Assessment Of Fibrosis In Patients Research Articles

Fibulin-4 as a potential extracellular vesicle marker of fibrosis in patients with cirrhosis.

Chronic liver injury leads to decreased liver function and increased fibrosis. Fibrosis is not only associated with the development of portal hypertension and carcinogenesis, but with the occurrence of events and a poor prognosis, highlighting the importance of non-invasive fibrosis assessment in patients. In the present study, we searched for markers related to liver fibrosis via proteomic analysis of small extracellular vesicles (sEVs). In the discovery cohort, proteomic analysis was carried out in the sEVs extracted from the sera of 5 patients with decompensated cirrhosis, 5 patients with compensated cirrhosis, and 5 controls without liver disease. Interestingly, in this cohort, fibulin-4 was significantly associated with cirrhosis while in the validation cohort [formed by 191 patients: 7 patients without disease, 16 patients without liver disease (other diseases), 38 patients with chronic liver disease (CLD), 75 patients with cirrhosis of Child-Pugh class A (36 without hepatocellular carcinoma [HCC], 29 with HCC), and 65 patients with cirrhosis of Child-Pugh class B-C (39 without HCC, 26 with HCC)], fibulin-4/CD9 levels increased with cirrhosis progression. Furthermore, the fibulin-4/CD9 ratio was significantly higher in patients with varices. Immunostaining also revealed strong fibulin-4 expression in cholangiocytes within the fibrous areas and mesothelial cells in liver tissue blood vessels. Taken together, our results suggest that fibulin-4, essential for lysyl oxidase activation, might be a new liver fibrosis marker found in the sEVs of patients with cirrhosis.

The deep abdominal ultrasound transducer (DAX) increases the success rate and diagnostic accuracy of shear wave elastography for liver fibrosis assessment in patients with obesity-A prospective biopsy-controlled study.

Obesity impacts the diagnostic accuracy of shear wave elastography (SWE). A deep abdominal ultrasound transducer (DAX) capable of point (pSWE) and two-dimensional (2D)-SWE has recently been introduced to address this issue. We performed a prospective study in a cohort of mostly patients with obesity undergoing liver biopsy with a high prevalence of metabolic dysfunction-associate steatotic liver disease (MASLD). Liver stiffness measurement (LSM) was measured using vibration-controlled transient elastography (VCTE), as well as pSWE and 2D SWE on the standard (5C1) and the DAX transducers. We included 129 patients with paired LSM and liver biopsy: median age 44.0 years, 82 (63.6%) women, median BMI: 43.2 kg/m2. Histologic fibrosis stages: F0: N = 55 (42.6%), F1: N = 14 (10.9%), F2: N = 50 (38.8%), F3: N = 2 (1.6%), F4: N = 8 (6.2%). VCTE-LSM failed (N = 13) or were unreliable (IQR/median ≤30% in ≥7.1 kPa, N = 14) in 20.9% of patients. The Pearson correlation of reliable VCTE-LSM with both pSWE and 2D SWE was strong (all >0.78). The diagnostic accuracy for all LSM techniques was poor for significant fibrosis (≥F2, AUC: 0.54-0.63); however, it was good to excellent for advanced fibrosis (≥F3, AUC: 0.87-0.99) and cirrhosis (F4, AUC: 0.86-1.00). In intention-to-diagnose analysis, pSWE on DAX was significantly superior to VCTE-LSM. pSWE- and 2D-SWE enable the non-invasive identification of advanced fibrosis and cirrhosis in patients with obese MASLD. The use of the DAX transducer for acoustic radiation force imaging (ARFI)-LSM avoids technical failures in an obese population and subsequently offers advantages over VCTE-LSM for the evaluation of fibrosis in an obese MASLD population at risk for fibrosis.

Combined effect of histological findings and diabetes mellitus on liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events. A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices. Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis. While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.

Diagnostic accuracy of computer morphometry for steatosis and fibrosis assessment in patients with chronic liver disease of various etiologies

Background. Accurate assessment of the fibrosis stage is crucial for effective treatment. Histological examination, the primary method used for assessing liver fibrosis, has certain limitations due to variation within each stage. Computer morphometry offers an objective and quantitative approach to complement histological analysis, providing additional diagnostic information. The purpose of this study was to analyze the computer morphometry data in patients with chronic liver diseases (CLD) of different etiologies and determine their diagnostic accuracy for liver fibrosis diagnosis. Materials and methods. Seventy-five patients with CLD, namely 24 with non-alcoholic fatty liver disease (NAFLD), 8 with alcoholic liver disease (ALD), 1 with toxic hepatitis, and 42 with chronic hepatitis C (CHC), were included in the study. Percutaneous liver biopsy was performed under ultrasound guidance using a semi-automatic needle Colt Shot 16 G. The severity of fibrosis was assessed using the Metavir scale. For computer morphometry, biopsies were photographed and evaluated using the ImageJ 1.45S program (National Institutes of Health, USA). The computerized fibrosis index (CFI), steatosis index, and the number of apoptotic cells in 5 consecutive high-power fields were calculated. Receiver operating characteristic analysis was performed for CFI diagnostic accuracy assessment. Results. Advanced liver fibrosis (F3-F4) was diagnosed in 62.5 % of ALD cases and 31.0 % of CHC. The highest CFI was found in ALD, it exceeded the level of NAFLD and CHC patients by 3.3 (p < 0.01) and 2 times (p < 0.05), respectively. At the same time, people with NAFLD had the highest steatosis index (0.36 ± 0.11), which was 1.7 times higher (p < 0.05) than in ALD and CHC. Moreover, CFI correlated with the fibrosis stage (r = 0.71, p < 0.05). Stage I of liver fibrosis according to the Metavir scale is characterized by CFI up to 0.040, stage II — 0.041–0.130, stage III — 0.131–0.219, and stage IV — more than 0.220. CFI cut-off value was 0.017, which confirms the presence of liver fibrosis in patients with chronic liver diseases regardless of the etiology (sensitivity — 85.2 %, specificity — 100.0 %). Conclusions. Computer morphometry significantly improves the accuracy and reliability of histological examination, and allows to objectify morphological assessment of liver steatosis and fibrosis and to ensure long-term storage of the results.

Atrial contractile function and fibrosis in patients with paroxysmal atrial fibrillation in sinus rhythm

The aim of the study was to investigate atrial contractile function in patients with paroxysmal atrial fibrillation (AF) in sinus rhythm using transthoracic echocardiography (EchoCG). Thirty-five patients with paroxysmal AF and arterial hypertension (mean age 62 ± 10 years, 43% male) in sinus rhythm were enrolled in the study. The control group was composed of comparable patients with arterial hypertension without heart rhythm disturbances. EchoCG was performed during sinus rhythm according to an extended protocol, which included the ejection fraction (EF) of the left atrium (LA) and tissue Doppler measurements. Myocardial fibrosis was assessed quantitatively by videodensitometry in intraventricular and intraatrial (IAS) septa using an original image post-processing algorithm. We found a significant decrease in the left atrial contraction function during sinus rhythm in patients with AF when compared to controls. LA EF (34 ± 14 vs. 54 ± 17, p = 0.03) and A' velocity (0.17 ± 0.04 vs. 0.22 ± 0.04, p = 0.008) decreased while A/A' ratio (2.7 ± 0.2 vs. 1.9 ± 0.1, p = 0.006) increased. Peak A velocity was not affected. Videodensitometric analysis revealed a 2.3-fold increase in IAS fibrosis fraction in AF patients compared with controls (p = 0.01). Patients with AF in sinus rhythm have markedly depressed atrial contractile function. Videodensitometry of IAS has the potential to be used as inexpensive method of atrial fibrosis assessment in patients with AF.

Shear wave elastography-based liver fibrosis assessment in patients with chronic hepatitis E displays elevated liver stiffness regardless of previous antiviral therapy.

Hepatitis E virus (HEV) infection especially in immunocompromised individuals can lead to chronic hepatitis. Aggressive courses of chronic hepatitis E leading to liver cirrhosis in a short period of time have been described, but evidence on the degree of liver involvement in chronic hepatitis E is rare. We therefore aimed to quantify liver fibrosis in patients with chronic active hepatitis E compared to patients with sustained virological response after ribavirin (RBV) treatment using 2D-shear wave elastography (2D-SWE) to measure liver stiffness. Patients with chronic hepatitis E underwent 2D-SWE, B-mode and Doppler ultrasound and laboratory testing in order to assess severity of liver involvement. In this cross-sectional study, we included 14 patients of whom 8 had ongoing chronic hepatitis E and 6 patients had been successfully treated for chronic hepatitis E. The most frequent cause for immunosuppression was prior kidney transplantation (n=12), one patient was a multivisceral transplant recipient, one had been treated for lymphoma. Five patients cleared HEV after RBV therapy, one patient reached viral clearance after reduction of his immunosuppressive medication. Using 2D-SWE measurement, 71.4% displayed increased stiffness indicative of liver fibrosis: 57.1% classified as significant fibrosis and 14.3% as severe fibrosis. Liver stiffness did not differ between patients with active chronic hepatitis E and in patients who had cleared HEV (1.59 and 1.54 m/s respectively). Compared with a control group of kidney transplant recipients without hepatitis E (1.44 m/s), the patients with a history of hepatitis E displayed a significantly higher liver stiffness (P=0.04). In our cohort of chronic hepatitis E patients, elevated liver stiffness indicating liver fibrosis was common and significantly higher than in controls. This is consistent with prior sparse reports of the presence of liver fibrosis or cirrhosis in chronic hepatitis E and emphasizes the need for HEV testing, therapy and research on new therapeutic options. As elevated liver stiffness was also present in patients after HEV treatment, continuous liver surveillance including elastography and ultrasound should be considered.

Artificial Intelligence Improves Pathologist Agreement for Fibrosis Scores in Nonalcoholic Steatohepatitis Patients

Artificial Intelligence Improves Pathologist Agreement for Fibrosis Scores in Nonalcoholic Steatohepatitis Patients

Comparison of invasive and non-invasive methods for assessment of liver fibrosis in patients with chronic hepatitis B and hepatitis C virus infections

Introduction: Different methods are employed to determine the severity of chronic viral hepatitis and liver fibrosis Objectives: This study was conducted to compare invasive and non-invasive tests for assessment of liver fibrosis in the patients with chronic hepatitis B and C. Patients and Methods: In this study, the results of liver biopsy based on the METAVIR scoring system were compared with biomarkers, including fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) for identifying liver fibrosis. Results: Out of 194 patients, 63 and 131 patients had hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, respectively. There was a significant difference between patients with METAVIR stages 0-1 and patients with METAVIR stages 2-3, based on the FIB-4, aspartate aminotransferase (AST) to platelet ratio index (APRI) and the mean prothrombin time (PT), international normalized ratio (INR), platelet (PLT), alanine transaminase (ALT) and AST. A correlation was found between the FIB-4 and APRI indices and the METAVIR score of patients with hepatitis. The FIB-4 index, with a cut-off value <1.1 for detecting liver fibrosis in patients with HBV infection, showed sensitivity of 83.3%, specificity of 64.7%. Further, a positive predictive value (PPV) of 35.7%, and a negative predictive value (NPV) of 94.3% was detected. On the other hand, the APRI index, with a cut-off value <0.73, showed 59% sensitivity, 76.5% specificity, PPV of 33.3% and NPV of 86.7%. The FIB-4 index, with a cut-off value <1.47 for detecting liver fibrosis in patients with HCV infection, showed 73.7% sensitivity, 73.2% specificity, PPV of 31.8%, and NPV of 94.3%. Additionally, the APRI index, with a cut-off value <1.7, showed 42.1% sensitivity, 97.3% specificity, PPV of 72.7% and NPV of 90.8%. Conclusion: According to the results, in patients with chronic hepatitis, the severity of liver fibrosis increased with an increase in the APRI and FIB-4 indices. Therefore, these two indices can replace biopsy under certain circumstances.

Non-invasive tests for liver fibrosis assessment in patients with chronic liver diseases: a prospective study

There is an urgent need of non-invasive tests (NITs) for monitoring treatment response and disease progression in chronic liver disease. Liver stiffness (LS) evaluated by transient elastography (TE), shear wave elastography (SWE), and magnetic resonance elastography (MRE) and serum markers e.g. APRI and FIB-4 scores were assessed at baseline and the 1-year follow-up. In all, 89 chronic hepatitis C virus (HCV) patients with sustained virological response and 93 non-alcoholic fatty liver disease (NAFLD) patients were included. There was a significantly strong correlation among imaging techniques. Using MRE as the reference standard, the area under the receiver operating characteristics curves for TE, SWE, APRI, and FIB-4 in detecting stage1–4 fibrosis were 0.88–0.95, 0.87–0.96, 0.83–0.89, and 0.79–0.92, respectively. In chronic HCV patients, the values of TE, SWE, MRE, APRI and FIB-4 significantly decreased from baseline to the 1-year follow-up. Liver steatosis did not significantly change over time. In NAFLD, compared to obese patients, non-obese patients had less LS and steatosis at baseline, and these values did not show significant changes at the 1-year follow-up. Our study suggests that the current NITs have a good correlation and accuracy in monitoring the treatment outcomes in patients with chronic liver diseases.

Role of Serum M2BPGi Levels in Predicting Persistence of Advanced Fibrosis in Chronic Hepatitis B Virus Infection.

Serum mac-2-binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis assessment in patients with different liver diseases. For chronic hepatitis B infection (CHB), advanced fibrosis or cirrhosis is a risk factor for liver cancer and hepatic decompensation. We aimed to assess the role of serum M2BPGi in prediction of persistence of advanced fibrosis in CHB patients despite potent antiviral therapy. CHB patients with advanced fibrosis or cirrhosis who were put on nucleos(t)ide analogs for ≥ 3years with normal alanine aminotransferase and undetectable serum HBV DNA were prospectively recruited. Assessment of liver fibrosis with transient elastography (TE) and M2BPGi measurements were performed at baseline and repeated at 3years. Advanced fibrosis and cirrhosis were defined by liver stiffness (LS) ≥ 9.0kPa and ≥ 12.0kPa, respectively. A total of 143 patients (M:F = 101:42; median age 58.7years; 53.8% cirrhotic) were recruited and completed paired assessment. The median value of baseline LS and M2BPGi were 12.0 (IQR: 10.5-18.2) kPa and 0.99 cut-off-index (IQR: 0.75-1.74) (COI), respectively, with 96% concordance for diagnosing F3/F4. Ninety-six (67.1%) patients had persistent advanced fibrosis or cirrhosis at 3years despite continuation of long-term antiviral treatment. Upon multivariate analysis, baseline M2BPGi (OR 2.128, 95% CI 1.037-4.366) and presence of central obesity (OR 4.648, 95% CI 1.742-12.402) were significantly associated with persistent advanced fibrosis or cirrhosis at 3years. Baseline M2BPGi ≥ 1.265 COI has 50.6% sensitivity and 79.4% specificity for predicting persistent advanced fibrosis or cirrhosis at 3years (area under the receiver-operating characteristic curve: 0.695). The presence of central obesity in combination with baseline M2BPGi ≥ 1.265 COI was associated with 95.7% patients having persistent advanced fibrosis or cirrhosis at 3years. HCC development was observed in five patients during follow-up and was associated with bigger median increase in the level of serum M2BPGi compared to patients without HCC (46% vs 6.2%, P = 0.038). Persistent advanced fibrosis or cirrhosis was observed in two-thirds of CHB patients despite potent antiviral therapy. High serum M2BPGi and central obesity were associated with more than twofold and fourfold increase in risk of persistent advanced fibrosis or cirrhosis, respectively.

Efficacy of Lipid Ratios and Platelet Distribution Width for Assessment of Liver Fibrosis in Patients With Non-alcoholic Fatty Liver Disease.

IntroductionThe clinical course of non-alcoholic fatty liver disease (NAFLD) in its long term may follow a benign course or have an adverse outcome leading to hepatocellular carcinoma (HCC) or end-stage liver disease requiring liver transplantation. Such patients represent only a small proportion of all NAFLD cases, making case finding a real challenge.AimsThis study was planned to test the efficacy of simple laboratory parameters for their ability to screen advanced cases of NAFLD who need early attention to extricate them from the cumbersome outcome.Material and methodThe study protocol enrolled 129 diagnosed cases of NAFLD. Patients were categorized as group I with mild/moderate fibrosis (MF) comprising of F0 to F2 and group II with advanced fibrosis (AF) comprising of F3 and F4 based on Fibroscan kPa (kilopascal) score.ResultsGroup I consisted of 96 MF patients, while group II included 33 AF patients. Mean values of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), triglyceride (TG), triglyceride/high-density lipoprotein (TG/HDL) ratio, total cholesterol/high-density lipoprotein (TC/HDL) ratio, and platelet distribution width (PDW) were significantly higher in patients with AF (group II), while platelet count (PC) was significantly lower in group II. The area under the receiver operative characteristic (AUROC) curve was highest for PDW [0.730 (0.644-0.815)] and TG/HDL ratio [0.719 (0.612-0.827)]. TG/HDL ratio at a cut-off of >2.4 had a sensitivity and specificity of 84.85% and 34.38%, respectively, and PDW at a cut-off of >16.40 had a sensitivity and specificity of 84.85% and 54.17%, respectively.ConclusionDecent sensitivity at particular cut-offs for TG/HDL ratio and PDW makes them suitable to be applied for screening advanced cases of NAFLD that require early ministration and medication to block its further progression to its intricate form.

Fibrosis assessment in patients with nonalcoholic fatty liver disease: Adherence to proposed algorithms and barriers to complying with them

Introduction and aimsFibrosis staging in patients with nonalcoholic fatty liver disease (NAFLD) is carried out through the application of stepwise algorithms but there is little real-world data on their use. Our aim was to calculate the number of patients with NAFLD and indeterminate or high risk for fibrosis, assessed through noninvasive scores, that consequently underwent further staging evaluation. Materials and methodsA cross-sectional multicenter cohort study was conducted on patients with NAFLD evaluated by hepatologists within the time frame of June 1 and July 31, 2018. The FIB-4 and NAFLD fibrosis scores were calculated in all the patients, and if at least one of the scores suggested indeterminate or high risk for fibrosis, we believed the patient should have undergone additional fibrosis staging assessment. ResultsThe study included 238 patients. The median time interval from NAFLD diagnosis and inclusion in the analysis was 12.2 months (IQR 3.0–36.5). A total of 128 (54%) patients had at least one noninvasive score that suggested indeterminate or high risk for fibrosis but studies to confirm the fibrosis grade (elastography, biopsy, etc.) were performed on only 72 (56%). The main barriers encountered by the physicians for applying the staging algorithms were related to health insurance coverage and imaging study costs. ConclusionsA high percentage of patients with NAFLD were at indeterminate or high risk for fibrosis, according to noninvasive scores, but additional studies were carried out on only half of them, showing low adherence to current recommendations.

Could native T1 mapping replace late gadolinium enhancement in the assessment of myocardial fibrosis in patients with cardiomyopathy?

BackgroundCardiomyopathy is a myocardial disease, which usually demonstrates improper ventricular morphology, function, or both. It is classified into two classes based on the organ involved. Primary cardiomyopathy is confined mainly to the myocardium and can be genetic, non-genetic, or acquired. Secondary cardiomyopathy is caused by generalized systemic disorder. Myocardial fibrosis produces abnormal myocardial stiffness and increases arrhythmias risk. Native T1-mapping is an innovative technique that provides quantitative assessment of edema, diffuse myocardial fibrosis, and inflammation in a number of disease states. Furthermore native T1 mapping provides a future method for quantifying myocardial fibrosis in advanced chronic kidney disease and dialysis patients without the use of gadolinium-based contrast agents. So our aim is to assess the potential value of segmental quantification of myocardial fibrosis using native T1 mapping in different types of cardiomyopathy in comparison to late gadolinium enhancement (LGE) imaging.ResultsThe native T1 values of a total 1152 segments (16 segments in 72 patients of cardiomyopathy), 192 segments in 12 patients with hypertrophic cardiomyopathy (HCM), 800 segments in 50 patients with dilated cardiomyopathy (DCM), 80 segments in 5 patients with infiltrative cardiomyopathy, and 80 segments in 5 patients with non-compaction were assessed. These were compared with 160 segments of 10 healthy volunteers. Native T1 values were significantly higher in most of myocardial segments with LGE than in those without including the control group; non-contrast T1 values in mid LV septal segments were found the most significant (1130.85 ± 79.79 ms vs 1047.74 ± 42.74 ms; P = 0.001). Also the current study showed T1 values were significantly higher than normal even in segments unaffected by LGE (P<0.01) in both HCM and DCM groups. A receiver operating characteristic (ROC) analysis revealed the required cutoff value of 1070 ms for detecting myocardial fibrosis with a sensitivity 66% and specificity of 68%.ConclusionContrast-free T1-mapping is a new technique for detecting myocardial fibrosis objectively with a high diagnostic performance especially in patients who cannot afford gadolinium contrast agents as patients with end-stage renal disease.

Performance of non-invasive fibrosis scores in non-alcoholic fatty liver disease with and without morbid obesity

BackgroundNon-invasive scores, such as the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS), are increasingly used for liver fibrosis assessment in patients with NAFLD. The aim of this study was to assess the applicability and reliability of non-invasive fibrosis scores in NAFLD patients with and without morbid obesity.MethodsThree hundred sixty-eight patients with biopsy-proven NAFLD identified between January 2012 and December 2015 were studied; 225 with morbid obesity (biopsy obtained during bariatric surgery) and 143 patients without (termed as “conventional”).ResultsMedian age was 47 years, 57% were female. Median body mass index (BMI) was 42.9 kg/m2 with significant differences between our conventional and morbidly obese patients (BMI 29.0 vs. 50.8 kg/m2, p < 0.001). Overall, 42% displayed mild/moderate and 16% advanced liver fibrosis (stage III/IV). All tested scores were significantly linked to fibrosis stage (p < 0.001 for all). FIB-4 (AUROC 0.904), APRI (AUROC 0.848), and NFS (AUROC 0.750) were identified as potent predictors of advanced fibrosis, although NFS overestimated fibrosis stage in morbid obesity. Limiting BMI to a maximum of 40 kg/m2 improved NFS’ overall performance (AUROC 0.838). FIB-4 > 1.0 indicated high probability of advanced fibrosis (OR = 29.1). FIB-4 predicted advanced fibrosis independently from age, sex, BMI, and presence of morbid obesity.ConclusionsOur data suggest that FIB-4 score is an accurate predictor of advanced fibrosis in NAFLD throughout all BMI stages. Without adjustment, NFS tends to overestimate fibrosis in morbidly obese NAFLD patients. This problem may be solved by implementation of an upper BMI limit (for NFS) or adjustment of diagnostic thresholds.

Noninvasive assessment of endometrial fibrosis in patients with intravoxel incoherent motion MR imaging

Recently, few noninvasive methods have been reported to evaluate endometrial fibrosis. Our study was to investigate the feasibility of intravoxel incoherent motion (IVIM) MR imaging in the detection of endometrial fibrosis in patients with intrauterine injury. 30 patients with hysteroscopy-confirmed endometrial fibrosis and 28 healthy women were enrolled to undergo MR examination including the IVIM sequence. Endometrial thickness (ET); apparent diffusion coefficient (ADC); and IVIM parameters, including pure diffusion coefficient (D), pseudodiffusion coefficient (D*) and vascular fraction (f) were evaluated. A multivariable model combing ADC, D, and f values using binary logistic regression analysis was built to diagnose endometrial fibrosis. Endometrial fibrosis patients demonstrated lower endometrial ADC, D, f values and ET (all p < 0.05). The multivariable model, ADC, D, f values and ET performed well in diagnosing endometrial fibrosis with AUC of 0.979, 0.965, 0.920, 0.901 and 0.833, respectively. The multivariable model revealed a better diagnostic accuracy than D, f and ET (all p < 0.05). Although ADC achieved a better diagnostic value than ET (z = 2.082, p < 0.05), no difference in AUC was shown among ADC, D, and f (all p > 0.05); between ET and D (p > 0.05); and between ET and f (p > 0.05). The reproducibility of ADC, D, f and D* values in patients with endometrial fibrosis and healthy women were good to excellent (ICC: 0.614–0.951). IVIM parameters exhibit promising potential to serve as imaging biomarkers in the noninvasive assessment of endometrial fibrosis.

Diagnostic value of magnetic resonance parametric mapping for non-invasive assessment of liver fibrosis in patients with primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by bile duct inflammation and destruction, leading to biliary fibrosis and cirrhosis. The purpose of this study was to investigate the utility of T1 and T2 mapping parameters, including extracellular volume fraction (ECV) for non-invasive assessment of fibrosis severity in patients with PSC.MethodsIn this prospective study, patients with PSC diagnosis were consecutively enrolled from January 2019 to July 2020 and underwent liver MRI. Besides morphological sequences, MR elastography (MRE), and T1 and T2 mapping were performed. ECV was calculated from T1 relaxation times. The presence of significant fibrosis (≥ F2) was defined as MRE-derived liver stiffness ≥ 3.66 kPa and used as the reference standard, against which the diagnostic performance of MRI mapping parameters was tested. Student t test, ROC analysis and Pearson correlation were used for statistical analysis.Results32 patients with PSC (age range 19–77 years) were analyzed. Both, hepatic native T1 (r = 0.66; P < 0.001) and ECV (r = 0.69; P < 0.001) correlated with MRE-derived liver stiffness. To diagnose significant fibrosis (≥ F2), ECV revealed a sensitivity of 84.2% (95% confidence interval (CI) 62.4–94.5%) and a specificity of 84.6% (CI 57.8–95.7%); hepatic native T1 revealed a sensitivity of 52.6% (CI 31.7–72.7%) and a specificity of 100.0% (CI 77.2–100.0%). Hepatic ECV (area under the curve (AUC) 0.858) and native T1 (AUC 0.711) had an equal or higher diagnostic performance for the assessment of significant fibrosis compared to serologic fibrosis scores (APRI (AUC 0.787), FIB-4 (AUC 0.588), AAR (0.570)).ConclusionsHepatic T1 and ECV can diagnose significant fibrosis in patients with PSC. Quantitative mapping has the potential to be a new non-invasive biomarker for liver fibrosis assessment and quantification in PSC patients.

Virtual Touch Quantification using Acoustic Radiation Force Impulse Imaging Technology versus Transient Elastography for the Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B or C using Liver Biopsy as the Gold Standard.

Our aim was to assess the diagnostic performance of transient elastography (TE) and Virtual Touch Quantification (VTQ), a point Shear Wave Elastography (pSWE) technique, using Acoustic Radiation Force Impulse (ARFI) technology, for liver fibrosis assessment, as compared to percutaneous liver biopsy (LB), in patients with chronic hepatitis B or C. We analyzed 157 patients (80 with chronic hepatitis B and 77 with chronic hepatitis C) with reliable liver stiffness (LS) measurements, in whom we compared TE and VTQ to the LB performed during the same session (evaluated according to the Metavir scoring system: F0-F4). LS was assessed by TE (FibroScan, EchoSens, Paris, France) and VTQ using the Siemens Acuson S2000TM ultrasound system (Siemens AG, Erlangen, Germany). We defined reliable LS measurements as the median value of 10 measurements with an IQR/M <30% for both TE (obtained using the M probe) and VTQ. The areas under receiver operating characteristic curves (AUROCs) were used to assess the diagnostic performance of TE and VTQ. Correlation analysis determined the relationship between LSM values and liver histology. On LB 31 (19.7%) patients had no fibrosis, 35 (22.3%) had F1, 43 (27.4%) had F2, 28 (17.8%) had F3 and 20 (12.7%) had cirrhosis. The mean size of the liver specimen in LB was 27 mm. A strong, linear correlation (Spearman ρ=0.826; p<0.001) with 95% confidence interval for rho (0.769- 0.870), was found between the TE and VTQ measurements. By comparing the AUROC curves, TE and VTQ had similar predictive values for the presence of F≥1 Metavir: AUROC TE=0.876, AUROC VTQ=0.832, p=0.358, for F≥2 Metavir: AUROC TE=0.826, AUROC VTQ=0.862, p=0.313, for F≥3 Metavir: AUROC TE=0.907, AUROC VTQ=0.880, p=0.434 and for F=4 Metavir: AUROC TE=0.981, AUROC VTQ=0.974, p= 0.423. Both methods, TE and VTQ (pSWE) offer excellent diagnostic accuracy for liver fibrosis assessment in patients with chronic hepatitis B or C with similar performance.

Evaluation of Point Shear Wave Elastography Using Acoustic Radiation Force Impulse Imaging for Longitudinal Fibrosis Assessment in Patients with HBeAg-Negative HBV Infection.

Background: Accurate assessment of hepatic fibrosis in patients with chronic HBeAg-negative Hepatitis B is of crucial importance not only to predict the long-term clinical course, but also to evaluate antiviral therapy indication. The aim of this study was to prospectively assess the utility of point shear wave elastography (pSWE) for longitudinal non-invasive fibrosis assessment in a large cohort of untreated patients with chronic HBeAg-negative hepatitis B virus (HBV) infection. Methods: 407 consecutive patients with HBeAg-negative HBV infection who underwent pSWE, transient elastography (TE) as well as laboratory fibrosis markers, including fibrosis index based on four factors (FIB-4), aspartate to platelet ratio index (APRI) and FibroTest, on the same day were prospectively followed up for six years. Patients were classified into one of the three groups: inactive carriers (IC; HBV-DNA <2000 IU/mL and ALT <40 U/L); grey zone group 1 (GZ-1; HBV DNA <2000 IU/mL and ALT >40 U/L); grey zone group 2 (GZ-2; HBV-DNA >2000 IU/mL and ALT <40 U/L). Results: pSWE results were significantly correlated with TE (r = 0.29, p < 0.001) and APRI (r = 0.17; p = 0.005). Median pSWE values did not differ between IC, GZ-1 and GZ-2 patients (p = 0.82, p = 0.17, p = 0.34). During six years of follow-up, median pSWE and TE values did not differ significantly over time (TE: p = 0.27; pSWE: p = 0.05). Conclusion: Our data indicate that pSWE could be useful for non-invasive fibrosis assessment and follow-up in patients with HBeAg-negative chronic HBV infection.

Value of serum fibronectin for assessment of liver fibrosis in chronic hepatitis C virus patients

BackgroundThe stage of liver fibrosis is the most important predictive factor for initiation and duration of antiviral treatment, where patients with early fibrosis stages respond to treatment better with a higher sustained virologic response rate. Several noninvasive tests to stage the degree of fibrosis in patients with chronic hepatitis C virus (HCV) infection have been used. No single test is known to have high accuracy and the results of each test must be carefully interpreted. The objective of the study is to evaluate the value of serum fibronectin (FN) as a noninvasive predictor for the assessment of HCV-induced liver fibrosis.Patients and methodsA total of 100 patients with chronic HCV infection proved by HCV antibodies and HCV RNA preparing for antiviral treatment were exposed to full history, physical examination, and laboratory assessment. Serum FN level and fibroscan were done for all patients. According to the results of fibroscan, the patients were divided into four groups of liver fibrosis and compared.ResultsAll patients were proved to have HCV viremia with average PCR of 1990.52 ±3144.29 copies/ml. A statistically significant difference was found as regards FN, fibroscan, and APRI score between patients with fibrosis in comparison to patients without fibrosis. According to fibroscan results, 20 patients were found with fibrosis stage 0, 24 patients with stage 1, 24 patients with stage 2, eight patients with stage 3, and 24 patients with stage 4 (cirrhosis). On comparison of different stages of fibrosis as regards FN level, we found no statistically significant difference between stages. FN have a sensitivity of 67.5% and a specificity of 47.4% with 84.4% positive predictive value.ConclusionFN is a good noninvasive marker for the assessment of liver fibrosis in patients with chronic HCV. Larger scale multicenter studies are needed to assess its validity in the detection of fibrosis caused by causes other than HCV.

Magnetic Resonance Elastography Predicts Fibrosis Progression in Nonalcoholic Fatty Liver Disease

Use of magnetic resonance elastography (MRE) as an imaging technique has been shown to be highly accurate in hepatic fibrosis assessment in patients