An Australian Community-Based Metabolic Dysfunction-Associated Steatotic Liver Disease Care Pathway for People with Type 2 Diabetes: Barriers and Considerations.

Background: Although clinical guidelines endorse screening for metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis in people with type 2 diabetes (T2D), the feasibility of and barriers and considerations relevant to implementing this approach in the community remain unclear. Methods: Sequential adults with T2D attending selected community clinics during 2021-2023 were invited to receive a "liver health check" (n=543). A further 95 participants were referred directly from their general practitioner (GP) or self-referred to the study. A total of 302 participants underwent a point of care assessment of hepatic steatosis and stiffness (FibroScan) and were advised to see their GP to discuss the results. "Template" letters containing key results, their interpretation and advice about management of cardiometabolic risk, patient follow-up and referral criteria, were sent to participants' GPs. Results: Referral to a tertiary liver clinic was advised in GP letters for 45 (15%) participants with an increased risk of clinically significant fibrosis (liver stiffness measurement ≥8), 15 participants with 'red flags' (eg splenomegaly, thrombocytopenia) and 2 with unsuccessful FibroScan examinations. A referral from GPs to the liver clinic was received for 27 (44%) of these 62 participants. Approximately 90% of GPs rated the "template" letters favourably on a Likert rating scale. Conclusion: The low rate of participation in the "liver health check" and liver clinic referral reflects a real-world scenario and may stem from societal under-recognition and engagement with MASLD, competing health priorities or under-appreciation of the link between liver fibrosis severity and mortality risk. Further studies need to address strategies to enhance participation in liver health assessments and determine their impact on liver-related morbidity/mortality and overall survival.

FibroScan compared to liver biopsy for accurately staging recurrent hepatic steatosis and fibrosis after transplantation for MASH.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) recurrence after liver transplantation (LT) seems unavoidable and gradual. We aimed to evaluate the diagnostic accuracy in the post-LT setting of patients transplanted for metabolic dysfunction-associated steatohepatitis (MASH) of recurrent hepatic steatosis and fibrosis identified with FibroScan, compared to biopsy findings. METHODS: This prospective cohort study included adults transplanted for MASH between 2010 and 2022 in three LT centres in Spain who underwent FibroScan and biopsy at least 1-year after LT. RESULTS: In total, 44 patients transplanted for MASH after LT were included. The median time from LT to biopsy and FibroScan was 24.5 (interquartile range [IQR]:16-46) and 26.0 (IQR: 16.8-41.5) months, respectively. The median time between biopsy and FibroScan was 2.0 (IQR: 0-5) months. On FibroScan, significant steatosis was diagnosed in about half of the patients (n = 21, 47.7%), yet advanced fibrosis in only two cases (4.6%). On biopsy, a quarter of biopsied patients (n = 11, 25%) had a MASH diagnosis, two (4.6%) with significant fibrosis and one (2.3%) with cirrhosis. All patients with liver stiffness measurement (LSM) values <8 kPa (n = 35, 79.5%) had a fibrosis stage ≤F1 (negative predictive value = 100%). The combination of post-LT hypertension (odds ratio [OR]: 12.0, 95% confidence interval [CI]: 1.8-80.4, p = .010) and post-LT dyslipidaemia (OR: 7.9, 95% CI: 1.3-47.1, p = .024) with LSM (OR: 1.7, 95% CI: 1.1-2.8, p = .030) was independently associated with MASLD. CONCLUSIONS: Although biopsy remains the gold standard for detecting fibrosis, our results suggest that LSM values <8 kPa after LT for MASH are strongly correlated with absence of significant/advanced fibrosis.

FIB-4 Index and Liver Stiffness Measurement are Potential Predictors of Atherosclerosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

AIMS: Cardiovascular disease (CVD) is a common cause of death in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, CVD surveillance is important, but it is not well established. We evaluated the association between liver fibrosis, carotid artery atherosclerosis, and coronary artery stenosis in patients with MASLD. METHODS: Overall, 153 patients with MASLD who underwent carotid artery ultrasound were enrolled. Maximum intima-media thickness including plaques (Max-IMT) was measured by ultrasound. To predict liver fibrosis, liver stiffness was measured by vibration-controlled transient elastography and the fibrosis 4 (FIB-4) index was calculated. Coronary computed tomography angiography was performed to detect coronary artery stenosis based on a Max-IMT of ≥ 1.1 mm. RESULTS: The median Max-IMT was 1.3 mm, and 63 patients (41.2%) had a Max-IMT of ≥ 1.5 mm. FIB-4 index and liver stiffness was significantly correlated with Max-IMT, respectively (ρ=0.356, p＜0.001, ρ=0.25, p=0.002). Liver stiffness was significantly associated with a Max-IMT of ≥1.5 mm, independent of age. Individuals with higher FIB-4 index had moderate or severe coronary artery stenosis more frequently. Individuals with higher LSM level also had moderate or severe coronary artery stenosis more frequently, especially severe stenosis. CONCLUSIONS: Liver fibrosis parameters were associated with carotid artery atherosclerosis and coronary artery stenosis. Evaluation of liver fibrosis may be useful to identify significant atherosclerosis and coronary artery stenosis in patients with MASLD.

Comparing imaging modalities in the assessment of fibrosis in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children. Liver biopsy is considered the gold standard for diagnosis. Magnetic resonance elastography (MRE) and transient elastography (TE) are imaging modalities that can monitor fibrosis and steatosis noninvasively. More studies are needed to identify whether imaging modalities can provide accurate and reproducible data. We hypothesize that MRE provides reliable data similar to that of TE when compared to liver biopsy in children with MASLD/metabolic dysfunction-associated steatohepatitis. METHODS: We conducted a retrospective chart review of children with liver biopsy-proven MASLD at Children's Hospital Los Angeles between September 2017 and January 2023, investigating and comparing the predictive accuracy of MRE and TE in the detection of high-grade fibrosis on liver biopsy. RESULTS: Seventy-seven patients were reviewed, all of whom had undergone liver biopsy, MRE and TE for evaluation of MASLD. Fibrosis was identified in 90% of liver biopsies. The area under the receiver operating characteristic curves (AUROC) of MRE and TE for detection of high-grade fibrosis were 0.817 and 0.750, respectively, and not significantly different (p = 0.4785). CONCLUSION: We demonstrate that MRE and TE did not accurately predict high-grade fibrosis on liver biopsy. Between the two noninvasive imaging modalities, the correlation of identifying high-grade fibrosis was not statistically different; however, the AUROC for MRE was slightly superior to that of TE. Studies with larger cohorts will be required to validate these findings.

Imeglimin for Type 2 Diabetes Mellitus: Its Efficacy and Insight Into the Potential Benefit for Renal and Liver Function.

Introduction Imeglimin is a novel oral antihyperglycaemic drug used to treat type 2 diabetes mellitus (T2DM). In 2022, its clinical use was approved in Japan; however, there is limited data on its practical efficacy. Thus, we retrospectively investigated the clinical efficacy of imeglimin for six months at the National Defense Medical College, Tokorozawa, Japan. Material and methods We conducted a single-center retrospective analysis to elucidate the efficacy of imeglimin in the treatment of T2DM. Ten patients were enrolled, and their biomarkers and geographic data were analyzed. The primary endpoint was the change in HbA1c level at six months after imeglimin treatment compared to the baseline values. Other demographic and laboratory parameters, including sex, age, BMI, renal function, liver function, lipid profile, and transient elastography data, were also analyzed. Results A significant improvement in the HbA1c levels (8.1 % at baseline to 6.9 % at six months after treatment, P value = 0.01) was observed in this study, suggesting that imeglimin is a promising option for treating T2DM. In addition, no negative effects on renal function were observed, and albumin levels tended to decrease from baseline values. Among the nonalcoholic fatty liver disease (NAFLD) cases, liver conditions, especially fat content, tended to improve in this short-term period. Conclusions Imeglimin is suggested to have a beneficial effect not only on glycemic control but also on renal and liver function. However, further studies are required to better understand the long-term efficacy of this drug.

A Comparative Study of Novel Fibrosis Index and Other Non-invasive Serum Indices for Predicting Fibrosis in Patients of Chronic Liver Disease.

Introduction Chronic liver disease progression leads to liver fibrosis/cirrhosis. Transient Elastography is used for staging liver fibrosis but ascites, obesity, and operator experience limit its applicability. In this study, we compared various non-invasive serum indices in predicting fibrosis in chronic liver disease patients. Materials and methods A total of 142 cases of confirmed Chronic Liver Disease were included. Quantitative determination of liver stiffness by Transient Elastography and relevant blood investigations was done. We compared the liver stiffness measurement by Transient Elastography and fibrosis indices, i.e., Aspartate Transaminase (AST) to Alanine Transaminase (ALT) Ratio (AAR), AST to Platelet Ratio Index (APRI), Fibrosis Index (FI), Fibrosis-4 (FIB-4) Index, Age-Platelet Index (API), Pohl score, and Fibrosis Cirrhosis Index (FCI) with Novel Fibrosis Index (NFI), to predict liver fibrosis stages. Results The optimum cutoff of NFI for the F4 stage was ≥ 6670 with a sensitivity of 75.8% and specificity of 81.8%, for the F3 stage was ≥ 2112 with a sensitivity of 63.6% and specificity of 72.7%, and for the F2 stage was ≥ 1334 with a sensitivity of 100% and specificity of 56.3%. The NFI had the maximum area under the curve compared to other indices in predicting fibrosis stages. Conclusion The Novel Fibrosis Index was the best in predicting fibrosis stages in Chronic Liver Disease patients, with good performance in predicting the F4 stage.

One-step non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis and fibrosis in high-risk population.

BACKGROUND AND AIM: Type 2 Diabetes mellitus (T2DM), age, and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess the performance of non-invasive tests (NITs) for the diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis in high-risk subjects. METHODS: Multicentre cross-sectional study that included 124 biopsy-proven MASLD in more than 50 years-old patients with overweight/obesity and T2DM. Vibration-controlled transient elastography, Fibrosis-4 index (FIB-4), Non-alcoholic fatty liver disease fibrosis score (NFS), OWLiver Panel (OWLiver DM2 + Metabolomics-Advanced Steatohepatitis Fibrosis Score -MASEF) and FibroScan-AST were performed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC) were calculated. NITs were assessed individually and in sequential/parallel combinations. RESULTS: 35 (28.2%) patients had early MASH and 66 (53.2%) had MASH with significant fibrosis (at-risk MASH). The OWLiver Panel correctly classified 86.1% as MASH, showing an accuracy, sensitivity, specificity, PPV, and NPV of 0.77, 0.86, 0.35, 0.85, and 0.36, respectively. Class III obesity, diabetes control, or gender did not impact on the performance of the OWLiver Panel (p > 0.1). NITs for at-risk MASH showed an AUC > 0.70 except for NFS. MASEF showed the highest accuracy and NPV for at-risk MASH (AUC 0.77 [0.68-0.85], NPV 72%) and advanced fibrosis (AUC 0.80 [0.71-0.88], NPV 92%). Combinations of NITs for the identification of at-risk MASH did not provide any additional benefit over using MASEF alone. CONCLUSION: One-step screening strategy with the OWLiver Panel has high accuracy to detect MASH and at-risk MASH in high-risk subjects for MASLD.

Associations between Per- and polyfluoroalkyl substance exposures and metabolic dysfunction associated steatotic liver disease (MASLD) in adult National Health and Nutrition Examination Survey 2017-2018.

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants previously associated with elevated liver enzymes in human cohorts and steatotic liver disease in animal models. We aimed to evaluate the associations between PFAS exposures, and liver enzymes and vibration controlled transient elastography (VCTE) biomarkers of metabolic dysfunction associated steatotic liver disease (MASLD) in adult National Health and Nutrition Examination Survey (NHANES) 2017-2018. VCTE was determined by FibroScan®. Serum PFAS (n = 14), measured by mass spectrometry, were analyzed individually and by principal component (PC). Univariate and multivariable associations were determined between PFAS exposures and liver disease outcome variables: Alanine aminotransferase (ALT), controlled attenuation parameter (CAP), liver stiffness measurement (LSM), FibroScan®-based Score (FAST), using R. 1400 participants including 50% women with a mean age of 48 ± 19 years and a mean BMI of 29 ± 7 kg/m2 were analyzed. Four PFAS clustered to PC1, while three PFAS clustered to PC2. PC1 was significantly associated with ALT (ß = 0.028), CAP (ß = 0.041), LSM (ß = 0.025) and FAST (ß = 0.198) in univariate analysis. Individual PFAS exposures were oftentimes inversely associated with these measurements in multivariate analysis. In adult NHANES 2017-2018, PFAS may not be a significant burden for MASLD, because of the inconsistent associations between the environmental PFAS exposures and biomarkers of liver steatosis, inflammation, and fibrosis. More data are required to better understand the relationships between PFAS exposures and liver disease.

Diagnostic performance of liver stiffness as marker of liver involvement in systemic immunoglobulin light chain (AL) amyloidosis.

OBJECTIVE: To investigate the diagnostic performance of liver stiffness for detecting liver involvement in immunoglobulin light chain (AL) amyloidosis. METHODS: Liver stiffness was measured using transient elastography in 71 patients with systemic AL amyloidosis and 18 patients with wild type transthyretin (ATTRwt) amyloidosis with cardiomyopathy. Both non-invasive consensus criteria and serum amyloid P component (SAP) scintigraphy were used as substitute standards instead of liver biopsy for establishing liver involvement. RESULTS: Liver stiffness was higher in AL amyloidosis patients with liver involvement than in those without: this was observed using both consensus criteria (median 14.4 kPa vs. 8.1 kPa; p = 0.001) and SAP scintigraphy (median 20.9 kPa vs. 6.2 kPa; p < 0.001). Liver stiffness was also higher in AL amyloidosis patients with liver involvement compared to AL and ATTRwt amyloidosis patients with cardiac involvement. Based on receiver operating characteristic (ROC) curves a cut-off value of 14.4 kPa for stiffness was optimal to indicate liver involvement, providing sensitivity and specificity of 50% and 74%, respectively, using the consensus criteria and 63% and 90%, respectively, using SAP scintigraphy as standard. CONCLUSION: Liver stiffness is a promising tool to establish liver involvement in AL amyloidosis having potential to become part of updated criteria for liver involvement.

Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial.

Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.

Assessment of Liver Involvement in Patients With Type 2 Diabetes Mellitus in Basrah City, Iraq, Using FibroScan and Correlation With Risk Factors.

Background Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases caused by the accumulation of fat in the liver, which can progress to fibrosis, cirrhosis, and primary liver cancer. Insulin resistance is a causative factor in the development of NAFLD. FibroScan, or transient elastography, is a noninvasive imaging technique for evaluating liver disease. Aim To use FibroScan for evaluating liver involvement in type 2 diabetes mellitus (T2DM) patients with some associated risk factors. Materials and methods A cross-sectional prospective study was conducted from February to August 2023 in the outpatient clinic of Basrah Gastroenterology and Hepatology Hospital. Data collection included demographic data, past medical history, and biochemical tests including fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid profile (consisting of low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum triglycerides, and total cholesterol), then, patients underwent FibroScan examination. Results The study included 50 patients with T2DM, of whom 23 (46%) were male and 27 (54%) were female. The mean age of the studied population was 47.72 ± 8.31 years, with a range of 28-64 years. The mean BMI was 28.44 ± 4.24, with most patients being either overweight or obese. The fibrosis score was 4.74 ± 1.02 kPa (stage 0), while the mean steatosis score was 282.88 ± 44.99 (grade III). Diastolic blood pressure (BP), serum ALT, and serum HDL level were the variables that showed statistically significant differences when compared according to the stages of steatosis measured by FibroScan, with p-values of 0.016, 0.048, and 0.028, respectively. Conclusion Some risk factors associated with diabetes, such as dyslipidemia, liver enzymes, and BP, are highly associated with the development of steatosis rather than fibrosis.

Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease.

BACKGROUND AND AIM: Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). METHODS: This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM - baseline LSM)/baseline LSM × 100]. We recorded LREs and all-cause mortality during a median follow-up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. RESULTS: Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11). CONCLUSIONS: Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.

Value of Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) in Assessing Liver Fibrosis in Metabolic Dysfunction-Associated Liver Disease: A Comprehensive Review of its Serum Biomarker Role.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) is a broad condition characterized by lipid accumulation in the liver tissue, which can progress to fibrosis and cirrhosis if left untreated. Traditionally, liver biopsy is the gold standard for evaluating fibrosis. However, non-invasive biomarkers of liver fibrosis are developed to assess the fibrosis without the risk of biopsy complications. Novel serum biomarkers have emerged as a promising tool for non-invasive assessment of liver fibrosis in MAFLD patients. Several studies have shown that elevated levels of Mac-2 binding protein glycosylation isomer (M2BPGi) are associated with increased liver fibrosis severity in MAFLD patients. This suggests that M2BPGi could serve as a reliable marker for identifying individuals at higher risk of disease progression. Furthermore, the use of M2BPGi offers a non-invasive alternative to liver biopsy, which is invasive and prone to sampling errors. Overall, the usage of M2BPGi in assessing liver fibrosis in MAFLD holds great promise for improving risk stratification and monitoring disease progression in affected individuals. Further research is needed to validate its utility in clinical practice and establish standardized protocols for its implementation.

Is Aspartate Aminotransferase to Platelet Ratio Index a Better Noninvasive Score for Predicting Advanced Fibrosis in Nonalcoholic Fatty Liver Disease Patients?

Background: In the 21st century, nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder. The prevalence of NAFLD within the general population in India ranges from 9 to 53%. The gold standard for assessing the severity of liver fibrosis is liver biopsy. However, due to various difficulties involved with liver biopsy, it is imperative to identify different non-invasive tools that can replace liver biopsy. Methodology: A prospective observational study of 130 patients meeting the inclusion criteria for NAFLD was done for a period of 18 months. We aimed to compare the performance characteristics of different noninvasive scores [fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI)] in predicting advanced fibrosis as assessed by FibroScan. Results: In the study, 76.9% of patients were male. Advanced fibrosis was seen in 12.3% of the patients. Majority of the patients with advanced fibrosis had metabolic syndrome. Based on the area under the receiver operating characteristic curve (AUROC), the new cut-off for ruling out advanced fibrosis for FIB-4, NFS, and APRI were 1.18, -0.9, and 0.65, respectively, and APRI had the best AUROC (0.768). Conclusion: Abnormal glycemic status and metabolic syndrome were risk factors for advanced fibrosis. The newly derived cut-offs for the FIB-4 score, NFS score, and APRI score had a better Negative predictive value compared to the original cut-offs. How to cite this article: Bhayani PD, Parameswaran SA, Palaniswamy KR, et al. Is Aspartate Aminotransferase to Platelet Ratio Index a Better Noninvasive Score for Predicting Advanced Fibrosis in Nonalcoholic Fatty Liver Disease Patients? Euroasian J Hepato-Gastroenterol 2024;14(1):35-39.

Association of circulating Z-polymer with adverse clinical outcomes and liver fibrosis in adults with alpha-1 antitrypsin deficiency.

BACKGROUND: Circulating polymerized mutant Z-alpha-1 antitrypsin (Z-polymer) constitutes a characteristic feature in alpha-1 antitrypsin deficiency (AATD), but there is limited knowledge about its association with adverse clinical outcomes and liver fibrosis. We explored this association using data from a large cohort of adults with AATD. METHODS: A total of 836 (431 PiZZ, 405 PiMZ) adults with AATD and 312 controls (PiMM) from the European Alpha-1 Liver Cohort (2015-2020) were included. Time-to-event analyses were conducted for adults with the PiZZ genotype followed for adverse clinical outcomes (earliest occurrence of liver-related hospitalization, liver transplant or all-cause mortality). Cox proportional hazard models were used to describe the association between binary circulating Z-polymer levels and adverse clinical outcomes. Correlations between baseline circulating Z-polymer levels and baseline liver fibrosis (liver stiffness measurement [LSM] determined by transient elastography [FibroScan®]) were evaluated. The analyses were stratified by augmentation therapy status. RESULTS: Of 324 adults with the PiZZ genotype and longitudinal follow-up data, 28 reported adverse clinical outcomes. Higher baseline circulating Z-polymer levels were associated with an increased risk of adverse clinical outcomes in both crude (hazard ratio [95% confidence interval, CI], 2.88 [1.21, 6.87]) and age-adjusted (1.96 [0.78, 4.94]) analyses. In adults with the PiZZ genotype, circulating Z-polymer levels were weakly positively correlated with baseline LSM (Spearman's rho [95% CI]: 0.21 [0.11, 0.31]). Similar results were observed after stratification by augmentation therapy status. CONCLUSIONS: In adults with the PiZZ genotype, higher circulating Z-polymer levels were associated with a shorter time to adverse clinical outcome, and positively correlated with baseline LSM. Circulating Z-polymer levels may be a prognostic biomarker of clinically relevant disease in AATD.

Alcohol consumption and liver phenotype of individuals with alpha-1 antitrypsin deficiency.

BACKGROUND AND AIMS: Alpha-1 antitrypsin deficiency is an inherited disorder caused by alpha-1 antitrypsin (AAT) mutations. We analysed the association between alcohol intake and liver-related parameters in individuals with the heterozygous/homozygous Pi*Z AAT variant (Pi*MZ/Pi*ZZ genotype) found in the United Kingdom Biobank and the European Alpha1 liver consortium. METHODS: Reported alcohol consumption was evaluated in two cohorts: (i) the community-based United Kingdom Biobank (17 145 Pi*MZ, 141 Pi*ZZ subjects, and 425 002 non-carriers [Pi*MM]); and (ii) the European Alpha1 liver consortium (561 Pi*ZZ individuals). Cohort (ii) included measurements of carbohydrate-deficient transferrin (CDT). RESULTS: In both cohorts, no/low alcohol intake was reported by >80% of individuals, while harmful consumption was rare (~1%). Among Pi*MM and Pi*MZ individuals from cohort (i), moderate alcohol consumption resulted in a <30% increased rate of elevated transaminases and ~50% increase in elevated gamma-glutamyl transferase values, while harmful alcohol intake led to an at least twofold increase in the abnormal levels. In Pi*ZZ individuals from both cohorts, moderate alcohol consumption had no marked impact on serum transaminase levels. Among Pi*ZZ subjects from cohort (ii) who reported no/low alcohol consumption, those with increased CDT levels more often had signs of advanced liver disease. CONCLUSIONS: Pi*MZ/Pi*ZZ genotype does not seem to markedly aggravate the hepatic toxicity of moderate alcohol consumption. CDT values might be helpful to detect alcohol consumption in those with advanced fibrosis. More data are needed to evaluate the impact of harmful alcohol consumption.

The application of B1 inhomogeneity-corrected variable flip angle T1 mapping for assessing liver fibrosis.

PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of the B1 inhomogeneity-corrected variable flip angle (VFA) method using native T1 values in the staging of liver fibrosis. METHODS: Eighty-three patients who presented for liver biopsy due to varying degrees of liver damage, underwent MR examinations and had T1-mapping images of the liver acquired using the B1 inhomogeneity-corrected VFA VIBE method. Among them, 65 patients underwent Fibroscan, and their results were used to evaluate the elasticity of liver tissue. Additionally, T1-mapping images were collected from 19 normal control patients. Independent sample t-tests were used to analyze the correlation between T1 mapping and Fibroscan. The diagnostic efficacy of T1 mapping in patients with different stages of liver fibrosis was evaluated using receiver operating characteristic (ROC) curves. RESULTS: The consistency between different observer groups was intraclass correlation coefficient (ICC) =0.802. T1 mapping demonstrated significant differences between mid-stage liver fibrosis (S = 2) and late-stage liver fibrosis (S = 3), as well as moderate inflammation (G = 2) and severe inflammation (G = 3), P < 0.05. The Area Under Curve(AUC) values of T1 mapping for early liver fibrosis (S ≥ 1), significant liver fibrosis (S ≥ 2), advanced liver fibrosis (S ≥ 3), and end-stage liver fibrosis (S = 4) were 0.760, 0.709, 0.790, and 0.768, respectively. T1 mapping combined with Fibroscan had an AUC value of 0.860. CONCLUSIONS: The B1 inhomogeneity-corrected VFA T1 mapping may be useful for the staging of liver fibrosis. It has a superior diagnostic efficiency for diagnosing advanced fibrosis (≥S3), while native T1 values combined with Fibroscan have potential value for the staging of liver fibrosis.

Evaluation of hepatic injury in chronic hepatitis B and C using APRI and FIB-4 indices compared to fibroscan results.

Background: Hepatitis B (HBV) and hepatitis C viruses (HCV) are significant causes of liver disease worldwide. Liver fibrosis (LF) is a complication of chronic liver damage caused by HBV and HCV due to our limited knowledge comparing the diagnostic performance of platelet to aspartate aminotransferase ratio index (APRI) and fibrosis-4 (FIB-4) index with fibroscan. Methods: This study evaluated liver damage in HBV and HCV using APRI, FIB-4, and fibroscan indices. This retrospective cohort descriptive-analytical study was conducted on patients with HBV and HCV. This study uses laboratory results and imaging to investigate liver damage in chronic HBV and HCV patients. APRI and FIB-4 were computed based on laboratory results. Results: A total of 185 patients (82 hepatitis B and 103 hepatitis C) were included in the study. Thirteen patients had liver cirrhosis. There was no statistically significant difference between the fibroscan results in the two groups (P=0.99). The HBV group's mean APRI and FIB-4 were lower than HCV, but no significant difference was observed (P>0.05). Our results in HBV and HCV patients showed that APRI and FIB-4 accomplished well anticipating cirrhosis with an area under the receiver operating characteristic curve (AUC) of 0.771-0.845 and 0.871-0.910, respectively. Conclusion: Fibroscan is a powerful tool superior to APRI and FIB-4 in predicting LF and cirrhosis. Nevertheless, APRI and FIB-4 are inexpensive and non-invasive indicators with acceptable efficacy in predicting advanced fibrosis or cirrhosis. However, these two measures are not reliable in low-grade fibrosis.

Fetuin-A: a relevant novel serum biomarker for non-invasive diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD): a retrospective case-control study.

OBJECTIVES: To determine how fetuin-A contributes to diagnosing and assessing MASLD severity. METHODS: Fifty MASLD patients and fifty healthy control participants were involved in this retrospective case-control research. Abdominal ultrasonography, fibroscan with controlled attenuated parameter scan (CAP scan), laboratory investigation (including fetuin-A assessment), clinical examination, and history-taking were performed on every case. RESULTS: Fetuin-A level was considerably higher in the Cases group (1154.85 ± 629.89) than in the Control group (505.29 ± 150.4) (p < 0.001). Fetuin-A had significant validity in the prediction of MASLD at a cut-off > 702.5 with 82% sensitivity, 90% specificity, and 86% overall accuracy. CONCLUSION: One possible marker for MASLD diagnosis could be fetuin-A. Furthermore, a substantial association between such marker and the severity of the disease as it revealed a significant correlation with ultrasound grading and fibroscan with controlled attenuated parameters. Trial registration 1- Pan African Clinical Trial Registry. Unique Identifying number/registration ID: PACTR202309644280965. URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=26860 . Registration Approval date: 21/09/2023. 2- ClinicalTrials.gov. Unique Identifying number /registration ID: NCT06097039. URL: https://clinicaltrials.gov/study/NCT06097039?cond=NCT06097039&rank=1 . Registration Approval date: 25/10/2023.

Rapid improvement of hepatic steatosis and liver stiffness after metabolic/bariatric surgery: a prospective study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and related steatohepatitis (MASH) are common among obese patients and may improve after metabolic/bariatric surgery (MBS). 93 Patients undergoing MBS in 2021-2022 were prospectively enrolled. Liver stiffness measurement (LSM; via vibration-controlled transient elastography [VCTE], point [pSWE] and 2D [2DSWE] shear wave elastography) and non-invasive steatosis assessment (via controlled attenuation parameter [CAP]) were performed before (baseline [BL]) and three months (M3) after surgery. 93 patients (median age 40.9 years, 68.8% female, median BL-BMI: 46.0 kg/m2) were included. BL-liver biopsy showed MASLD in 82.8% and MASH in 34.4% of patients. At M3 the median relative total weight loss (%TWL) was 20.1% and the median BMI was 36.1 kg/m2. LSM assessed by VCTE and 2DSWE, as well as median CAP all decreased significantly from BL to M3 both in the overall cohort and among patients with MASH. There was a decrease from BL to M3 in median levels of ALT (34.0 U/L to 31 U/L; p = 0.025), gamma glutamyl transferase (BL: 30.0 to 21.0 U/L; p < 0.001) and MASLD fibrosis score (BL: - 0.97 to - 1.74; p < 0.001). Decreasing LSM and CAP, as well as liver injury markers suggest an improvement of MASLD/MASH as early as 3 months after MBS.