnosing, staging, and monitoring CLD.

Hepatic steatosis modeling and MRI signal simulations for comparison of single- and dual-R2* models and estimation of fat fraction at 1.5T and 3T.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) has emerged as a noninvasive clinical tool for assessment of hepatic steatosis. Multi-spectral fat-water MRI models, incorporating single or dual transverse relaxation decay rate(s) (R2*) have been proposed for accurate fat fraction (FF) estimation. However, it is still unclear whether single- or dual-R2* model accurately mimics in vivo signal decay for precise FF estimation and the impact of signal-to-noise ratio (SNR) on each model performance. Hence, this study aims to construct virtual steatosis models and synthesize MRI signals with different SNRs to systematically evaluate the accuracy of single- and dual-R2* models for FF and R2* estimations at 1.5T and 3.0T. METHODS: Realistic hepatic steatosis models encompassing clinical FF range (0-60 %) were created using morphological features of fat droplets (FDs) extracted from human liver biopsy samples. MRI signals were synthesized using Monte Carlo simulations for noise-free (SNRideal) and varying SNR conditions (5-100). Fat-water phantoms were scanned with different SNRs to validate simulation results. Fat water toolbox was used to calculate R2* and FF for both single- and dual-R2* models. The model accuracies in R2* and FF estimates were analyzed using linear regression, bias plot and heatmap analysis. RESULTS: The virtual steatosis model closely mimicked in vivo fat morphology and Monte Carlo simulation produced realistic MRI signals. For SNRideal and moderate-high SNRs, water R2* (R2*W) by dual-R2* and common R2* (R2*com) by single-R2* model showed an excellent agreement with slope close to unity (0.95-1.01) and R2 > 0.98 at both 1.5T and 3.0T. In simulations, the R2*com-FF and R2*W-FF relationships exhibited slopes similar to in vivo calibrations, confirming the accuracy of our virtual models. For SNRideal, fat R2* (R2*F) was similar to R2*W and dual-R2* model showed slightly higher accuracy in FF estimation. However, in the presence of noise, dual-R2* produced higher FF bias with decreasing SNR, while leading to only marginal improvement for high SNRs and in regions dominated by fat and water. In contrast, single-R2* model was robust and produced accurate FF estimations in simulations and phantom scans with clinical SNRs. CONCLUSION: Our study demonstrates the feasibility of creating virtual steatosis models and generating MRI signals that mimic in vivo morphology and signal behavior. The single-R2* model consistently produced lower FF bias for clinical SNRs across entire FF range compared to dual-R2* model, hence signifying that single-R2* model is optimal for assessing hepatic steatosis.

Intravoxel incoherent motion assessment of liver fibrosis staging in MASLD.

PURPOSE: Partial correlation analysis was performed to account for the interference of steatosis changes and inflammatory factors, to determine the true correlation between fibrosis and IVIM parameters (Dfast, Dslow, and F), and to evaluate the diagnostic efficacy of IVIM for liver fibrosis. METHODS: A total of 106 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) examined by IVIM from November 2016 to November 2023 at our hospital were retrospectively included. Preliminary analysis of each IVIM parameter and correlations with pathological findings were performed using Spearman correlation analysis, and partial correlation analysis was used to exclude the interference of other pathological factors, thus yielding the true correlations between IVIM parameters (Dfast, Dslow, and F) and pathology. The diagnostic efficacy of IVIM parameters for diagnosing MASLD was assessed via receiver operating characteristic (ROC) curve analysis. RESULTS: Spearman correlation analysis of all the IVIM parameters revealed correlations with steatosis, lobular inflammation, and ballooning. Partial correlation analysis indicated that Dfast was correlated with the pathological fibrosis stage (r = - 0.593, P < 0.001), Dslow was correlated with the pathological steatosis score (r = - 0.313, P < 0.05), and F was correlated with the pathological fibrosis stage and steatosis score (r = - 0.456 and 0.255, P < 0.001 and P < 0.05). In the diagnosis of hepatic fibrosis, significant hepatic fibrosis, advanced liver fibrosis and cirrhosis, Dfast achieved areas under the ROC curve of 0.763, 0.801, 0.853, and 0.897, respectively. The threshold values for diagnosing different fibrosis stages using Dfast (10-3 mm2/s) were 57.613, 54.587, 52.714, and 51.978, respectively. CONCLUSION: According to our partial correlation analysis, there was a moderate correlation between Dfast and F according to fibrosis stage, and Dfast was not influenced by inflammation or steatosis when diagnosing fibrosis in MASLD patients. A relatively close Dfast threshold is insufficient for accurately and noninvasively assessing various stages of MASLD fibrosis. In clinical practice, this approach can be considered an alternative method for the preliminary assessment of fibrosis in MASLD patients.

Recent advances in noninvasive assessment of liver steatosis.

Due to the steatosis epidemic, noninvasive quantification of liver fat content is of great interest. Magnetic resonance (MR) techniques, including proton MR spectroscopy (MRS) and MR chemical shift imaging can quantify liver fat by measuring, directly or indirectly (the latter), the proton density fat fraction (PDFF). They have shown excellent diagnostic accuracy and are currently the reference standard for the noninvasive assessment of liver steatosis and are used in clinical trials for evaluating the change in liver fat over time. Using ultrasound (US), three different quantitative parameters can be obtained to estimate liver fat: attenuation coefficient, backscatter coefficient, and speed of sound. Controlled attenuation parameter (CAP), which estimates the attenuation of the US beam, was the first algorithm available and is performed with a non-imaging system. Currently, several other algorithms are available on B-mode imaging ultrasound systems, and they have shown an accuracy similar to or higher than the CAP. This article reports the current knowledge about their application in patients with metabolic dysfunction-associated steatotic liver disease.

Non-invasive assessment of hepatic steatosis by ultrasound-derived fat fraction in individuals at high-risk for metabolic dysfunction-associated steatotic liver disease.

AIMS: Given the increasing number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD) and the low rate of those with progressive liver disease, there is a pressing need to conceive affordable biomarkers to assess MASLD in general population settings. Herein, we aimed to investigate the performance of the ultrasound-derived fat fraction (UDFF) for hepatic steatosis in high-risk individuals. METHODS: A total of 302 Europeans with obesity, type 2 diabetes, or a clinical history of hepatic steatosis were included in the analyses. Clinical, laboratory, and imaging data were collected using standardized procedures during a single screening visit in Rome, Italy. Hepatic steatosis was defined by controlled attenuation parameter (CAP) or ultrasound-based Hamaguchi's score. UDFF performance for hepatic steatosis was estimated by the area under the receiver operating characteristic curve (AUC). RESULTS: Overall, median (IQR) UDFF was 12% (7-20). UDFF was positively correlated with CAP (ρ = 0.73, p < 0.0001) and Hamaguchi's score (ρ = 0.79, p < 0.0001). Independent predictors of UDFF were circulating triglycerides, alanine aminotransferase (ALT), and ultrasound-measured visceral adipose tissue (VAT). UDFF AUC was 0.89 (0.85-0.93) and 0.92 (0.88-0.95) for CAP- and ultrasound-diagnosed hepatic steatosis, respectively. UDFF AUC for hepatic steatosis was higher than those of fatty liver index (FLI), hepatic steatosis index (HSI), CAP-score (CAPS), and ALT (p < 0.0001). Lower age, ALT, and VAT were associated with discordance between UDFF and ultrasound. CONCLUSIONS: UDFF may be a simple and accurate imaging biomarker to assess hepatic steatosis and monitor changes in hepatic fat content over time or in response to therapeutic interventions beyond clinical trials.

Cardiovascular risk assessment in inflammatory bowel disease with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been reported to increase the risk of early atherosclerosis even in young patients. Moreover, metabolic dysfunction-associated steatotic liver disease (MASLD), which has been linked to IBD, is a well-recognized but underdiagnosis entity related to cardiovascular risk. We analyze the impact of MASLD in IBD patients' cardiovascular risk through both advanced lipoprotein profile sorted by nuclear magnetic resonance spectroscopy, and carotid artery intima-media thickness (CIMT). METHODS: Cross-sectional cohort study which involves 941 IBD adult outpatients. Of them, 50 patients with IBD who met criteria for MASLD and 50 with IBD without MASLD, matched by sex and age were included. Alterations in CIMT were evaluated considering abnormal measures above the 75th percentile adjusted for sex and age. Specific advanced lipoprotein profile was also carried out. RESULTS: Most of the patients had an abnormal CIMT (58%). MASLD (OR=5.05, CI 95%=1.71-14.92) and female sex (OR=3.32, CI 95%=1.03-10) were significantly associated with CIMT alterations. Dense LDL particles (with high cholesterol composition in general cohort (OR=3.62, 95% CI=1.07-12.19) and high triglycerides density in young subgroup (OR=6.25, 95% CI=1.04-50) but not total LDL cholesterol were associated with CIMT alterations. CONCLUSIONS: MASLD and female sex are associated with early atherosclerosis in IBD patients. Dense LDL particle in combination with vascular imaging findings should be evaluated as non-invasive tools in the management of cardiovascular risk in IBD patients.

Incidental findings during donor liver assessment: Single center experience.

Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental pathologic findings discovered during the pretransplant evaluation of liver donors in our Institution from 1/2010 to 12/2022. During this 13-year period 369 intraoperative consultations from 262 liver donors were performed. Of those cases, incidental findings were identified in 22 cases (5.9 %) from 19 donors (7.3 %); two donors had more than one lesion. The median age of this subset of patients was 53 years (range: 18-70) and females predominated (63 %). Sixteen of the donors had abnormal findings in the liver: 6 bile duct hamartoma (BDH), 5 hyalinized nodule with Histoplasma capsulatum, 5 focal nodular hyperplasia (FNH), 2 bile duct adenomas (BDA), 1 biliary cyst and 1 hemangioma. One donor had both FNH and a BDH. One BDH and 1 BDA case was misdiagnosed as malignancy during the frozen section evaluation. Three donors had extrahepatic pathologies: a pancreatic tail schwannoma, a low-grade appendiceal mucinous neoplasm, and a lymph node with metastatic endometrial endometrioid adenocarcinoma. Of the 19 livers, the final organ disposition was available for 9: 6 were transplanted (67 %) and 3 were discarded (33 %). Two of the 3 discarded organs were misdiagnosed BDH and BDA cases, and one was incorrectly reported as having 90 % microvesicular steatosis during the frozen assessment. We present the clinicopathologic characteristics of liver donors with incidental findings during the pre-transplant evaluation which could lead to unwarranted graft dismissal if misdiagnosed. Additionally, incidental fungal infections can have implications for immunosuppressive therapy and the decision to use or reject the graft.

Assessment of transient elastography in diagnosing MAFLD and the early effects of sleeve gastrectomy on MAFLD among the Chinese population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease among patients with obesity. Bariatric surgery, such as sleeve gastrectomy (SG), shows promise in improving the unfavorable condition of MAFLD. Transient elastography (TE) can be utilized to assess the extent of steatosis and liver fibrosis, providing a noninvasive method for preoperative prediction and postoperative evaluation of MAFLD. This study aims to investigate the effectiveness of TE in diagnosing MAFLD by evaluating liver steatosis and tissue stiffness, as well as assessing the early impact of SG in the treatment of obesity-associated MAFLD. METHODS: In this study, the authors collected preoperative and 6-month postoperative data from patients with obesity who were diagnosed with MAFLD by intraoperative liver biopsy. The patients underwent SG at our hospital between August 2021 and April 2023. The authors estimated the diagnostic accuracy for the steatosis and fibrosis categories using the area under the receiver operating characteristic curve (AUROC). The authors also evaluated the influence of disease prevalence on the positive predictive value and negative predictive value. MAFLD diagnosis was based on the liver steatosis activity and fibrosis scoring system. The authors used univariate and multivariate logistic regression analyses to identify factors contributing to severe MAFLD. To visualize the results, the authors created a nomogram and enhanced it with bootstrap resampling for internal validation. Additionally, the authors plotted receiver operating characteristic and calibration curves. The authors compared preoperative and postoperative data, including general information, laboratory tests, and TE results, to assess the early impact of SG in the treatment of obesity-associated MAFLD. RESULTS: Based on the results of liver biopsy, the AUROC for controlled attenuation parameter (CAP) in identifying steatosis was found to be 0.843 (95% CI: 0.729-0.957) for S≥S1, 0.863 (95% CI: 0.786-0.940) for S≥S2, and 0.872 (95% CI: 0.810-0.934) for S=S3. The Youden limits for S≥S1, S≥S2, and S≥S3 were determined to be 271 dB/m, 292 dB/m, and 301 dB/m, respectively. Similarly, the AUROC for liver stiffness measurement (LSM)/E in detecting liver fibrosis was 0.927 (95% CI: 0.869-0.984) for F≥F2, 0.919 (95% CI: 0.824-0.979) for F≥F3, and 0.949 (95% CI: 0.861-0.982) for F=F4, with Youden cutoff values of 7.5 kPa, 8.3 kPa, and 10.4 kPa, respectively. Patients with A≥3 and/or F≥3 were classified as having severe MAFLD. Multivariate logistic regression analysis identified CAP, E, LDL, and AST as the best diagnostic factors for severe MAFLD, and a nomogram was constructed based on these factors. The AUROC of the nomogram for the assessment of severe MAFLD was 0.824 (95% CI: 0.761-0.887), which was further validated by 1000 bootstrap resamplings with a bootstrap model area under curve of 0.823. Finally, after a 6-month follow-up period, the steatosis grade and fibrosis stage of the patients were graded based on the optimal cutoff values for CAP and LSM. Significant reductions in BMI, waist circumference, HbA1c, fasting glycemia, triglycerides, high density lipoprotein (HDL), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), gamma glutamyl transpeptidase (GGT), CAP, LSM, steatosis grade, and fibrosis stage were observed compared to the preoperative values. CONCLUSION: In this prospective study, the authors investigated the use of CAP and LSM as alternatives to liver biopsy for evaluating hepatic steatosis and fibrosis in patients with obesity combined with MAFLD. Furthermore, the authors examined the impact of SG on metabolic indicators and the progression of fatty liver disease during the early postoperative period, and observed significant improvements in both aspects.

Assessment of endocrine disruptor impacts on lipid metabolism in a fatty acid-supplemented HepaRG human hepatic cell line.

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide. This disease encompasses several stages, from steatosis to steatohepatitis and, eventually, to fibrosis and cirrhosis. Exposure to environmental contaminants is one of the risk factors and an increasing amount of evidence points to a role for endocrine disrupting compounds (EDCs). This study assesses the impact of selected EDCs on the formation of lipid droplets, the marker for steatosis in a hepatic model. The mechanisms underlying this effect are then explored. Ten compounds were selected according to their obesogenic properties: bisphenol A, F and S, butyl-paraben, cadmium chloride, p,p'-DDE, DBP, DEHP, PFOA and PFOS. Using a 2D or 3D model, HepaRG cells were exposed to the compounds with or without fatty acid supplementation. Then, the formation of lipid droplets was quantified by an automated fluorescence-based method. The expression of genes and proteins involved in lipid metabolism and the impact on cellular respiration was analyzed. The formation of lipid droplets, which is revealed or enhanced by oleic acid supplementation, was most effectively induced by p,p'-DDE and DEHP. Experiments employing either 2D or 3D culture conditions gave similar results. Both compounds induced the expression of PLIN2. p,p'-DDE also appears to act by decreasing in fatty acid oxidation. Some EDCs were able to induce the formation of lipid droplets, in HepaRG cells, an effect which was increased after supplementation of the cells with oleic acid. A full understanding of the mechanisms of these effects will require further investigation. The novel automated detection method described here may also be useful in the future as a regulatory test for EDC risk assessment.

Alcohol-associated liver disease: Epidemiology and management.

Alcohol is the leading cause of preventable liver morbidity and mortality worldwide, as it is also the most frequent cause of advanced liver disease. Alcohol-associated liver disease (ALD) covers different phenotypes ranging from steatosis to the development of inflammation (steatohepatitis), fibrosis and ultimately, in a proportion of patients, the development of liver cirrhosis and its associated complications. ALD has a complex pathogenesis that includes the interplay of both genetic and environmental factors, yet the precise mechanisms are largely unknown. Alcohol-associated hepatitis (AH) is a severe clinical presentation of ALD, which is characterized by abrupt jaundice and clinical decompensations of liver disease. AH occurs in a percentage of patients with underlying ALD and active alcohol consumption. Currently, there are no approved targeted therapies able to interfere in the pathogenesis of ALD and halt the progression of the disease, therefore alcohol abstinence is the most effective measure to improve prognosis in this patient population. In this regard, alcohol cessation remains the first-line treatment in all stages of alcohol disease. In patients with advanced ALD nonresponding to medical therapy, liver transplantation is the only approach that improves prognosis, and it should be considered in patients with decompensated cirrhosis. In the last years, AH has emerged as a new indication of early liver transplantation in non-responders to medical therapy, with promising results in highly selected patients. In this review, we provide an update on the epidemiology, risk factors, natural history, diagnosis, pathogenesis, and current treatments for ALD, taking into account the importance of assessing and managing alcohol consumption as the etiological factor and the main driver of prognosis in patients with ALD.

Improved assessment of donor liver steatosis using Banff consensus recommendations and deep learning algorithms.

BACKGROUND & AIMS: The Banff Liver Working Group recently published consensus recommendations for steatosis assessment in donor liver biopsy, but few studies reported their use and no automated deep-learning algorithms based on the proposed criteria have been developed so far. We evaluated Banff recommendations on a large monocentric series of donor liver needle biopsies by comparing pathologists' scores with those generated by convolutional neural networks (CNNs) we specifically developed for automated steatosis assessment. METHODS: We retrospectively retrieved 292 allograft liver needle biopsies collected between January 2016 and January 2020 and performed steatosis assessment using a former intra-institution method (pre-Banff method) and the newly introduced Banff recommendations. Scores provided by pathologists and CNN models were then compared, and the degree of agreement was measured with the intraclass correlation coefficient (ICC). RESULTS: Regarding the pre-Banff method, poor agreement was observed between the pathologist and CNN models for small droplet macrovesicular steatosis (ICC: 0.38), large droplet macrovesicular steatosis (ICC: 0.08), and the final combined score (ICC: 0.16) evaluation, but none of these reached statistically significance. Interestingly, significantly improved agreement was observed using the Banff approach: ICC was 0.93 for the low-power score (p <0.001), 0.89 for the high-power score (p <0.001), and 0.93 for the final score (p <0.001). Comparing the pre-Banff method with the Banff approach on the same biopsy, pathologist and CNN model assessment showed a mean (±SD) percentage of discrepancy of 26.89 (±22.16) and 1.20 (±5.58), respectively. CONCLUSIONS: Our findings support the use of Banff recommendations in daily practice and highlight the need for a granular analysis of their effect on liver transplantation outcomes. IMPACT AND IMPLICATIONS: We developed and validated the first automated deep-learning algorithms for standardized steatosis assessment based on the Banff Liver Working Group consensus recommendations. Our algorithm provides an unbiased automated evaluation of steatosis, which will lay the groundwork for granular analysis of steatosis's short- and long-term effects on organ viability, enabling the identification of clinically relevant steatosis cut-offs for donor organ acceptance. Implementing our algorithm in daily clinical practice will allow for a more efficient and safe allocation of donor organs, improving the post-transplant outcomes of patients.

Liver stiffness as a cornerstone in heart disease risk assessment.

Metabolic dysfunction-associated steatotic liver disease (MASLD) typically presents with hepatic fibrosis in advanced disease, resulting in increased liver stiffness. A subset of patients further develops liver cirrhosis and hepatocellular carcinoma. Cardiovascular disease is a common comorbidity in patients with MASLD and its prevalence is increasing in parallel. Recent evidence suggests that especially liver stiffness, whether or not existing against a background of MASLD, is associated with heart diseases. We conducted a narrative review on the role of liver stiffness in the prediction of highly prevalent heart diseases including heart failure, cardiac arrhythmias (in particular atrial fibrillation), coronary heart disease, and aortic valve sclerosis. Research papers were retrieved from major scientific databases (PubMed, Web of Science) until September 2023 using 'liver stiffness' and 'liver fibrosis' as keywords along with the latter cardiac conditions. Increased liver stiffness, determined by vibration-controlled transient elastography or hepatic fibrosis as predicted by biomarker panels, are associated with a variety of cardiovascular diseases, including heart failure, atrial fibrillation, and coronary heart disease. Elevated liver stiffness in patients with metabolic liver disease should lead to considerations of cardiac workup including N-terminal pro-B-type natriuretic peptide/B-type natriuretic peptide determination, electrocardiography, and coronary computed tomography angiography. In addition, patients with MASLD would benefit from heart disease case-finding strategies in which liver stiffness measurements can play a key role. In conclusion, increased liver stiffness should be a trigger to consider a cardiac workup in metabolically compromised patients.

Liver biopsy for assessment of suspected drug-induced liver injury in metabolic dysfunction-associated steatohepatitis clinical trials: Expert consensus from the Liver Forum.

BACKGROUND: Causality assessment of suspected drug-induced liver injury (DILI) during metabolic dysfunction-associated steatohepatitis (MASH) clinical trials can be challenging, and liver biopsies are not routinely performed as part of this evaluation. While the field is moving away from liver biopsy as a diagnostic and prognostic tool, information not identified by non-invasive testing may be provided on histology. AIM: To address the appropriate utilisation of liver biopsy as part of DILI causality assessment in this setting. METHODS: From 2020 to 2022, the Liver Forum convened a series of webinars on issues pertaining to liver biopsy during MASH trials. The Histology Working Group was formed to generate a series of consensus documents addressing these challenges. This manuscript focuses on liver biopsy as part of DILI causality assessment. RESULTS: Expert opinion, guidance and recommendations on the role of liver biopsy as part of causality assessment of suspected DILI occurring during clinical trials for a drug(s) being developed for MASH are provided. Lessons learned from prior MASH programs are reviewed and gaps identified. CONCLUSIONS: Although there are no pathognomonic features, histologic evaluation of suspected DILI during MASH clinical trials may alter patient management, define the pattern and severity of injury, detect findings that favour a diagnosis of DILI versus MASH progression, identify prognostic features, characterise the clinicopathological phenotype of DILI, and/or define lesions that influence decisions about trial discontinuation and further development of the drug.