Presence Of Significant Fibrosis Research Articles

Do Hepatic Fibrosis and Steatosis Measured by Hepatic Transient Elastography (FibroScan) Predict Cardiovascular Risk in Patients with Non-alcoholic Fatty Liver Disease: An Observational Cross-sectional Study

Objectives: Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk (CVR) in the previous studies. In the majority, ultrasonography has been used to diagnose and stage NAFLD, which lacks sensitivity and is non-quantitative. Other more sensitive, comprehensive, and quantitative diagnostic tools such as vibration-controlled transient elastography (TE) have largely been underused in research work. TE-driven liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) provide an accurate and simplified estimation of liver fibrosis and steatosis, respectively. Therefore, we aimed to analyze the association between these two objective, robust parameters and CVR. Materials and Methods: In this observational cross-sectional study, NAFLD participants were divided into two distinct categories of steatosis (CAP <290 and ≥290 dB) and fibrosis (LSM <10 and ≥10 kPa). Their CVR assessment was done by calculating Framingham risk score (FRS), American College of Cardiology/American Heart Association Pooled Cohort Equation Score (ACC/AHA PCES), and carotid intimal medial thickness (CIMT). Results: A greater number of participants presented with mild-moderate fibrosis (n = 41, 62.1%) as compared to severe fibrosis (n = 25, 37.8%) whereas severe steatosis participants predominated (n = 52, 78%) as compared to mild-moderate steatosis. The presence of significant fibrosis (LSM ≥10 kPa) was independently and significantly associated with FRS, ACC/AHA PCES, and CIMT. On the other hand, the presence of significant steatosis (CAP ≥290 dB/m) was not significantly associated with any CVR marker (FRS, ACC/AHA PCES, or CIMT), though a greater number of participants with CIMT >0.7 belonged to severe steatosis group. Conclusion: Subjects with severe fibrosis (LSM ≥10) had a significantly higher CVR, whereas severe steatosis (CAP ≥290) alone failed to predict CVR. Therefore, CVR reduction strategies can be targeted primarily in NAFLD subjects with fibrosis, particularly in resource-limited healthcare settings.

Comparison of the fibrosis degree using acoustic radiation force impulse elastography and diffusion-weighted magnetic resonance imaging in chronic hepatitis cases.

The aim of this study was to investigate the correlation of fibrosis stages in cases of chronic hepatitis by comparing shear wave elastography and diffusion-weighted magnetic resonance imaging. A total of 46 chronic hepatitis patients with an age range of 20-50 years were classified into three groups based on their fibrosis stages. Comparison group 1: the presence of fibrosis (S0 and S1≤); comparison group 2: the presence of significant fibrosis (≤S2 and S3≤); and comparison group 3: the presence of cirrhosis (≤S4 and S6). Shear wave velocities were measured by acoustic radiation force impulse elastography. Diffusion-weighted magnetic resonance imaging was performed on a 3.0 Tesla MRI device. In comparison group 1 (S0 and S1≤), the area under the curve, sensitivity, and specificity of acoustic radiation force impulse values were 0.784, 87, and 60%, respectively, while these values were 0.718, 80, and 66%, respectively, for apparent diffusion coefficient . In comparison group 2 (≤S2 and S3≤), the area under the curve, sensitivity, and specificity of acoustic radiation force impulse values were 0.917, 80, and 86%, respectively, and the apparent diffusion coefficient values were 0.778, 90, and 66%, respectively. In comparison group 3, the area under the curve, sensitivity, and specificity of acoustic radiation force impulse values were 0.977, 100, and 95%, respectively. There was no statistically significant difference between the apparent diffusion coefficient values of the cases in the three groups (p=0.132). Noninvasive methods are gaining importance day by day for staging hepatic fibrosis. Acoustic radiation force impulse elastography was evaluated as a more reliable examination than diffusion-weighted magnetic resonance imaging in revealing the presence of fibrosis, determining significant fibrosis, and diagnosing cirrhosis.

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

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

Association of cardiovascular factors in diabetic patients with non-alcoholic fatty liver disease.

To evaluate the association between severity of hepatic steatosis/fibrosis with clinical, laboratory, and echocardiographic characteristics, including visceral obesity and type 2 diabetes mellitus (T2DM)-related micro- and macrovascular complications in diabetic patients with non-alcoholic fatty liver disease (NAFLD). We studied 60 consecutive NAFLD outpatients with T2DM, recording several demographic and clinical characteristics, trunk and visceral fat, cardiac ultrasound, and micro- and macrovascular complications of diabetes mellitus including microalbuminuria, diabetic peripheral neuropathy, peripheral vascular disease, and cardiac autonomic function. Severity of steatosis and fibrosis was evaluated with abdominal ultrasound and liver stiffness measurements, respectively. Twenty-three (41%) of the patients had grade 1 steatosis and mean liver stiffness was 7.5 ± 3kPa. After applying Bonferroni correction for multiple comparisons, ferritin concentration was the only factor significantly different between patients with mild (grade 1) compared to those with moderate/severe (grade 2/3) steatosis and showed good discriminative ability for the presence of moderate/severe steatosis (AUC: 0.74, sensitivity 88%, specificity 48%, PPV 74%, and NPV 72%). In addition, waist circumference was the only factor associated with the presence of significant fibrosis (≥ F2) with very good discriminative ability (AUC: 0.77, sensitivity 89%, specificity 45%, PPV 75%, and NPV 70%). Specific clinical and laboratory characteristics, which may be determined via widely accessible and noninvasivetechniques, were associated withseverity of diabetics NAFLD, taking into account echocardiographic characteristics, visceral obesity, and T2DM-related systemic complications.

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.

Non-alcoholic fatty liver disease in lean individuals or another rare differential diagnosis - a clinical case

Non-alcoholic fatty liver disease in lean individuals or another rare differential diagnosis - a clinical case

Non-Alcoholic Steatohepatitis Decreases Microsomal Liver Function in the Absence of Fibrosis.

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The 13C-aminopyrine breath test (ABT) evaluates the microsomal liver function and could be a potential candidate. We aimed to evaluate a potential change in liver function in NASH patients and to evaluate the diagnostic power of ABT to detect NASH. We performed a retrospective analysis on patients suspected of NAFLD who underwent a liver biopsy and ABT. 440 patients were included. ABT did not decrease in patients with isolated liver steatosis but decreased significantly in the presence of NASH without fibrosis and decreased even further with the presence of significant fibrosis. The predictive power of ABT as a single test for NASH was low but improved in combination with ALT and ultrasonographic steatosis. We conclude that microsomal liver function of patients with NASH is significantly decreased, even in the absence of fibrosis. The ABT is thus a valuable tool in assessing the presence of NASH; and could be used as a supplementary diagnostic tool in clinical practice.

Non-invasive assessment of liver fibrosis in autoimmune hepatitis: Diagnostic value of liver magnetic resonance parametric mapping including extracellular volume fraction

PurposeAutoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that leads to severe fibrosis and cirrhosis. The aim of this study was to determine the diagnostic value of T1 and T2 mapping as well as extracellular volume fraction (ECV) for non-invasive assessment of liver fibrosis in AIH patients.MethodsIn this prospective study, 27 patients (age range: 19–77 years) with AIH underwent liver MRI. T1 and T2 relaxation times as well as ECV were quantified by mapping techniques. The presence of significant fibrosis (≥ F2) was defined as magnetic resonance elastography (MRE)-based liver stiffness ≥ 3.66 kPa. MRE was used as reference standard, against which the diagnostic performance of MRI-derived mapping parameters was tested. Diagnostic performance was compared by utilizing receiver-operating characteristic (ROC) analysis.ResultsMRE-based liver stiffness correlated with both, hepatic native T1 (r = 0.69; P < 0.001) as well as ECV (r = 0.80; P < 0.001). For the assessment of significant fibrosis, ECV yielded a sensitivity of 85.7% (95% confidence interval (CI): 60.1–96.0%) and a specificity of 84.6% (CI 60.1–96.0%); hepatic native T1 yielded a sensitivity of 85.7% (CI 60.1–96.0%); and a specificity of 76.9% (CI 49.7–91.8%). Diagnostic performance of hepatic ECV (area under the curve (AUC): 0.885), native hepatic T1 (AUC: 0.846) for assessment of significant fibrosis was similar compared to clinical fibrosis scores (APRI (AUC: 0.852), FIB-4 (AUC: 0.758), and AAR (0.654) (P > 0.05 for each comparison)).ConclusionQuantitative mapping parameters such as T1 and ECV can identify significant fibrosis in AIH patients. Future studies are needed to explore the value of parametric mapping for the evaluation of different disease stages.

Predicting pulmonary hypertension in sarcoidosis; value of PH probability on echocardiography.

Pulmonary hypertension (PH) is a well-recognised complication of sarcoidosis. Non-invasive diagnosis is challenging due to limited accuracy of echocardiography in interstitial lung disease. This study evaluates the value of echocardiographic PH probability for diagnosing PH in pulmonary sarcoidosis. All consecutive patients between August 2015 and November 2018 were prospectively screened for PH, and classified as low, intermediate or high PH probability. Patients with intermediate or high PH probability were referred for right heart catheterisation. PH was defined as a mean pulmonary artery pressure of ≥ 25mm Hg. Additional data on pulmonary function and chest-CT was collected. Of all 479 patients, PH was present in 17 and absent in 19 patients. Six patients refused right heart catheterisation. PH was present in 33% and 75% of patients with intermediate and high PH probability respectively (n = 36). TRV max was measurable in 46% of all patients. Measurability did not correlate with FVC% predicted or presence of significant fibrosis. In intermediate and high PH probability, TRV max < 2.9m/s successfully ruled out PH whereas a TRV max > 3.4 confirmed PH in all patients. If TRV max was absent or in between 2.9 and 3.4, secondary echocardiographic signs were not able to improve the diagnostic accuracy. PH is unlikely in patients with a TRV max < 2.9m/s on echocardiography, whereas PH is highly suspected in a TRV max > 3.4m/s. Discrimination is challenging if the TRV max is between 2.9-3.4m/s or absent. Additional secondary signs do not improve discrimination. Decision making for further investigations should be made by an expert team.

Hepatitis B Surface Antigen Levels Can Be Used to Rule Out Cirrhosis in Hepatitis B e Antigen-Positive Chronic Hepatitis B: Results From the SONIC-B Study.

BackgroundSerum hepatitis B surface antigen (HBsAg) levels correlate with the duration of chronic hepatitis B virus (HBV) infection and may predict the extent of hepatic fibrosis.MethodsWe analyzed data from the SONIC-B database, which contains data from 8 global randomized trials and 2 large hepatology centers. Relationship between HBsAg levels and presence of significant fibrosis (Ishak 3–4) or cirrhosis (Ishak 5–6) were explored, and clinically relevant cutoffs were identified to rule out cirrhosis.ResultsThe dataset included 2779 patients: 1866 hepatitis B e antigen (HBeAg)-positive; 322 with cirrhosis. Among HBeAg-positive patients, lower HBsAg levels were associated with higher rates of significant fibrosis (odds ratio [OR], 0.419; P < .001) and cirrhosis (OR, 0.435; P < .001). No relationship was observed among HBeAg-negative patients. Among HBeAg-positive patients, genotype-specific HBsAg cutoffs had excellent negative predictive values (>97%) and low misclassification rates (≤7.1%) and may therefore have utility in ruling out cirrhosis. Diagnostic performance of the HBsAg cutoffs was comparable among patients in whom cirrhosis could not be ruled out with fibrosis 4 (FIB-4).ConclusionsHepatitis B virus genotype-specific HBsAg cutoffs may have utility in ruling out presence of cirrhosis in HBeAg-positive patients with genotypes B, C, and D and can be an adjunct to FIB-4 to reduce the need for further testing.

The natural course of non-alcoholic fatty liver disease.

Background and AimThe present study aims to describe the characteristics and long-term clinical outcomes of patients with non-alcoholic fatty liver disease (NAFLD).Material and MethodsA total of 1308 individuals with NAFLD were seen in the Liver Diseases Outpatient Clinic. Diagnosis of NAFLD in each case was based on biochemical, radiological and histological criteria, when available. After diagnosis, all NAFLD patients were administered a conventional diet and exercise program. The median follow-up period was 55.3 months.ResultsAt the time of the diagnosis, the mean age was 50.8±11.3 years, and female gender was slightly predominant (51.4%). The median body mass index was 29.2±4.7 kg/m2: 39% were obese. Seventeen percent of the patients had diabetes mellitus, 53% insulin resistance, 60% hyperlipidemia, and 32% hypertension. Median serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels were 31 U/L (range: 10–248 U/L), 45 U/L (range: 10–285 U/L) and 41 (range: 8–1200 U/L), respectively. Liver biopsy was performed in 293 individuals. The median NAFLD activity score was 5.0, median hepatic steatosis 2, ballooning 1, lobular inflammation 1, portal inflammation 0, and fibrosis 0. Of note, 41.3% of the samples (121/293) revealed the presence of fibrosis and 31% of the samples (37/121) showed significant fibrosis. With multivariate analysis, diabetes and obesity were associated with the presence of significant fibrosis. Among them, 765 patients (M/F: 353/412, mean age: 51.0±10.9) had at least six months of follow-up. In this group, from baseline to the end of the follow-up period, a significant improvement in the serum AST and ALT levels was observed.ConclusionNAFLD is a potentially progressive disease. Diabetes and obesity were associated with the presence of advanced fibrosis.

Assessing significant fibrosis using imaging-based elastography in chronic hepatitis B patients: Pilot study

BACKGROUNDAccurate detection of significant fibrosis (fibrosis stage 2 or higher on the METAVIR scale) is important especially for chronic hepatitis B (CHB) patients with high viral loads but with normal or mildly elevated alanine aminotransferase (ALT) levels because the presence of significant fibrosis is accepted as the indication for antiviral treatment. Liver biopsy is the reference standard for diagnosing significant fibrosis, but it is an invasive procedure. Consequently, noninvasive imaging-based measurements, such as magnetic resonance elastography (MRE) or two-dimensional shear-wave elastography (2D-SWE), have been proposed for the quantitative assessment of liver fibrosis.AIMTo explore MRE and 2D-SWE to identify fibrosis stage, and to compare their performance with that of serum-based indices.METHODSThe study enrolled 63 treatment-naïve CHB patients with high viral loads but with normal or mildly elevated ALT levels who underwent liver biopsy before a decision was made to initiate antiviral therapy. MRE and 2D-SWE were performed, and serum-based indices, such as FIB-4 and aspartate transaminase to platelet ratio index (APRI), were calculated. The diagnostic performances of MRE, 2D-SWE, FIB-4, and APRI for assessing significant fibrosis (≥ F2) and cirrhosis (F4) were evaluated with liver histology as the reference standard, using receiver operating characteristic analyses.RESULTSThe liver fibrosis stage was F0/F1 in 19, F2 in 14, F3 in 14, and F4 in 16 patients, respectively. MRE significantly discriminated F2 from F0/1 (P = 0.022), whereas 2D-SWE showed a broad overlap in distinguishing those stages. MRE showed a higher correlation coefficient value with fibrosis stage than 2D-SWE with fibrosis stage (0.869 vs 0.649, Spearman test; P < 0.001). Multivariate linear regression analyses showed that fibrosis stage was the only factor affecting the values of MRE (P < 0.001), whereas body mass index (P = 0.042) and fibrosis stage (P < 0.001) were independent factors affecting 2D-SWE values. MRE performance for diagnosing significant fibrosis was better [area under the curve (AUC) = 0.906, positive predictive value (PPV) 97.3%, negative predictive value (NPV) 69.2%] than that of FIB-4 (AUC = 0.697, P = 0.002) and APRI (AUC = 0.717, P = 0.010), whereas the performance of 2D-SWE (AUC = 0.843, PPV 86%, NPV 65%) was not significantly different from that of FIB-4 or APRI.CONCLUSIONCompared to SWE, MRE might be more precise non-invasive assessment for depicting significant fibrosis and for making-decision to initiate antiviral-therapy in treatment-naïve CHB patients with normal or mildly-elevated ALT levels.

Evaluating feasibility and accuracy of non-invasive tests for nonalcoholic fatty liver disease in severe and morbid obesity.

In obese individuals, nonalcoholic fatty liver disease (NAFLD) is common but often goes undiagnosed, and therefore untreated. The presence of significant fibrosis is a key determinant of NAFLD progression, and liver steatosis has substantial cardiovascular implications. We aimed to determine the diagnostic accuracy of common noninvasive diagnostic tests for steatosis and fibrosis in the obese. We recruited 182 severely and morbidly obese individuals undergoing bariatric surgery (age 44 ± 12 years, body mass index 45.1 ± 8.3 kg/m2). Medical history, blood tests and liver biopsy were taken on the day of surgery. Serum steatosis and fibrosis scores were calculated. In a subgroup of patients, transient elastography with controlled attenuation parameter (TE/CAP) (n = 82) and proton magnetic resonance spectroscopy (1H-MRS) (n = 49) were performed. 1H-MRS had excellent diagnostic accuracy for steatosis, with strong correlation to steatosis (r = 0.647, p < 0.001), good AUROC (0.852, p = 0.001), sensitivity (81.3%) and specificity (87.5%). However, due to low feasibility in this cohort (65.3% success), this was substantially decreased with intention-to-diagnose analysis (sensitivity 50.0%, specificity 60.9%). CAP had good feasibility (80.5%), and performed better in intention-to-diagnose analysis (AUROC 0.688, sensitivity 84.8%, specificity 47.2%). Serum steatosis scores performed poorly, with comparable accuracy to ALT. For significant fibrosis, TE had the best accuracy (AUROC 0.903, p = 0.007), which remained reasonable after intention-to-diagnose analysis (sensitivity 100%, specificity 59.0%). A combination approach using CAP with ALT for steatosis and TE with Forn index for fibrosis yielded reasonable overall accuracy. 1H-MRS and TE/CAP had greatest accuracy for NAFLD-related steatosis and fibrosis. Failure rates in obesity significantly diminished diagnostic ability. Use of a combination of serum and imaging tests improved overall feasibility of assessment and diagnostic accuracy in obese individuals.

Reproducibility of shear wave elastography (SWE) in patients with chronic liver disease.

The presence of significant fibrosis is an indicator for liver disease staging and prognosis.The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14–16.7 kPa and were 4.49 kPa and 2.92–7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87–0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity.

Characteristics of Significant Fibrosis by Transient Elastography and Evaluation of Non-Invasive Fibrosis Tests in Patients With Primary Biliary Cholangitis

Introduction: Primary biliary cirrhosis (PBC) affects up to 40 thousand persons in the United States of America. Liver fibrosis can be assessed by transient elastography (TE) and serum tests such as Fibrosis-4 index (FIB- 4), aspartate transaminase to platelet ratio index (APRI) and aspartate transaminase to alanine transaminase ratio (AST/ALT). Comparison of serum tests with TE in PBC patients has not been studied. The aim was to characterize the population of PBC patients and assess liver fibrosis using transient elastrography (TE) and validated serum tests.Figure: Correlation of non significant fibrosis (F0-F1) and significant fibrosis (F2-F4) to validated serum tests in patients with primary biliary cholangitis (PBC).Table: Table. General characteristics and mean values for common lab testsMethods: This is a cross-sectional retrospective study focusing on patients with PBC. A total of 31 patients who have PBC and had TE from March 2014 to March 2017 were included. The correlation between the presence of significant fibrosis by TE and data of other non-invasive tests were performed with crosstab analysis. Chi-square tests were performed to determine statistical significance. Results: The study group was consisting mainly of patients with Caucasian ethnicity at 71 %, and the predominant gender was female at 90.3%. The results of LSMs showed a mean value of 5.6 ± 2.9 kPa. The LSM values corresponding to F2-F4 were seen in 4 of 31 patients (12.9%). A total of 85.7% were anti mitochondrial antibody (AMA) positive, 29.4 % were anti-nuclear antibody (ANA) positive. Twelve of 31 patients (39.3%) with available data were alcohol users at the time of the TE procedure. Among the four with F2-F4 fibrosis per TE measurements, 3 were females (75%) and the mean age was 66±7.1 years. The mean BMI was 27.9±8.3 kg/m2. Fibrosis-4-index tests showed statistical correlation with data from serum tests. For Fib-4-index 100% of patients with F2-F4 by LSM had a value of >1.45 and 64% of patients with F0-F2 had Fib-4 <1.45. For APRI score no patients had a positive value of >1 and no crosstab evaluation could be performed. Conclusion: Our study population were predominantly elderly Caucasian females consistent with other studies but other ethnicity groups are also represented. In PBC patients, Fib-4 was more predictive of significant fibrosis than APRI and AST/ALT, Fib-4 was better for excluding PBC patients with significant fibrosis than including. Considering the fact that liver biopsy is invasive. Use of these serum tests can be questionable if used alone but It can be a useful tool taking into consideration overall clinical context as well as additional tests used.

Current Modalities of Fibrosis Assessment in Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health concern. In the subset of NAFLD patients with non-alcoholic steatohepatitis (NASH), the presence of significant fibrosis at index assessment is associated with poor prognosis and increased mortality. Hence, there is a growing need to accurately assess and stage fibrosis. Liver biopsy, the current gold standard, has limitations with sampling error and is invasive, with associated inherent risk. This has led to a host of non-invasive means of assessing fibrosis, which has garnered relevance in a disease that requires serial assessment of fibrosis longitudinally over time. This review discusses, comprehensively, the various tools available to the clinician for the assessment of fibrosis, including the various scoring systems used in liver biopsy, the non-invasive means of serum biomarkers, such as the highly-validated NAFLD fibrosis score, and the imaging-based modalities, such as transient elastography and magnetic resonance elastography.

Serum platelet-derived growth factor BB levels: a potential biomarker for the assessment of liver fibrosis in patients with chronic hepatitis B.

Few studies have investigated serum levels of platelet-derived growth factor (PDGF) in patients with chronic hepatitis B (CHB). The present study aimed to determine whether PDGF-BB could serve as a potential biomarker for the detection of liver fibrosis. From October 2013 to August 2015, 465 patients with CHB were enrolled prospectively in this study. All patients underwent liver biopsy and staging based on the Ishak system. The serum PDGF-BB level was measured quantitatively by ELISA. The serum PDGF-BB level was negatively correlated with fibrosis stage in all patients (p = 0.003, Spearman's rho=-0.16) and was significantly different between fibrosis stages. The areas under the receiver operating characteristics curves (AUROCs) for serum PDGF-BB level and PGT score (a combination of PDGF-BB, gamma-glutamyl transpeptidase, and platelet levels) were 0.667 and 0.831, respectively, for patients with significant fibrosis and normal alanine aminotransferase (ALT) levels. The AUROCs for aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) were 0.823 and 0.821, respectively. Importantly, a cut-off value of 1.05 and 1.43, respectively, resulted in a sensitivity of 0.95 and 0.52, a specificity of 0.29 and 0.95, a positive predictive value of 0.30 and 0.79, and a negative predictive value of 0.96 and 0.86. The rate of correct diagnosis was up to 88.4% when using cut-offs of 1.05 and 1.43 for the absence or presence of significant fibrosis, respectively. Serum PDGF-BB decreased remarkably as fibrosis progressed, and this could be used as a non-invasive biomarker for the assessment of fibrosis stage in patients with CHB.

Early non-invasive selection of patients at high risk of severe hepatitis C recurrence after liver transplantation.

The early identification of patients at high risk of severe post liver transplant hepatitis C recurrence is relevant, as these patients may be treated using interferon (IFN)-free regimens. In a retrospective study with prospectively collected data, we investigated whether the use of several non-invasive methods (fibrosis 4 index [FIB-4], AST-to-platelets ratio index [APRI], enhanced liver fibrosis test [ELF], IFN-γ-inducible protein 10 [IP-10], and transient elastography by Fibroscan) and their combinations 6 months after transplantation could identify those recipients at higher risk of severe recurrence, defined by the presence of significant fibrosis (F ≥2) and/or portal hypertension (hepatic venous pressure gradient ≥6 mmHg) 12 months after transplant. Seventy-two hepatitis C virus (HCV)-infected liver transplant patients and 10 recipients in whom HCV was eradicated before transplantation were included in the study. The levels of all biomarkers were significantly higher in HCV-infected recipients than in controls. Among HCV recipients, levels of biomarkers were significantly higher in patients with severe recurrence. Although there were no statistically significant differences between biomarkers, APRI, ELF, and FIB-4 obtained the highest area under the ROC curve values. The combination of serum biomarkers with Fibroscan increased the negative and positive predictive values, although diagnostic accuracy of individual tests was not significantly improved. Patients at higher risk of severe HCV recurrence can be identified early, 6 months after transplantation, using readily available non-invasive methods.

Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution.

Conventional ultrasound (US) is reliable to reveal the presence of non-alcoholic fatty liver disease (NAFLD), but it is neither sensitive nor specific to reveal fibrosis clues, except in advanced stages where signs of cirrhosis are evident. NALFD fibrosis score is a non-invasive parameter that predicts well the presence of significant fibrosis, but correlations with US parameters are lacking. The aim of this study was, therefore, to compare resistive index of hepatic artery (HARI) of NAFLD patients with different severity degrees of diffuse fatty liver disease vs HARI of controls, and to compare HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls. This was a spontaneous, no-profit observational study conducted in our US department between December 2013 and July 2014. Patients with NAFLD with different severity of disease and healthy controls were included. Echogenicity and size of liver and spleen, maximum portal vein velocity, RI, peak systolic velocity (PSV), and end diastolic velocity (EDV) of splenic artery, PSV, EDV, and RI of hepatic artery, and NAFLD fibrosis score were acquired and compared between groups. HARI was significantly lower in NAFLD patients than controls (p<0.0001). A significant difference was also found between the groups of NAFLD severity (p<0.0001). There was also a difference between HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls (p<0.0001) with a positive correlation between HARI and NAFLD fibrosis score. Conventional Doppler US can be helpful to detect NAFLD patients with the risk of fibrous tissue accumulation. HARI tends to exceed the range of controls for patients with NAFLD fibrosis score greater than 0.675. The detection of HARI greater than 0.9 in NAFLD patients, regardless of the US degree of severity of steatosis, might suggest the execution of biopsy to predict the risk of progression to steatohepatitis and fibrous tissue accumulation. Low values of HARI may be expression of lower risk, which does not necessitate any biopsy.

Liver Fibrosis in HIV Patients Receiving a Modern cART: Which Factors Play a Role?

Liver-related death in human immunodeficiency virus (HIV)-infected individuals is about 10 times higher compared with the general population, and the prevalence of significant liver fibrosis in those with HIV approaches 15%. The present study aimed to assess risk factors for development of hepatic fibrosis in HIV patients receiving a modern combination anti-retroviral therapy (cART). This cross-sectional prospective study included 432 HIV patients, of which 68 (16%) patients were anti-hepatitis C virus (HCV) positive and 23 (5%) were HBsAg positive. Health trajectory including clinical characteristics and liver fibrosis stage assessed by transient elastography were collected at inclusion. Liver stiffness values >7.1 kPa were considered as significant fibrosis, while values >12.5 kPa were defined as severe fibrosis. Logistic regression and Cox regression uni- and multivariate analyses were performed to identify independent factors associated with liver fibrosis. Significant liver fibrosis was detected in 10% of HIV mono-infected, in 37% of HCV co-infected patients, and in 18% of hepatitis B virus co-infected patients. The presence of diabetes mellitus (odds ratio [OR] = 4.6) and FIB4 score (OR = 2.4) were independently associated with presence of significant fibrosis in the whole cohort. Similarly, diabetes mellitus (OR = 5.4), adiposity (OR = 4.6), and the FIB4 score (OR = 3.3) were independently associated with significant fibrosis in HIV mono-infected patients. Importantly, cumulative cART duration protected, whereas persistent HIV viral replication promoted the development of significant liver fibrosis along the duration of HIV infection. Our findings strongly indicate that besides known risk factors like metabolic disorders, HIV may also have a direct effect on fibrogenesis. Successful cART leading to complete suppression of HIV replication might protect from development of liver fibrosis.