Early Detection Of Liver Fibrosis Research Articles

Early detection of liver fibrosis in patients with Fontan circulation using multiparametric magnetic resonance imaging

Abstract Introduction Fontan procedure (FP), serving as the palliative intervention for complex congenital heart diseases characterized by single-ventricle physiology, precipitates a spectrum of late-stage complications. Fontan-associated liver disease (FALD) encompassing liver fibrosis (LF) which may progress to liver cirrhosis (LC) and thereby hepatocellular carcinoma (HCC) is among the most serious. Despite its importance, optimal surveillance of FALD remains undefined. Multiparametric Liver Multiscan (LMS) with corrected T1 (cT1) value emerges as a novel magnetic resonance (MRI) based non-invasive quantitative tool for liver inflammation and fibrosis evaluation. Aim of this study was to ascertain prevalence and severity of LF utilizing LMS, alongside identifying contributory risk factors for LF in adults post-FP. Material and methods Our cohort included 29 adult patients after FP who underwent LMS. Median age was 25y (20-43y) 54% were females. Liver morphology was assessed by ultrasound (USG) and MRI-based LMS protocol. Hepatic scoring systems, including the Aspartate Aminotransferase to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) Index, and Model for End-Stage Liver Disease (MELD), were computed. Additionally, presence of fenestrations in the Fontan circulation, hemoglobin levels (Hb), and blood oxygen saturation both at rest and during exercise (SatO2%) were evaluated. Results Median cT1 was 914 (±207) ms, in 87% exceeding normal threshold . In those with elevated cT1, LF was undetected by USG in 38%. LC was identified in 27% of the cohort by USG. LC group exhibited significantly higher cT1 values (P<0.001) compared to non-LC group. cT1 value >933ms was associated with a sensitivity of 89% and a specificity of 80% for diagnosing LC (AUC 0.92). Significant correlation was found between cT1 values and Hb (P=0.01) and desaturation (SatO2 <90%/ interventional closure of fenestration, P=0.004). Conventional liver tests and hepatic scoring systems (APRI/FIB-4/MELD) did not predict cT1 nor LC. Conclusion Our study confirmed that LF is almost widely prevalentamong adult patients with single-chamber circulation. Risk factors for LF are systemic desaturation (SatO2 <90% or interventional closure of fenestration) and polyglobulia. However, reliable FALD surveillance remains challenging. Conventional liver assessments and scoring algorithms fall short in delineating the full scope of LF or LC. Consequently, the integration of non-invasive LMS into routine follow-up regimens is advocated, given its pronounced sensitivity for detecting subclinical FALD manifestations and predicting LC. The LMS-derived cT1 value >933ms is a critical predictor for LC, underscoring its importance in guiding further patient monitoring, treatment, and facilitating early HCC detection.

Ultrasonic Assessment of Liver Fibrosis Using One-Dimensional Convolutional Neural Networks Based on Frequency Spectra of Radiofrequency Signals with Deep Learning Segmentation of Liver Regions in B-Mode Images: A Feasibility Study.

The early detection of liver fibrosis is of significant importance. Deep learning analysis of ultrasound backscattered radiofrequency (RF) signals is emerging for tissue characterization as the RF signals carry abundant information related to tissue microstructures. However, the existing methods only used the time-domain information of the RF signals for liver fibrosis assessment, and the liver region of interest (ROI) is outlined manually. In this study, we proposed an approach for liver fibrosis assessment using deep learning models on ultrasound RF signals. The proposed method consisted of two-dimensional (2D) convolutional neural networks (CNNs) for automatic liver ROI segmentation from reconstructed B-mode ultrasound images and one-dimensional (1D) CNNs for liver fibrosis stage classification based on the frequency spectra (amplitude, phase, and power) of the segmented ROI signals. The Fourier transform was used to obtain the three kinds of frequency spectra. Two classical 2D CNNs were employed for liver ROI segmentation: U-Net and Attention U-Net. ROI spectrum signals were normalized and augmented using a sliding window technique. Ultrasound RF signals collected (with a 3-MHz transducer) from 613 participants (Group A) were included for liver ROI segmentation and those from 237 participants (Group B) for liver fibrosis stage classification, with a liver biopsy as the reference standard (Fibrosis stage: F0 = 27, F1 = 49, F2 = 51, F3 = 49, F4 = 61). In the test set of Group A, U-Net and Attention U-Net yielded Dice similarity coefficients of 95.05% and 94.68%, respectively. In the test set of Group B, the 1D CNN performed the best when using ROI phase spectrum signals to evaluate liver fibrosis stages ≥F1 (area under the receive operating characteristic curve, AUC: 0.957; accuracy: 89.19%; sensitivity: 85.17%; specificity: 93.75%), ≥F2 (AUC: 0.808; accuracy: 83.34%; sensitivity: 87.50%; specificity: 78.57%), and ≥F4 (AUC: 0.876; accuracy: 85.71%; sensitivity: 77.78%; specificity: 94.12%), and when using the power spectrum signals to evaluate ≥F3 (AUC: 0.729; accuracy: 77.14%; sensitivity: 77.27%; specificity: 76.92%). The experimental results demonstrated the feasibility of both the 2D and 1D CNNs in liver parenchyma detection and liver fibrosis characterization. The proposed methods have provided a new strategy for liver fibrosis assessment based on ultrasound RF signals, especially for early fibrosis detection. The findings of this study shed light on deep learning analysis of ultrasound RF signals in the frequency domain with automatic ROI segmentation.

Screening for liver fibrosis: lessons from colorectal and lung cancer screening.

Many countries have incorporated population screening programmes for cancer, such as colorectal and lung cancer, into their health-care systems. Cirrhosis is more prevalent than colorectal cancer and has a comparable age-standardized mortality rate to lung cancer. Despite this fact, there are no screening programmes in place for early detection of liver fibrosis, the precursor of cirrhosis. In this Perspective, we use insights from colorectal and lung cancer screening to explore the benefits, challenges, implementation strategies and pathways for future liver fibrosis screening initiatives. Several non-invasive methods and referral pathways for early identification of liver fibrosis exist, but in addition to accurate detection, screening programmes must also be cost-effective and demonstrate benefit through a reduction in liver-related mortality. Randomized controlled trials are needed to confirm this. Future randomized screening trials should evaluate not only the screening tests, but also interventions used to halt disease progression in individuals identified through screening.

Suboptimal reliability of FIB-4 and NAFLD-fibrosis scores for staging of liver fibrosis in general population.

The burden and incidence of liver cirrhosis are increasing worldwide. Early detection of liver fibrosis would help in early interventions and preventing the progression of fibrosis and cirrhosis. The accepted noninvasive markers for liver fibrosis staging, namely fibrosis-4 (FIB-4) and nonalcoholic fatty liver disease fibrosis score (NFS), have shown inconsistent performance for detecting the fibrosis stage. We aimed to evaluate the efficacy of FIB-4 score and NFS for the detection of liver fibrosis in the general population. From a general population referred from a single, community-based family-physician clinic, we included study participants between the ages of 45 and 65 years, with no knowledge of liver disease and no record of alcohol consumption. Liver fibrosis was evaluated by the FIB-4 score and NFS using shear wave elastography (SWE) or transient elastography (TE) measurements as a reference. A total of 76 participants (aged 61.5 ± 0.37 years, 33% females) were included in the study cohort. We observed a nonsignificant correlation between liver stiffness measurement (LSM) and FIB-4 and NFS (r = 0.1, P = 0.37; r = 0.16, P = 0.15, respectively). Our results showed that only 5.2% with FIB-4 >3.25 and 9.7% with NFS >0.675 had LSM >12 kPa. The compatibility of fibrosis staging was 55% between FIB-4 score and LSM and only 18% between NFS and LSM. We found that FIB-4 and NFS are unreliable tools for liver fibrosis estimation in the general population. There is a need for more reliable noninvasive methods for the early detection of liver fibrosis.

Noninvasive assessment of hepatic decompensation.

Noninvasive tests (NITs) are used in all aspects of liver disease management. Their most prominent break-through since the millennium has been in advancing early detection of liver fibrosis, but their use is not limited to this. In contrast to the symptom-driven assessment of decompensation in patients with cirrhosis, NITs provide not only opportunities for earlier diagnoses but also accurate prognostication, targeted treatment decisions, and a means of monitoring disease. NITs can inform disease management and decision-making based on validated cutoffs and standardized interpretations as a valuable supplement to clinical acumen. The Baveno VI and VII consensus meetings resulted in tangible improvements to pathways of care for patients with compensated and decompensated advanced chronic liver disease, including the combination of platelet count and transient elastography to diagnose clinically significant portal hypertension. Furthermore, circulating NITs will play increasingly important roles in assessing the response to interventions against ascites, variceal bleeding, HE, acute kidney injury, and infections. However, due to NITs' wide availability, there is a risk of inaccurate use, leading to a waste of resources and flawed decisions. In this review, we describe the uses and pitfalls of NITs for hepatic decompensation, from risk stratification in primary care to treatment decisions in outpatient clinics, as well as for the in-hospital management of patients with acute-on-chronic liver failure. We summarize which NITs to use when, for what indications, and how to maximize the potential of NITs for improved patient management.

Serum α-SMA is a potential noninvasive biomarker of liver fibrosis

The severity of fibrosis is central to the therapeutic course for patients with chronic liver disease; therefore, early detection of liver fibrosis is critical for timely therapeutic interventions. Liver biopsy is the gold standard for the diagnosis of liver fibrosis; however, it is contraindicated in several pathological conditions. Activated hepatic stellate cells (HSCs) are the main cells for fibrotic tissue synthesis, such as that of alpha-smooth muscle actin (α-SMA). This study aimed to determine whether serum α-SMA levels are a suitable noninvasive, sensitive, and reliable liver fibrosis marker. Fibrosis was induced in male Wistar rats via chronic CCl4 administration. Fibrosis was determined in the liver tissues by quantifying the hydroxyproline content and visualized using Masson’s trichrome staining. Rats chronically administered CCl4 exhibited a progressive increment in the hepatic collagen content, as well as both hepatic and serum α-SMA levels in a time-dependent manner. Moreover, serum levels of α-SMA significantly correlated with hepatic α-SMA levels (p ≤ 0.001), as well as with the severity of liver fibrosis (p ≤ 0.001). These findings suggest that increased levels of serum α-SMA can be considered a potential reliable and noninvasive biomarker for early liver fibrosis.

1582-P: Association of Low eGFR with Novel Liver Fibrosis Biomarker Mac-2 Binding Protein Glycosylation Isomer in Type 2 Diabetes Patients

Objective: Advanced liver fibrosis, which leads to liver cirrhosis and cancer, has been one of the major causes of death in type 2 diabetes (T2D). Efficient screening system is needed to detect liver fibrosis early and prevent its progression. A novel serum fibrosis biomarker Mac-2 binding protein glycan isomer (M2BPGi) has high sensitivity plus specificity, and can be used in combination with FIB-4 screening index (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]/platelet ratio). This study aimed to investigate the predictive factors for the early detection of liver fibrosis using a combination of these two approaches. Methods: This cross-sectional study consisted of T2D patients, with negative results for hepatitis viruses and no history of heavy drinking. FIB-4 high patients were divided into two groups based on M2BPGi (high, M2BPGi > 1.00; normal level, M2BPGi < 1.00. The levels of clinical biomarkers were measured among two groups and predictive factors were calculated for M2BPGi high patients. Results: From July to December 2021, a total of 311 FIB-4 high T2D patients (male/female, 202/109; age, 71.1 + 9.8; Body Mass Index, 24.5 + 3.9; HbA1c 7.4 + 3.3 %) were enrolled in this study. The M2BPGi high group (44,3%, n=138) showed a significantly longer duration of diabetes, high alkaline phosphatase (ALP), AST, ALT, and low eGFR than M2BPGi normal group (55.7%, n=173). In multiple logistic regression analysis, eGFR < 60 mL/min/1.73m2 was independently identified as a predictive factor for M2BPGi high (Odds Ratio [OR] 2.61, 95% C.I. 1.55-4.39 P < 0.01) as well as AST > 30 IU/ml (OR, 3.37) and ALP > 113 IU/ml (OR, 1.88). Conclusions: low eGFR is associated with liver fibrosis in type 2 diabetes patients, and requires more careful attention to liver related disease. Disclosure E.Suzuki: None. Y.Shinya: None. B.Kanari: None. M.Kambara: None. H.Takahashi: None.

Relationship between disease severity and myeloperoxidase in chronic viral hepatitis: a prospective study.

Aim: To measure serum myeloperoxidase (MPO) levels and to evaluate the relationship between this parameter and histological findings in chronic hepatitis B and C patients. Materials & methods: Three groups were formed: chronic hepatitis B, chronic hepatitis C and a control group. Serum MPO levels were determined by ELISA. Results: MPO level was found to be higher in both patient groups compared with the control group (p<0.05). It was also higher in chronic hepatitis B and C patients with significant fibrosis compared with patients with mild fibrosis (p<0.05). Conclusion: Our results show that increased MPO level can be used as an important noninvasive marker in both the early detection of liver fibrosis and the prediction of significant fibrosis.

Progressive changes in platelet counts and Fib-4 scores precede the diagnosis of advanced fibrosis in NASH patients.

Cirrhosis and its complications develop in a subgroup of patients with non-alcoholic fatty liver disease (NASH). Early detection of liver fibrosis represents an important goal of clinical care. To test the hypothesis that the development of cirrhosis in nonalcoholic fatty liver disease patients is preceded by the long-term trends of platelet counts and Fib-4 scores. We identified all patients in our healthcare system who had undergone fibrosis staging by liver biopsy or magnetic resonance elastography (MRE) for non-alcoholic fatty liver disease during the past decade (n = 310). Platelet counts, serum glutamic-pyruvic transaminase and serum glutamic oxalacetic transaminase values preceding the staging tests were extracted from the electronic medical record system, and Fib-4 scores were calculated. Potential predictors of advanced fibrosis were evaluated using multivariate regression analysis. Significant decreases in platelet counts and increases in Fib-4 scores were observed in all fibrosis stages, particularly in patients with cirrhosis. In the liver biopsy group, the presence of cirrhosis was best predicted by the combination of the Fib-4 score at the time closest to staging (P < 0.0001), the presence of diabetes (P = 0.0001), and the correlation coefficient of the preceding time-dependent drop in platelet count (P = 0.044). In the MRE group, Fib4 score (P = 0.0025) and platelet drop (P = 0.0373) were significant predictors. In comparison, the time-dependent rise of the Fib-4 score did not contribute in a statistically significant way. Time-dependent changes in platelet counts and Fib-4 scores contribute to the prediction of cirrhosis in NASH patients with biopsy- or MRE-staged fibrosis. Their incorporation into predictive algorithms may assist in the earlier identification of high-risk patients.

Machine learning improves early detection of liver fibrosis by quantitative ultrasound radiomics.

Progression of liver fibrosis to cirrhosis, a severe non-reversible process, is one of the most critical risk factors in developing hepatocellular carcinoma and liver failure. Detection of liver fibrosis at an early stage is therefore essential for better patient management. Ultrasound (US) imaging can provide a noninvasive alternative to biopsies. This study evaluates quantitative US texture features to improve early-stage versus advanced liver fibrosis detection. 157 B-mode US images of different liver lobes acquired from early and advanced fibrosis rat cases were used for analysis. 5-6 regions of interest were placed on each image. Twelve quantitative features that describe liver texture changes were extracted from the images, including first-order histogram, run length (RL), and gray level co-occurrence matrix (GLCM). The diagnostic performance of individual features was high with AUC ranging from 0.80 to 0.94. Logistic regression with leave-one-out cross-validation was used to evaluate the performance of the combined features. All features combined showed a slight improvement in performance with AUC = 0.95, sensitivity = 96.8%, and specificity = 93.7%. Quantitative US texture features characterize liver fibrosis changes with high accuracy and can differentiate early from advanced disease. Quantitative ultrasound, if validated in future clinical studies, can have a potential role in identifying fibrosis changes that are not easily detected by visual US image assessments.

Early detection of liver fibrosis with serum Mac-2 binding protein glycosylation-modified isomer (M2BPGi) during follow-up intestinal failure patients without intestinal failure-associated liver disease (IFALD).

Mac-2 binding protein glycosylation-modified isomer (M2BPGi) is a new marker for hepatic fibrosis progression. We examined the relationship between serum M2BPGi levels and liver histological findings in intestinal failure (IF) patients without IF-associated liver disease (IFALD). This study included IF patients without IFALD followed at our hospital. All patients underwent routine liver biopsies per protocol every 1-2years. We examined M2BPGi levels and histological findings in relation to aspartate aminotransferase (AST) to platelet ratio index, fibrosis-4 index, and AST/ALT ratio. Liver fibrosis was evaluated based on the METAVIR score. Total 18 liver biopsies out of eight patients were included. The median age was 11.5years. Mean M2BPGi was 0.44 cutoff index (COI) in patients with F0 fibrosis, 0.78 COI in patients with F1 fibrosis and 1.63 COI in patients with F2 fibrosis. Mean M2BPGi was significantly higher in patients with F2 versus F1 or F0 fibrosis (P < 0.016 and P < 0.028, respectively). M2BPGi levels were more strongly correlated with fibrosis stage than with other conventional fibrosis markers. Serum M2BPGi is a novel marker of liver fibrosis in patients with IF. It is useful for follow-up prior to IFALD. Serum M2BPGi levels can support the interpretation of liver status.

OS018 - ADAPT, a score incorporating PRO-C3, for the early detection of liver fibrosis in a large population-based study

OS018 - ADAPT, a score incorporating PRO-C3, for the early detection of liver fibrosis in a large population-based study

Growth Differentiation Factor 15: An Emerging Diagnostic Biomarker of Liver Fibrosis in Chronic Hepatitis C Patients

Abstract Background Chronic liver disease and cirrhosis are a major health concern worldwide being the sixth leading cause of all-cause mortality in people aged 25–64 years. Assessment of liver fibrosis is necessary to determine disease severity and prognosis at the time of presentation to determine suitable treatment. The gold standard method of diagnosis is liver biopsy; however, this procedure is invasive; thus, multiple laboratory and radiologic tests are used to help determine the degree of fibrosis. Growth differentiation factor 15 (GDF-15) is a pleiotropic cytokine involved in regulating inflammatory and apoptotic pathways. It plays a role in cardiovascular disease, inflammation, body weight regulation and cancer. It is suggested that GDF-15 plays an important role in pathogenesis of liver fibrosis. Aim of the Work In this study we aimed to evaluate efficiency of growth differentiation factor 15 in diagnosing liver fibrosis. Patients and Methods The study was a case- control study conducted on 55 chronic HCV patients recruited from Hepatitis C virus Clinic at Faculty of Medicine Ain Shams Research Institute (MARSI), and 30 healthy subjects age and sex matched. The patients were classified into three subgroups according to the degree of liver fibrosis assessed by fibro-scan. Serum concentration of GDF-15 was determined by enzyme-linked immunosorbent assay (ELISA). Results Results of our study revealed a highly significant statistical rise in GDF-15 levels among studied chronic HCV patients with liver fibrosis when compared to the control group (p &amp;lt; 0.01). Furthermore, there was a significant positive correlation between the degree of fibrosis assessed by fibro-scan and GDF-15 serum levels. Levels of GDF-15 were significantly higher in patients with mild degree of fibrosis (patients’ subgroup І when compared with the controls’ group (p &amp;lt; 0.01) suggesting the role of this marker in early detection of liver fibrosis. A statistically significant increase in serum GDF-15 levels was noticed among patients with advanced fibrosis “subgroup ІІІ” compared to those with mild fibrosis “subgroup І” (p &amp;lt; 0.05). The diagnostic sensitivity and specificity of GDF-15 were 96.7%, 98.2%, respectively at a cutoff value of 150 ng/L for discrimination between patients’ and controls’ groups. Conclusion Growth differentiation factor 15 could be a potential marker of liver fibrosis especially in early detection as its levels were significantly higher in patients’ group with liver fibrosis than controls’ group and there was a significant positive correlation between the degree of liver fibrosis and GDF-15 serum levels.

Correlation between APRI, FIB-4 and GPR Indices to Fibroscan and HBeAg Status in Patients with Chronic Hepatitis B

Liver fibrosis is a complication of chronic hepatitis B. Early detection of liver fibrosis is important for therapy. The aspartate aminotransferase index (AST)-to-platelet ratio index (APRI) and the fibrosis index based on 4 factors (FIB-4) in chronic hepatitis B have been widely studied despite the inconsistent results. Research on other serum markers is extensively carried out, including Gamma-Glutamyl Transpeptidase (GGT)-to-platelet ratio (GPR). Previous studies have shown that the GPR index was more accurate than APRI and FIB-4. HBeAg status is an indication for therapy. There have not been many studies on the correlation of serum markers with HBeAg status. This study aimed to determine the correlation of APRI, FIB-4, and GPR with Fibroscan and HBeAg status in chronic hepatitis B patients. A cross-sectional study was carried out from June to September 2020 and found 50 chronic hepatitis B patients. Platelet count was measured using a Sysmex XN-1000 hematology device; AST, alanine aminotransferase (ALT), and GGT levels were measured using the Dimension RXL clinical chemistry device; and the degree of fibrosis was determined using transient elastography (Fibroscan). Spearman correlation test was used in this study for the correlation analysis. The results showed a significant correlation between APRI, FIB-4 and GPR indices with Fibroscan (r=0.454, p 0.001; r=0.610, p &lt; 0.001; r=0.540, p &lt; 0.001, respectively). A significant correlation was found between APRI, FIB-4 and GPR indices with negative (-) HBeAg (r=0.486, p 0.004; r=0.648, p &lt; 0.001; r=0.595, p &lt; 0.001, respectively). In addition, a significant correlation was found between FIB-4 and positive (+) HBeAg (r=0.499, p 0.049), but no correlation was found between APRI and GPR with positive (+) HBeAg (r=0.295, p 0,267; r=0.386, p 0.140, respectively).

Systematic Review with Meta-Analyses: Diagnostic Accuracy of FibroMeter Tests in Patients with Non-Alcoholic Fatty Liver Disease

Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F ≥ 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58–0.94); specificity: 91.1% (95%CI 0.89–0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73–0.90); specificity: 84.4% (95%CI 0.62–0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63–0.79); specificity: 82.8% (95%CI 0.71–0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains.

Growth differentiation factor 15: an emerging diagnostic biomarker of liver fibrosis in chronic hepatitis C patients

BackgroundChronic liver disease and cirrhosis are of the major health concern worldwide. Assessment of liver fibrosis is necessary to determine disease severity and prognosis at the time of presentation to determine suitable treatment. Liver biopsy is considered as standard golden method in diagnosis of liver fibrosis. However, this procedure is invasive; thus, multiple laboratory and radiologic tests are used to help determination of the degree of fibrosis. Growth differentiation factor 15 (GDF-15) is a pleiotropic cytokine involved in regulating inflammatory and apoptotic pathways. It is suggested that GDF-15 plays an important role in pathogenesis of liver fibrosis. In this study, we aimed to evaluate efficiency of growth differentiation factor 15 in diagnosing liver fibrosis. The study was a case-control study conducted on 55 chronic HCV patients recruited from hepatitis C virus clinic at Faculty of Medicine Ain Shams Research Institute (MASRI), and 30 healthy subjects age- and sex-matched. The patients were classified into three subgroups according to the degree of liver fibrosis assessed by fibro-scan. Serum concentration of GDF-15 was determined by enzyme-linked immunosorbent assay.ResultsOur results revealed a highly significant statistical rise in GDF-15 levels among studied chronic HCV patients with liver fibrosis when compared to the control group (p < 0.01). Furthermore, there was a significant positive correlation between the degree of fibrosis assessed by fibro-scan and GDF-15 serum levels. Levels of GDF-15 were significantly higher in patients with mild degree of fibrosis (patients’ subgroup І) when compared with the controls’ group (p < 0.01) suggesting the role of this marker in early detection of liver fibrosis. A statistically significant increase in serum GDF-15 levels was noticed among patients with advanced fibrosis “subgroup ІІІ” compared to those with mild fibrosis “subgroup І” (p < 0.05). The diagnostic sensitivity and specificity of GDF-15 were 96.7%, 98.2%, respectively at a cut-off value of 150 ng/L for discrimination between patients’ and controls’ groups.ConclusionGrowth differentiation factor 15 could be a potential marker of liver fibrosis especially in early detection as its levels were significantly higher in patients’ group with liver fibrosis than controls’ group and there was a significant positive correlation between the degree of liver fibrosis and GDF-15 serum levels.

Serum N-glycan fingerprint nomogram predicts liver fibrosis: a multicenter study.

Liver cirrhosis (LC) is the end-stage of fibrosis in chronic liver diseases, non-invasive early detection of liver fibrosis (LF) is particularly essential for therapeutic decision. Aberrant glycosylation of glycoproteins has been demonstrated to be closely related to liver abnormalities. This study was designed to enroll a total of 1,565 participants with LC/LF, chronic hepatitis virus (CHB) and healthy controls. Fibrosis was confirmed by liver biopsy. Using capillary electrophoresis N-glycan fingerprint (NGFP) analysis, we developed a nomogram algorithm (FIB-G) to discriminate LC from non-cirrhotic subjects. The FIB-G demonstrated good diagnostic performances in identifying LC with the area under the curve (AUC) 0.895 (95%CI: 0.857-0.915). Furthermore, the diagnostic efficiencies of FIB-G were superior to that of log (P2/P8), procollagen III N-terminal (PIIINP), type IV collage (IV-C), laminin (LN), hyaluronic acid (HA), aspartate transaminase to platelets ratio index (APRI), and FIB-4 when detecting significant fibrosis (S0-1 vs. S2-4, AUC: 0.787, 95%CI: 0.701-0.873), severe fibrosis (S0-2 vs. S3-4, AUC: 0.844, 95%CI: 0.763-0.924), and LC (S0-3 vs. S4, AUC: 0.773, 95%CI: 0.667-0.880). Besides, changes of FIB-G were associated well with the regression of fibrosis and liver function Child-Pugh classification. FIB-G is an accurate multivariant N-glycomic algorithm for LC prediction and fibrosis progression/regression monitoring. The high throughput feasible NGFP using only 2μL of serum could help physicians make the more precise non-invasive staging of LF or cirrhosis and reduce the need for invasive liver biopsy.

Tagging incidental finding of fatty liver on ultrasound: A novel intervention to improve early detection of liver fibrosis

It is not uncommon to see that a large proportion of patients with cirrhosis due to nonalcoholic steatohepatitis never had any prior evaluation or diagnosis of liver disease, and most of the times their first clinical presentation is decompensated cirrhosis. Acknowledging incidental finding of fatty liver on abdominal imaging and identifying patients at risk of having advanced liver fibrosis may help in preventing its progression to cirrhosis. We aimed to increase acknowledgement and improve evaluation of steatosis through radiology recommendation to consider hepatology referral, and to identify the predictors of hepatology referral and significant fibrosis. We performed a retrospective study of 812 patients with hepatic steatosis tagged on ultrasound (US), over 18 months, at a single center. Patients with secondary causes of fatty liver were excluded from the study. We evaluated the yield of this intervention and factors correlated with hepatology referral and presence of significant fibrosis. Diagnosis of fatty liver was acknowledged for 69% of patients with tagged US, although only 29% were ultimately seen by hepatology. Patients who had US ordered by a primary care provider (PCP) were more likely to have hepatology evaluation (64.8% vs. 56.9%, P = 0.0183). Sixty-six percent of patients seen by hepatology had elevated alanine transaminase (ALT) compared to 52% not seen by hepatology (P < 0.0005). Among patients further evaluated, 53% underwent staging, and 18% had ≥stage 2 (F2) fibrosis. Type II diabetes correlated with significant to advanced fibrosis (43.5% vs. 21.4%, P = 0.0357), while ALT and Body Mass Index did not. Tagging US reports led to clinical acknowledgement of fatty liver in 7 of 10 patients, although fewer than 1 in 3 had further hepatology evaluation. Of those who underwent staging for incidentally noted steatosis, 18% had significant fibrosis, suggesting that we are failing to evaluate patients with potentially advanced liver disease. Identifying incidental finding of fatty liver on US provides a unique opportunity in diagnosing liver fibrosis at an early stage and can help prevent its progression to cirrhosis. PCP should consider using noninvasive scoring systems on a regular basis to assess the risk of fibrosis in patients with fatty liver, and timely referral to hepatology should be provided in patients at high risk of having advanced fibrosis.

Ultrasound Detection of Liver Fibrosis in Individuals with Hepatic Steatosis Using the Homodyned K Distribution

Acoustic structure quantification (ASQ) based on the analysis of ultrasound backscattered statistics has been reported to detect liver fibrosis without significant hepatic steatosis. This study proposed using ultrasound parametric imaging based on the parameter α of the homodyned K (HK) distribution for staging liver fibrosis in patients with significant hepatic steatosis. Raw ultrasound image data were acquired from patients (n = 237) to construct B-mode and HK α parametric images, which were compared with the focal disturbance (FD) ratio obtained from ASQ on the basis of histologic evidence (METAVIR fibrosis score and hepatic steatosis severity). The data were divided into group I (n = 173; normal to mild hepatic steatosis) and group II (n = 64; with moderate to severe hepatic steatosis) for statistical analysis through one-way analysis of variance and receiver operating characteristic (ROC) curve analysis. The results showed that the HK α parameter monotonically decreased as the liver fibrosis stage increased (p < .05); concurrently, the FD ratio increased (p < .05). For group I, the areas under the ROC (AUROCs) obtained using the FD ratio and the α parameter (AUROCFD and AUROCα) were, respectively, 0.56 and 0.55, 0.68 and 0.68, 0.64 and 0.64 and 0.62 and 0.62 for diagnosing liver fibrosis ≥F1, ≥F2, ≥F3 and ≥F4. The values of AUROCFD and AUROCα for group II were, respectively, 0.88 and 0.91, 0.81 and 0.81, 0.77 and 0.76 and 0.78 and 0.73 for diagnosing liver fibrosis ≥F1, ≥F2, ≥F3 and ≥F4. As opposed to previous studies, ASQ was found to fail in characterizing liver fibrosis in group I; however, it was workable for identifying liver fibrosis in patients with significant hepatic steatosis (group II). Compared with ASQ, HK imaging provided improved diagnostic performance in the early detection of liver fibrosis coexisting with moderate to severe hepatic steatosis. Ultrasound HK imaging is recommended as a strategy to evaluate early fibrosis risk in patients with significant hepatic steatosis.

Modern Principles of Liver Fibrosis Diagnosis in Patients With Chronic Diffuse Liver Lesions: Literature Review and Clinical Case Description

Introduction. Chronic diffuse liver lesions, which is at a certain stage and phase of the disease characterized by excessive accumulation of components of the extracellular matrix, namely fibrosis, – are a heterogeneous multi etiological group of diseases that are characterized by the high prevalence, subclinical course in the initial stages, low curability and reversibility of the pathological process in the late stages, and therefore cause considerable clinical, epidemiological and socio-economic problem of our time. The main way of progression of chronic diffuse liver lesions, regardless of the etiological factor that led to its damage – is the process of fibrogenesis. Quantitative indicators of the severity and rate of fibrosis progression are the most important clinical parameter, the determination of which is crucial for choosing the right treatment and for monitoring its effectiveness. Today, there is no universal method and only a combination of different laboratory and instrumental methods of examination can significantly increase their diagnostic value for early detection of liver fibrosis in the case of chronic diffuse liver diseases. However, the range of possibilities of certain diagnostic methods is constantly expanding and recently the elastographic method has become increasingly important. The aim of the study. To make the literature review concerning the modern principles of liver fibrosis diagnosis in patients with chronic diffuse liver lesions, to describe the clinical case. Materials and methods. The content analysis, method of the system and comparative analysis, the bibliosemantic method of study of the actual scientific studies concerning modern principles of diagnosis of patients with diffuse liver disease, a clinical case is described. Results. The literature review demonstrates the importance and relevance of early and comprehensive diagnosis of chronic diffuse liver disease. Hepatic fibrosis is the basis for portal hypertension, varicose veins, ascites and liver failure. Decompensated cirrhosis is associated with high mortality and the only effective treatment is liver transplantation. Assessment of the degree of liver fibrosis is important for several reasons: to determine the prognosis of chronic liver damage, to select patients for specific (etiotropic) treatment and possible liver transplantation. Therefore, the problem of diagnosis and detection of early initial stages of liver fibrosis for the timely appointment of therapeutic agents, which are aimed at reducing the rate of its progression and prevent cirrhosis and liver cancer, is extremely important for modern medicine. It is known that the “gold standard” for the diagnosis of liver fibrosis is a liver biopsy, but the method has many limitations and contraindications. Elastography is one of the most promising non-invasive methods to diagnose liver fibrosis and steatosis in the case of chronic diffuse liver lesions, which can be used as an alternative to biopsy. Given its widespread implementation in clinical practice, groups of scientists from around the world are paying more and more attention to the study of factors that may affect the results of elastometry and its diagnostic effectiveness. The advantages of the method of liver elastography include: non-invasive, no contraindications, simplicity, fast execution and interpretation; the ability to determine the stage of fibrosis in patients who can not perform a liver biopsy (coagulopathy, thrombocytopenia); the possibility of repeated procedures to assess the increase in severity. Conclusions. Thanks to modern scientific achievements, the latest technologies have been introduced into clinical practice, with the help of which clinicians successfully improve the diagnosis of chronic diffuse liver diseases, in particular, through the use of quantitative detection of fibrotic changes in it, establishing the nature of abdominal fluid (serous or mucinous), assessment of hepatic venous pressure due to safe non-invasive and informative method of shear wave elastography of the liver, a method that not only allows to objectify the verification of the diagnosis, but also to dynamically assess the efficiency of treatment.