Non-invasive Assessment Of Liver Fibrosis Research Articles

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.

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.

Reply: Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

Reply: Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

Alpha-fetoprotein and APRI as predictive markers for patients with Type C hepatitis B-related acute-on-chronic liver failure: a retrospective study

BackgroundType C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF.MethodPatients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model.ResultsA total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH‐ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (<-9.07) survived longer.ConclusionsA new prognostic scoring system for patients with type C HBV-ACLF based on seven routine indices was established in our study and can accurately predict short-term mortality and might be used to guide clinical management.

Imaging-based non-invasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

Transient elastography (TE), shear-wave elastography (SWE), and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). A comprehensive search for studies assessing LSM by TE, SWE, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), utilizing histopathology as standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV co-infection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. LSM from TE, SWE, and MRE show acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

Development and validation of a noninvasive prediction model for significant hepatic liver fibrosis in Chinese patients with autoimmune hepatitis

Introduction and ObjectivesAutoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. Materials and MethodsThe clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. ResultsLogistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819–0.924) and external validation (0.829, 95%CI: 0.753–0.904). ConclusionsOur predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.

Utility and impact of magnetic resonance elastography in the clinical course and management of chronic liver disease

We aimed to characterize scenarios where magnetic resonance elastography (MRE) of the liver was ordered and its impact on clinical course and management. 96 consecutive MRE examinations and subsequent encounters over 14 months were reviewed. Indication for MRE of the liver and subsequent management were abstracted from the medical record. In all cases, non-invasive assessment of liver fibrosis was the primary indication and at least one additional rationale was noted. There was a significant decrease in recommendations to undergo liver biopsy after MRE. Additionally, a greater percentage of those recommended to undergo biopsy completed the procedure after discussion of the results. Given the significant cost and rare but serious risks of liver biopsy, MRE of the liver provides an attractive, safer alternative that may have a comparable impact on management, or select cases where biopsy is essential to guide management. We demonstrate the versatility of MRE in real-world hepatology practice, including its utility as a non-invasive surrogate for liver biopsy.

Noninvasive assessment of liver fibrosis can predict clinical outcomes at late follow-up after a sustained virological response in HCV patients?

ObjectivesThe primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. MethodsA total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. ResultsAt 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. ConclusionTransient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Correlation Between Coronavirus Disease 2019 Severity and Noninvasive Assessment of Liver Fibrosis in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated fatty liver disease is a crucial global health concern. Studies have shown that metabolic dysfunction-associated fatty liver disease patients are at higher risk of severe coronavirus disease 2019. However, there are no precise measures of the correlation between the degree of metabolic dysfunction-associated fatty liver disease fibrosis and coronavirus disease 2019 severity. This study evaluated the association between metabolic dysfunction-associated fatty liver disease with varying degrees of fibrosis and coronavirus disease 2019 prognosis. All hospitalized coronavirus disease 2019 patients who had liver steatosis as determined by computed tomography scan were included. Metabolic dysfunction-associated fatty liver disease was diagnosed in accordance with international consensus criteria. Liver fibrosis was assessed using the nonalcoholic fatty liver disease fibrosis score, FIB-4 and FIB-8 indexes. Coronavirus disease 2019 severity was defined using World Health Organization criteria. Logistic regression was used to determine the associations between varying degrees of fibrosis and the severity of coronavirus disease 2019. A total of 996 confirmed hospitalized coronavirus disease 2019 cases with complete data were reviewed; of these, 296 (29.7%) cases of metabolic dysfunction-associated fatty liver disease were diagnosed. Metabolic dysfunction-associated fatty liver disease patients with any fibrotic state had more severe coronavirus disease 2019 than nonmetabolic dysfunction-associated fatty liver disease patients (adjusted odds ratio 1.912, 95% CI 1.363-2.684; P < .05). Multiple logistic regression analysis showed that metabolic dysfunction-associated fatty liver disease patients with significant fibrosis according to the FIB-8 score were more likely to have severe coronavirus disease 2019 (adjusted odds ratio 5.458, 95% CI 1.481-20.110; P < .05). The presence of metabolic dysfunction-associated fatty liver disease in hospitalized coronavirus disease 2019 patients strongly correlated with the severity of coronavirus disease 2019. The hepatic FIB-8 index appears to provide the best prognostic value among the fibrosis scores in metabolic dysfunction-associated fatty liver disease patients with coronavirus disease 2019.

Assessment of hepatic fibrosis, portal hemodynamic changes, and disease severity in patients with HCV-related liver cirrhosis after sustained virologic response to direct-acting antiviral drugs (DAAs)

BackgroundRegression of fibrosis and improvement of portal hemodynamics after achievement of sustained viral response (SVR) in patients with chronic hepatitis C (HCV) is a subject of debate in different studies. Some studies reported improvement in the degree of fibrosis, while others did not find significant changes.ObjectiveWe aimed to evaluate changes in liver fibrosis, portal hemodynamics and clinical outcomes in patients with chronic HCV-related liver cirrhosis after the achievement of SVR with direct-acting antiviral drugs (DAAs).Patients and methodsIn our prospective longitudinal study, a total of 100 patients with chronic HCV infection-related liver cirrhosis were recruited, received DAAs, and completed the follow-up period. Clinical evaluation for assessment of liver disease severity using MELD and Child–Pugh class and scores were done. A noninvasive assessment of liver fibrosis using serum biomarkers (APRI index & FIB4 score) and share wave elastography (SWE) was done. Portal hemodynamic evaluation using Doppler ultrasound was done. All were done at baseline and 3 and 12 months after the end of therapy.ResultsA significant reduction in the degree of fibrosis was observed. Share wave elastography (SWE) readings showed 19.79% and 30.45% reduction 3 and 12 months after the end of therapy respectively (P < 0.001). Regarding the FIB4 score, the percentage of score reduction was 19.8% and 26.46% 3 and 12 months after the end of therapy, respectively (P < 0.01). APRI scores showed 22.6% and 41.09% reduction 3 and 12 months after the end of therapy respectively (P < 0.001). Significant improvement in Child–Pugh scores 3 and 12 months after the end of treatment was observed. Doppler ultrasound showed a significant increase in portal vein flow velocity, a significant decrease in time average mean velocity, and cross-section area 12 months after the end of treatment.ConclusionThere was a considerable degree of reduction of liver fibrosis, improvement of portal hemodynamics, and Child–Pugh score in cirrhotic HCV patients who achieved SVR after DAAs.Trial registrationClinicalTrials.gov, ID: NCT03241823. Registered on 08 May 2017.

Identifying High-Risk Patients With Nonalcoholic Fatty Liver Disease: An Opportunity for Intervention Within the Primary Care Setting.

Patients with metabolic syndrome (MetS) are likely to have nonalcoholic fatty liver disease (NAFLD), which can progress to advanced fibrosis. Early recognition of those at highest risk may ameliorate outcomes. Noninvasive liver fibrosis assessment through validated scoring systems such as the fibrosis-4 (FIB-4) index is helpful to identify these high-risk patients, with the process ideally beginning in the primary care setting. The primary objective of this study was to determine rates of disease recognition and initial management of patients with NAFLD and advanced fibrosis in a diverse primary care setting. The secondary objective was to define demographic and clinical predictors of NAFLD identification and management in this population. Medical charts from patients seen at three university-based primary care practices in New York City from January 2016 to December 2019 were reviewed. Inclusion criteria consisted of: age 18 years and above, persistent alanine transaminase (ALT) elevation (2 values ≥40IU/mL ≥6mo apart), and body mass index ≥30kg/m 2 . Patients with viral hepatitis or alcohol misuse were excluded. Patients were defined as likely having NAFLD if they met 2 of the following criteria indicating MetS: systolic blood pressure >135mmHg or diastolic blood pressure >85mmHg or active treatment for hypertension; high-density lipoprotein <40g/dL; triglycerides >150mg/dL or active treatment for hyperlipidemia; or hemoglobin A1c ≥5.7% or active treatment for insulin resistance. The primary study endpoints were the frequency of providers' recognition of NAFLD and referral to specialist and/or for imaging based on visit diagnosis codes or chart documentation. The secondary endpoints were frequency of detecting those with NAFLD and advanced fibrosis utilizing previously defined FIB-4 index cutoffs as well as predictors of disease recognition and management. Analysis was completed using descriptive statistics and logistical regression modeling. A total of 295 patients were identified as having persistently elevated ALT, a body mass index ≥30kg/m 2 , and MetS consistent with likely NAFLD diagnosis. In patients meeting these criteria, ALT elevation was documented by primary care providers in 129 patients (43.7%), NAFLD was noted in chart documentation in 76 patients (25.8%), and a NAFLD ICD-10 diagnosis was assigned to 7 patients (2.4%). 50 patients (16.9%) were referred for ultrasound. Among 51 patients (17.2%) at high risk for advanced fibrosis based on FIB-4 >3.25, 23 patients (45.1%) had NAFLD recognized by their provider and 3 (5.9%) were referred to a specialist. On logistic regression, female gender, dyslipidemia, and private insurance were predictors of disease identification by the primary care physician. ALT elevation and NAFLD are under recognized among patients with MetS in the primary care setting. Importantly, while 17.2% of patients with likely NAFLD in our cohort were high risk for advanced fibrosis, less than half of this group had a NAFLD diagnosis recognized by their primary care provider and only three were referred to a liver specialist. Further investigation of disease recognition and management algorithms in the primary care setting are necessary to enhance NAFLD detection, implement clinical care pathways, and reduce disease progression and complications.

Development and validation of a non-invasive model for predicting significant fibrosis based on patients with nonalcoholic fatty liver disease in the United States.

Liver fibrosis is closely related to abnormal liver function and liver cancer. Accurate noninvasive assessment of liver fibrosis is of great significance for preventing disease progression and treatment decisions. The purpose of this study was to develop and validate a non-invasive predictive model for the asses`sment of significant fibrosis in patients with non-alcoholic fatty liver disease. Information on all participants for 2017-2018 was extracted from the NHANES database. The eligible patients with significant fibrosis (n=123) and non-significant fibrosis (n=898) were selected to form the original dataset. Variable selection was performed using least absolute shrinkage and selection operator (Lasso) regression, and multivariate logistic regression analysis was used to develop a prediction model. The utility of the model is assessed in terms of its discrimination, calibration and clinical usability. Bootstrap-resampling internal validation was used to measure the accuracy of the prediction model. This study established a new model consisting of 9 common clinical indicators and developed an online calculator to show the model. Compared with the previously proposed liver fibrosis scoring system, this model showed the best discrimination and predictive performance in the training cohort (0.812,95%CI 0.769-0.855) and the validation cohort (0.805,95%CI 0.762-0.847), with the highest area under curve. Specificity(0.823), sensitivity(0.699), positive likelihood ratio(3.949) and negative likelihood ratio(0.366) were equally excellent. The calibration plot of the predicted probability and the actual occurrence probability of significant fibrosis shows excellent consistency, indicating that the model calibration is outstanding. Combined with decision curve analysis, this model has a great benefit in the range of 0.1-0.8 threshold probability, and has a good application value for the diagnosis of clinical significant fibrosis. This study proposes a new non-invasive diagnostic model that combines clinical indicators to provide an accurate and convenient individualized diagnosis of significant fibrosis in patients with non-alcoholic fatty liver disease.

Effect of Liver Fibrosis on Oral and Gut Microbiota in the Japanese General Population Determined by Evaluating the FibroScan-Aspartate Aminotransferase Score.

The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan-asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of Fusobacteria strains and a decrease in the relative abundance of Faecalibacterium, with the presence of Fusicatenibacter in the gut microbiota. Feacalibacterium was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.

Non-invasive assessment of liver fibrosis by serum metabolites in non-human primates and human patients

Liver fibrosis, a rising cause of chronic liver diseases, could eventually develop into cirrhosis and liver failure. Current diagnosis of liver fibrosis relies on pathological examination of hepatic tissues acquired from percutaneous biopsy, which may produce invasive injuries. Here, for non-invasive assessment of liver fibrosis, we applied comparative multi-omics in non-human primates (rhesus macaques) and subsequent serum biopsy in human patients. Global transcriptomics showed significant gene enrichment of metabolism process, in parallel with oxidative stress and immune responses in fibrotic primates. Targeted metabolomics were concordant with transcriptomic patterns, identifying elevated lipids and porphyrin metabolites during hepatic fibrosis. Importantly, liquid biopsy results validated that specific metabolites in the serum (e.g., biliverdin) were highly diagnostic to distinguish human patients from healthy controls. Findings describe the interconnected transcriptional and metabolic network in primate liver fibrosis and provide potential indices for non-invasive detection of liver fibrosis in humans.

Associations between higher plasma ferritin and hepcidin levels with liver stiffness in patients with type 2 diabetes: An exploratory study.

Currently, there is no information about the association between circulating levels of ferritin and hepcidin and liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). We enrolled 153 patients with T2DM with no known liver diseases, who consecutively attended our diabetes outpatient service and who underwent liver ultrasonography and liver stiffness measurement (LSM) by vibration-controlled transient elastography (Fibroscan® for the non-invasive assessment of liver fibrosis). Plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. After stratification of patients by LSM tertiles [1st tertile median LSM: 3.6 (interquartile range: 3.3-4.0) kPa, 2nd tertile: 5.3 (4.9-5.9) kPa and 3rd tertile: 7.9 (6.7-9.4) kPa], we found that plasma ferritin and hepcidin concentrations increased across LSM tertiles [median ferritin: 68.7 (interquartile range: 25.1-147) vs. 85.8 (48.3-139) vs. 111 (59.3-203) μg/L, p = 0.021; median hepcidin: 2.5 (1.1-5.2) vs. 4.4 (2.5-7.3) vs. 4.1 (1.9-6.8) nmol/L, p = 0.032]. After adjustment for age, sex, diabetes duration, waist circumference, haemoglobin A1c, HOMA-insulin resistance score, triglycerides, haemoglobin, presence of hepatic steatosis on ultrasonography and patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genetic variant, higher plasma ferritin levels were associated with greater LSM values (adjusted-odds ratio 2.10, 95% confidence interval 1.23-3.57, p = 0.005). Higher plasma hepcidin levels were also associated with greater LSM values (adjusted-odds ratio 1.90, 95% confidence interval 1.15-3.13, p = 0.013). Higher levels of plasma ferritin and hepcidin were associated with greater NAFLD-related liver fibrosis (assessed by LSM) in patients with T2DM, even after adjustment for established cardiometabolic risk factors, diabetes-related variables and other potential confounders.

Two-dimensional shear wave elastography (ElastQ) accurately rules out liver fibrosis and rules in advanced chronic liver disease across liver disease etiologies: a prospective multicenter study.

This study evaluated ElastQ, a two-dimensional shear wave elastography (2D-SWE) technique, for the non-invasive assessment of liver fibrosis risk using liver stiffness measurement (LSM). The aim was to determine its diagnostic accuracy and establish LSM cutoffs for clinical risk stratification. A prospective multicenter study was conducted, employing vibration-controlled transient elastography (VCTE) as a reference standard. The statistical analysis utilized Pearson correlations and Lin concordance correlation coefficients, diagnostic areas under the curve (AUCs), and 90%-specific rule-in and 90%-sensitive rule-out ElastQ cutoffs. The study included 875 patients at risk for liver disease, of whom 816 (376 women, 46.1%; median age, 57.0 years [interquartile range, 19.0]) had successful and reliable VCTE- and ElastQ-LSMs. The median LSM was 13.0 kPa (range, 2.0 to 75.0 kPa) for VCTE and 6.6 kPa (range, 2.9 to 26.5 kPa) for ElastQ. The correlation between VCTE-LSM and ElastQ-LSM was adequate for VCTE-LSM <15 kPa (Pearson r=0.63) but lower for VCTE-LSM ≥15.0 kPa (Pearson r=0.27). VCTE-LSM indicated no fibrosis risk (<5.0 kPa) in 178 cases (21.8%), gray zone (5.0-9.9 kPa) in 347 cases (42.5%), and advanced chronic liver disease (ACLD; ≥10.0 kPa) in 291 cases (35.7%). The diagnostic AUC for ElastQ-LSM was 0.82 for fibrosis risk and 0.90 for ACLD. The clinically relevant ElastQ cutoffs for ruling out fibrosis risk and ruling in compensated ACLD (cACLD) were <5.0 kPa and ≥9.0 kPa, respectively. ElastQ 2D-SWE enables accurate, non-invasive assessments of liver fibrosis and cACLD risk. In clinical practice, ElastQ-LSM <5.0 kPa rules out fibrosis, while ElastQ-LSM ≥9.0 kPa rules in cACLD.

Predicting clinical outcomes in people with NAFLD: no need for a crystal ball?

A key challenge in the management of non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases globally, is to identify people at highest risk of progression to advanced liver disease. 1 Younossi ZM Non-alcoholic fatty liver disease—a global public health perspective. J Hepatol. 2019; 70: 531-544 Summary Full Text Full Text PDF PubMed Scopus (1051) Google Scholar Early detection is crucial so that individuals who are at risk can be offered interventions and appropriate care before they develop liver-related complications. The most important predictor of progression to advanced liver disease and mortality in individuals with NAFLD is the extent of liver fibrosis. 2 Dulai PS Singh S Patel J et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017; 65: 1557-1565 Crossref PubMed Scopus (1050) Google Scholar Historically, liver biopsy was the only reliable method to assess liver fibrosis. However, it has a number of limitations (eg, cost, invasiveness, sampling bias, and intra-observer and inter-observer variability) and is not a suitable test for screening or monitoring liver disease progression. In clinical practice, non-invasive tests are increasingly used to provide prognostic information about liver disease severity. 3 Sanyal AJ Castéra L Wai-Sun Wong V Non-invasive assessment of liver fibrosis in NAFLD. Clin Gastroenterol Hepatol. 2023; (published online April 14.)https://doi.org/10.1016/j.cgh.2023.03.042 Summary Full Text Full Text PDF Google Scholar The individual participant data meta-analysis reported by Ferenc E Mózes and colleagues in The Lancet Gastroenterology & Hepatology4 Mózes FE Lee JA Vali Y et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2023; (published online June 5.)https://doi.org/10.1016/S2468-1253(23)00141-3 Google Scholar shows that non-invasive tests can also provide prognostic information about key clinical outcomes. 4 Mózes FE Lee JA Vali Y et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2023; (published online June 5.)https://doi.org/10.1016/S2468-1253(23)00141-3 Google Scholar Their analysis compared the performance of three non-invasive tests and liver biopsy in predicting a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, and cirrhosis complications in patients with NAFLD. Non-invasive tests were as good as liver biopsy as predictors of clinical outcomes after adjusting for potential confounders. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysisSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases. Full-Text PDF Open Access

Noninvasive assessment of significant liver fibrosis in rabbits by spectral CT parameters and texture analysis.

Noninvasive assessment of significant liver fibrosis in rabbits by spectral CT parameters and texture analysis. Thirty-three rabbits were randomly divided into 27 carbon tetrachloride-induced liver fibrosis group and 6 control group. Spectral CT contrast-enhanced scan was performed in batches, and the liver fibrosis was staged according to the histopathological results. The portal venous phase spectral CT parameters [70keV CT value, normalized iodine concentration (NIC), spectral HU curve slope (λHU)] were measured, and MaZda texture analysis was performed on 70keV monochrome images. Three dimensionality reduction methods and four statistical methods in B11 module were used to perform discriminant analysis and calculate misclassified rate (MCR), and ten texture features under the lowest combination of MCR were statistically analyzed. Receiver operating characteristic curve (ROC) was used to calculate the diagnostic performance of spectral parameters and texture features for significant liver fibrosis. Finally, the binary logistic regression was used to further screen independent predictors and establish model. A total of 23 experimental rabbits and 6 control rabbits were included, of which 16 had significant liver fibrosis. Three spectral CT parameters with significant liver fibrosis were significantly lower than those of non-significant liver fibrosis (p < 0.05), and the AUC ranged from 0.846 to 0.913. The combination analysis of mutual information (MI) and nonlinear discriminant analysis (NDA) had the lowest MCR, which with 0%. In the filtered texture features, four were statistically significant and AUC > 0.5, ranges from 0.764 to 0.875. The logistic regression model showed that Perc.90% and NIC could be used as independent predictors, the overall prediction accuracy of the model was 89.7% and the AUC was 0.976. Spectral CT parameters and texture features have high diagnostic value for predicting significant liver fibrosis in rabbits, and the combination of the two can improve its diagnostic efficiency.

Diagnostic Accuracy of Vibration Controlled Transient Elastography as Non-invasive Assessment of Liver Fibrosis in Patients with Non-alcoholic Fatty Liver Disease.

Background: Liver biopsy remain as the gold standard for diagnosing hepatic fibrosis; however, it has some limitations, such as life-threatening complications, low acceptance by the patients, and variations in the related sample. Therefore, there is a need for the development of non-invasive investigations for diagnosing hepatic fibrosis. Vibration-controlled transient elastography (VCTE) is one of these non-invasive methods. Methods: This study included 73 patients suffering from non-alcoholic fatty liver disease (NAFLD) who were older than 18 years. The patients underwent VCTE at the Baqiatallah and Firoozgar hospitals. Then, they underwent a liver biopsy by an experienced radiologist in the same hospital. A receiver operating characteristic (ROC) curve of different fibrosis stages was used to evaluate the VCTE verification. Results: VCTE could detect any fibrosis levels (stage 1 and higher) with an area under the ROC curve (AUROC) of 0.381. Moreover, it detected stage 2-4 fibrosis with an AUROC of 0.400, stage 3-4 fibrosis with an AUROC of 0.687, and stage 4 fibrosis with an AUROC of 0.984. Conclusion: The VCTE has high clinical validity in diagnosing the advanced stages of fibrosis (stages 3, 4) and can be a suitable alternative to the invasive method of liver biopsy with high reliability.

Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality

Liver fibrosis is critical for liver-related outcomes and mortality in chronic liver disease, irrespective of etiology, including nonalcoholic fatty liver disease (NAFLD). NAFLD has been viewed as an independent correlate of cardiovascular risk. This review article briefly describes the cellular and molecular pathomechanisms underlying hepatic fibrosis. We then address noninvasive assessment of liver fibrosis. Finally, we discuss published evidence supporting fibrosis biomarkers’ role in assessing cardiovascular risk among patients with NAFLD. While histological assessment is the diagnostic standard of hepatic fibrosis, we specifically address noninvasive techniques, including equations based on anthropometric parameters, laboratory indices, and elastometry obtained with imaging techniques. The former group includes AST: ALT ratio, the Forns Index, the AST-to-platelet ratio index score, BARD (BMI, AAR, Diabetes) score, the fibrosis-4 index (FIB-4), the NAFLD fibrosis score, the gamma-glutamyl transferase-to-platelet ratio, and the Hepamet fibrosis score. The latter comprises elastographic techniques associated with ultrasonography or magnetic resonance. Our literature review identified numerous studies demonstrating that biomarkers of fibrosis (the most common being FIB-4) and elastographic techniques predict overall mortality and major cardiovascular events among NAFLD patients. The mechanisms accounting for this association are briefly reviewed. In addition to assessing hepatic fibrosis at baseline, during follow-up, and after therapeutic interventions in NAFLD patients, noninvasive assessment of hepatic fibrosis may predict cardiovascular events and overall mortality in these patients.