Measurement Of Liver Fibrosis Research Articles

Diagnostic role of the fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score as a noninvasive tool for liver fibrosis scoring.

Nonalcoholic fatty liver disease (NAFLD) is characterized by liver fibrosis, which serves as a crucial indicator of its progression and prognosis. Owing to the limitations of biopsy, which is the gold standard for measuring liver fibrosis, a reliable and noninvasive marker is required. We evaluated the diagnostic role of the fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) in patients with NAFLD with varying severities of liver fibrosis. The FIB-4 index and NFS were calculated using laboratory data from 121 patients who underwent liver biopsies between January 2022 and December 2023. The results were compared with those of the Scheuer scoring system for liver biopsies (F0, F1 + F2, and F3 + F4) to determine the sensitivity and specificity of the FIB-4 index and the liver disease fibrosis score in detecting and staging liver fibrosis. Twenty-one patients had advanced fibrosis (F3-F4), and 100 had minimal or mild fibrosis (F0-F2). The degree of liver fibrosis increased with decreased albumin, alanine aminotransferase and platelet count levels, and increasing age. Receiver operating characteristic curve analysis for the FIB-4 index and NFS revealed that the areas under the curve for the FIB-4 index and NFS were 0.895 (95% confidence interval: 0.836-0.954) and 0.882 (95% confidence interval: 0.813-0.952), respectively. The FIB-4 indices showed 95.24% sensitivity at a cutoff point of 1.30, and 85% specificity at a cutoff point of 2.67, while the NFS indices showed 95.24% sensitivity at -1.455 cutoff point and 95% specificity at a cutoff point of 0.676. The FIB-4 index and NFS may replace biopsy for the detection of fibrosis in patients with NAFLD.

PREDICTIVE VALUE OF FIBROSIS-4 INDEX FOR HIGHER TROPONIN LEVELS IN ACUTE CORONARY SYNDROME

Objective: Non-alcoholic fatty liver disease, a condition that affects nearly one-third of the population, is associated with cardiovascular disease and is the leading cause of death. Studies have found that peak troponin level is a strong predictor of all- cause death and infarct area width in the left ventricle after acute coronary syndrome. The fibrosis-4 (FIB-4) index is a noninvasive clinical tool that combines four laboratory parameters to measure liver fibrosis. The relationship between the FIB-4 index and peak troponin level is unclear. We speculated that a higher FIB-4 index might be associated with higher peak troponin levels, as it is linked to cardiovascular disease. We aimed to explore the relationship between peak troponin levels and the FIB-4 index in patients with acute coronary syndrome. Material and Methods: This was an observational, cross- sectional cohort study. A total of 302 inpatients with acute coronary syndrome admitted to our clinic between June and September 2023 were enrolled. The FIB-4 index and peak troponin levels were evaluated. The maximum mean troponin level was determined, and two patient groups were formed and compared according to whether it was below or above this level. Results: We demonstrated for the first time that the FIB-4 index is a strong indicator of peak troponin levels in patients with acute coronary syndrome (odds ratio: 2.301, 95% CI 1.667-3.172, p

Diagnostic performance of Mac-2-binding protein glycosylation isomer (M2BPGi) as a liver fibrosis marker in chronic hepatitis C patients with chronic kidney disease on hemodialysis

Liver fibrosis assessment is essential to determine the initiation, duration, and evaluation of chronic hepatitis C treatment. Therefore, the study aimed to assess the role of Mac-2-binding protein glycosylation isomer (M2BPGi) as a biomarker to measure liver fibrosis in chronic hepatitis C patients with chronic kidney disease on hemodialysis. This study used a cross-sectional design. Serum M2BPGi level and transient elastography results were evaluated in 102 chronic hepatitis C patients with CKD on HD, 36 CKD on HD patients, and 48 healthy controls. ROC analysis was conducted to identify the optimal cutoff values to assess significant fibrosis and cirrhosis among chronic hepatitis C patients with CKD on HD. In chronic hepatitis C patients with CKD on HD, the level of serum M2BPGi had a moderately significant correlation with transient elastography (r = 0.447, p < 0.001). The median serum M2BPGi was higher among CKD on HD patients compared to healthy controls (1.260 COI vs. 0.590 COI, p < 0.001) and was even higher in chronic hepatitis C patients with CKD on HD compared to CKD on HD group (2.190 COI vs. 1.260 COI, p < 0.001). It is also increased according to the severity of liver fibrosis: 1.670 COI, 2.020 COI, and 5.065 COI for F0-F1, significant fibrosis, and cirrhosis, respectively. The optimal cutoff values for diagnosing significant fibrosis and cirrhosis were 2.080 and 2.475 COI, respectively. Serum M2BPGi could be a simple and reliable diagnostic tool for evaluating cirrhosis in chronic hepatitis C patients with CKD on HD.

Single Breath-Hold 3-Dimensional Magnetic Resonance Elastography Depicts Liver Fibrosis and Inflammation in Obese Patients.

Three-dimensional (3D) magnetic resonance elastography (MRE) measures liver fibrosis and inflammation but requires several breath-holds that hamper clinical acceptance. The aim of this study was to evaluate the technical and clinical feasibility of a single breath-hold 3D MRE sequence as a means of measuring liver fibrosis and inflammation in obese patients. From November 2020 to December 2021, subjects were prospectively enrolled and divided into 2 groups. Group 1 included healthy volunteers (n = 10) who served as controls to compare the single breath-hold 3D MRE sequence with a multiple-breath-hold 3D MRE sequence. Group 2 included liver patients (n = 10) who served as participants to evaluate the clinical feasibility of the single breath-hold 3D MRE sequence in measuring liver fibrosis and inflammation. Controls and participants were scanned at 60 Hz mechanical excitation with the single breath-hold 3D MRE sequence to retrieve the magnitude of the complex-valued shear modulus (|G*| [kPa]), the shear wave speed (Cs [m/s]), and the loss modulus (G" [kPa]). The controls were also scanned with a multiple-breath-hold 3D MRE sequence for comparison, and the participants had histopathology (Ishak scores) for correlation with Cs and G". For the 10 controls, 5 were female, and the mean age and body mass index were 33.1 ± 9.5 years and 23.0 ± 2.1 kg/m 2 , respectively. For the 10 participants, 8 were female, and the mean age and body mass index were 45.1 ± 16.5 years and 33.1 ± 4.0 kg/m 2 (obese range), respectively. All participants were suspected of having nonalcoholic fatty liver disease. Bland-Altman analysis of the comparison in controls shows there are nonsignificant differences in |G*|, Cs, and G" below 6.5%, suggesting good consensus between the 2 sequences. For the participants, Cs and G" correlated significantly with Ishak fibrosis and inflammation grades, respectively ( ρ = 0.95, P < 0.001, and ρ = 0.84, P = 0.002). The single breath-hold 3D MRE sequence may be effective in measuring liver fibrosis and inflammation in obese patients.

Intra-individual comparison of two-dimensional shear wave elastography techniques using plane wave imaging and the multi-beam technique: are they interchangeable in measuring liver fibrosis?

This study compared two different two-dimensional shear wave elastography techniques-plane wave imaging (PWI) and multi-beam (MB) imaging-from the same vendor to evaluate liver fibrosis. In this prospective study, 42 patients with chronic liver disease who had recently undergone magnetic resonance elastography (<3 months) were enrolled, and their liver stiffness (LS) values were measured using PWI or MB. The LS values (kPa) were compared using the Wilcoxon rank-sum test. Inter-technique reproducibility and intra-observer repeatability were assessed using Bland-Altman analysis with 95% limits of agreement (LOA) and coefficients of variation (CVs). The cutoff values for predicting severe fibrosis (≥F3) were estimated using receiver operating characteristic curve (ROC) analysis, with magnetic resonance elastography as the reference standard. PWI exhibited technical failure in four patients. Therefore, 38 patients underwent both examinations. The LS values showed moderate agreement between PWI and MB (CV, 22.5%) and 95% LOA of -3.71 to 7.44 kPa. The MB technique showed good intra-observer agreement (CV, 8.1%), while PWI showed moderate agreement (CV, 11.0%). The cutoff values of PWI and MB for diagnosing ≥F3 were 12.3 kPa and 13.8 kPa, respectively, with areas under the ROC curve of 0.89 and 0.95 (sensitivity, 100% and 100%; specificity, 65.6% and 85.7%). The LS values significantly differed between PWI and MB, hindering their interchangeable use in longitudinal follow-up. Considering its low technical failure rate and better repeatability, the MB technique may be preferable for evaluating liver fibrosis in chronic liver disease patients.

New FIB-4 and NFS cutoffs to guide sequential non-invasive assessment of liver fibrosis by magnetic resonance elastography in NAFLD

Introduction and ObjectivesLiver fibrosis is an important prognosis marker in non-alcoholic fatty liver disease (NAFLD). Biopsy has been considered the gold-standard method for measuring liver fibrosis; however, it is an invasive procedure. Non-invasive diagnostic tools have been developed, such as clinical scores and magnetic resonance elastography (MRE), which is the most accurate non-invasive method to determine liver fibrosis. Thus, the aim was to determine the NAFLD Fibrosis Score (NFS) and the Fibrosis-4 Score (FIB-4) cut-off points that best identify NAFLD patients at risk for developing liver fibrosis. Patients and MethodsSingle-center cross-sectional study with prospective recruitment of NAFLD (training-cohort) and MAFLD (validation-cohort) patients undergoing MRE. The NFS and the FIB-4 cut-off points that best-differentiated patients with fibrosis, using the MRE as the standard method, were determined. ResultsTwo cohorts were analyzed, a training cohort that included the initial 183 patients with NAFLD and a validation cohort that included 289 patients. In the training cohort, 60.1% had mild steatosis and 11.5% had liver fibrosis ≥ F1 by MRE. ROC curves were developed for FIB-4 and NFS, and the cut-off points chosen were 1.505 (sensitivity=85% and specificity=86%) for FIB-4 and -0.835 (sensitivity=100% and specificity=70%) for NFS, showing greater specificity than the cut-off points currently used (51% and 76%, respectively). The two cohorts exhibited similar characteristics and similar sensitivity and specificity results for the chosen cut-off points. ConclusionsThis study has shown cut-off points with greater specificity and excellent sensitivity to guide the indication for further liver evaluation by MRE in NAFLD patients.

346.8: Liver Fibrosis Measured by Magnetic Resonance Elastography Predicts Late Recurrence of HCC After Hepatic Resection

Introduction: Hepatocellular carcinoma is one of the most common cancers in the world. The best curative treatment for hepatocellular carcinoma is liver resection. However, it has been known that there is a high possibility of recurrence if there is cirrhosis even after liver resection. Some studies recently explored the differences between early and late recurrence and investigated the risk factors for each type of recurrence. Predictive factors for early recurrence, i.e. recurrence within 24 months of surgery, are well established and are mainly tumor- and treatment related (i.e. tumor size, tumor number, presence of microsatellites, and vascular invasion). By contrast only poor data are available for the drediction of late recurrence, io.e. recurrence 24 months post-surgery, which is probably related to the evolution of the underlying chronic liver disease. Among the possivle predictive factors for late HCC recurrence, the presence and the degree of portal hypertension(PH) could play an important role. In the last decede, several authros have tried to assess PH with non-invasive methods.in particular the role of liver stiffness have been investigated as non-invasive marker of PH and its complication.Generally, transient elastography (TE) used for liver stiffness measurement (LSM) for a long time. In addition to TE, magnetic resonance elastography (MRE) has emerged as another non-invasive method to evaluated liver fibrosis. MRE has advantages over TE including the acquisition of images that can be referred for LSM and a larger sampling area. Owing to these theoretical merits of MRE over TE, MRE provided significantly better performance in assessing liver fibrosis than TE in previous studies. Method: Between January 2014 and December 2018, 603 patients underwent Hepatic resection (HR) for HCC. Among 603 patients, 245 patient checked MRE, but 5 cases had technical failure. We analyzed 241 patients. HCC recurrence was defined the recent AASLD guidelines as early (if occurring <24 months) or late (if occurring >24 months). The follow-up protocol included a clinical assessment by physical examination, US and laboratory exams every 3 months. HCC recurrence was diagnosed according to modifications of alpha-fetoprotein levels and US appearance, confirmed either by multiphasic CT or multiphasic MRI. Clinical data were analyzed disease-free survival rate (DFSR) according to serum alpha-fetoprotein (AFP) level, Magnetic resonance elastography (MRE). Result: Between January 2014 and December 2018, HR for HCC group has incidence of recurrence is 40.2% (97/241). Early recurrence rate is 22.0% (53/241) rate recurrent rate is 18.3% (44/241). Conclusion: Magnetic resonance elastography that measure liver fibrosis predict de novo recurrence after hepatic resection for hepatocellular carcinoma. So we consider liver transplantation in severe stiffness liver parenchyma.

Evaluation of galectin-3 and intestinal fatty acid binding protein as serum biomarkers in autosomal recessive polycystic kidney disease.

Autosomal recessive polycystic kidney disease (ARPKD) causes fibrocystic kidney disease, congenital hepatic fibrosis, and portal hypertension. Serum galectin-3 (Gal-3) and intestinal fatty acid binding protein (I-FABP) are potential biomarkers of kidney fibrosis and portal hypertension, respectively. We examined whether serum Gal-3 associates with kidney disease severity and serum I-FABP associates with liver disease severity in ARPKD. Cross-sectional study of 29 participants with ARPKD (0.2-21years old) and presence of native kidneys (Gal-3 analyses, n = 18) and/or native livers (I-FABP analyses, n = 21). Serum Gal-3 and I-FABP were analyzed using enzyme linked immunosorbent assay. Kidney disease severity variables included estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV). Liver disease severity was characterized using ultrasound elastography to measure liver fibrosis, and spleen length and platelet count as markers of portal hypertension. Simple and multivariable linear regression examined associations between Gal-3 and kidney disease severity (adjusted for liver disease severity) and between I-FABP and liver disease severity (adjusted for eGFR). Serum Gal-3 was negatively associated with eGFR; 1 standard deviation (SD) lower eGFR was associated with 0.795 SD higher Gal-3 level (95% CI -1.116, -0.473; p < 0.001). This association remained significant when adjusted for liver disease severity. Serum Gal-3 was not associated with htTKV in adjusted analyses. Overall I-FABP levels were elevated, but there were no linear associations between I-FABP and liver disease severity in unadjusted or adjusted models. Serum Gal-3 is associated with eGFR in ARPKD, suggesting its value as a possible novel biomarker of kidney disease severity. We found no associations between serum I-FABP and ARPKD liver disease severity despite overall elevated I-FABP levels.

Ezetimibe combination therapy with statin for non-alcoholic fatty liver disease: an open-label randomized controlled trial (ESSENTIAL study)

BackgroundThe effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD).MethodsA randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change.ResultsCombination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104).ConclusionsEzetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population.Trial registrationThe trial was registered at ClinicalTrials.gov (registration number: NCT03434613).

ID: 3527010 DEFINING OPTIMAL TECHNIQUE FOR ENDOSCOPIC ULTRASOUND SHEAR WAVE ELASTOGRAPHY (EUS-SWE): A COMBINED BENCHTOP AND ANIMAL MODEL STUDY WITH COMPARISON TO TRANSABDOMINAL SWE

Transabdominal shear wave elastography (SWE) is a non-invasive tool used to measure liver fibrosis and is similar to transient elastography (Fibroscan) for liver fibrosis staging. The accuracy of both transabdominal modalities may be strained in patients with large body habitus. In contrast, endoscopic ultrasound (EUS) SWE is a relatively new modality that could bypass this limitation, as the liver is closely visualized regardless of external abdominal fat. We aimed to define optimal technique with the EUS-SWE technology via benchtop and animal model studies, and compare its accuracy to transabdominal SWE.

Liver stiffness measurement predicts short-term and long-term outcomes in patients with hepatocellular carcinoma after curative liver resection

Background and aimHepatocellular carcinoma is one of the commonest cancer in the world. Despite curative resection, recurrence remains the largest challenge. Many risk factors were identified for predicting recurrence, including liver fibrosis and cirrhosis. Transient elastography (Fibroscan) is an accurate tool in measuring liver fibrosis. This study aimed to evaluate the use of preoperative liver stiffness measurement (LSM), with Fibroscan in predicting long-term recurrence of hepatocellular carcinoma (HCC) after curative resection. MethodA prospective cohort study was conducted from February 2010 – June 2017 in Prince of Wales hospital. All consecutive patients with HCC undergone hepatectomy were included. Demographic factors, preoperative LSM, tumor characteristics and operative details were assessed. Primary outcome and secondary outcome were overall survival and disease free survival at 1 year, 3 year and 5 year respectively. ResultsA total of 401 cases were included. Patients with LSM ≥12kPa had significantly lower 5-year overall survival rate (75.1% vs 57.3%, p < 0.001) and disease free survival rate (45.8% vs. 26.7%, p < 0.001). On multivariate analysis, pre-operative creatinine and vascular invasion of tumor were significant factors in predicting early recurrence (p = 0.012 and p = 0.004). LSM ≥12kPa were the only significant factor in predicting late recurrence (p = 0.048). ConclusionPre-operative liver stiffness measurement could predict the late recurrence of hepatocellular carcinoma after curative resection.

Non-obese patients with nonalcoholic fatty liver disease may use a lower liver stiffness cut-off to assess fibrosis stages.

We aimed to estimate the optimal cut-off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non-obese and obese patients with nonalcoholic fatty liver disease (NAFLD). NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non-obesity was defined as a body mass index (BMI) less than 25 kg/m2 . LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. A total of 158 patients were included. Average BMI of the non-obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2 , respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non-obese patients (P = 0.003). LSM values of the non-obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut-off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut-off values. In the non-obese NAFLD group, using a separate cut-off avoided underestimating 9.1% of patients with cirrhosis. Non-obese NAFLD group had lower LSM than the obese group. Different cut-off values should be used to measure liver fibrosis stage in non-obese and obese NAFLD patients.

Issue Highlights

Issue Highlights

Cutoff Values of Acoustic Radiation Force Impulse Two-Location Measurements in Different Etiologies of Liver Fibrosis.

Background:Acoustic radiation force impulse (ARFI) imaging is a popular modality to measure liver fibrosis. ARFI selects optimal locations for measurement under imaging guiding. However, there are concerns on study locations and observers bias. To decrease the variations, ARFI at two locations was measured with standardized protocol. This study attempted to establish its cutoff values according to Metavir fibrosis score in different etiologies.Methods:A consecutive series of patients who received liver histology study were prospectively enrolled. All cases had hemogram, liver biochemistry, viral markers, and ARFI two-location measurements within 4 weeks of histology study. A standardized protocol was performed by single technologist. We excluded patients with alanine aminotransferase >5x upper limit normal.Results:Five hundred and ten patients that included 153 seronegative for both HBsAg and anti-HCV Non-B non-C (NBNC), 33 autoimmune liver diseases (AILD), 261 chronic hepatitis B (CHB), and 63 chronic hepatitis C (CHC) were enrolled. About 83% of NBNC patients had fat cell >5%. For diagnosis of liver cirrhosis, the area under receiver operating characteristic curve of NBNC, AILD, CHB, and CHC groups was 0.937, 0.929, 0.784, and 0.937; the cutoff values for mean ARFI were 1.788, 2.095, 1.455, and 1.710 m/s, respectively. The sensitivity and specificity are both over 0.818 for patients with nonalcoholic fatty liver diseases, CHC, and AILD, but the corresponding data are only 0.727–0.756 in CHB. The Fibrosis-4 Score is as good as ARFI on fibrosis assessment in NBNC.Conclusion:The performance of ARFI two-location measurement is excellent in NBNC, AILD, and CHC, but is only satisfactory in CHB.

Longitudinal correlations between MRE, MRI-PDFF, and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib

Non-invasive tools for monitoring treatment response and disease progression in non-alcoholic steatohepatitis (NASH) are needed. Our objective was to evaluate the utility of magnetic resonance (MR)-based hepatic imaging measures for the assessment of liver histology in patients with NASH. We analyzed data from patients with NASH and stage 2 or 3 fibrosis enrolled in a phase II study of selonsertib. Pre- and post-treatment assessments included centrally read MR elastography (MRE)-estimated liver stiffness, MR imaging-estimated proton density fat fraction (MRI-PDFF), and liver biopsies evaluated according to the NASH Clinical Research Network classification and the non-alcoholic fatty liver disease activity score (NAS). Among 54 patients with MRE and biopsies at baseline and week 24, 18 (33%) had fibrosis improvement (≥1-stage reduction) after undergoing 24 weeks of treatment with the study drug. The area under the receiver operating characteristic curve (AUROC) of MRE-stiffness to predict fibrosis improvement was 0.62 (95% CI 0.46-0.78) and the optimal threshold was a ≥0% relative reduction. At this threshold, MRE had 67% sensitivity, 64% specificity, 48% positive predictive value, 79% negative predictive value. Among 65 patients with MRI-PDFF and biopsies at baseline and week 24, a ≥1-grade reduction in steatosis was observed in 18 (28%). The AUROC of MRI-PDFF to predict steatosis response was 0.70 (95% CI 0.57-0.83) and the optimal threshold was a ≥0% relative reduction. At this threshold, MRI-PDFF had 89% sensitivity and 47% specificity, 39% positive predictive value, and 92% negative predictive value. These preliminary data support the further evaluation of MRE-stiffness and MRI-PDFF for the longitudinal assessment of histologic response in patients with NASH. Liver biopsy is a potentially painful and risky method to assess damage to the liver due to non-alcoholic steatohepatitis (NASH). We analyzed data from a clinical trial to determine if 2 methods of magnetic resonance imaging - 1 to measure liver fat and 1 to measure liver fibrosis (scarring) - could potentially replace liver biopsy in evaluating NASH-related liver injury. Both imaging methods were correlated with biopsy in showing the effects of NASH on the liver.

Putting it all together: established and emerging MRI techniques for detecting and measuring liver fibrosis.

Chronic injury to the liver leads to inflammation and hepatocyte necrosis, which when untreated can lead to myofibroblast activation and fibrogenesis with deposition of fibrous tissue. Over time, liver fibrosis can accumulate and lead to cirrhosis and end-stage liver disease with associated portal hypertension and liver failure. Detection and accurate measurement of the severity of liver fibrosis are important for assessing disease severity and progression, directing patient management, and establishing prognosis. Liver biopsy, generally considered the clinical standard of reference for detecting and measuring liver fibrosis, is invasive and has limitations, including sampling error, relatively high cost, and possible complications. For these reasons, liver biopsy is suboptimal for fibrosis screening, longitudinal monitoring, and assessing therapeutic efficacy. A variety of established and emerging qualitative and quantitative noninvasive MRI methods for detecting and staging liver fibrosis might ultimately serve these purposes. In this article, we review multiple MRI methods for detecting and measuring liver fibrosis and discuss the diagnostic performance and specific strengths and limitations of the various techniques.

Rheological determinants for simultaneous staging of hepatic fibrosis and inflammation in patients with chronic liver disease.

The purpose of this study is to investigate the use of fundamental rheological parameters as quantified by MR elastography (MRE) to measure liver fibrosis and inflammation simultaneously in humans. MRE was performed on 45 patients at 3T using a vibration frequency of 56Hz. Fibrosis and inflammation scores were obtained from liver biopsies. Biomechanical properties were quantified in terms of complex shear modulus G* as well as shear wave phase velocity c and shear wave attenuation α. A rheological fractional derivative order model was used to investigate the linear dependence of the free model parameters (dispersion slope y, intrinsic speed c0 , and intrinsic relaxation time τ) on histopathology. Leave-one-out cross-validation was then utilized to demonstrate the effectiveness of the model. The intrinsic speed c0 increases with hepatic fibrosis, while an increased relaxation time τ is reflective of more inflammation of the liver parenchyma. The dispersion slope y does not depend either on fibrosis or on inflammation. The proposed rheological model, given this specific parameterization, establishes the functional dependences of biomechanical parameters on histological fibrosis and inflammation. The leave-one-out cross-validation demonstrates that the model allows identification, from the MRE measurements, of the histology scores when grouped into low-/high-grade fibrosis and low-/high-grade inflammation with significance levels of P=0.0004 (fibrosis) and P=0.035 (inflammation). The functional dependences of intrinsic speed and relaxation time on fibrosis and inflammation, respectively, shed new light onto the impact hepatic pathological changes on liver tissue biomechanics in humans. The dispersion slope y appears to represent a structural parameter of liver parenchyma not impacted by the severity of fibrosis/inflammation present in this patient cohort. This specific parametrization of the well-established rheological fractional order model is valuable for the clinical assessment of both fibrosis and inflammation scores, going beyond the capability of the plain shear modulus measurement commonly used for MRE.

Prevalence of chronic hepatitis B virus infection and infrastructure for its diagnosis in Madagascar: implication for the WHO\u2019s elimination strategy

BackgroundWHO developed a global strategy to eliminate hepatitis B by 2030 and set target to treat 80% of people with chronic hepatitis B virus (HBV) infection eligible for antiviral treatment. As a first step to achieve this goal, it is essential to conduct a situation analysis that is fundamental to designing national hepatitis plans. We therefore estimated the prevalence of chronic HBV infection, and described the existing infrastructure for HBV diagnosis in Madagascar.MethodsWe conducted a stratified multi-stage serosurvey of hepatitis B surface antigen (HBsAg) in adults aged ≥18 years using 28 sentinel surveillance sites located throughout the country. We obtained the list of facilities performing HBV testing from the Ministry of Health, and contacted the person responsible at each facility.ResultsA total of 1778 adults were recruited from the 28 study areas. The overall weighted seroprevalence of HBsAg was 6.9% (95% CI: 5.6–8.6). Populations with a low socio-economic status and those living in rural areas had a significantly higher seroprevalence of HBsAg. The ratio of facilities equipped to perform HBsAg tests per 100,000 inhabitants was 1.02 in the capital city of Antananarivo and 0.21 outside the capital. There were no facilities with the capacity to perform HBV DNA testing or transient elastography to measure liver fibrosis. There are only five hepatologists in Madagascar.ConclusionMadagascar has a high-intermediate level of endemicity for HBV infection with a severely limited capacity for its diagnosis and treatment. Higher HBsAg prevalence in rural or underprivileged populations underlines the importance of a public health approach to decentralize the management of chronic HBV carriers in Madagascar by using simple and low-cost diagnostic tools.

Adipose tissue and liver.

Adipose tissue and liver are central tissues in whole body energy metabolism. Their composition, structure, and function can be noninvasively imaged using a variety of measurement techniques that provide a safe alternative to an invasive biopsy. Imaging of adipose tissue is focused on quantitating the distribution of adipose tissue in subcutaneous and intra-abdominal (visceral) adipose tissue depots. Also, detailed subdivisions of adipose tissue can be distinguished with modern imaging techniques. Adipose tissue (or adipocyte) accumulation or infiltration of other organs can also be imaged, with intramuscular adipose tissue a common example. Although liver fat content is now accurately imaged using standard magnetic resonance imaging (MRI) techniques, inflammation and fibrosis are more difficult to determine noninvasively. Liver imaging efforts are therefore concerted on developing accurate imaging markers of liver fibrosis and inflammatory status. Magnetic resonance elastography (MRE) is presently the most reliable imaging technique for measuring liver fibrosis but requires an external device for introduction of shear waves to the liver. Methods using multiparametric diffusion, perfusion, relaxometry, and hepatocyte-specific MRI contrast agents may prove to be more easily implemented by clinicians, provided they reach similar accuracy as MRE. Adipose tissue imaging is experiencing a revolution with renewed interest in characterizing and identifying distinct adipose depots, among them brown adipose tissue. Magnetic resonance spectroscopy provides an interesting yet underutilized way of imaging adipose tissue metabolism through its fatty acid composition. Further studies may shed light on the role of fatty acid composition in different depots and why saturated fat in subcutaneous adipose tissue is a marker of high insulin sensitivity.

The Cutoff Values of ARFI Two-Location Measurement in Different Metavir Fibrosis Scores and Etiologies

Assessment of liver fibrosis with acoustic radiation force impulse (AFRI) imaging is a popular modality to measure liver fibrosis. ARFI may select an optimal location for measurement under imaging guiding. However, there are some debates on standardized protocol for ARFI in compared with well-established protocol in Fibroscan. To decrease the variation of ARFI, we developed two-location measurement with standardized protocol. We would like to establish the cutoff values according to Metavir fibrosis score in different etiologies. A consecutive series of patients who received liver histology study were prospectively enrolled. All cases had hemogram, liver biochemistry, viral markers and ARFI two-location measurement within 4 weeks of histology study. A standardized protocol was used and carried out by a single technologist. A total of 457 patients that included 84 negative for both HBsAg and anti-HCV (NBNC), 20 autoimmune liver diseases, 283 chronic hepatitis B (CHB) and 70 hepatitis C (CHC) were enrolled. Among patients in NBNC, 64 with fat cell >10% and non-alcoholism are considered as non-alcoholic fatty liver disease (NAFLD). The AUROC for Metavir 4 fibrosis were 0.949, 0.766 and 0.939 for NAFLD, CHB and CHC, respectively. The cutoff values for Metavir F4 were 1.750, 1.505 and 1.750 for NAFLD, CHB and CHC, respectively. The sensitivity and specificity were satisfactory and both were over 0.8 for patients with NAFLD and CHC, but was between 0.718 and 0.741 in CHB. The diagnostic performance of two-location measurement is accurate for NAFLD and CHC, but is relatively poor in CHB.