Fibrosis Stages F4 Research Articles

Impact of Direct Acting Antivirals Therapy on Novel Fibrosis Index for Assessment of Hepatic Fibrosis in Comparison with AST to Platelet Ratio and Fibrosis-4 (FIB-4) Indices in Egyptian Patients with Chronic Hepatitis C Infection in Correlation with Fibroscan

Abstract Background Chronic viral infection causes multiple waves of inflammation and tissue repair which involves deposition of extracellular matrix resulting in scarring or progressive fibrosis over time and ultimately leading to liver cirrhosis. The introduction of DAAs has improved eradication rate of HCV and achievement of SVR. In addition to the high rates of sustained virological response (SVR), hepatic fibrosis may regress, and the risks of complications, such as hepatic failure and portal hypertension are reduced after SVRs, Stage of liver fibrosis in chronic HCV infection is a well-established factor that determines the severity of disease and associated complications. Numerous noninvasive fibrosis scores, imaging techniques and new serum fibrosis markers have been applied to evaluate the phases of liver fibrosis, and have mostly replaced liver biopsy Transient elastography (TE) is the most accurate method with high sensitivity and specificity for advanced fibrosis the aminotransferase (AST)/platelet ratio index (APRI) and the fibrosis-4 (FIB-4) scores are the most widely used in viral hepatitis C patients, particularly in those with significant fibrosis and cirrhosis. Objective The aim of this study is to evaluate Impact of Direct Acting Antivirals therapy on Novel fibrosis index for assessment of hepatic fibrosis in comparison with AST to Platelet ratio and fibrosis-4(FIB-4) indices in Egyptian patients with chronic hepatitis C infection in correlation with fibro scan. Patients and Methods This is a prospective Cohort clinical study performed on 100 Egyptian patients are ≥18 years of age who have chronic infection with hepatitis C who will be treated with combination of IFN-free DAAs (Sofosbuvir & Daclatasvir ± Ribavirin) for 3 months. oral informed consent was taken from all patients included in the study. Results In the current study, there was significant regression of degree of fibrosis after treatment with DAAs in all patients achieving SVR by fibroscan, APR and fib4. novel fibrosis index is reliable and good tool in assessment of liver fibrosis in correlation to fibroscan, APRI and FIB4 especially significant fibrosis with the cut off value in prediction of hepatic fibrosis stage 4 was >3.1 and has sensitivity of 81.5% while the specificity was 74.1%. The positive predictive value was 66% while the negative predictive value was 86.8% Conclusion Novel fibrosis index has been found to be good reliable marker for assessment of liver fibrosis with high accuracy of predicting f4 fibrosis stage. There was significant marked reduction of fibrosis degree by fibroscan and non invasive indices (APRI &FIB4) after treatment with directly acting antiviral in both cirrhotic and non cirrhotic patients regardless the treatment regimen used with improved overall liver function tests especially albumin level, liver enzymes, hemoglobin level and platelet count in patients who reached SVR.

A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis

BackgroundDual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction–associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibrosis are unclear.MethodsIn this 48-week, phase 2 trial, we randomly assigned adults with biopsy-confirmed MASH and fibrosis stage F1 through F3 in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of survodutide at a dose of 2.4, 4.8, or 6.0 mg or placebo. The trial had two phases: a 24-week rapid-dose-escalation phase, followed by a 24-week maintenance phase. The primary end point was histologic improvement (reduction) in MASH with no worsening of fibrosis. Secondary end points included a decrease in liver fat content by at least 30% and biopsy-assessed improvement (reduction) in fibrosis by at least one stage.ResultsA total of 293 randomly assigned participants received at least one dose of survodutide or placebo. Improvement in MASH with no worsening of fibrosis occurred in 47% of the participants in the survodutide 2.4-mg group, 62% of those in the 4.8-mg group, and 43% of those in the 6.0-mg group, as compared with 14% of those in the placebo group (P<0.001 for the quadratic dose–response curve as best-fitting model). A decrease in liver fat content by at least 30% occurred in 63% of the participants in the survodutide 2.4-mg group, 67% of those in the 4.8-mg group, 57% of those in the 6.0-mg group, and 14% of those in the placebo group; improvement in fibrosis by at least one stage occurred in 34%, 36%, 34%, and 22%, respectively. Adverse events that were more frequent with survodutide than with placebo included nausea (66% vs. 23%), diarrhea (49% vs. 23%), and vomiting (41% vs. 4%); serious adverse events occurred in 8% with survodutide and 7% with placebo.ConclusionsSurvodutide was superior to placebo with respect to improvement in MASH without worsening of fibrosis, warranting further investigation in phase 3 trials. (Funded by Boehringer Ingelheim; 1404-0043 ClinicalTrials.gov number, NCT04771273; EudraCT number, 2020-002723-11.)

Validation study of age-independent fibrosis score (Fibrosis-3 index) in patients with metabolic dysfunction-associated steatotic liver disease.

Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort. The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study. The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60years (0.645 and 0.529, respectively; p<0.0001). The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age.

Estimating utility values for non-alcoholic steatohepatitis health states: a discrete choice experiment.

Background: This study estimated utility values for non-alcoholic steatohepatitis (NASH). Previous studies have assumed that health-related quality of life does not vary between the early stages of NASH. Materials & Methods: Discrete choice experiment (DCE) surveys estimated the value of avoiding fibrosis progression. Patients also completed the EQ-5D-5L. Marginal rates of substitution estimated utility change associated with fibrosis progression. Results: DCE surveys were completed by the UK general public (n=520) and patients with NASH (n=154). The utility decline between fibrosis stages F1 and F4 decompensated was between -0.521 to -0.646 (depending on method). Conclusion: Three methods were used to estimate utilities for NASH, each one showed sensitivity to advancing fibrosis, including in the early stages, which is often considered asymptomatic.

Serum level of proteins involved in apoptosis and autophagy in patients with type 2 diabetes and non-alcoholic fatty liver disease

Aim of the study was to estimate the blood serum level of microtubule-associated protein 1 light chain 3 alpha (MAP1LC3alpha), beclin-1 (BECN-1), Bcl-2 (BCL-2), caspase-3 (CASP3) and autophagy related 5 (ATG-5) protein as potential markers of liver fibrosis in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD).Material and methods. A single center cross-sectional observational study was performed. Seventy four patients with T2D and NAFLD were included, 23 men and 51 women, aged 18 to 74 years. Transient elastography was used for the assessment of liver fibrosis. The severity of fibrosis was estimated using the Metavir sсore. In addition, indirect liver fibrosis indices APRI and FIB-4 were calculated. Serum concentration of MAP1LC3alpha, BECN-1, BCL-2, CASP and ATG-5 was measured by ELISA. We applied ROC analysis to assess the value of studied indicators in diagnosis of liver fibrosis.Results. Liver fibrosis stage F1 was verified in 16 subjects, stage F2 in 12, stage F3 in 7, and stage F4 in 19 individuals. Patients with advanced liver fibrosis (stage 3-4) when compared to those without fibrosis (stage 0–2) had higher content of MAP1LC3alpha (p = 0.01) and BECN-1 (p = 0.01). There were no significant differences in the level of BCL-2, CASP3 and ATG-5 between patients with different severity of fibrosis. In the ROC analysis, MAP1LC3alpha and BECN-1 showed significance for the diagnosis of severe liver fibrosis, which, however, did not exceed that of the APRI index.Conclusions. In patients with T2D and NAFLD, serum levels of MAP1LC3alpha and BECN-1 are associated with severe liver fibrosis.

IL-6 Trans-Signaling Is Increased in Diabetes, Impacted by Glucolipotoxicity, and Associated With Liver Stiffness and Fibrosis in Fatty Liver Disease.

IL-6 and its circulating coreceptor sgp130 are increased in people with fatty liver disease and steatohepatitis. High glucose and lipids stimulated IL-6 and sgp130 secretion from hepatic stellate cells. sgp130 levels correlated with HbA1c, and diabetes concurrent with steatohepatitis further increased circulating levels of all IL-6 trans-signaling mediators. Circulating sgp130 positively correlated with liver stiffness and hepatic fibrosis. Metabolic stress to liver associated with fatty liver disease might shift the balance of IL-6 classical versus trans-signaling, promoting liver fibrosis that is accelerated by diabetes.

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background Hepatitis C virus (HCV) infection is the major cause of liver cirrhosis and hepatocellular carcinoma (HCC); thus, effective and safe treatment is crucial. Aim of the Work to evaluate the serum angiopoietin-2 as non-invasive marker of fibrosis regression in patients with Hepatitis C Virus receiving DAA drugs. Patients and Methods This study was conducted on 40 chronic HCV-patients who received DAA therapy in the Hepatic Virology Unit and the gastroenterology department of Ain Shams University hospitals. All patients were subjected to the following: Full history taking with stress concerning the hepatology system, clinical evaluation, laboratory investigations, Routine investigations: Abdominal and Pelvic ultrasonography and Transient elastography (Fibroscan) to measure liver stiffness measurement (LSM) for detection the degree of liver fibrosis in the chronic HCV-patients. Results Hematological findings, biochemical liver profile and liver fibrosis indices except hemoglobin level and platelets counts were significantly improved after DAA therapy. There was a significant improvement concerning the fibrosis stage after the treatment fibrosis staging at SVR12. The liver size, the spleen size and portal vein diameter were also significant after DAA therapy. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant. There was a statistically significant higher mean of Ang-2 levels in higher stages of liver fibrosis stages. Overall, serum Ang-2 levels significantly decrease after DAA therapy. In F0, F1, F2 &amp; F3 fibrosis stage; the mean Ang2 levels decrease after DAA therapy but in F4 fibrosis stage; the mean Ang2 levels did not change almost. Baseline Ang-2 and WBCs, AST, ALT, total bilirubin, INR, serum albumin, alpha-fetoprotein, serum creatinine, LSM, FIB-4 index, APRI score, liver size and portal vein diameter were significantly correlated. There were also a significant correlation between Ang-2 and all the fibrosis stages (from F0 to F4) before DAA treatment. Ang-2 levels were significantly associated with LSM based liver fibrosis stage regression after successful DAA therapy. Ang-2 levels did not correlate with hemoglobin, platelets and spleen size at baseline. Ang-2 levels did not correlate with hemoglobin, platelets, WBCs, INR, spleen size and portal vein diameter after DAA therapy. Ang-2 levels did not show significant correlation with the Child-Pugh score after DAA therapy. Conclusion Liver fibrosis stage after successful HCV eradication by DAAs. But in stage F4 (cirrhosis), mean Ang-2 remained almost unchanged after DAA therapy. Significant decrease of Serum Ang-2 could suggest its use as a predictor of liver fibrosis regression in Hepatitis C Virus-patients after Direct Acting Antiviral drugs after DAA therapy.

Real-Time Shear Wave Elastography for Determining the Ideal Site of Liver Biopsy in Diffuse Liver Disease.

Objectives The objective of the study was to identify accurate site of liver biopsy under ultrasound and elastography guidance and compare the shear wave elastography (SWE) and transient elastography (TE) diagnostic accuracy with histopathological correlation. Methods This was a prospective single-center study where patients scheduled for nonfocal liver biopsy were divided into two groups (group U: ultrasound; group E elastography) by sequential nonrandom selection of patients. Elastography was performed before the biopsy and biopsies from the maximum stiffness segment were taken. Results There was no significant difference of intersegmental liver stiffness with mean velocity; however, biopsy segment velocities show significant difference with mean liver stiffness suggestive of heterogenous distribution of fibrosis. The rho ( r ; Spearman's correlation) value between biopsy segments and mean velocities shows excellent correlation. The diagnostic performance of TE was good for fibrosis stages F2, F3, and F4, while SWE was fair for the diagnosis of fibrosis stages F1 and F2 and fairly equal for the diagnosis stages F2 and F3. Area under the curve (AUC) values in differentiating mild (F1) or no fibrosis from significant fibrosis (≥F2) were 95.5 with cutoff value of at least 1.94 m/s. Conclusions The diagnostic performance of SWE is comparable with TE in liver fibrosis staging and monitoring. Fibrosis is heterogeneously distributed in different segments of the right lobe liver. Therefore, elastography at the time of biopsy may help in defining the accurate site for biopsy and improve histopathological yield in detecting liver fibrosis in patients with chronic liver disease. Advances in Knowledge Elastography-guided biopsy is helpful to determine the ideal site of biopsy.

Convolutional neural network classification of ultrasound images by liver fibrosis stages based on echo-envelope statistics

Introduction: Assessing the stage of liver fibrosis during the diagnosis and follow-up of patients with diffuse liver disease is crucial. The tissue structure in the fibrotic liver is reflected in the texture and contrast of an ultrasound image, with the pixel brightness indicating the intensity of the echo envelope. Therefore, the progression of liver fibrosis can be evaluated non-invasively by analyzing ultrasound images.Methods: A convolutional-neural-network (CNN) classification of ultrasound images was applied to estimate liver fibrosis. In this study, the colorization of the ultrasound images using echo-envelope statistics that correspond to the features of the images is proposed to improve the accuracy of CNN classification. In the proposed method, the ultrasound image is modulated by the 3rd- and 4th-order moments of pixel brightness. The two modulated images and the original image were then synthesized into a color image of RGB representation.Results and Discussion: The colorized ultrasound images were classified via transfer learning of VGG-16 to evaluate the effect of colorization. Of the 80 ultrasound images with liver fibrosis stages F1–F4, 38 images were accurately classified by the CNN using the original ultrasound images, whereas 47 images were classified by the proposed method.

Cellular and Molecular Mechanisms of Liver Fibrosis in Patients with NAFLD.

The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance detecting the progressors among F1/F2 NAFLD patients. We also characterized immune cell changes using multiplex immunofluorescence platforms. Fibrotic areas were strongly enriched in CD3+ T cells compared to CD68+ macrophages. While the number of CD68+ macrophages increased with fibrosis severity, the increase in CD3+ T-cell density was more substantial and progressive from F1 to F4. The strongest correlation with fibrosis progression was observed for CD3+CD45R0+ memory T cells, while the most significant increase in density between F1/F2 and F3/F4 was for CD3+CD45RO+FOXP3+CD8- and CD3+CD45RO-FOXP3+CD8- regulatory T cells. A specific increase in the density of CD68+CD11b+ Kupffer cells with liver fibrosis progression was also observed.

CD24 Gene Expression as a Risk Factor for Non-Alcoholic Fatty Liver Disease.

This study enrolled eighty individuals divided into two groups; a study group included forty cases with bright liver and a group of healthy subjects with normal liver. Steatosis was quantified by CAP. Fibrosis assessment was performed by FIB-4, NFS, Fast-score, and Fibroscan. Liver enzymes, lipid profile, and CBC were evaluated. Utilizing RNA extracted from whole blood, the CD24 gene expression was detected using real-time PCR technique. It was detected that expression of CD24 was significantly higher in patients with NAFLD than healthy controls. The median fold change was 6.56 higher in NAFLD cases compared to control subjects. Additionally, CD24 expression was higher in cases with fibrosis stage F1 compared to those with fibrosis stage F0, as the mean expression level of CD24 was 7.19 in F0 cases as compared to 8.65 in F1 patients but without significant difference (p = 0.588). ROC curve analysis showed that CD24 ∆CT had significant diagnostic accuracy in the diagnosis of NAFLD (p = 0.034). The optimum cutoff for CD24 was 1.83 for distinguishing patients with NAFLD from healthy control with sensitivity 55% and specificity 74.4%; and an area under the ROC curve (AUROC) of 0.638 (95% CI: 0.514-0.763) was determined. In the present study, CD24 gene expression was up-regulated in fatty liver. Further studies are required to confer its diagnostic and prognostic value in the detection of NAFLD, clarify its role in the progression of hepatocyte steatosis, and to elucidate the mechanism of this biomarker in the progression of disease.

A qualitative patient interview study to understand the experience of patients with nonalcoholic steatohepatitis.

NASH is a potentially progressive form of NAFLD characterized by hepatocyte injury and liver inflammation which can cause fibrosis. Currently, there are limited data on the patient experience of NASH. Our aim was to use both literature review and patient interviews to understand the signs/symptoms and life impacts of NASH fibrosis stages F1-F4 that are important to patients, as well as begin to investigate the applicability of an instrument (ie, questionnaire) that may be used to capture patients' experiences. The literature review identified concepts (signs/symptoms and impacts) related to NASH fibrosis stages F1-F4 and the NASH-specific patient-reported outcome instrument (NASH-CHECK) for reporting patient experience of NASH. Interviews with 22 patients from Canada and the USA with NASH fibrosis stages F1-F4 revealed 27 signs/symptoms and 32 impacts that they felt were important, including fatigue, pain in the abdomen, worry, and frustration. Three concepts reported during patient interviews were not identified in the literature review. No concepts appeared to be exclusive to a specific fibrosis stage or presence/absence of obesity and no linear trends were identified between fibrosis stage or presence/absence of obesity and level of disturbance reported for concepts. The patient interviews supported the concepts included in the NASH-CHECK overall, demonstrating that it could be used to report the patient experience of NASH fibrosis stages F1-F4. Interviews with patients with NASH fibrosis stages F1-F4 revealed patients can self-report and elaborate on signs/symptoms and impacts related to the disease regardless of fibrosis stage. The NASH-CHECK was identified as a suitable instrument that could be used by patients with fibrosis stages F1-F4.

Serum MFAP4, a novel potential biomarker for liver cirrhosis screening, correlates with transient elastography in NAFLD patients.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in different countries. Liver fibrosis is considered as the most appropriate predictor of NAFLD-associated outcome. Microfibrillar-associated protein 4 (MFAP4) is a glycoprotein located in the extracellular matrix. Circulatory MFAP4 has been suggested as a noninvasive biomarker for the assessment of hepatitis C virus and alcoholic liver disease associated liver fibrosis. In this study, we aimed to investigate the association between serum MFAP4 and liver fibrosis severity in NAFLD patients. A case-control study was conducted in which NAFLD patients (n=25) and healthy participants (n=12) were recruited. Liver fibrosis/cirrhosis was assessed by transient elastography (TE) and biochemical parameters were collected. Serum MFAP4 was measured by sandwich ELISA based on two monoclonal anti-MFAP4 antibodies and calibrated with a standard of recombinant MFAP4. Serum MFAP4 levels increased with fibrosis severity and were highly upregulated in patients with cirrhosis (F4 fibrosis stage). In addition, serum MFAP4 levels positively correlated with TE measurement and showed significant association with the severely advanced fibrotic stage in NAFLD patients, in multiple linear regression analysis following adjustment for age, gender, and body mass index. This study suggests the use of MFAP4 as a potential diagnostic noninvasive biomarker for cirrhosis screening in NAFLD patients.

Диагностическая эффективность контраст-усиленного ультразвукового исследования у пациентов с хроническими вирусными гепатитами

Aim: to determine the diagnostic efficiency of contrast-enhanced ultrasound of the liver in patients with chronic viral hepatitis B and C. Study Design: open randomized study. Materials and methods. 240 people were examined on the basis of the Smolensk Clinical Hospital No. 1 from 2019 to 2021: patients with chronic viral hepatitis who have been examined by contrast-enhanced ultrasound; patients with chronic viral hepatitis who have not been examined by contrast-enhanced ultrasound to determine the diagnostic effectiveness of the method in assessing the complicated course development, patients without chronic viral hepatitis who have been examined by contrast-enhanced ultrasound to determine the standardized CEUS parameters. Liver biopsy and shear wave elastography were used as reference methods. Results. It was found that the greatest changes in contrast-enhanced ultrasound parameters were observed in patients with F4 fibrosis stage according to the METAVIR score. It was also found that the assessment of qualitative parameters according to the proposed standardized program has the highest diagnostic potential, and among the quantitative parameters — the difference of quantitative parameters in the proximal and distal zones (time of arrival, time to peak, peak intensity, half-time washout). Conclusion. The use of a contrast agent increases the value of the ultrasound method in the diagnostic algorithm for patients with chronic viral hepatitis. Keywords: contrast-enhanced ultrasound, chronic viral hepatitis, contrast agent, arterial phase, portal venous phase, late venous phase, qualitative parameters, quantitative parameters.

The usefulness of a newly developed full-core biopsy needle in liver biopsy.

To evaluate the usefulness and safety of a newly developed full-core biopsy needle. We selected 149 patients who underwent percutaneous liver biopsy at our institution from February 2019 to April 2021. We excluded 35 patients with hepatic fibrosis stage F3 or higher, which made it histopathologically difficult to measure the number of complete portal triads. The patients were divided into two groups as follows: 62 cases with the 18-G conventional automated needle (TruCore needle: T needle), and 52 cases with the 18-G full-core needle (CorVocet needle: C needle). We measured the number of complete portal triads in the liver tissue specimens, and the sum of the length and width of the collected tissues. Moreover, we compared the number of session counts, fragmentations, and complications. The sum of the length and the width was 12.8mm (11.2-14.3) and 15.9mm (13.1-17.3; p<0.001), and 0.68mm (0.63-0.74) and 0.82mm (0.78-0.90; p<0.001) for the T needle and C needle, respectively. The number of complete portal triads and fragmentation was six (3-8) and 10 (6-13; p<0.001), and one (1-10) and one (1-3; p<0.001), for the T needle and C needle, respectively. There was one session count (1-2) in both groups; however, there were significantly higher cases of two sessions with the T needle than that with the C needle (p=0.018). There were no serious adverse events. Compared with the conventional needles, the newly developed full-core needles enabled the acquisition of a larger amount of tissue sample in liver biopsy.

Diagnostic Accuracy of Elastography and Liver Disease: A Meta-Analysis.

Ultrasound-based transient elastography (TE) is a non-invasive alternative to liver biopsy for the staging of hepatic fibrosis due to various chronic liver diseases. This meta-analysis aims to assess the diagnostic accuracy of TE for detecting liver cirrhosis (F4) and severe fibrosis (F3) in patients with chronic liver diseases, in comparison to the gold standard liver biopsy. A systematic search was performed using PubMed search engine following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from inception to May 2021. The meta-analysis studies evaluating the diagnostic accuracy of TE for severe fibrosis and cirrhosis were identified. We conducted a meta-meta-analysis to generate pooled estimates of the sensitivity, specificity, and diagnostic odds ratios (ORs) for F3 and F4 fibrosis stage. We included five studies with a total of 124 sub-studies and 20,341 patients in our analysis. Three studies have reported the diagnostic accuracy of TE in detecting F3/severe fibrosis stage and found 81.9% pooled sensitivity (95% confidence interval (CI): 79.9-83.7%; P < 0.001) (I2 = 0%), 84.7% pooled specificity (95% CI: 81.3-87.6%) (I2 = 81%; P = 0.02). All five studies reported the diagnostic accuracy of TE in detecting F4/liver cirrhosis stage. We found 84.8% pooled sensitivity (95% CI: 81.4-87.7%) (I2 = 86.4%; P < 0.001), 87.5% pooled specificity (95% CI: 85.4-89.3%) (I2 = 90%; P < 0.001) and pooled diagnostic OR (41.8; 95% CI: 3.9 - 56.5) (I2 = 87%; P < 0.001). Ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis and liver fibrosis stages 3. Future studies should focus on estimating the diagnostic accuracy of other fibrosis stages in chronic liver disease patients. This will eventually decrease the risk associated with invasive liver biopsy.

Sound touch elastography for assessing cirrhosis preoperatively in infants with biliary atresia: Comparison with serum fibrosis biomarkers.

IntroductionThe accurate assessment of the stages of hepatic fibrosis in children with biliary atresia (BA) before performing Kasai portoenterostomy (KPE) is of utmost importance. Some studies demonstrated that ultrasound elastography can be used to assess the stages of hepatic fibrosis by detecting liver stiffness. Therefore, the aim of this work was to explore the usefulness of sound touch elastography (STE) for preoperatively assessing liver cirrhosis in infants with BA.MethodsA total of 189 children from the Hunan Children’s Hospital with highly suspected BA were selected for this study, and their preoperative liver STE values and related clinical data were collected. The pathological results of the liver stages were considered as the gold standard. Spearman correlation was used to analyze the correlation between each parameter and the stage of hepatic fibrosis, and the receiver operator characteristic (ROC) curve was used to analyze the diagnostic performance for cirrhosis of each parameter.ResultsAmong the selected 189 patients with suspected BA, 159 were included in this study and were composed of 3 at hepatic fibrosis stage F1, 45 at stage F2, 41 at stage F3, and 70 at stage F4, while no patients at stage F0 were present. Spearman correlation analysis showed that the liver STE value had the highest correlation with the stage of hepatic fibrosis, with a correlation coefficient of 0.813 (P < 0.001). The liver STE value had the highest diagnostic performance for hepatic cirrhosis compared to other biomarkers of serum fibrosis; the area under the ROC curve was 0.899 when the best cut-off value was 14.57 kPa. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 78.6, 84.3, 79.7, 83.3, and 81.8%, respectively.ConclusionThe liver STE value has a high correlation with the stage of hepatic fibrosis in children with BA. STE has a good diagnostic performance in evaluating cirrhosis before KPE in children with BA.

Efficacy and Safety of a Botanical Formula Fuzheng Huayu for Hepatic Fibrosis in Patients with CHC: Results of a Phase 2 Clinical Trial.

Background Hepatitis C virus (HCV) is a common cause of progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma worldwide. Despite the availability of effective direct-acting antivirals, patients often have significant hepatic fibrosis at the time of diagnosis due to delay in diagnosis and comorbidities which promote fibrogenesis. Thus, antifibrotic agents represent an attractive adjunctive therapy. Fuzheng Huayu (FZHY), a traditional Chinese medicine botanical formulation, has been used as an antifibrotic agent in chronic HBV infection. Our aim was to assess FZHY in patients with HCV infection and active viremia. Method We randomized 118 patients with active viremia from 8 liver centers in the U.S. to receive oral FZHY (n = 59) or placebo (n = 59) for 48 weeks. Efficacy was assessed by histopathologic changes at the end of therapy. A subset of biopsies was further analyzed using qFibrosis to detect subtle changes in fibrosis in different zones of the hepatic lobules. Results FZHY was well tolerated and safe. Patients with baseline Ishak fibrosis stages F3 and F4 had better response rates to FZHY than patients with baseline F0–F2 (p=0.03). qFibrosis zonal analysis showed significant improvement in fibrosis in all zones in patients with regression of the fibrosis stage. Conclusions FZHY produced antifibrotic effects in patients with baseline Ishak F3 and F4 fibrosis stages. Reduction in fibrosis severity was zonal and correlated with the severity of inflammation. Based on its tolerability, safety, and efficacy, FZHY should be further investigated as a therapy in chronic liver diseases because of its dual anti-inflammatory and antiibrotic properties. Lay Summary. This is the first US-based, multicenter and placebo-controlled clinical trial that shows statistically significant reduction in fibrosis in patients with active HCV using an antifibrotic botanical formula. This has important implications as there is an immediate need for effective antifibrotic agents in treating many chronic diseases including NASH that lead to scarring of the liver. With artificial intelligence-based methodology, qFibrosis, we may provide a more reliable way to assess the FZHY as a therapy in chronic liver diseases because of its dual anti-inflammatory and antifibrotic properties.

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General evaluation score for predicting the development of hepatocellular carcinoma in patients with advanced liver fibrosis associated with hepatitis C virus genotype 1 or 2 after direct-acting antiviral therapy.

Background and AimTo validate a composite predictive model for hepatocellular carcinoma (HCC) development in patients with advanced liver fibrosis associated with chronic hepatitis C virus (HCV) who have received direct‐acting antiviral (DAA) therapy and achieved sustained virologic response (SVR).MethodsThis study included 1258 patients with advanced liver fibrosis associated with HCV genotype 1, 2, or both. General evaluation score (GES), which is based on sex, age, fibrosis stage, albumin, and α‐fetoprotein, was used as a composite predictive model.ResultsThere were 645 (51.3%) patients in the low‐risk group, 228 (18.1%) in the intermediate‐risk group, and 385 (30.6%) in the high‐risk group based on GES categories. The 12‐, 36‐, and 60‐month cumulative incidence of HCC was 0.7%, 5.3%, and 13.0%, respectively. Multivariable analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 1.863; 95% confidence interval [CI], 1.204–2.883), F4 fibrosis stage (HR, 3.199; 95% CI, 1.696–6.036), and albumin (HR, 0.489; 95% CI, 0.288–0.828) are independently associated with HCC development. The incidence of HCC differed significantly by GES‐based risk category (P < 0.001). Cox proportional hazards models showed that, with the low‐risk group as the referent, the HR for HCC development was 1.875 (95% CI, 1.000–3.514) in the intermediate‐risk group and 2.819 (95% CI, 1.716–4.630) in the high‐risk group. GES had better predictive ability for HCC development than fibrosis‐4 index according to time‐dependent receiver operating characteristic analysis.ConclusionGES is useful for predicting HCC development in patients with advanced liver fibrosis after SVR.