Fibrosis In Chronic Liver Disease Research Articles

Uridine alleviates carbon tetrachloride-induced liver fibrosis by regulating the activity of liver-related cells.

At present, liver fibrosis is a major challenge of global health. When hepatocyte regeneration cannot compensate for hepatocyte death, it will develop into liver fibrosis in chronic liver disease. Initially, collagen produced by myofibroblasts plays a role in maintaining liver integrity, but excessive collagen accumulation can inhibit the residual liver function, leading to liver failure. At present, many scientists are actively looking for drugs to alleviate liver fibrosis. In the current study, we investigated the potential role of uridine in the treatment of liver fibrosis (uridine is a plant/animal‐derived pyrimidine nucleoside, therefore uridine can also be ingested and absorbed by the body, accompanied by the process of food intake). For this, we systematically studied the effect of uridine on CCl4‐induced liver fibrosis in vitro and in vivo through a series of technologies, such as Western blot, laser confocal scanning microscope, ELISA and immunohistochemistry. The experimental results showed that uridine can effectively reduce the accumulation of collagen in liver. Furthermore, uridine can improve the activity of liver cells and alleviate CCl4‐induced liver injury. Furthermore, uridine can significantly alleviate the risk factors caused by hepatic stellate cell activation, uridine treatment significantly down‐regulated the expression of α‐SMA, collagen type‐I and fibronectin. In conclusion, the current research shows that uridine can alleviate CCl4‐induced liver fibrosis, suggesting that uridine can be used as a potential drug to alleviate liver fibrosis.

Assessing the progression of segmental fibrosis in chronic liver disease using extracellular volume fractions

PurposeTo assess the segmental difference of liver fibrosis during the progression of chronic liver disease (CLD) using hepatic extracellular volume fractions (fECVs) obtained by dual-energy CT. MethodsA total of 218 patients (92 men and 126 women; mean age, 67.8 ± 11.7 years) with CLD and 85 patients (44 men and 41 women; mean age, 62.8 ± 13.7 years) without CLD as a control underwent dual-energy computed tomography (CT) of the liver (5-min equilibrium phase images). The iodine densities of the lateral, medial, anterior, and posterior segments and the aorta were measured, and fECVs were calculated. Comparisons of the fECV of each segment and for each albumin–bilirubin (ALBI) grade were then statistically analyzed. ResultsIn the control group and ALBI grades 1 and 3, no significant difference in fECV was found between each segment, whereas in ALBI grade 2, the fECVs were significantly larger in the medial and anterior than in the other segments (p < 0.001). The fECVs of the lateral and posterior segments significantly increased with higher ALBI grade (p < 0.001). The fECVs of the medial and anterior segments were significantly increased with higher ALBI grade, up to grade 2 (p < 0.001), but no significant difference was found between ALBI grades 2 and 3. ConclusionDuring the progression of CLD, fibrosis antecedently progressed in the medial and anterior segments, followed by the other liver segments.

Magnetic resonance elastography of the liver: everything you need to know to get started.

Magnetic resonance elastography (MRE) of the liver has emerged as the non-invasive standard for the evaluation of liver fibrosis in chronic liver diseases (CLDs). The utility of MRE in the evaluation of different CLD in both adults and children has been demonstrated in several studies, and MRE has been recommended by several clinical societies. Consequently, the clinical indications for evaluation of CLD with MRE have increased, and MRE is currently used as an add-on test during routine liver MRI studies or as a standalone test. To meet the increasing clinical demand, MRE is being installed in many academic and private practice imaging centers. There is a need for a comprehensive practical guide to help these practices to deliver high-quality liver MRE studies as well as troubleshoot the common issues with MRE to ensure smooth running of the service. This comprehensive clinical practice review summarizes the indications and provides an overview on why to use MRE, technical requirements, system set-up, patient preparation, acquiring the data, and interpretation.

Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease

Reliable and available non-invasive methods for hepatic fibrosis assessment are important in chronic liver disease (CLD). Our aim was to compare stepwise algorithms combining standard ultrasound with serum markers and transient elastography (TE) for detecting advanced fibrosis (F3-4) and cirrhosis. Retrospective single center study between 2012 and 2018 of CLD patients with biopsy, TE, blood tests, and liver ultrasound parameters of surface nodularity (SN), lobar redistribution, and hepatic vein nodularity. Our cohort included 157 patients (51.6% males), mean age 47.6 years, predominantly non-alcoholic fatty liver disease and viral hepatitis (61%), with F3-4 prevalence of 60.5%. Area under the curve for F3-4 was 0.89 for TE ≥ 9.6 kPa and 0.80 for FIB-4 > 3.25. In multivariate modeling, TE ≥ 9.6 kPa (OR 21.78) and SN (OR 3.81) had independent association with F3-4; SN (OR 5.89) and TE ≥ 10.2 kPa (OR 15.73) were independently associated with cirrhosis. Two stepwise approaches included FIB-4 followed by SN or TE; sensitivity and specificity of stepwise SN were 0.65 and 1.00, and 0.89 and 0.33 for TE ≥ 9.6 kPa, respectively. Ultrasound SN and TE were independently predictive of F3-4 and cirrhosis in our cohort. FIB-4 followed by SN had high specificity for F3-4.

O-6 NON-INVASIVE ASSESSMENT OS HEPATIC FIBROSIS BEFORE AND AFTER HCV CURE AND CORRELATION WITH CLINICAL OUTCOMES

Liver stiffness measurement (LSM) is a widely used non-invasive test to assess the stage of liver fibrosis in chronic liver diseases, particularly in HCV but its clinical usefulness after viral elimination is uncertain. To identify the course of liver fibrosis by LSM 3 years after viral elimination in patients with HCV and its association with clinically relevant outcomes: progression to advanced liver fibrosis/cirrhosis (≥F3) in those with F<3 at baseline, and decompensation (ascites, variceal hemorrhage, encephalopathy) or HCC in those with F3/F4 or F4 at baseline. LSM were performed by Fibroscan in 228 patients (32 stage F0-1; 47 F2; 36 F3; 23 F3-4; 90 F4 as determined by LS of <7.1; 7.2-9.5; 9.6-12.5; 12.6-14.5 and >14.5 KPa respectively) prior to treatment and at 6 months, 1, 2 and 3 years after cure. The course of changes in LSM are depicted in figure1. There was no progression to F≥3 in any of the patients at stages F0-1, F2. Among patients with F≥3, 23 patients developed decompensation (1 F3, 2 F3/F4 and 20 F4) and 9 developed HCC (all F4). Probability of decompensation is lower in patients in whom LSM decreases at 6 months, while it is higher in those in whom LSM increases, however CI are large (Table). While in patients with F0-1, F2 prior to antiviral therapy, there is no need to follow LSM as progression does not occur, LSM should be continued in those with F3/F4 or F4 (>12.5 kPa). Changes in LSM at 6 months can help determine probability of outcomes but larger studies combining other parameters are necessary to improve predictive value.

Comparison between shear wave elastography and serological findings for the evaluation of fibrosis in chronic liver disease.

Aim: In this study, we sought to examine the optimal cutoff values for predicting different stages of liver fibrosis, and to determine the level of agreement between shear wave elastography and aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4) scores in patients with chronic liver disease. Methodology: A descriptive, cross-sectional study was performed at the Radiology Department of Shaukat Khanum Memorial Hospital Lahore from 1 Jun 2019 until 1 June 2020. FIB-4 and APRI scores were determined by the following formula: FIB-4 = (age × AST) ÷ (platelet count × (√ (ALT)) and APRI = (AST÷AST upper limit of normal) ÷ platelet × 100. Data was analyzed with the help of SPSS version 24.0 and Microsoft Excel 2013. Results: Eighty individuals were conveniently selected, of which 62.5% were men and 37.5% were women. The mean age of the subjects was 43.47 SD ± 13.85 years. APRI and FIB-4 scores predicted F4 patients using the cutoff values of 0.47 (Sn. 72%, Sp. 70%) and 1.27 (Sn. 78%, Sp. 73%), respectively. The cutoff values of 0.46 for APRI and 1.27 for FIB-4 predicted F3–F4 patients (Sn. 74% and 77%; Sp. 76% and 76%), respectively. To predict F1–F4 compared to F0, the cutoff value was 0.34 (Sn. 68%, Sp. 75%) for APRI, while the cutoff value for FIB was 0.87 (Sn. 72%, Sp. 75%). The findings suggest that FIB-4 shows better diagnostic accuracy than APRI. Conclusion: This study provides optimal cutoff values for different groups of fibrosis patients for both serum markers. Also, the diagnostic accuracy of FIB-4 for predicting liver fibrosis was found to be superior to APRI in all disease stages.

Methoxyeugenol deactivates hepatic stellate cells and attenuates liver fibrosis and inflammation through a PPAR-ɣ and NF-kB mechanism

Ethnopharmacological relevanceStudies have shown interest in nutraceuticals for the prevention of liver diseases. Methoxyeugenol, is a molecule found in foods, such as nutmeg (Myristica fragrans Houtt.) and Brazilian red propolis. These two sources of methoxyeugenol, propolis and nutmeg, are used in folk medicine for the treatment of hepatic and gastrointestinal disorders, although little is known about their effects on the prevention of liver fibrosis. Natural PPAR (Peroxisome proliferator-activated receptor) agonists would represent unique molecules for therapy, considering the lack of therapeutics to treat liver fibrosis in chronic liver disease. Thus, investigation on new alternatives are necessary, including the search for natural compounds from renewable and sustainable sources. Liver fibrosis is a pathological process characterized by an exacerbated cicatricial response in the hepatic tissue, which compromises liver function. Therefore, inhibition of HSC (hepatic stellate cell) activation and hepatocyte damage are considered major strategies for the development of new anti-fibrotic treatments. Aim of the studyThis study aimed to investigate the effects of methoxyeugenol treatment on HSC phenotype modulation in human and murine cells, hepatocyte damage prevention, and protective effects in vivo, in order to evaluate its therapeutic potential for liver fibrosis prevention. MethodsWe investigated the effects of methoxyeugenol in (i) in vitro models using human and murine HSC and hepatocytes, and (ii) in vivo models of CCl4 (carbon tetrachloride) -induced liver fibrosis in mice. ResultsWe herein report that methoxyeugenol decreases HSC activation through the activation of PPAR-ɣ, ultimately inducing a quiescent phenotype highlighted by an increase in lipid droplets, loss of contraction ability, and a decrease in the proliferative rate and mRNA expression of fibroblast markers. In addition, methoxyeugenol prevented hepatocytes from oxidative stress damage. Moreover, in mice submitted to chronic liver disease through CCl4 administration, methoxyeugenol decreased the inflammatory profile, liver fibrosis, mRNA expression of fibrotic genes, and the inflammatory pathway signaled by NF-kB (Nuclear factor kappa B). ConclusionWe propose methoxyeugenol as a novel and potential therapeutic approach to treat chronic liver disease and fibrosis.

Comparison of Visual Transient Elastography and Shear Wave Elastography in Evaluating Liver Fibrosis in Patients with Chronic Liver Disease.

PurposeThis study investigated the effectiveness and feasibility of shear wave elastography ((sound touch elastography) STE and (shear wave elastography) SWE) and visual transient elastography (ViTE) in the noninvasive quantitative diagnosis of liver fibrosis in chronic liver disease (CLD).Patients and MethodsA total of 106 patients with CLD underwent STE, SWE and ViTE elastography evaluation. The Young’s modulus of the three elastography was valuated and the diagnostic performances of the three techniques for liver fibrosis staging were compared. The area under the receiver operating curve (ROC) for the diagnosis of liver fibrosis was compared. The final diagnosis was based on the histological findings on the liver biopsy.Results1) The correlation between ViTE and SWE, ViTE and STE, SWE and STE stiffness values were 0.72, 0.75, 0.75 (P<0.001). 2) The relationship between the results of each elastography technique and the stage of pathological liver fibrosis showed that the more severe the liver fibrosis was, the higher the stiffness value was (all P <0.001). 3) When the three elastography techniques were used to detect the degree of liver fibrosis in different pathological stages, there was no statistical difference in the stabilities of the boxplots. 4) The ROCs of the three elastography techniques (ViTE, SWE and STE) were 0.88, 0.91, 0.92, F0 vs F1-3; 0.84, 0.84, 0.84, F0-1 vs F2-4; 0.80, 0.79, 0.77, F0-2 vs F3-4; 0.80, 0.76, 0.71, F0-3 vs 4; the AUC of ViTE was higher than the AUC of STE in the identification of F4, but there were no statistical differences in the AUCs of other groups.ConclusionViTE has good stability for the liver stiffness measurement (LSM) and a high consistency with shear-wave elastography (SWE and STE). It is an effective tool for evaluating CLD, and its performance is comparable to SWE and STE. The combination of ViTE and STE can improve the specificity of disease diagnosis and do not add extra cost and may improve cost performance.

Combining hepatic surface nodularity and serum tests better predicts hepatic fibrosis stages in chronic liver disease.

Hepatic surface nodularity quantified on CT images has shown promising results in staging hepatic fibrosis in chronic hepatitis C. The aim of this study was to evaluate hepatic surface nodularity, serum fibrosis indices, and a linear combination of them for staging fibrosis in chronic liver disease, mainly chronic hepatitis B. We developed a semiautomated software quantifying hepatic surface nodularity on CT images. Hepatic surface nodularity and serum fibrosis indices were assessed in the development group of 125 patients to generate 3 linear models combining hepatic surface nodularity with the aspartate aminotransferase to platelet ratio index, fibrosis-4 index, or platelet count in reference to the METAVIR scoring system. The models were validated in 183 patients. Hepatic surface nodularity and serum fibrosis indices all significantly correlated with fibrosis stages. For binary classifications into cirrhosis (F4), advanced fibrosis (≥ F3), and significant fibrosis (≥ F2), hepatic surface nodularity was significantly different across categories. The areas under the curve (AUCs) of the best model were 0.901, 0.872, and 0.794 for cirrhosis, advanced fibrosis, and significant fibrosis, respectively, higher than serum fibrosis indices alone (0.797-0.802, 0.799-0.818, and 0.761-0.773). In the validation group, the same model likewise showed higher AUCs (0.872, 0.831, and 0.850) compared to serum fibrosis indices (0.722-0.776, 0.692-0.768, and 0.695-0.769; p < 0.001 for F4). Hepatic surface nodularity combined with serum blood test could be a practical method to predict cirrhosis, advanced fibrosis, and significant fibrosis in chronic liver disease patients, providing higher accuracy than using serum fibrosis indices alone.

Comparing radiomics models with different inputs for accurate diagnosis of significant fibrosis in chronic liver disease.

The non-invasive discrimination of significant fibrosis (≥ F2) in patients with chronic liver disease (CLD) is clinically critical but technically challenging. We aimed to develop an updated deep learning radiomics model of elastography (DLRE2.0) based on our previous DLRE model to achieve significantly improved performance in ≥ F2 evaluation. This was a retrospective multicenter study with 807 CLD patients and 4842 images from three hospitals. All of these patients have liver biopsy results as referenced standard. Multichannel deep learning radiomics models were developed. Elastography images, gray-scale images of the liver capsule, gray-scale images of the liver parenchyma, and serological results were gradually integrated to establish different diagnosis models, and the optimal model was selected for assessing ≥ F2. Its accuracy was thoroughly investigated by applying different F0-1 prevalence cohorts and independent external test cohorts. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the area under the ROC curve (AUC) for significance of fibrosis (≥ F2) and cirrhosis (F4). The AUC of the DLRE2.0 model significantly increased to 0.91 compared with the DLRE model (AUC 0.83) when evaluating ≥ F2 (p = 0.0167). However, it did not show statistically significant differences as integrating gray-scale images and serological data into the DLRE2.0 model. AUCs of DLRE and DLRE2.0 increased, when there was higher F0-1 prevalence. All radiomics models had good robustness in the independent external test cohort. DLRE2.0 was the most suitable model for staging significant fibrosis while considering the balance of diagnostic accuracy and clinical practicability. • The non-invasive discrimination of significant fibrosis (≥ F2) in patients with chronic liver disease (CLD) is clinically critical but technically challenging. • We aimed to develop an updated deep learning radiomics model of elastography (DLRE2.0) based on our previous DLRE model to achieve significantly improved performance in ≥ F2 evaluation. • Our study based on 807 CLD patients and 4842 images with liver biopsy found that DLRE2.0 was the most suitable model for staging significant fibrosis while considering the balance of diagnostic accuracy and clinical practicability.

Magnetic resonance quantitative susceptibility mapping in the evaluation of hepatic fibrosis in chronic liver disease: a feasibility study.

Noninvasive methods for the early diagnosis and staging of hepatic fibrosis are needed. The present study aimed to investigate the alteration of magnetic susceptibility in the liver of patients with various fibrosis stages and to evaluate the feasibility of using susceptibility to stage hepatic fibrosis. A total of 30 consecutive patients with chronic liver diseases (CLDs) underwent magnetic resonance imaging (MRI) and liver biopsy evaluation of hepatic fibrosis, necroinflammatory activity, iron load, and steatosis. Quantitative susceptibility mapping (QSM), R2* and proton density fat fraction (PDFF) images were postprocessed from the same gradient-echo data for quantitative tissue characterization using region of interest (ROI) analysis. The differences for MRI measurements between cohorts of non-significant (Ishak-F <3) and significant fibrosis (Ishak-F ≥3) and the correlation of MRI measurements with fibrosis stages and necroinflammatory activity grades were tested. Receiver operating characteristic (ROC) analysis was also performed. There was a significant difference in liver susceptibility between the cohorts of significant and non-significant fibrosis (Z=-2.880, P=0.004). A moderate negative correlation between the stages of liver fibrosis and liver susceptibility was observed (r=-0.471, P=0.015). Liver magnetic susceptibility differentiated non-significant from significant hepatic fibrosis with an area under the receiver operating curve (AUC) of 0.836 (P=0.004). A highly sensitive diagnostic performance with an AUC of 0.933 was obtained using magnetic susceptibility and PDFF together (P<0.001). A noninvasive liver QSM-based evaluation promises an accurate assessment of significant fibrosis in patients with CLDs.

Assesmentof Fibro Q test, AAR &amp; APRI indices as markers of fibrosis in chronic liver disease

Chronic liver disease can vary from mild hepatic inflammation without fibrosis to advanced hepatic fibrosis and cirrhosis. The use of ultrasound for the confirmation of complications during biopsy procedures increases the cost of treatment and may also increase the duration of hospitalization. Fibro Q test (FQT), Aspartate amino transferase – Alanine amino transferase ratio (AAR) &amp; Aspartate amino transferase- platelet ratio index (APRI) are the three non-invasive and simple indices proposed for assessing fibrosis in CLD. To know the efficacy of the indices- Fibro Q test, AAR, APRI as markers of Fibrosis in CLD. To know which among these indices would be the high sensitive marker of liver fibrosis.This study includes 60 subjects, out of which 30 were clinically diagnosed as CLD and were confirmed by abdominal ultrasound and 30 were age matched healthy controls. Fibro Q, AAR &amp; APRI were significantly increased in cases compared to controls. The increase in Fibro Q test in cases was highly significant (p-0.0001) when compared to controls.Fibro Q test, AAR &amp; APRIindicesare efficient markers to evaluate liver fibrosis in CLD patients. Fibro Q, a novel non-invasive test, is highly sensitive marker than AAR &amp; APRI.

Interferon lambda 4 genotype and pathway in alcoholic hepatitis

Objectives Single nucleotide polymorphisms within the interferon lambda 4 (IFNL4) gene influence liver inflammation and fibrosis in chronic liver disease. We investigated whether this is also the case during acute liver disease, alcoholic hepatitis. We, therefore, related variants within the IFNL4 gene to the clinical course of acute alcoholic hepatitis, and characterized the activation state of the IFN lambda system in these patients. Methods In this pilot study, 58 patients with alcoholic hepatitis were genotyped for the rs368234815IFNL4 single nucleotide polymorphism (deltaG, deltaG/TT: IFN lambda 4 positive, TT/TT: IFN lambda 4 negative). The genotypes were related to mortality, infection and inflammation and expression of the IFNL receptor 1 and IFN inducible genes were measured in liver and peripheral leukocytes. Results Amongst the alcoholic hepatitis patients who died, the IFN negative patients live longer after diagnosis, and also the IFN negative patients tended to have an overall short-term survival benefit compared to IFN lambda positive patients (p = .058). The IFN lambda 4 negative patients at diagnosis had fewer circulating monocytes and lower plasma soluble CD163. The patients with alcoholic hepatitis had reduced expression of the IFNL receptor 1in both liver and blood compared with healthy controls. In blood, the expression of IFN stimulated genes was lower than in healthy controls and most so in the patients, who died. Conclusions The IFN lambda 4 pathway seems involved in the acute disease processes of alcoholic hepatitis and patients without IFN lambda expression seem to have a short-term survival benefit.

Cytoplasmic vacuolation with endoplasmic reticulum stress directs sorafenib induced non-apoptotic cell death in hepatic stellate cells

The activated hepatic stellate cells (HSCs) are the major cells that secrete the ECM proteins and drive the pathogenesis of fibrosis in chronic liver disease. Targeting of HSCs by modulating their activation and proliferation has emerged as a promising approach in the development of anti-fibrotic therapy. Sorafenib, a multi-kinase inhibitor has shown anti-fibrotic properties by inhibiting the survival and proliferation of HSCs. In present study we investigated sorafenib induced cytoplasmic vacuolation mediated decreased cell viability of HSCs in dose and time dependent manner. In this circumstance, sorafenib induces ROS and ER stress in HSCs without involvement of autophagic signals. The protein synthesis inhibitor cycloheximide treatment significantly decreased the sorafenib-induced cytoplasmic vacuolation with increasing cell viability. Antioxidant human serum albumin influences the viability of HSCs by reducing sorafenib induced vacuolation and cell death. However, neither caspase inhibitor Z-VAD-FMK nor autophagy inhibitor chloroquine could rescue the HSCs from sorafenib-induced cytoplasmic vacuolation and cell death. Using TEM and ER organelle tracker, we conclude that the cytoplasmic vacuoles are due to ER dilation. Sorafenib treatment induces calreticulin and GPR78, and activates IRE1α-XBP1s axis of UPR pathway, which eventually trigger the non-apoptotic cell death in HSCs. This study provides a notable mechanistic insight into the ER stress directed non-apoptotic cell death with future directions for the development of efficient anti-fibrotic therapeutic strategies.

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.

Predictive performance of eLIFT for liver inflammation and fibrosis in chronic liver diseases.

Objective: The easy liver fibrosis test (eLIFT) is a novel predictor of liver fibrosis in chronic liver disease (CLD). This study aimed to evaluate the predictive value of the eLIFT for liver inflammation and fibrosis in CLD patients.Methods: We enrolled 1125 patients with CLD who underwent liver biopsy. The predictive accuracy for liver inflammation and fibrosis of the eLIFT was assessed and compared to that of the aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 score (FIB-4), and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) by ROC (Receiver Operating Characteristic) analysis and decision curve analysis (DCA).Results: The areas under the ROC curves (AUROCs) of the eLIFT for assessing liver inflammation G ≥ 2 and G ≥ 3 were 0.77 (0.75-0.80) and 0.81 (0.79-0.84), with cut-offs of 8.0 and 11.0, respectively. The AUROCs of the eLIFT for predicting fibrosis stages S ≥ 2 and S4 were 0.72 (0.70-0.76) and 0.76 (0.72-0.80), with cut-offs of 9.0 and 10.0, respectively. In discriminating G≥2 inflammation, the AUROC of the eLIFT was better than that of the FIB-4, with no difference compared with the GPR, but lower than that of the APRI. When discriminating G≥3 inflammation, the AUROC of the eLIFT was comparable to that of the APRI and GPR but superior to that of the FIB-4. There were no significant differences between the four indexes for predicting S≥2 and S4.Conclusion: The eLIFT is a potentially useful noninvasive predictor of liver inflammation and fibrosis in patients with CLD.

Acoustic radiation force impulse (ARFI) in the evaluation of liver fibrosis in chronic liver disease: Where do we stand today?

Chronic liver disease (CLD) is common in clinical practice, and the estimation of liver fibrosis (FIB) is crucial for the treatment of these patients. Liver elastography is more widely used in the evaluation of hepatic steatosis and FIB. Acoustic radiation force impulse (ARFIs) are an imaging technique which is available on ultrasonography machines to indicate tissue stiffness of various organs as it correlates with tissue elasticity. Various etiologies can cause moderate-to-severe hepatic FIB which can lead to altered liver function with structural and biochemical abnormalities which eventually result in liver failure. Commercially available ultrasound machines with incorporated ability for shear-wave (SW) technology and available software systems can perform ARFI. Usually, curved array 3.5–4 MHz transducers are used for obtaining SW velocities. We aim to review the clinical applications of ARFI as a noninvasive method using SW velocity measurements to assess the severity of liver FIB in liver parenchymal diseases. In this article, we have discussed the efficacy of quantitative assessment to evaluate the severity of liver disease which has a direct impact on the management and outcome of CLD.

Efficacy of the fibrosis index for predicting end-stage renal disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Kidney involvement is a major manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and may progress to end-stage renal disease (ESRD), requiring renal replacement therapy. Unfortunately, there is no reliable kidney-specific index for predicting the progression of renal disease to ESRD. The fibrosis index (FI) reflects the degree of fibrosis in chronic liver disease. This study aimed to investigate whether the FI at the time of diagnosis could predict the development of ESRD in AAV patients. We retrospectively reviewed the medical records of 211 immunosuppressive drug-naïve AAV patients and extrapolated the cut-off FI value for predicting the development of ESRD using receiver operating characteristic curves. The associations between the FI and clinical outcomes, including mortality, relapse, and ESRD development, were determined. Overall, 39 (18.5%) patients developed ESRD owing to the progression of AAV-associated renal disease. The median FI was higher in AAV patients with ESRD than in those without (1.61 vs 1.04; P=.001). The FI cut-off was 1.72. The incidence of ESRD was higher in patients with FI≥1.72 at the time of diagnosis than in those with an FI<1.72 at the time of diagnosis (relative risk: 4.655; 95% confidence interval: 2.242-9.662; P<.001). Kaplan-Meier survival analysis revealed that patients with an FI≥1.72 at the time of diagnosis exhibited significantly lower ESRD-free survival rates than those with an FI<1.72 at the time of diagnosis (P<.001). FI≥1.72 at the time of diagnosis may be an independent predictive marker for ESRD in AAV patients.

Current ultrasound-related strategies for assessing liver fibrosis in chronic liver disease.

Current ultrasound-related strategies for assessing liver fibrosis in chronic liver disease.

Comparative evaluation of fibroscan, liver biopsy and non-invasive serum markers for assessment of hepatic fibrosis in chronic liver disease

Introduction: Chronic liver disease is a disease of the liver that lasts over a period of six months or more, involving a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis.In this study, we have compared three main tools to assess liver fibrosis including fibroscan, liver biopsy and non-invasive biomarkers. Materials and Methods: Inthis prospective study, a total of 30 cases of chronicliver disease were included. Fibrosis stage was assessed using fibroscan. In liver biopsy, Grading of fibrosis was done by modified activity grading system and staging was done using Ishak staging system. Serum markers were analysed using various scoring systems including AST/ALT ratio (AAR), AST/platelet ratio index (APRI), FIB-4 index and Forn Index. The obtained results were analyzed and evaluated using chi square test and area under receiver operator characteristic curve (AUROC) using SPSS version 20. Results: A significant association was found between fibroscan and Ishak fibrosis stage (p 0.049), fibroscan and APRI (p 0.02) and FIB-4 and liver biopsy (p 0.03). AAR and Forn index did not have any significant association with either fibroscan (p 0.969 and 0.889) or liver biopsy (p 2.56 and 0.98). Conclusion: The accuracy of fibroscan in evaluating fibrosis is comparable to that of liver biopsy. Thus, liver biopsy can be replaced with fibroscan in the future. Though, the non-invasive biomarkers are useful in assessing fibrosis, a combination of these markers may perform better than each alone. Keywords: Chronic liver disease, Liver biopsy, Fibroscan, Non invasive biomarkers.