Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes of chronic liver disease globally. Based on the 2023 definition, MASLD is characterized by the presence of metabolic dysfunction and limited alcohol consumption (<140 grams/week for women, <210 grams/week for men). Given the significant burden of MASLD in Latin America, this guidance was developed by the Latin American Association for the Study of the Liver (ALEH) Working Group to address key aspects of its clinical assessment and therapeutic strategies. In Latin America, ultrasonography is recommended as the initial screening tool for hepatic steatosis due to its accessibility, while Fibrosis-4 (FIB-4) is preferred for fibrosis risk stratification, with further evaluation using more specific techniques (i.e., vibration-controlled transient elastography or Enhanced Liver Fibrosis [ELF] test). A Mediterranean diet is advised for all MASLD patients, with a target of 7-10% weight loss for those with excess weight. Complete alcohol abstinence is recommended for patients with significant fibrosis, and smoking cessation is encouraged regardless of fibrosis stage. Pharmacological options should be tailored based on the presence of steatohepatitis, liver fibrosis, excess weight, and diabetes, including resmetirom, incretin-based therapies, pioglitazone, and sodium-glucose cotransporter-2 inhibitors. Bariatric surgery may be considered for MASLD patients with obesity unresponsive to lifestyle and medical interventions. Hepatocellular carcinoma screening is advised for all cirrhotic patients, with consideration given to those with advanced fibrosis based on individual risk. Finally, routine cardiovascular risk assessment and proper diabetes prevention and management remain crucial for all patients with MASLD.

Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints.

Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least 6 months. Cohort 2 consisted of 135 Pi∗ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least 2 years later, both including LSM.

During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Forty-one Pi∗ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, that is, LSM (24 vs 5 kPa, P < .001) and aspartate aminotransferase-to-platelet ratio index (1.1 vs 0.3 units, P < .001). Liver-related endpoints within 5 years were most accurately predicted by LSM (area under the curve 0.95) followed by aspartate aminotransferase-to-platelet ratio index (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within 5 years (forced expiratory volume in the first second area under the curve 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors.

Noninvasive liver fibrosis surrogates accurately stratify liver-related risks in Pi∗ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi∗ZZ patients.

Introduction: The non-invasive assessment of disease severity remains pivotal in patients with chronic liver disease (CLD) as it has wide implications in predicting liver-related complications or death. Shear-wave elastography (SWE) is an emerging ultrasound-based method to non-invasively measure liver stiffness. The aim of our study was to evaluate two-dimensional (2D) and point (p) SWE to predict the presence of esophageal varices (EV) or clinically significant portal hypertension (CSPH). Methods: This was a retrospective analysis of a prospectively performed cohort study of patients with CLD treated in the outpatient clinic of the Frankfurt University Hospital. PSWE using the Hitachi HI Vision ASCENDUS system and the Siemens ACUSON S2000TM system or 2D-SWE using the Toshiba APLIO500 system were analyzed at baseline and during follow-up to predict EV or surrogate parameters of CSPH. ROC curves were calculated for pooled liver stiffness measurements (LSMs) using a bootstrap approach. A combined model of SWE and platelet count was created and a mixed-effect logistic regression analysis using log-transformed values was performed. Results: Overall, 511 patients with CLD and 919 consecutive LSMs were included and 315 patients (61.6%) had signs of CSPH. 2D-SWE performed best to predict EV and CSPH, and the addition of platelet count to the predictive model significantly increased test results for EV (AUC 0.83, 95%-CI: 0.76-0.89; difference in AUC 0.11, 95%-CI: 0.03-0.19, p = 0.004), but only marginally for CSPH (AUC 0.75, 95%-CI: 0.64-0.85; difference in AUC 0.06, 95%-CI: 0.02-0.14, p = 0.150). LSM > 18.5 and >20 kPa were indicative of CSPH and EV, while LSM < 10 kPa and <11 kPa ruled out CSPH and EV, respectively. Conclusions: Our study found that 2D-SWE in combination with platelet count performed best (in comparison to the other SWE methods) to predict EV or CSPH in patients with CLD. Future prospective trials are needed to validate our results.

Some patients treated with ursodeoxycholic acid (UDCA) or combined fenofibrate had well-controlled biochemical parameters but high liver stiffness, and the prognosis as well as therapeutic options for these patients may be an area worthy of further exploration.

To explore the prognosis and treatment of patients with low-risk and high liver stiffness.

A retrospective study included 424 cases of UDCA monotherapy and 102 cases of combined fenofibrate treatment.

The combination of liver stiffness measurement (LSM) and the GLOBE score improved prognostic prediction for patients with UDCA monotherapy (area under the receiver operating characteristic curve [AUC] of 0.868 (0.811-0.925) for the fitted model and 0.834 (0.767-0.900) for the GLOBE score, p = 0.006). Further analyses revealed that LSM had an additive prognostic effect mainly in low-risk patients defined by GLOBE < 0.5 (AUC, 0.777 [0.724-0.825] vs 0.642 [0.583-0.699], p = 0.001). For patients in the low-risk group, the prognosis was worse when LSM > 11 kPa (7/53 [13%] vs 2/227 [1%], p = 0.001). The prognosis was consistent between patients in the "low-risk and LSM > 11 kPa" group and the medium-risk group defined by 0.5 < GLOBE < 1.8 (7/53 [13%] vs 22/121 [18%], p = 0.418). In low-risk patients treated with combined fenofibrate therapy, the prognosis was worse when LSM > 11 kPa (3/21 [14%] vs 0/47 [0%], p = 0.022). The prognosis was consistent between patients in the "low-risk and LSM > 11 kPa" and the medium-risk groups (3/21 [14%] vs 6/27 [22%], p = 0.353). Antifibrotic drugs failed to reduce the incidence of the primary outcome (5/45 [11%] vs 5/27 [19%], p = 0.598), and delayed the progression of LSM in patients with low-risk and LSM > 11 kPa at 36 months of follow-up (changes in LSM, - 3.31 [- 5.04 to - 1.52] vs - 1.74 [- 2.83 to 1.5], p = 0.046).

Patients with GLOBE-defined low-risk and LSM > 11 kPa had a poor prognosis, and antifibrotic therapy may slow the progression of liver stiffness in these patients.

Cirrhosis is one of the major causes of morbidity and mortality worldwide and the second leading cause of digestive disease mortality. Portal hypertension is the main driver of cirrhosis-related complications such as ascites and variceal bleeding. Portal hypertension is defined as a hepatic venous pressure gradient >5 mm Hg, although it is clinically significant and associated with clinical complications when >10 mm Hg.

Therefore, detection of clinically significant portal hypertension (CSPH) in chronic advanced liver disease or compensated cirrhosis is of paramount importance to guide the management of these patients.

This study aimed at revising the non-invasive and invasive tools for assessment of portal hypertension and risk stratification for CSPH in patients with chronic liver disease.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it the leading etiology of chronic liver diseases and a prime cause of liver-related mortality. MASLD can progress into steatohepatitis (termed MASH), fibrosis, cirrhosis, and ultimately cancer. MASLD is associated with increased risks of hepatocellular carcinoma (HCC) and also extrahepatic malignancies, which can develop in both cirrhotic and non-cirrhotic patients, emphasizing the importance of identifying patients with MASLD at risk of developing MASLD-associated malignancies. However, the optimal screening, diagnostic, and risk stratification strategies for patients with MASLD at risk of cancer are still under debate. Individuals with MASH-associated cirrhosis are recommended to undergo surveillance for HCC (e.g. by ultrasound and biomarkers) every six months. No specific screening approaches for MASLD-related malignancies in non-cirrhotic cases are established to date. The rapidly developing omics technologies, including genetics, metabolomics, and proteomics, show great potential for discovering non-invasive markers to fulfill this unmet need. This review provides an overview on the incidence and mortality of MASLD-associated malignancies, current strategies for HCC screening, surveillance and diagnosis in patients with MASLD, and the evolving role of omics technologies in the discovery of non-invasive markers for the prediction and risk stratification of MASLD-associated HCC.

Diabetic retinopathy (DR), a prevalent complication in patients with type 2 diabetes, has attracted increasing attention. Recent studies have explored a plausible association between retinopathy and significant liver fibrosis. The aim of this investigation was to develop a sophisticated machine learning (ML) model, leveraging comprehensive clinical datasets, to forecast the likelihood of significant liver fibrosis in patients with retinopathy and to interpret the ML model by applying the SHapley Additive exPlanations (SHAP) method.

This inquiry was based on data from the National Health and Nutrition Examination Survey 2005-2008 cohort. Utilizing the Fibrosis-4 index (FIB-4), liver fibrosis was stratified across a spectrum of grades (F0-F4). The severity of retinopathy was determined using retinal imaging and segmented into four discrete gradations. A ten-fold cross-validation approach was used to gauge the propensity towards liver fibrosis. Eight ML methodologies were used: Extreme Gradient Boosting, Random Forest, multilayer perceptron, Support Vector Machines, Logistic Regression (LR), Plain Bayes, Decision Tree, and k-nearest neighbors. The efficacy of these models was gauged using metrics, such as the area under the curve (AUC). The SHAP method was deployed to unravel the intricacies of feature importance and explicate the inner workings of the ML model.

The analysis included 5,364 participants, of whom 2,116 (39.45%) exhibited notable liver fibrosis. Following random allocation, 3,754 individuals were assigned to the training set and 1,610 were allocated to the validation cohort. Nine variables were curated for integration into the ML model. Among the eight ML models scrutinized, the LR model attained zenith in both AUC (0.867, 95% CI: 0.855-0.878) and F1 score (0.749, 95% CI: 0.732-0.767). In internal validation, this model sustained its superiority, with an AUC of 0.850 and an F1 score of 0.736, surpassing all other ML models. The SHAP methodology unveils the foremost factors through importance ranking.

Sophisticated ML models were crafted using clinical data to discern the propensity for significant liver fibrosis in patients with retinopathy and to intervene early.

Improved early detection of liver fibrosis risk in retinopathy patients enhances clinical intervention outcomes.

The prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population.

We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD.

Among 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302. A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters.

A higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD.

The utilization of non-invasive techniques for liver fibrosis and steatosis assessment has gained acceptance as a viable substitute for liver biopsy in clinical practice. This study aimed to establish normative data for the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by age and gender, as well as to explore the relationship between anthropometric measures, clinical status, and biochemical profile according to the 90th percentile cut-off values for CAP/LSM in a U.S. adult population.

In this cross-sectional analysis, 7.522 US adults aged 20-80 years from the National Health and Nutrition Examination Survey (NHANES 2017-2020) were included. CAP and LSM were quantified using the FibroScan® 502-v2 device. A comprehensive range of data was collected, including sociodemographic, anthropometric, biochemical, lifestyle, and clinical conditions. Participants were segmented by sex and age. The median ± standard deviation (SD) for CAP was significantly lower in women (258.27 ± 61.02 dB/m) than in men (273.43 ± 63.56 dB/m), as was the median ± SD for LSM (women: 5.50 ± 4.12 kPa, men: 6.36 ± 5.63 kPa). Although median CAP and LSM values displayed an upward trend with age, statistical significance was not achieved. Notably, higher liver CAP values (above the 90th percentile) correlated with more pronounced clinical and biochemical profile differences compared to lower CAP values (below the 90th percentile) (p < 0.001).

Our study provides age- and sex-stratified standard values for CAP and LSM in a sizeable, nationally representative cohort of adults. The evidence of sex-specific variations in TE test results from our study sets the stage for future research to further corroborate these findings.

There is high prevalence of non-alcoholic fatty liver disease in individuals with type 2 diabetes mellitus (T2D), and available evidence suggests higher prevalence of NASH and advanced stages of fibrosis among T2D. Data regarding prevalence of clinically significant liver fibrosis (CSLF) in individuals with T2D is scarce. We investigated the prevalence of transient elastography (TE)-proven CSLF among patients of T2D attending a diabetes clinic at a tertiary care center.

A cross-sectional descriptive evaluation study of 603 consecutive adults with T2D was conducted to detect CSLF using TE. Steatosis was diagnosed using a controlled attenuation parameter >237 dB/m.

The prevalence of CSLF was 22.7%, and the prevalence of steatosis was 58.9% in our study. A higher body mass index (BMI) (P = 0.001), aspartate aminotransferase (AST; P = 0.0001), alanine aminotransferase (ALT; P = 0.0001), and low platelets (P = 0.0001) were independent factors associated with CSLF. Elevated ALT and AST (≥40 units/L) levels were present in only 27.7% and 37.2% of individuals with CSLF, respectively. Twenty-six (4.31%) individuals had LSM > 13.0 kPa.

CSLF is highly prevalent in T2D patients attending a diabetes clinic at a tertiary care center, and the majority of such individuals have normal transaminase levels. Higher BMI, AST, and ALT values and lower platelet counts are associated with liver fibrosis.

Ultrasound shear wave elastography (SWE) is a non-invasive, low risk technology allowing the assessment of tissue stiffness. Used clinically for nearly two decades to diagnose and stage liver fibrosis and cirrhosis, it has recently been appreciated for its ability to differentiate between more subtle forms of liver dysfunction. In this review, we will discuss the principle of ultrasound shear wave elastography, its traditional utilization in grading liver cirrhosis, as well as its evolving role in identifying more subtle degrees of liver injury. Finally, we will show how this capacity to distinguish nuanced changes may provide an opportunity for its use in perioperative risk stratification.

Liver histology has prognostic relevance and is used in surveillance and therapeutic strategies. This longitudinal study was designed to evaluate the prognostic relevance of ARFI elastography in comparison to liver histology and to the FIB-4 score in a 5-year observation interval.

Based on the hospital database, patients with an elastography examination of the liver between 2010-2012, a liver biopsy, and a follow-up of 5 years were included in the study. The AUROCs of the events liver-related death, HCC, and liver decompensation/variceal bleeding were calculated for ARFI elastography, liver histology, and FIB-4 and compared using the DeLong test.

In the final analysis 113 patients were included with 30 (26.5 %) patients having high-grade fibrosis and 19 (16.8 %) having liver cirrhosis in histology. The AUROC for liver-related death in the 5-year interval (9.7 %, n=11) was 0.80 [0.68-0.92] for ARFI elastography, 0.79 [0.66-0.92] for liver histology, and 0.66 [0.53-0.79] for FIB-4 with a p-value of 0.83 comparing ARFI to histology and a p-value of 0.02 comparing ARFI to FIB-4. The AUROC for liver decompensation/variceal bleeding (13.3 %, n=15) was 0.86 [0.76-0.94] for ARFI, which is significantly higher than the AUROC of liver histology with 0.71 [0.56-0.86] (p=0.02) and FIB-4 with 0.67 [0.54-0.80] (p=0.003). There was no significant difference for the event HCC when comparing ARFI to histology (p=0.33) or FIB-4 (p=0.14).

The prognostic value of ARFI elastography seems to not be inferior to liver histology regarding liver-related survival and might even outperform histology and the FIB-4 score for predicting some liver-related complications.

Noninvasive tests (NITs) have been proposed as an alternative to liver biopsy for diagnosing liver cirrhosis. The evidence of NIT performance in patients with chronic hepatitis D (CHD) is limited.

To evaluate the diagnostic performance of liver stiffness measurement (LSM) and other NITs in CHD patients.

We evaluated the diagnostic performance of LSM by transient elastography for the detection of liver cirrhosis in a retrospective, multicentre cohort of 144 CHD patients with paired (±6 months) LSM and liver biopsies.

Cirrhosis was diagnosed histologically in 22 patients (15.3%). Mean LSM was significantly higher in patients with cirrhosis compared to those without fibrosis (23.4 vs 10.2 kPa, p < 0.0001) or with intermediate fibrosis (23.4 vs 13.5 kPa, p < 0.0001). In the detection of liver cirrhosis, LSM was superior to other NITs (AUROCs: 0.89 [LSM], 0.87 [D4FS], 0.74 [APRI], 0.73 [FIB-4], and 0.69 [AAR]). The optimal cut-off for identifying patients with liver cirrhosis was ≥15.2 kPa (Se 91%, Sp 84%, PPV 50%, NPV 98%). The ideal cut-off for diagnosing non-advanced liver fibrosis (Metavir ≤2) was <10.2 kPa (Se 55%, Sp 86%, PPV 90%, NPV 45%), correctly identifying 90% of patients. Data were validated in an independent cohort of 132 CHD patients.

LSM is a useful tool for identifying patients at risk for liver cirrhosis and is superior to other NITs. The cut-offs of <10.2 and < 15.2 kPa reliably diagnose non-advanced liver fibrosis and exclude cirrhosis in the majority of patients. However, LSM cannot completely replace liver biopsy in CHD patients.

α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown.

Liver-related parameters were assessed in a multinational cohort of 760 adults with severe AATD (Pi∗ZZ genotype) and available liver phenotyping, of whom 344 received augmentation therapy and 416 did not. Liver fibrosis was evaluated noninvasively via the serum test AST-to-platelet ratio index and via transient elastography-based liver stiffness measurement. Histologic parameters were compared in 15 Pi∗ZZ adults with and 35 without augmentation.

Compared with nonaugmented subjects, augmented Pi∗ZZ individuals displayed lower serum liver enzyme levels (AST 71% vs 75% upper limit of normal, P < .001; bilirubin 49% vs 58% upper limit of normal, P = .019) and lower surrogate markers of fibrosis (AST-to-platelet ratio index 0.34 vs 0.38, P < .001; liver stiffness measurement 6.5 vs 7.2 kPa, P = .005). Among biopsied participants, augmented individuals had less pronounced liver fibrosis and less inflammatory foci but no differences in AAT accumulation were noted.

The first evaluation of AAT augmentation on the Pi∗ZZ-related liver disease indicates liver safety of a widely used treatment for AATD-associated lung disease. Prospective studies are needed to confirm the beneficial effects and to demonstrate the potential efficacy of exogenous AAT in patients with Pi∗ZZ-associated liver disease.

Nonalcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic, and it is the most common cause of liver diseases. The patients with severe insulin-resistant diabetes having high body mass index (BMI), high-grade adipose tissue insulin resistance, and high hepatocellular triacylglycerols (triglycerides; TAG) content develop hepatic fibrosis within a 5-year follow-up. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol (DAG), fatty acyl CoA, or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/nonalcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with an increase in saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in the liver tissue of patients with NASH. Hepatocyte lipoapoptosis is a critical feature of NASH. In the "second hit," reduced glutathione levels due to oxidative stress lead to the overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused at least by two ineffectual cyclical pathways. First is the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and the second is the Kelch like-ECH-associated protein 1 (Keap1)-nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways. In clinical practice, on ultrasonographic examination, the elevation of transaminases, γ-glutamyltransferase, and the aspartate transaminase to platelet ratio index indicates NAFLD. Fibrosis-4 index, NAFLD fibrosis score, and cytokeratin18 are used for grading steatosis, staging fibrosis, and discriminating the NASH from simple steatosis, respectively. In addition to ultrasonography, "controlled attenuation parameter," "magnetic resonance imaging proton-density fat fraction," "ultrasound-based elastography," "magnetic resonance elastography," "acoustic radiation force impulse elastography imaging," "two-dimensional shear-wave elastography with supersonic imagine," and "vibration-controlled transient elastography" are recommended as combined tests with serum markers in the clinical evaluation of NAFLD. However, to confirm the diagnosis of NAFLD, a liver biopsy is the gold standard. Insulin resistance-associated hyperinsulinemia directly accelerates fibrogenesis during NAFLD development. Although hepatocyte lipoapoptosis is a key driving force of fibrosis progression, hepatic stellate cells and extracellular matrix cells are major fibrogenic effectors. Thereby, these are pharmacological targets of therapies in developing hepatic fibrosis. Nonpharmacological management of NAFLD mainly consists of two alternatives: lifestyle modification and metabolic surgery. Many pharmacological agents that are thought to be effective in the treatment of NAFLD have been tried, but due to lack of ability to attenuate NAFLD, or adverse effects during the phase trials, the vast majority could not be licensed.

Point shear-wave elastography (pSWE) alias acoustic radiation force impulse (ARFI) imaging is a well-established ultrasound-based technique for the non-invasive assessment of liver tissue stiffness. As cut-off values for liver cirrhosis cannot be transferred from one ultrasound system to another, this study aimed at determining cut-off values for the newly developed Siemens ACUSON Sequoia ultrasound system.

In a pilot study phase, two independent examiners conducted 10 pSWE measurements in an elasticity phantom and 32 healthy individuals for the determination of inter-examiner agreement. Afterwards, 22 cirrhotic patients and 57 patients with chronic liver disease undergoing liver biopsy underwent pSWE. Patient characteristics and stiffness values were compared for individuals with and without liver cirrhosis. Diagnostic accuracies of cut-off values for the diagnosis of liver cirrhosis were calculated using areas under the receiver operating characteristics analysis and Youden's index. In a subsequent validation study phase, these cut-off values were validated prospectively in 107 cirrhotic and 68 non-cirrhotic patients.

Inter-examiner agreement was excellent for measurements in the elasticity phantom (intra-class correlation coefficient [ICC] = 0.998; P  < 0.001), and good for measurements in patients (ICC = 0.844; P  < 0.001). The best cut-off value for the diagnosis of liver cirrhosis was 1.405 m/s with an AUC of 0.872, a sensitivity of 88.2% and a specificity of 88.2% ( P  < 0.001).

ARFI elastography using the Siemens ACUSON Sequoia showed a good inter-examiner agreement. The optimal cut-off value was lower than the cut-off values described for former generations of ultrasound devices. These preliminary results should be confirmed in larger patient collectives with histology as the reference standard.

Liver stiffness (LS) is regarded as an indicator of the stages of liver fibrosis and liver cirrhosis. Numerous studies have investigated the relationship between body mass index (BMI) and LS; however, the conclusions remain controversial. In the current study, we utilized transient elastography (TE) technique, which could measure LS in a non-painful and noninvasive way, to explore the relationship between BMI and the risk of elevated LS in common community residents.

5791 participants were included in the present study. To calculate BMI value, height and weight of the participants were carefully measured. Liver stiffness measurement (LSM) > 9.1 kPa was considered as a cutoff suggesting elevated LS. The relationship of BMI and risk of elevated LS was derived using generalized linear regression models, and the threshold effect was then analyzed by smooth curve fitting and segmented regression model.

Elevated LS was detected in 230 participants (3.97%) using the TE technique. After potential confounders were adjusted according to the individual's demographic variables, underlying comorbidities and blood biochemical test results, we observed a J-shaped relationship between BMI and the risk of elevated LS, with the inflection point at 23.05 kg/m2. The effect size (and confidence interval) was 0.84 (0.71, 0.98) on the left side of the inflection point, and 1.32 (1.24, 1.41) on the right side of it.

Our study found a novel J-shaped relationship between BMI and the risk of elevated LS assessed by TE technique. Abnormal BMI, either higher or lower, was associated with an increased risk of elevated LS.

No prospective diagnostic studies have directly compared widespread non-invasive liver tests in patients with type 2 diabetes (T2D) using the intention-to-diagnose method for each of the three main histological features of metabolic dysfunction associated steatotic liver disease - namely fibrosis, metabolic dysfunction-associated steatohepatitis (MASH), and steatosis.

To compare the performance of nine tests using the intention-to-diagnose rather than the standard method, which would exclude non-evaluable participants METHODS: Biopsy was used as the reference with predetermined cut-offs, advanced fibrosis being the main endpoint. The Nash-FibroTest panel including FibroTest-T2D, SteatoTest-T2D and MashTest-T2D was optimised for type 2 diabetes. FibroTest-T2D was compared to vibration-controlled transient elastography stiffness (VCTE), two-dimensional shear-wave elastography stiffness (TD-SWE), and Fibrosis-4 blood test. NashTest-T2D was compared to aspartate aminotransferase. SteatoTest-T2D was compared to the controlled attenuation parameter and the hepatorenal gradient.

Among 402 cases, non-evaluable tests were 6.7% for VCTE, 4.0% for hepatorenal gradient, 3.2% for controlled attenuation parameter, 1.5% for TD-SWE, 1.2% for NashTest-T2D, and 0.02% for Fibrosis-4, aspartate aminotransferase and SteatoTest-T2D. The VCTE AUROC for advanced fibrosis was over-estimated by 6% (0.83 [95% CI: 0.78-0.87]) by standard analysis compared to intention-to-diagnose (0.77 [0.72-0.81] p = 0.008). The AUROCs for advanced fibrosis did not differ significantly in intention-to-diagnose between FibroTest-T2D (0.77; 95% CI: 0.73-0.82), VCTE (0.77; 95% CI: 0.72-0.81) and TD-SWE(0.78; 0.74-0.83) but were all higher than the Fibrosis-4 score (0.70; 95% CI all differences ≥7%; p ≤ 0.03). For MASH, MashTest-T2D had a higher AUROC (0.76; 95% CI: 0.70-0.80) than aspartate aminotransferase (0.72; 95% CI: 0.66-0.77; p = 0.035). For steatosis, AUROCs did not differ significantly between SteatoTest-T2D, controlled attenuation parameter and hepatorenal gradient.

In intention-to-diagnose analysis, FibroTest-T2D, TD-SWE and VCTE performed similarly for staging fibrosis, and out-performed Fibrosis-4 in outpatients with type 2 diabetes. The standard analysis over-estimated VCTE performance.

gov: NCT03634098.

Currently, most primary hospitals cannot routinely perform liver stiffness measurements (LSMs) and spleen stiffness measurements (SSMs), which are recommended by guidelines to exclude high-risk varices (HRVs). We tried to find more convenient indicators for HRV screening. We enrolled 213 cirrhosis patients as the training cohort (TC) and 65 primary biliary cirrhosis patients as the validation cohort (VC). We included indicators such as SSM by two-dimensional shear wave elastography, LSM by transient elastography, and other imaging and laboratory tests. Variable analysis revealed SSM, platelets (PLT), and spleen thickness (ST) as independent risk indicators for HRV. In TC, ST+PLT (ST < 42.2 mm and PLT > 113.5 × 109/L) could avoid 35.7% of the esophagogastroduodenoscopies (EGDs), with a 2.4% missed HRV rate. Although the proportion of EGDs spared by ST+PLT was less than SSM+PLT (SSM < 29.89 kPa + PLT > 113.5 × 109/L) (35.7% vs. 44.1%), it was higher than that of the Baveno VI criteria (B6) (35.7% vs. 28.2%). We did not validate SSM+PLT in VC considering our aims. ST+PLT safely spared 24.6% of EGDs in VC, identical to B6. Conclusions: The ability of ST+PLT to exclude HRVs was superior to B6 but slightly inferior to SSM+PLT. When SSM cannot be routinely performed, ST+PLT provides an extra option for patients to exclude HRVs as a more convenient model.

Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic diseases and is caused by mutations in the SERPINA1 gene. The homozygous Pi*Z variant is responsible for the majority of the classic severe form of alpha-1 antitrypsin deficiency, which is characterized by markedly decreased levels of serum alpha-1 antitrypsin (AAT) with a strong predisposition to lung and liver disease. The diagnosis and early treatment of AATD-associated liver disease are challenges in clinical practice. In this review, the authors aim to summarize the current evidence of the non-invasive methods in the assessment of liver fibrosis, as well as to elucidate the main therapeutic strategies under investigation that may emerge in the near future.

• In compensated cirrhosis, using non-invasive methods would exempt the patient from the need of an endoscopy. • The Baveno VII presented the "rule of 5" for Vibration-Controlled Transient Elastography; liver stiffness measurement ≤15 kPa and platelets >150.000/mm3 exclude clinically significant portal hypertension (CSPH), while when ≥25 kPa is highly suggestive of CSPH. • Spleen stiffness measurement has been proposed as a more specific technique to predict the presence of CSPH. • Elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH. This is a narrative review that aims to discuss the importance of elastographic methods in the evaluation of clinically significant portal hypertension (CSPH) in cirrhotic patients, where the authors propose an algorithm for evaluating these patients. In compensated advanced chronic liver disease, the goal is to prevent the development of CSPH and, in those already with CSPH, prevent the appearance of gastroesophageal varices (GEV) and other complications of portal hypertension. In compensated cirrhosis, the prevalence of GEV is 30-40%, of which 10-20% are at risk of bleeding. Therefore, using non-invasive methods would exempt the patient from the need of an endoscopy. Hepatic Elastography is a non-invasive, safe, reproducible method, available through many techniques: Vibration-Controlled Transient Elastography (VCTE), Shear Wave Elastography (SWE) and Magnetic Resonance Elastography (MRE). The Baveno VII presented the "rule of 5" for VCTE: liver stiffness measurement (LSM) ≤15 kPa and platelets >150.000/mm3 exclude CSPH, while an LSM ≥25 kPa is highly suggestive of CSPH. Also, the "rule of 4" for SWE has been proposed: patients with ≥17 kPa could be considered as having CSPH. At last, spleen stiffness measurement (SSM) has been proposed as a more specific technique to predict the presence of CSPH. In conclusion, elastography has gained prestige in the non-invasive evaluation of patients with advanced chronic liver disease by allowing prophylactic measures to be taken when suggesting the presence of CSPH.

Limited access to diagnostic tests for liver fibrosis remains one of the main reasons for late diagnosis, especially in rural and remote communities. Saliva diagnostics is accessible with excellent patient compliance. The aim of this study was to develop a saliva-based diagnostic tool for liver fibrosis/cirrhosis. Salivary concentrations of hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), and α-2-macroglobulin (A2MG) were significantly increased (p < 0.05) in patients with liver fibrosis/cirrhosis. By combining these biomarkers, we developed the Saliva Liver Fibrosis (SALF) score, which identified patients with liver cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.970 and 0.920 in a discovery and validation cohorts, respectively. The SALF score had a performance that was similar to that of the current Fibrosis-4 (AUROC:0.740) and Hepascore (AUROC:0.979). We demonstrated the clinical utility of saliva to diagnose liver fibrosis/cirrhosis with a potential to improve the screening for cirrhosis in asymptomatic populations.

Histological evaluation by liver biopsy is considered the gold standard for assessing liver disease; however, it is highly invasive. Non-invasive liver stiffness measurement by shear wave elastography (SWE) is effective for evaluating the hepatic fibrosis stage and related diseases. In this study, we investigated the correlations of liver stiffness with hepatic inflammation/fibrosis, functional hepatic reserve, and related diseases in patients with chronic liver disease (CLD).

Shear wave velocity (Vs) values were measured using point SWE in 71 patients with liver disease from 2017 to 2019. Liver biopsy specimens and serum biomarkers were collected at the same time, and splenic volume was measured using computed tomography images with the software Ziostation2. Esophageal varices (EV) were evaluated by upper gastrointestinal endoscopy.

Among CLD-related function and complications, Vs values were highly correlated with liver fibrosis and EV complication rates. The median Vs values for liver fibrosis grades F0, F1, F2, F3, and F4 were 1.18, 1.34, 1.39, 1.80, and 2.12 m/s, respectively. Comparison of receiver operating characteristic (ROC) curves to predict cirrhosis showed that area under the ROC (AUROC) curve for Vs values was 0.902, which was not significantly different from the AUROCs for the FIB-4 index, platelet count, hyaluronic acid, or type IV collagen 7S, while it was significantly different from the AUROC for mac-2 binding protein glycosylation isomer (M2BPGi) (P < 0.01). Comparison of ROC curves to predict EV showed that the AUROC for Vs values was 0.901, which was significantly higher than the AUROCs for FIB-4 index (P < 0.05), platelet count (P < 0.05), M2BPGi (P < 0.01), hyaluronic acid (P < 0.05), and splenic volume (P < 0.05). In patients with advanced liver fibrosis (F3 + F4), there was no difference in blood markers and splenic volume, while Vs value was significantly higher in patients with EV (P < 0.01).

Hepatic shear wave velocity was highly correlated with EV complication rates in chronic liver diseases as compared to blood markers and splenic volume. In advanced CLD patients, Vs values of SWE are suggested to be effective in predicting the appearance of EV noninvasively.

The aim of this study was to investigate the feasibility, the correlation with previously validated 2D-SWE by supersonic imagine (SSI), and the accuracy in fibrosis-staging of a novel point shear-wave elastography device (X+pSWE) in patients with chronic liver disease.

This prospective study included 253 patients with chronic liver diseases, without comorbidities potentially affecting liver stiffness. All patients underwent X+pSWE and 2D-SWE with SSI. Among them 122 patients also underwent liver biopsy and were classified according to histologic fibrosis. Agreement between the equipment was assessed with Pearson coefficient and Bland-Altman analysis, while receiver operator characteristic curve (ROC) analysis with Youden index was used to establish thresholds for fibrosis staging.

A very good correlation was found between X+pSWE and 2D-SWE with SSI (r2 = 0.94; p < 0.001), with X+pSWE average liver stiffness values 0.24 kPa lower than those obtained with SSI. AUROC of X+pSWE for the staging of significant fibrosis (F2), severe fibrosis (F3) and cirrhosis (F4) using SSI as a reference standard was 0.96 (95% CI, 0.93-0.99), 0.98 (95% CI, 0.97-1) and 0.99 (95% CI, 0.98-1), respectively. The best cut-off values for diagnosing fibrosis ≥F2, ≥F3 and F4 were, respectively, 6.9, 8.5 and 12 for X+pSWE. According to histologic classification, X+pSWE correctly identified 93 out of 113 patients (82%) for F ≥ 2 and 101 out of 113 patients (89%) for F ≥ 3 using the aforementioned cut-off values.

X+pSWE is a useful novel non-invasive technique for staging liver fibrosis in patients with chronic liver disease.

To investigate the value of contrast-enhanced portal vein imaging at the hepatobiliary phase obtained with gadobenate dimeglumine for predicting clinical outcomes in patients with chronic liver disease (CLD).

Three hundred and fourteen CLD patients who underwent gadobenate dimeglumine-enhanced hepatic magnetic resonance imaging were stratified into three groups: nonadvanced CLD (n = 116), compensated advanced CLD (n = 120), and decompensated advanced CLD (n = 78) groups. The liver-to-portal vein contrast ratio (LPC) and liver-spleen contrast ratio (LSC) at the hepatobiliary phase were measured. The value of LPC for predicting hepatic decompensation and transplant-free survival was assessed using Cox regression analysis and Kaplan-Meier analysis.

The diagnostic performance of LPC was significantly better than LSC in evaluating the severity of CLD. During a median follow-up period of 53.0 months, the LPC was a significant predictor for hepatic decompensation (p < 0.001) in patients with compensated advanced CLD. The predictive performance of LPC was higher than that of the model for end-stage liver disease score (p = 0.006). With the optimal cut-off value, patients with LPC ≤ 0.98 had a higher cumulative incidence of hepatic decompensation than patients with LPC > 0.98 (p < 0.001). The LPC was also a significant predictive factor for transplant-free survival in patients with compensated advanced CLD (p = 0.007) and those with decompensated advanced CLD (p = 0.002).

Contrast-enhanced portal vein imaging at the hepatobiliary phase obtained with gadobenate dimeglumine is a valuable imaging biomarker for predicting hepatic decompensation and transplant-free survival in CLD patients.

• The liver-to-portal vein contrast ratio (LPC) significantly outperformed liver-spleen contrast ratio in evaluating the severity of chronic liver disease. • The LPC was a significant predictor for hepatic decompensation in patients with compensated advanced chronic liver disease. • The LPC was a significant predictor for transplant-free survival in patients with compensated and those with decompensated advanced chronic liver disease.

Iodine concentrations measured using dual-energy spectral CT (DESCT) have been recently proposed as providing good performance for examining tissues hemodynamics.

To evaluate the diagnostic efficacy of DESCT-derived parameters in evaluating portal venous pressure in patients with liver cirrhosis.

A total of 71 patients with liver cirrhosis who underwent percutaneous transhepatic portal vein puncture procedures were included in this study. All participants underwent DESCT and gastrointestinal endoscopy within one month before the operation. The direct portal venous pressure of each participant was measured preoperatively.

Stepwise multivariate linear regression analysis showed that the iodine concentrations in the portal vein and hepatic parenchyma during the portal venous phase and the platelet count were independently correlated with the direct portal venous pressure (P < 0.001, P < 0.001, and P = 0.030, respectively). Receiver operating characteristic analysis revealed that the normalized iodine concentration of the hepatic parenchyma had the best performance for identifying clinically significant portal hypertension (≥10 mmHg), esophageal varices, and high-risk esophageal varices (the area under the curve values were 0.951, 0.932, and 0.960, respectively).

The normalized iodine concentration of the hepatic parenchyma is a reliable parameter to non-invasively assess portal venous pressure in patients with liver cirrhosis.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

Autoantibodies occur in healthy subjects as well as in children with Wilson's disease (WD), but their prevalence and significance are unknown. Thus, we aimed to assess the prevalence of autoantibodies and autoimmune markers, and their relationship to liver injury in WD children. The study included 74 WD and 75 healthy children as a control group. Patients with WD underwent transient elastography (TE) examinations, as well as determination of liver function tests, copper metabolism markers, and serum immunoglobulins (Ig). In the sera of the WD patients and controls, anti-nuclear (ANA), anti-smooth muscle, anti-mitochondrial, anti-parietal cell, anti-liver/kidney microsomal, anti-neutrophil cytoplasmic autoantibodies, and specific celiac antibodies were determined. Among the autoantibodies, only the prevalence of ANA in children with WD was higher than in the controls. There was no significant relationship between the presence of autoantibodies and liver steatosis or stiffness after TE. However, advanced liver stiffness (E > 8.2 kPa) was related to IgA, IgG, and gamma globulin production. The type of treatment did not influence the prevalence of autoantibodies. Our results suggest that autoimmune disturbances in WD might not be directly related to liver damage as expressed by steatosis and/or liver stiffness after TE.

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common liver disease worldwide, and its burden is expected to increase due to the growing epidemic of obesity and diabetes. The key challenge among NAFLD patients is to identify those with advanced fibrosis (F3F4), who are at high risk of developing complications and will benefit from specialized management and treatment with new pharmacotherapies when they are approved. Liver biopsy appears unrealistic and unsuitable in practice, given the large number of high-risk patients and its well-known limitations. Non-invasive sequential algorithms using fibrosis-4 index as first-line test, followed by vibration-controlled transient elastography or patented blood test, are the best strategy for case finding of high-risk subjects. In fact, they are now recommended by several international guidelines, and should be used and disseminated to increase awareness among physicians beyond liver clinics where most NAFLD patients are seen.

Portal hypertension (PH) and esophageal varices (EVs) are a matter of extensive research. According to current Baveno VII guidelines, in patients with compensated advanced chronic liver disease (cACLD), liver stiffness measurement (LSM) < 15 kPa and PLT count > 150 × 10⁹/L, upper endoscopy (UE) is not mandatory, and the emphasis should be set on non-invasive methods for evaluation of clinically significant portal hypertension (CSPH). The aim of this study is to establish whether liver stiffness (LS) measured by 2D-SWE could be used as a predictor for the presence and severity of EVs in cirrhotic patients. In total, 86 patients of whom 32 with compensated liver cirrhosis (cLC) and 54 with decompensated liver cirrhosis (dLC) were examined in the Gastroenterology clinic of University hospital "Kaspela", Plovdiv, Bulgaria. Each patient underwent LS assessment by 2D-SWE and EVs grading by UE. EVs were detected in 47 (54.7%) patients, 23 (49%) of them were stage 4-high-risk EVs (HREV). The cut-off value for LS that differentiates HREV from the rest was set at 2.49 m/s with 100% sensitivity and 100% specificity (AUC 1.000, CI 0.925). Conclusions: 2D-SWE can be used as a non-invasive method in the assessment of only high-grade esophageal varices. For the other grades, upper endoscopy remains the method of choice.

In Non-Alcoholic Fatty Liver Disease (NAFLD), events driving early hepatic dysfunction with respect to specific metabolic pathways are still poorly known.

We enrolled 84 subjects with obesity and/or type 2 diabetes (T2D). FibroScan® served to assess NAFLD by controlled attenuation parameter (CAP), and fibrosis by liver stiffness (LS). Patients with LS above 7 kPa were excluded. APRI and FIB-4 were used as additional serum biomarkers of fibrosis. The stable-isotope dynamic breath test was used to assess the hepatic efficiency of portal extraction (as DOB₁₅) and microsomal metabolization (as cPDR₃₀) of orally-administered (¹³C)-methacetin.

NAFLD occurred in 45%, 65.9%, and 91.3% of normal weight, overweight, and obese subjects, respectively. Biomarkers of liver fibrosis were comparable across subgroups, and LS was higher in obese, than in normal weight subjects. DOB₁₅ was 23.2 ± 1.5‰ in normal weight subjects, tended to decrease in overweight (19.9 ± 1.0‰) and decreased significantly in obese subjects (16.9 ± 1.3, P = 0.008 vs. normal weight). Subjects with NAFLD had lower DOB₁₅ (18.7 ± 0.9 vs. 22.1 ± 1.2, P = 0.03) but higher LS (4.7 ± 0.1 vs. 4.0 ± 0.2 kPa, P = 0.0003) than subjects without NAFLD, irrespective of fibrosis. DOB₁₅ (but not cPDR₃₀) decreased with increasing degree of NAFLD (R = -0.26; P = 0.01) and LS (R = -0.23, P = 0.03). Patients with T2D showed increased rate of NAFLD than those without T2D but similar LS, DOB₁₅ and cPDR₃₀.

Overweight, obesity and liver fat accumulation manifest with deranged portal extraction efficiency of methacetin into the steatotic hepatocyte. This functional alteration occurs early, and irrespective of significant fibrosis and presence of T2D.

(1) Background: The inherited alpha-1 antitrypsin (A1AT) deficiency variant 'Pi*Z' emerged as a genetic modifier of chronic liver disease. Controversial data exist on the relevance of heterozygous Pi*Z carriage ('Pi*MZ' genotype) as an additional risk factor in patients with chronic viral hepatitis C to develop progressive liver fibrosis. (2) Methods: Two prospectively recruited cohorts totaling 572 patients with therapy-naïve chronic viral hepatitis C (HCV) were analyzed. The Frankfurt cohort included 337 patients and a second cohort from Leipzig included 235 patients. The stage of liver fibrosis was assessed by liver biopsy, AST-to-platelet ratio index (APRI) score and Fibrosis-4 (FIB-4) score (Frankfurt) as well as liver stiffness measurement (LSM) via transient elastography (Leipzig). All patients were genotyped for the Pi*Z variant (rs28929474) of the SERPINA1 gene. (3) Results: In the Frankfurt cohort, 16/337 (4.7%) patients carried the heterozygous Pi*Z allele while 10/235 (4.3%) in the Leipzig cohort were Pi*Z carriers. In both cohorts, there was no higher proportion of Pi*Z heterozygosity in patients with cirrhosis compared to patients without cirrhosis or patients with cirrhosis vs. no liver fibrosis. Accordingly, Pi*Z frequency was not different in histological or serological stages of liver fibrosis (F0-F4) and showed no clear association with LSM. (4) Conclusions: Evaluation in two representative HCV cohorts does not indicate Pi*Z heterozygosity as a clinically relevant disease modifier in chronic HCV infection. However, validation in even larger cohorts with longitudinal follow-up is warranted.

The redefinition of metabolic-associated fatty liver disease (MAFLD) from nonalcoholic fatty liver disease (NAFLD) has caused a revolution in clinical practice, and the characteristics of patients with steatosis but not MAFLD remain unclear. The aims were to compare the diagnosis rate of MAFLD in NAFLD using different steatosis methods and explore the features of non-MAFLD-NAFLD and MAFLD-non-NAFLD.

A cross-sectional study enrolling consecutive individuals was conducted at three medical centers in southern China from January 2015 to September 2020. Steatosis was evaluated by liver biopsy or magnetic resonance imaging-based proton density fat fraction (MRI-PDFF), ultrasound, controlled attenuation parameter (CAP), and fatty liver index (FLI). Fibrosis was assessed by the NAFLD fibrosis score, transient elastography, or shear wave elastography.

The study enrolled 14,985 Chinese adults. The agreement of MAFLD and NAFLD diagnoses were 83% for FLI, 95% for ultrasound, 94% for both CAP and MRI-PDFF, and 95% for liver biopsy. The body mass index, blood pressure and lipid levels among non-MAFLD-NAFLD patients were similar metabolic parameters (p>0.05 for all), but not the alanine aminotransferase and the proportion of patients with insulin resistance, which were significantly higher in non-MAFLD-NAFLD with significant fibrosis.

The new MAFLD definition ruled out 5-17% of NAFLD cases. NAFLD and MAFLD-NAFLD involved more severe metabolic abnormalities than MAFLD and MAFLD-non-NAFLD. Non-MAFLD-NAFLD patients with significant fibrosis had more severe liver injury and increased glycemic dysregulation within the normal range. Attention should be paid to its progression.