Mild Fibrosis Group Research Articles

Ultrasonic renal length as an indicator of renal fibrosis severity in non-diabetic patients with chronic kidney disease.

Debate continues regarding the potential of the ultrasonic renal length to serve as an indicator for evaluating the advancement of renal fibrosis in chronic kidney disease (CKD). This study investigates the independent association between renal length and renal fibrosis in non-diabetic CKD patients and assesses its diagnostic performance. From April 2019 to December 2021, 144 non-diabetic patients diagnosed with CKD who underwent a renal ultrasound examination and kidney biopsy were prospectively enrolled. Patients were categorized into the mild fibrosis group (n = 70) and the moderate-severe group (n = 74) based on the extent of fibrotic involvement. Ultrasonic renal length was measured from pole-to-pole in the coronal plane. A receiver operating characteristic (ROC) curve, multivariable logistic regression analysis, and a generalized additive model were performed. A negative linear correlation was found between renal length and moderate-severe renal fibrosis risk. Each centimeter increase in renal length decreased the odds of moderate-severe fibrosis by 38% (OR: 0.62; 95% CI 0.41-0.93; P = 0.020). After adjusting for confounders, the relationship persisted (OR: 0.58; 95% CI 0.33-1.00; P = 0.048). However, renal length presented limited discrimination ability in distinguishing degrees of renal fibrosis while controlling the key confounding factors, yielding an area under the ROC curve of only 0.58 (95% CI 0.45-0.70). While an inverse relationship exists between renal length and risk of having moderate-severe renal fibrosis in non-diabetic CKD patients, renal length alone is insufficient for diagnosing fibrosis severity, underscoring the need for additional diagnostic parameters in CKD assessment.

Assessing renal interstitial fibrosis using compartmental, non-compartmental, and model-free diffusion MRI approaches

ObjectiveTo assess renal interstitial fibrosis (IF) using diffusion MRI approaches, and explore whether corticomedullary difference (CMD) of diffusion parameters, combination among MRI parameters, or combination with estimated glomerular filtration rate (eGFR) benefit IF evaluation.MethodsForty-two patients with chronic kidney disease were included, undergoing MRI examinations. MRI parameters from apparent diffusion coefficient (ADC), intra-voxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), and diffusion-relaxation correlated spectrum imaging (DR-CSI) were obtained both for renal cortex and medulla. CMD of these parameters was calculated. Pathological IF scores (1–3) were obtained by biopsy. Patients were divided into mild (IF = 1, n = 23) and moderate-severe fibrosis (IF = 2–3, n = 19) groups. Group comparisons for MRI parameters were performed. Diagnostic performances were assessed by the receiver operator’s curve analysis for discriminating mild from moderate-severe IF patients.ResultsSignificant inter-group differences existed for cortical ADC, IVIM-D, IVIM-f, DKI-MD, DR-CSI VB, and DR-CSI VC. Significant inter-group differences existed in ΔADC, ΔMD, ΔVB, ΔVC, ΔQB, and ΔQC. Among the cortical MRI parameters, VB displayed the highest AUC = 0.849, while ADC, f, and MD also showed AUC > 0.8. After combining cortical value and CMD, the diagnostic performances of the MRI parameters were slightly improved except for IVIM-D. Combining VB with f brings the best performance (AUC = 0.903) among MRI bi-variant models. A combination of cortical VB, ΔADC, and eGFR brought obvious improvement in diagnostic performance (AUC 0.963 vs 0.879, specificity 0.826 vs 0.896, and sensitivity 1.000 vs 0.842) than eGFR alone.ConclusionOur study shows promising results for the assessment of renal IF using diffusion MRI approaches.Critical relevance statementOur study explores the non-invasive assessment of renal IF, an independent and effective predictor of renal outcomes, by comparing and combining diffusion MRI approaches including compartmental, non-compartmental, and model-free approaches.Key PointsSignificant difference exists for diffusion parameters between mild and moderate-severe IF.Generally, cortical parameters show better performance than corresponding CMD.Bi-variant model lifts the diagnostic performance for assessing IF.Graphical

Improvement of carotid atherosclerosis and peripheral artery disease after hepatitis C virus eradication by direct-acting antivirals.

Recent research points to a link between chronic hepatitis C virus (HCV) infection and cardiovascular disease, especially carotid atherosclerosis, and suggests that HCV clearance may impact cardiovascular outcomes. To determine if viral eradication by the new oral direct-acting antiviral (DAA) agents has benefit regarding carotid atherosclerosis, peripheral artery disease (PAD), steatosis, and liver fibrosis. We conducted a prospective study on 168 patients diagnosed with chronic HCV infection or HCV-related cirrhosis. They were all treated with DAAs, with sustained virological response (SVR). Laboratory data, vibration-controlled transient elastography (VCTE), carotid intima-media thickness (IMT) measurement, and ankle-brachial index (ABI) were recorded in all patients. We found an average IMT of 1.22±0.2 mm, with a variance range from 1.14±0.19 mm in the mild and moderate fibrosis (≤F2) group to 1.29±0.25 mm in the severe fibrosis (≥F3) group. Also, patients with severe fibrosis (≥F3) present a more critical decrease of IMT values, with the carotid thickness affecting only 18.2% of individuals in the follow-up period. At the baseline, the best values of ABI were recorded in patients having F1-F2 fibrosis stage (mean value 1.02±0.19). Instead, in the group with severe fibrosis, the average value of ABI was lower (0.91±0.16) at the baseline, with a significant increase at SVR evaluation (p<0.001). Our research highlights the beneficial effect of viral eradication on both carotid atherosclerosis and PAD, especially in those with advanced fibrosis and cirrhosis.

Efficacy of Serum Ferritin-Zinc Ratio for Predicting Advanced Liver Fibrosis in Patients with Autoimmune Hepatitis.

Background/Aims: The search for noninvasive biomarkers that can efficiently estimate the extent of liver fibrosis progression is ongoing. Although Fibrosis-4 (FIB-4), the aspartate transaminase-to-platelet ratio index (APRI), and the Forns index have been reported as useful biomarkers, their investigation in autoimmune hepatitis (AIH) is limited. This study aimed to examine the usefulness of these serological indices and a newly developed index in predicting liver fibrosis progression in AIH. Methods: The study analyzed data from 190 patients diagnosed with AIH at our institution between 1990 and 2015. Their histological liver fibrosis progression and clinical long-term prognosis were evaluated retrospectively (cohort 1). In 90 patients, receiver operating characteristic (ROC) curves were compared to choose severe fibrosis cases with respect to existing indices (FIB-4, APRI, and Forns index) and the ferritin-zinc ratio (cohort 2). Results: In cohort 1, liver-related death and hepatocellular carcinoma rates were significantly higher in the severe (n = 27) than in the mild (n = 63) fibrosis group (p = 0.0001 and 0.0191, respectively). In cohort 2, liver-related death in the severe fibrosis group was significantly frequent (p = 0.0071), and their ferritin-zinc ratio was higher (median 2.41 vs. 0.62, p = 0.0011). ROC analyses were performed to compare the ability of the ferritin-zinc ratio, FIB-4, APRI, and the Forns index to predict severe and mild fibrosis. Accordingly, areas under the ROC were 0.732, 0.740, 0.721, and 0.729, respectively. Conclusions: The serum ferritin-zinc ratio can noninvasively predict liver fibrosis progression in AIH and be applied to predict long-term prognosis.

Ultrasound-based radiomics analysis in the assessment of renal fibrosis in patients with chronic kidney disease.

Assessment of renal fibrosis non-invasively in chronic kidney disease (CKD) patients is still a clinical challenge. In this study, we aimed to establish a radiomics model integrating radiomics features derived from ultrasound (US) images with clinical characteristics for the assessment of renal fibrosis severity in CKD patients. A total of 160 patients with CKD who underwent kidney biopsy and renal US examination were prospectively enrolled. Patients were classified into the mild or moderate-severe fibrosis group based on pathology results. Radiomics features were extracted from the US images, and a radiomics signature was constructed using the maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) regression algorithms. Multivariable logistic regression was employed to construct the radiomics model, which incorporated the radiomics signature and the selected clinical variables. The established model was evaluated for discrimination, calibration, and clinical utility in the derivation cohort and internal cross-validation (CV) analysis, respectively. The radiomics signature, consisting of nine identified fibrosis-related features, achieved moderate discriminatory ability with an area under the receiver operating characteristic curve (AUC) of 0.72 (95% confidence interval (CI) 0.64-0.79). By combining the radiomics signature with significant clinical risk factors, the radiomics model showed satisfactory discrimination performance, yielding an AUC of 0.85 (95% CI 0.79-0.91) in the derivation cohort and a mean AUC of 0.84 (95% CI 0.77-0.92) in the internal CV analysis. It also demonstrated fine accuracy via the calibration curve. Furthermore, the decision curve analysis indicated that the model was clinically useful. The proposed radiomics model showed favorable performance in determining the individualized risk of moderate-severe renal fibrosis in patients with CKD, which may facilitate more effective clinical decision-making.

Predictors of severe submucosal fibrosis during endoscopic submucosal dissection in patients with ulcerative colitis: Retrospective cohort study.

Severe submucosal fibrosis is a crucial technical difficulty encountered during endoscopic submucosal dissection (ESD) in patients with ulcerative colitis (UC). We aimed to identify predictors of severe submucosal fibrosis in patients with UC. We retrospectively included 55 tumors resected using ESD from 48 consecutive patients with UC. We analyzed the clinicopathological characteristics and treatment outcomes between the F0/1 (none to mild submucosal fibrosis) group (n = 28) and F2 (severe submucosal fibrosis) group (n = 27). No significant difference was found between the F0/1 and F2 groups in en bloc resection rate (100% vs. 96%, P = 0.49), the R0 resection rate (100% vs. 93%, P = 0.24), and the dissection speed (0.18 vs. 0.13 cm2 /min, P = 0.07). Intraoperative perforation was more common in the F2 group (30%) than in the F0/1 group (8%; P = 0.01). Multivariable analysis showed that a longer duration of UC (≥10 years; odds ratio [OR] 6.11; 95% confidence interval [CI] 1.20-31.03; P = 0.03) and scarring of background mucosa of the tumor (OR 39.61; 95% CI 3.91-400.78; P < 0.01) were independent predictors of severe submucosal fibrosis. Long UC duration and scarring background mucosa were predictors of severe submucosal fibrosis associated with perforation during ESD.

Association of Infrapatellar Fat Pad Fibrosis at 3 Months After ACL Reconstruction With Short-term Clinical Outcomes and Inflammatory Cytokine Levels in the Synovial Fluid

Infrapatellar fat pad (IFP) fibrosis is reportedly associated with anterior knee pain and the progression of patellofemoral osteoarthritis after anterior cruciate ligament reconstruction (ACLR). However, causes of IFP fibrosis after ACLR have not been sufficiently investigated. To compare the descriptive characteristics, clinical outcomes, and inflammatory cytokine levels in the synovial fluid between patients who underwent ACLR with versus without severe IFP fibrosis. Cohort study; Level of evidence, 3. Patients who underwent primary ACLR using autologous hamstring tendon were divided into 2 groups based on magnetic resonance imaging IFP fibrosis scoring (grades 0-5) at 3 months after surgery: the severe fibrosis group (grades 4 and 5) and mild fibrosis group (grades 0-3). Synovial fluid was aspirated on postoperative day 3 or 4 to measure inflammatory cytokine levels. Patient characteristics, clinical outcomes at 3 and 12 months after surgery, and inflammatory cytokine (interleukin [IL]-1β, IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ) levels were compared between the groups. Of the 36 patients included, 7 were allocated to the severe fibrosis group and 29 were allocated to the mild fibrosis group. The severe fibrosis group had a significantly longer operation time (153.0 vs 116.5 minutes for mild fibrosis; P = .007). Compared with the mild fibrosis group, the severe fibrosis group had greater pain during stair climbing (2.0 vs 0.7; P = .01) and a lower extension muscle strength ratio (operated/healthy side, 52.9% vs 76.1%; P < .001) at 3 months, and the severe fibrosis group had a lower Lysholm score (93.7 vs 97.3; P = .026) and greater knee extension (0.3° vs 1.9°; P = .043) and flexion angle restriction (142.9° vs 149.0°; P = .013) at 12 months. The severe fibrosis group demonstrated higher IL-1β (2.6 vs 1.4 pg/mL; P = .022), IL-6 (2.0 vs 1.1 ng/mL; P = .029), and interferon-γ levels (11.3 vs 4.0 pg/mL; P = .044). Severe IFP fibrosis was associated with a longer operation time, higher inflammatory cytokine level in the synovial fluid, and worse clinical outcomes at 3 and 12 months after ACLR.

Validation of Noninvasive Markers for HCC Risk Stratification in 1389 Patients With Biopsy-proven NAFLD

Nonalcoholic fatty liver diseases (NAFLD) and nonalcoholic steatohepatitis (NASH) can cause hepatocellular carcinoma (HCC). We examined histological features and reported noninvasive markers/models for stratifying the risk of HCC development in patients with biopsy-proven NAFLD or NASH. A total of 1389 patients who had a histological diagnosis of NAFLD or NASH based on liver biopsy and underwent regular surveillance for HCC were included. The ability to predict HCC development was compared between histological features including liver fibrosis and NAFLD activity score, and noninvasive markers/models including aMAP (age, male, albumin-bilirubin, and platelet) score, FIB-4 (Fibrosis-4) index, and ALBI (albumin-bilirubin) score calculated at the time of biopsy. The C index of aMAP score was 0.887, which was consistent with the original report, comparable to FIB-4 index (0.878), and higher than those of ALBI score (0.789), histological liver fibrosis (0.723), and NAFLD activity score (0.589). The hazard ratios for HCC development in the aMAP intermediate and high-risk groups were 21.0 (95% confidence interval [CI], 3.6-402.0) and 110.3 (95% CI, 16.3-2251.4), respectively, in comparison to the aMAP score low-risk group. Those in the FIB-4 index moderate- and high-fibrosis groups were 10.3 (95% CI, 1.7-199.8) and 93.1 (95% CI, 16.3-1773.8), respectively, in comparison to the FIB-4 index mild-fibrosis group. No patients in the aMAP score low-risk group developed HCC during the study period. For stratifying the risk of HCC development in patients with biopsy-proven NAFLD or NASH, both aMAP score and FIB-4 index showed high discriminative ability as noninvasive markers, which were superior histological features.

Noninvasive assessment of renal function and fibrosis in CKD patients using histogram analysis based on diffusion kurtosis imaging

PurposeTo investigate the potential of histogram analysis based on diffusion kurtosis imaging (DKI) in evaluating renal function and fibrosis associated with chronic kidney disease (CKD).Materials and methodsThirty-six CKD patients were enrolled, and DKI was performed in all patients before the renal biopsy. The histogram parameters of diffusivity (D) and kurtosis (K) were obtained using FireVoxel. The histogram parameters between the stable [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2] and impaired (eGFR < 60 ml/min/1.73 m2) eGFR group were compared. Besides, patients were classified into mild, moderate, and severe fibrosis group using a semi-quantitative standard. The correlations of histogram parameters with eGFR and fibrosis scores were investigated and the diagnostic performances of histogram parameters in assessing renal dysfunction and fibrosis were analyzed. The added value of combination of most significant parameter with 24 h urinary protein (24 h-UPRO) in evaluating fibrosis was also explored.ResultsSeven D histogram parameters in cortex (mean, median, 10th, 25th, 75th, 90th percentiles and entropy), two D histogram parameters in medulla (75th, 90th percentiles), seven K histogram parameters in cortex (mean, min, median, 10th, 25th, 75th, 90th percentiles) and three K histogram parameters in medulla (mean, median, 25th percentile) were significantly different between the two groups. The Dmean of cortex was the most relevant parameter to eGFR (r = 0.648, P < 0.001) and had the largest area under the curve (AUC) for differentiating the stable from impaired eGFR group [AUC = 0.889; 95% confidence interval (CI) 0.728–0.970]. The K90th of cortex presented the strongest correlation with fibrosis scores (r = 0.575, P < 0.001) and achieved the largest AUC for distinguishing the mild from moderate to severe fibrosis group (AUC = 0.849, 95% CI 0.706–0.993). Combining the K90th in cortex with 24 h-UPRO gained statistically higher AUC value (AUC = 0.880, 95% CI 0.763–0.996).ConclusionHistogram analysis based on DKI is practicable for the noninvasive assessment of renal function and fibrosis in CKD patients.

Diagnosis of Liver Cirrhosis and Liver Fibrosis by Artificial Intelligence Algorithm-Based Multislice Spiral Computed Tomography.

This research was aimed at investigating the artificial intelligence (AI) segmentation algorithm-based multislice spiral computed tomography (MSCT) in the diagnosis of liver cirrhosis and liver fibrosis. Besides, it was aimed at providing new methods for the diagnosis of liver cirrhosis and liver fibrosis. All patients were divided into the control group, mild liver fibrosis group, and significant liver fibrosis group. A total of 112 patients were included, with 40 cases in the mild liver fibrosis group, 48 cases in the significant liver fibrosis group, and 24 cases who underwent computed tomography (CT) examination in the control group. In the research, deconvolution algorithm of AI segmentation algorithm was adopted to process the images. The average hepatic arterial fraction (HAF) values of patients in the control group, mild liver fibrosis group, and severe liver fibrosis group were 17.59 ± 10.03%, 18.23 ± 5.57%, and 20.98 ± 6.63%, respectively. The average MTT values of patients in the control group, mild liver fibrosis group, and severe liver fibrosis group were 12.69 ± 1.78S, 12.53 ± 2.05S, and 12.04 ± 1.57S, respectively. The average blood flow (BF) values of patients in the control group, mild liver fibrosis group, and severe liver fibrosis group were 105.68 ± 15.57 mL 100 g−1·min−1, 116.07 ± 16.5 mL·100 g−1·min−1, and 110.39 ± 16.32 mL·100 g−1·min−1, respectively. Besides, the average blood volume (BV) values of patients in the control group, mild liver fibrosis group, and significant liver fibrosis group were 15.69 ± 4.35 mL·log−1, 16.97 ± 2.68 mL·log−1, and 16.11 ± 4.87 mL·100 g−1, respectively. According to statistics, the differences among the average HAF, MTT, BF, and BV values showed no statistical meaning. AI segmentation algorithm-based MSCT imaging could promote the diagnosis of liver cirrhosis and liver fibrosis effectively and offer new methods to clinical diagnosis of liver cirrhosis and liver fibrosis.

Prediction of Fibrosis in Chronic Hepatitis C by Mean Platelet Volume and Platelet to Lymphocyte Ratio

Abstract: Introduction: Hepatitis C is a chronic inflammatory condition that associated with fibrosis. Novel inflammatory markers have been suggested to be related inflammatory condition. Therefore, we aimed to investigate hemogram derived indices, such as, Mean Platelet Volume (MPV) and Platelet to Lymphocyte ratio (PLR) in hepatitis C subjects and to compare those in healthy controls. Materials and Methods: In present retrospective study, 17 HCV patients having mild fibrosis, 23 patients having advanced fibrosis and 68 control subjects were included whom visited outpatient clinics of our institution between 1.10. 2017 and 30.11.2019. Hemogram indices and laboratory characteristics were compared. Results: Median MPV values of the advanced fibrosis patients [8.3 (6.5-14) fL] was significantly higher than that of the mild fibrosis patients [7.9 (6.5-11.1) fL] (p=0.002) and control subjects [7.2 (4.6-10.7) fL] p&lt;0.001) whereas MPV values of mild and advanced fibrosis patients were similar (p=0.750). Median PLR values of the mild fibrosis, advanced fibrosis and control groups were 103 (58-223) %, 86 (45-358) %, and 77 (64-96) %, respectively (p=0.010). A ROC analysis revealed that a MPV value greater than 7.3 fL determines advanced fibrosis with 76% sensitivity and 59% specificity. A PLR greater than 92% determines advanced fibrosis with 73% sensitivity and 64% specificity. Conclusion: We suggest that elevated PLR and MPV could predict of advanced fibrosis in chronic hepatitis C. Keywords: Hepatitis C, Fibrosis, Platelet to lymphocyte ratio, Mean platelet volume, Hemogram indices, Liver cirrhosis.

Abstract 12365: Association Between Liver Fibrosis and Left Atrial Remodeling in Patients With Atrial Fibrillation: The Hokuriku-Plus AF Registry

Introduction: Fibrosis-4 score (FIB-4), a laboratory-based marker for liver fibrosis, is reportedly associated with increased risks for cardiovascular events and mortality in patients with atrial fibrillation (AF). However, it remains unclear whether FIB-4 is associated with cardiac remodeling in patients with AF. Hypothesis: We hypothesized that liver fibrosis might be associated with cardiac remodeling, such as left atrial dilatation and/or systolic dysfunction. Methods: The Hokuriku AF Registry is a multicenter, population-based, prospective cohort study including 1,492 AF patients aged 30-94 years from 19 affiliated hospitals. We excluded patients with valvular AF and missing variables at baseline. We conducted a cross-sectional analysis to assess the association between the severity of liver fibrosis based on the FIB-4 score and echocardiographic parameters. The severity of liver fibrosis was classified into three categories based on FIB-4 score (Mild, Intermediate, and Severe) (Table). Unadjusted and adjusted linear regression analysis was performed to compute beta coefficient with 95% confidence interval using the Mild liver fibrosis group as a referent. Results: A total of 1,139 non-valvular AF patients were analyzed after the exclusion (mean age 72 ± 10 years, male 73.0%, paroxysmal AF 38.4%). In unadjusted analysis, severe liver fibrosis was significantly associated with increased left atrial diameter (LAD) and decreased left ventricular ejection fraction (LVEF), but this association was not observed in intermediate liver fibrosis. In addition, severe liver fibrosis was independently associated with LAD, not LVEF, after adjusting for other covariates (Table). Conclusions: The present study demonstrated that severe liver fibrosis based on FIB-4 score was significantly associated with larger LAD, a surrogate marker for left atrial remodeling, in patients with AF.

Lung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis.

Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. Objectives: To identify the molecular determinants associated with progression of fibrosis. Methods: Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 samples/lung). According to microcomputed tomography measures, fHP cores were clustered into mild, moderate, and severe fibrosis groups. Gene expression profiles were assessed using weighted gene co-expression network analysis, xCell, gene ontology, and structure enrichment analysis. Gene expression of the prevailing molecular traits was also compared with idiopathic pulmonary fibrosis (IPF). The explant lung findings were evaluated in separate clinical fHP cohorts using tissue, BAL samples, and computed tomography scans. Measurements and Main Results: We found six molecular traits that associated with differential lung involvement. In fHP, extracellular matrix and antigen presentation/sensitization transcriptomic signatures characterized lung zones with only mild structural and histological changes, whereas signatures involved in honeycombing and B cells dominated the transcriptome in the most severely affected lung zones. With increasing disease severity, endothelial function was progressively lost, and progressive disruption in normal cellular homeostatic processes emerged. All six were also found in IPF, with largely similar associations with disease microenvironments. The molecular traits correlated with in vivo disease behavior in a separate clinical fHP cohort. Conclusions: We identified six molecular traits that characterize the morphological progression of fHP and associate with invivo clinical behavior. Comparing IPF with fHP, the transcriptome landscape was determined considerably by local disease extent rather than by diagnosis alone.

Is neutrophil/lymphocyte and platelet/lymphocyte ratio a predictive factor for the fibrous stage in patients with chronic hepatitis B?

Aim: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are an inexpensive inflammatory marker that can beeasily obtained from the blood count and can be used in many chronic diseases. In our study, we aimed to investigate the relationshipbetween fibrosis stage and NLR, PLR in patients with chronic hepatitis B virus (HBV).Materials and Methods: 173 patients with chronic HBV were included in the study. The demographic data and hemogram parameters of all patients were recorded. Histopathological data of the patients were documented. Accompanying comorbid diseases, medicationsand previous operations were questioned. In chronic HBV patients, fibrosis level was compared with hematological parameters.Results: A total of 173 patients, 100 (57.8%) of whom were male, were included in the study. As a result of the liver biopsy; mildfibrosis (steage/1-2) in 83(47.9%) patients, moderate fibrosis (steage/3-4) in 35(20.3%) patients and advanced fibrosis (stage/5-6)in 55(31.8%) patients. In advanced fibrosis group, liver function tests and bilirubin levels were significantly higher and albumin levelwas significantly lower (p<0.05). It was found that NLR level was significantly higher in moderate fibrosis than mild fibrosis, and PLRlevel was significantly lower in the advanced fibrosis group than in the mild and moderate fibrosis groups (p<0.05).Conclusions: We showed that there is a significant relationship between fibrosis level and NLR, PLR. However, with the availabledata, it does not seem possible to say that noninvasive methods can completely replace invasive procedures such as liver biopsy.Prospectively designed studies with larger patient participation are needed.

Serum Biglycan as a Diagnostic Marker for Non-Alcoholic Steatohepatitis and Liver Fibrosis.

Non-alcoholic steatohepatitis (NASH) has risen in prevalence substantially through the years. Although course and progression of the disease are variable, fibrosis is the most important factor. We intended to explore utility of serum biglycan (BGN) in NASH and its capacity in anticipating liver fibrosis. Serum tests of consecutive patients with biopsy-confirmed NASH and age, gender-matched healthy volunteers were utilized to evaluate serum BGN levels using ELISA kits. The correlation between BGN and histopathological highlights of NASH was examined. While patients with fibrosis scores < 2 were assembled in mild and scores of (≥ 2) were in significant fibrosis groups. Univariate/multivariate regression analyses were performed to assess the independent predictive variables of liver fibrosis. Receiver operating characteristics (ROC) were applied to locate the best cutoff values of BGN for NASH and fibrosis. Seventy patients with NASH and 70 controls were recruited in the study. BGN levels were lower in NASH patients contrasted with controls 137.70 ± 33.12 pg/mL vs. 259.61 ± 187.34 pg/mL, respectively, and p < 0.001. In correlation, serum BGN was related to liver fibrosis and inflammation. The comparison between mild and significant fibrosis groups regarding BGN was as follows 155.92 ± 49.97 pg/mL vs. 390.07 ± 214.746 pg/mL, respectively, (p < 0.001). In multivariate analyses, BGN was an independent predictive factor of significant fibrosis (OR, 1.030; 95% CI: 1.011 - 1.048; p < 0.001). ROC analysis revealed that BGN was statistically significant in determination of significant fibrosis (AUROC, 0.955; 95% CI, 0.877 - 0.990; p < 0.001). Best cutoff value was 189.58 pg/mL with the best sensitivity (93.55%) and specificity (87.18%). Serum BGN may be a new non-invasive indicative marker for the presence of NASH, significant fibrosis, and a treatment goal in the disease process.

Grading Bleomycin-Induced Pulmonary Fibrosis in ex vivo Mouse Lungs Using Ultrasound Image Analysis.

The aim of this study was to assess bleomycin-induced pulmonary fibrosis on ex vivo mouse lungs using ultrasound image grading and texture analysis. Excised mouse lungs were divided into 3 groups: control, mild fibrosis, and severe fibrosis based on the monitored indicators of health. B-mode ultrasound images were obtained via scanning the mouse lungs ex vivo. The surface smoothness, echo density, and angle of lesions or the lung margin were graded, and the imaging contrast, correlation, homogeneity, and entropy were assessed via texture analysis. The grades of surface smoothness, echo density, and angle were statistically higher for the severe fibrosis group compared with those of the control and mild fibrosis groups (P < .05). In addition, statistically significant differences in the contrast, correlation, and homogeneity between mild and severe fibrosis groups were observed (P < .05). The results obtained in this study suggest that ultrasound image grading and texture analysis are valuable and meaningful methods for assessing pulmonary fibrosis in a bleomycin mouse model.

Elevated mean platelet volume to platelet ratio predicts advanced fibrosis in chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is an important health problem that can cause liver cirrhosis and hepatocellular carcinoma. Recently, novel inflammatory markers from complete blood count have been used as a precursor of many clinical conditions. In this study, we investigated the role of hemogram parameters in predicting advanced liver fibrosis in chronic HCV patients. Patients who underwent percutaneous liver biopsy due to chronic HCV infection between 01.01.2011 and 01.08.2019 were included in this study. Liver biopsies were evaluated according to Ishak method. Patients were classified into those with mild fibrosis (F ≤ 2) and advanced fibrosis (F ≥ 3). Hemogram parameters of these groups were compared and their efficacy in predicting severe fibrosis was investigated. Of the 81 chronic HCV patients, 38 cases were in the mild fibrosis group and 43 cases were in the severe fibrosis group. Mean platelet volume, mean platelet volume to lymphocyte ratio, mean platelet volume to platelet ratio, and red cell distribution width to platelet ratio of the severe fibrosis group were significantly higher than those of the mild fibrosis group (P < 0.05 for all). In the ROC curve analysis, mean platelet volume to platelet ratio showed the biggest area under the curve in the prediction of advanced fibrosis. Mean platelet volume to platelet ratio may be an easy and practical biomarker to gain a preliminary insight into advanced fibrosis in chronic HCV patients.

Platelet indices significantly correlate with liver fibrosis in HCV-infected patients.

AimA total of 241 patients with chronic HCV infection were recruited to investigate the association between liver fibrosis and PLT counts, as well as with MPV, PDW and P-LCR indices.MethodsThe determination of PLT indices was carried out using a Sysmex XT-1800i automated hematology analyzer. Serological tests for HA, LN, C-IV and PIIINP were performed in 210 patients. The liver stiffness was measured in 69 patients by transient elastography (FibroScan).ResultsThe analysis showed that the four serum fibrosis markers were negatively correlated with PLT counts, but positively correlated with the MPV, PDW and P-LCR values. Moreover, a similar pattern was found after analyzing the FibroScan measurements, which were negatively correlated with PLT counts, but positively correlated with MPV, PDW and P-LCR values. We subdivided the HCV-infected patients into mild and advanced fibrosis groups. The PLT counts were significantly decreased and the MPV, PDW and P-LCR values were significantly increased in the advanced fibrosis group when compared with the mild fibrosis group.ConclusionsOur results demonstrate that not only the PLT counts but also the MPV, PDW and P-LCR indices significantly correlate with liver fibrosis in HCV-infected patients. Therefore, these indices may be useful laboratory measures for evaluating liver fibrosis progression.

A Predictive model of radiation-related fibrosis based on radiomic features of Magnetic Resonance Imaging

Radiation-related fibrosis of normal tissues remains unpredictable. To predict the fibrotic level of neck muscles after radiotherapy, we established a predictive model by using the magnetic resonance imaging (MRI) before and after radiotherapy based on Radionics in nasopharyngeal carcinoma patients. A total of three hundred and seven patients who received radical radiotherapy at a single institution were enrolled in this study. Patient's clinical were recorded systematically. The median follow-up time is 18 months (range, 11-22 months). According to the symptoms and physical signs, all patients were divided into two groups, the mild fibrosis group, and the severe fibrosis group. All MRI images included three sequences: T1 weighted scans, T2 weighted scans, and contrast-enhanced T1 weighted scans. Regions of interests (ROI), were delineated manually on an open infrastructure software platform, including sternocleidomastoids (SCMs), trapezius (T), levator scapulae (LS), and scalenus (S) muscles. The ROIs were divided into two parts by the level of the cricoid cartilage. The dose distribution was matched to each ROI individually via a software program, Min, Max, and Mean dose parameters were collected afterwards. One hundred ninety features were extracted via the software platform from pre- and post-radiotherapy images. The magnitude of change of each feature was computed as ‘delta change= [post-pre]/pre and then correlated to the grade of neck fibrosis using a machine learning algorithm, XGBoost. First, the image features delta changes with label information were both divided into training and testing sets. Then, based on the training dataset, a well-trained prediction model was provided by XGBoost. Afterward, the predictive model performance was assessed on the ‘testing’ set and reported in terms of area under the receiver operating characteristic curve (AUC). Most of the patients enrolled are male (73.6%), mean age was 47 years, locally advanced stage (89.3%), receiving concurrent chemo-radiotherapy as the primary treatment (90.6%). By the end of the final follow-up, most of the patients were rated as mild fibrosis (85.6%). We found that the image features from T1+C modality outperformed all the other feature combinations in terms of the prediction accuracy, with an AUC of 0.61. The prediction model based on radiomics features from T1+C modality have the best performance in prediction of the grade of severity of post-radiotherapy neck fibrosis. This might help to guide radiotherapy treatment planning and organs at risk sparing for the better quality of life outcomes.Abstract 3389; Table 1The categorization of muscle fibrosis on the neck after treatment among 307 patientsLevelConditionsMild1. Self-Rating: 0-4 points2. No facial edema3. No upper limb pains4. Neck activity is unrestrictedSevere1. Self-Rating: 5-10 points2. Facial edema3. Upper limb pains4. Neck activity is limited Open table in a new tab

PLATELET INDICES FOR PREDICTING LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B INFECTION

Chronic Hepatitis B involves liver parenchymal destruction leading to fibrosis. Decreased serum thrombopoietin associated with liver cell failure is thought as the leading cause of thrombocytopenia. Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) describe platelet size and degree of variation in platelet size respectively. The researchers intended to investigate whether platelet count, MPV, and PDW were variables to determine the severity of liver fibrosis in chronic hepatitis B patients. An observational study was carried out at the Dr. Wahidin Sudirohusodo Hospital Makassar from January 2015 until December 2016. A total of 100 chronic hepatitis B patients with negative HBeAg who underwent Fibroscan and complete blood count test were included in this study. A total of 100 chronic hepatitis B patients comprising, 11 with severe liver fibrosis, 16 with moderate liver fibrosis, 46 with mild liver fibrosis, and 27 with normal liver. There were significant differences in platelet count and MPV among liver fibrosis groups with p-value &lt;0.001 and 0.046 respectively. No significant difference was observed for PDW among liver fibrosis groups (p=0.131). This study showed that platelet count and MPV were significantly different among the normal group, mild liver fibrosis group, moderate liver fibrosis group and severe liver fibrosis group in chronic hepatitis B patients. The researchers recommend to carry out studies with larger samples in number and distributed more evenly.