Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients

Failure of liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) and unreliable results occur in ≈ 5% and 15% of patients, respectively, mainly due to obesity. In this multicenter study, we evaluated the feasibility and performance of the novel FibroScan XL probe in 276 patients with chronic liver disease (42% viral hepatitis, 46% nonalcoholic fatty liver disease [NAFLD]) and a body mass index (BMI) ≥ 28 kg/m(2) . Patients underwent liver biopsy and TE with the standard M and XL probes. TE failure was defined as no valid LSMs and unreliable examinations as <10 valid LSMs or an interquartile range (IQR)/LSM >30% or success rate <60%. Probe performance for diagnosing ≥ F2 fibrosis and cirrhosis (F4) versus biopsy were examined using areas under receiver operating characteristic curves (AUROC). FibroScan failure was less frequent with the XL probe than the M probe (1.1% versus 16%) and the XL probe was more often reliable (73% versus 50%; both P < 0.00005). Reliable results with the XL probe were obtained in 61% of patients in whom the M probe was unreliable. Among 178 patients with ≥ 10 valid LSMs using both probes, liver stiffness was highly correlated between probes (ρ = 0.86; P < 0.0005); however, median liver stiffness was lower using the XL probe (6.8 versus 7.8 kPa; P < 0.00005). The AUROC of the XL and M probes were similar for ≥ F2 fibrosis (0.83 versus 0.86; P = 0.19) and cirrhosis (0.94 versus 0.91; P = 0.28). CONCLUSION: Compared with the M probe, the FibroScan XL probe reduces TE failure and facilitates reliable LSM in obese patients. Although the probes have comparable accuracy, lower liver stiffness cutoffs will be necessary when the XL probe is used to noninvasively assess liver fibrosis.     

The feasibility and reliability of transient elastography using Fibroscan?: A practice audit of 2335 examinations

BACKGROUND:

Liver stiffness measurement (LSM) using transient elastography is widely used in the management of patients with chronic liver disease.

OBJECTIVES:

To examine the feasibility and reliability of LSM, and to identify patient and operator characteristics predictive of poorly reliable results.

METHODS:

The present retrospective study investigated the frequency and determinants of poorly reliable LSM (interquartile range [IQR]/median LSM [IQR/M] >30% with median liver stiffness ≥7.1 kPa) using the FibroScan (Echosens, France) over a three-year period. Two experienced operators performed all LSMs. Multiple logistic regression analyses examined potential predictors of poorly reliable LSMs including age, sex, liver disease, the operator, operator experience (<500 versus ≥500 scans), FibroScan probe (M versus XL), comorbidities and liver stiffness. In a subset of patients, medical records were reviewed to identify obesity (body mass index ≥30 kg/m²).

RESULTS:

Between July 2008 and June 2011, 2335 patients with liver disease underwent LSM (86% using the M probe). LSM failure (no valid measurements) occurred in 1.6% (n=37) and was more common using the XL than the M probe (3.4% versus 1.3%; P=0.01). Excluding LSM failures, poorly reliable LSMs were observed in 4.9% (n=113) of patients. Independent predictors of poorly reliable LSM included older age (OR 1.03 [95% CI 1.01 to 1.05]), chronic pulmonary disease (OR 1.58 [95% CI 1.05 to 2.37), coagulopathy (OR 2.22 [95% CI 1.31 to 3.76) and higher liver stiffness (OR per kPa 1.03 [95% CI 1.02 to 1.05]), including presumed cirrhosis (stiffness ≥12.5 kPa; OR 5.24 [95% CI 3.49 to 7.89]). Sex, diabetes, the underlying liver disease and FibroScan probe were not significant. Although reliability varied according to operator (P<0.0005), operator experience was not significant. In a subanalysis including 434 patients with body mass index data, obesity influenced the rate of poorly reliable results (OR 2.93 [95% CI 0.95 to 9.05]; P=0.06).

CONCLUSIONS:

FibroScan failure and poorly reliable LSM are uncommon. The most important determinants of poorly reliable results are older age, obesity, higher liver stiffness and the operator, the latter emphasizing the need for adequate training.     

Feasibility of liver transient elastography with FibroScan® using a new probe for obese patients

Background & Aims: Liver stiffness measurement (LSM) failure when using transient elastography occurs in 2–10% of patients, and is generally related to obesity. The aim of this prospective study was to assess the feasibility of LSM when using a new XL probe on patients with a body mass index (BMI)≥30 kg/m². Methods: For each patient, LSM was performed using both M probe (currently available and dedicated to patients with standard morphology) and XL probe (dedicated to overweighed patients). A blood sample was taken to assess usual biological variables and simple readily available fibrosis blood tests. Results: Ninety‐nine patients were included (27 men, mean age 52 years, mean BMI 40.5 kg/m²). LSM was successful (10 valid measurements) in 45% of the cases with the M probe, vs 76% of the cases with the XL probe (P<0.001). Fifty‐nine percent of those who could not be measured (<10 valid measurements) using the M probe could successfully be measured using the XL probe. In the 44 patients successfully measured with both probes, LSM was correlated with the platelet count, prothrombin time, γ‐glutamyltransferase, aspartate aminotransferase, fasting glucose, AST platelet ratio index, Forns score and FIB‐4. Conclusion: The new XL probe allows providing a higher rate of LSM than the M probe in patients with an increased BMI and shows promising results for the evaluation of liver fibrosis.     

Liver stiffness assessed by transient elastography in patients with β thalassaemia major

Rationale for the study. This cross-sectional multicenter study was conducted to investigate any difference in liver stiffness measurements (LSM), evaluated by transient elastography, between patients affected by β thalassaemia major, with and without hepatitis C virus (HCV) infection, and healthy blood donors (controls). Secondary aim was to assess any correlation between transient elastography and serum ferritin, liver magnetic resonance imaging (MRI) T2* or superconductive quantum interference device (SQUID) liver susceptometry values.Materials and methods. The study involved three centers. Transient elastography and MRI T2* examinations were performed in all centers. SQUID liver susceptometry was performed in center1 and center2. T-test for independent data or Mann-Whitney U test was used to analyse differences between two groups. Univariate Pearson’s rcoefficient was used to test correlations between liver stiffness measurements and all other variables.Results. In a study with 119 patients and 183 controls, patients who had never been infected with HCV showed significantly higher LSMs than controls [5.7 (95% CI, 5.2-6.2) kPa vs. 4.3 (95% CI, 4.1-4.4) kPa, p < 0.0001]. A moderate correlation between LSMs and ferritin values, adjusted for gender and age, was found in patients (r = 0.49, p < 0.0001) but not in controls (r = -0.22, p = 0.6). No correlation between LSMs and MRI T2* or SQUID liver susceptometry values was observed. In conclusion, compared to controls β thalassaemia major patients had a significant increase in LSMs independently from HCV infection.     

Liver fibrosis in young Egyptian beta-thalassemia major patients: relation to hepatitis C virus and compliance with chelation

Background. The main causes of liver fibrosis in transfusion-dependent thalassemia major are hepatitis C virus (HCV) infection and hepatic iron overload. The study aimed to assess liver fibrosis in Egyptian adolescents and young adult poly-transfused beta thalassemia patients infected with HCV using liver FibroScan in relation to iron overload and Liver iron concentration (LIC).Material and methods. Fifty-one regularly transfused beta thalassemia patients above 12 years old were subjected to measurement of serum alanine transaminase (ALT), serum ferritin (SF), HCV (antibody and RNA), LIC assessed by hepatic R2* and transient elastography (TE) (FibroScan). FibroTest and liver biopsy were done to 25 patients.Results. Eighty two% of studied thalassemia patients were HCV antibody positive; 21(49%) of them were viremic (HCV RNA positive); median LIC was 12 mg/gm dry weight. There were strong positive correlation between the degree of liver stiffness and Ishak fibrosis score assessed in liver biopsy specimens (P = 0.002) and between FibroScan and FibroTest results (P < 0.001). Patients with HCV viremia showed significantly higher ALT, γ-glutamyl transpeptidase (GGT), SF, LIC and increased liver stiffness compared to patients with no viremia (P = 0.0001, 0.001, 0.012, 0.006 and 0.001) respectively. Liver cirrhosis (TE values > 12.5kPa) was encountered in 23.5% and variable degrees of liver fibrosis (TE values > 6–12.5 kPa) in 35% of studied thalassemic patients.Conclusion. Young beta thalassemia patients with active hepatitis C infection may have hepatic cirrhosis or fibrosis at young age when accompanied with hepatic siderosis. Non invasive Liver FibroScan and Fibro-Test were reliable methods to assess liver fibrosis in young thalassemic-patients.     

Adherence to quality criteria improves concordance between transient elastography and ElastPQ for liver stiffness assessment—A multicenter retrospective study

BackgroundAssessment of liver stiffness provides important diagnostic and prognostic information in patients with chronic liver disease.AimsTo investigate whether the use of quality criteria (i) improves the concordance between transient elastography (TE) and a novel point shear wave elastography technique (ElastPQ^®) and (ii) impacts on the performance of ElastPQ^® for liver fibrosis staging using TE as the reference standard.MethodsIn this multicenter retrospective study, data of patients undergoing liver stiffness measurements (LSM) in five European centers were collected. TE was performed with FibroScan^® (Echosens, France) and ElastPQ^® with EPIQ^® or Affiniti^® systems (Philips, The Netherlands). The agreement between TE and ElastPQ^® LSMs was assessed with Lin’s concordance correlation coefficient (CCC). Diagnostic performance of ElastPQ^® was assessed by the area under receiver operating characteristic (AUROC) curves.ResultsOverall, 664 patients were included: mean age: 54.8(13.5) years, main etiologies: viral hepatitis (83.1%) and NAFLD (7.5%). CCC increased significantly when LSMs with ElastPQ^® were obtained with IQR/M ≤ 30% (p < 0.001). The diagnostic performance of ElastPQ^® for fibrosis staging also increased if LSM values were obtained with IQR/M ≤ 30%.ConclusionQuality criteria should be followed when using ElastPQ^® for LSM, since the concordance with TE fibrosis staging was better at an ElastPQ^® IQR/M ≤ 30.     

Non-invasive assessment of liver fibrosis with transient elastography (FibroScan®): applying the cut-offs of M probe to XL probe

Background and rationale for the study. Limited studies have aimed to define the cut-offs of XL probe (XL cut-offs) for different stages of liver fibrosis, whereas those of M probe (M cut-offs) may not be applicable to XL probe. We aimed to derive appropriate XL cut-offs in overweight patients. Patients with liver stiffness measurement (LSM) by both probes were recruited. XL cut-offs probe for corresponding M cut-offs were derived from an exploratory cohort, and subsequently validated in a subgroup patients also underwent liver biopsy. The diagnostic accuracy of XL cut-offs to diagnose advanced fibrosis was evaluated.Results. Total 517 patients (63% male, mean age 58) who had reliable LSM by both probes were included in the exploratory cohort. There was a strong correlation between the LSM by M probe (LSM-M) and LSM by XL probe (LSM-XL) (r² = 0.89, p < 0.001). A decision tree using LSM-XL was learnt to predict the 3 categories of LSM-M (< 6.0kPa, 6.0–11.9kPa and ≥ 12.0kPa), and XL cut-offs at 4.8kPa and 10.7kPa were identified. These cut-offs were subsequently validated in a cohort of 147 patients who underwent liver biopsy. The overall accuracy was 89% among 62 patients whose LSM-XL < 4.8kPa or ≥ 10.7kPa. These cut-offs would have avoided under-staging of fibrosis among patients with body mass index (BMI) > 25–30 kg/m² but not > 30 kg/m².Conclusions. XL cut-offs at 4.8kPa and 10.7kPa were the best estimates of 6.0kPa and 12.0kPa of M probe for patients with BMI > 25–30 kg/m². Patients with BMI > 30 kg/m² might use M probe cut-offs for XL probe.     

Applicability and accuracy improvement of transient elastography using the M and XL probes by experienced operators

Transient elastography (TE) is the reference method to obtain liver stiffness measurements (LSM), but no results are obtained in 3.1% and unreliable in 15.8%. We assessed the applicability and diagnostic accuracy of TE re‐evaluation using M and XL probes. From March 2011 to April 2012 868 LSM were performed with the M probe by trained operators (50–500 studies) (LSM1). Measurements were categorized as inadequate (no values or ratio <60% and/or IQR/LSM >30%) or adequate. Inadequate LSM1 were re‐evaluated by experienced operators (>500 explorations) (LSM2) and inadequate LSM2 using XL probe (LSMXL). Inadequate LSM1 were obtained in 187 (21.5%) patients, IQR/LSM >30% in 97 (51%), ratio <60% in 24 (13%) and TE failed to obtain a measurement in 67 (36%). LSM2 achieved adequate registers in 123 (70%) of 175 registers previously considered as inadequate. Independent variables (OR, 95%CI) related to inadequate LSM1 were body mass index (1.11, 1.04–1.18), abdominal circumference (1.03, 1.01–1.06) and age (1.03, 1.01–1.04) and to inadequate LSM2 were skin‐capsule distance (1.21, 1.09–1.34) and abdominal circumference (1.05, 1.01–1.10). The diagnostic accuracy (AUROC) to identify significant fibrosis improved from 0.89 (LSM1) to 0.91 (LSM2) (P = 0.046) in 334 patients with liver biopsy or clinically significant portal hypertension. A third evaluation (LSMXL) obtained adequate registers in 41 (93%) of 44 patients with inadequate LSM2. Operator experience increases the applicability and diagnostic accuracy of TE. The XL probe may be recommended for patients with inadequate values obtained by experienced operators using the M probe. http://clinicaltrials.gov (NCT01900808).     

Prevalence,risk factors and causes of discordance in fibrosis staging by transient elastography and liver biopsy

Background and aims: Liver stiffness measurement (LSM) by transient elastography (TE) is widely used for the noninvasive assessment of fibrosis. Our objectives were to examine the prevalence, risk factors and causes of discordance between fibrosis estimated by TE and liver biopsy. Methods: Two hundred and fifty‐one patients with hepatitis B, C and nonalcoholic fatty liver disease underwent LSM by TE and liver biopsy. Predictors of discordance (≥2 fibrosis stages) between measures, which occurred in 14% of patients (n=35), were identified by comparing patient, TE and biopsy characteristics of discordant and nondiscordant cases. Results: According to predefined criteria, 40% of discordances were attributed to TE error and 23% to biopsy error; 37% were indeterminate. In multivariate analysis, mild fibrosis (F0–2 vs. F3–4), and higher body mass index (BMI), ALT and LSM variability [assessed by the ratio of the interquartile range to median LSM (IQR/M)] were independently associated with discordance. Discordance was three‐fold more common in patients with obesity (28 vs. 9%), ALT≥60 U/L (20 vs. 7%) and IQR/M ≥0.17 (22 vs. 7%; all P<0.005). Based on these variables, a discordance risk score assigning 1 point to each factor was developed. The prevalence of discordance in patients with 0, 1, 2 and 3 factors were 2, 7, 20, and 55% respectively (P<0.0005). Conclusions: Discordance between liver fibrosis estimated by TE and biopsy occurs in one in seven patients. In assessing the validity of TE results, clinicians must recognize risk factors for discordance and in at‐risk patients, consider alternative measures including biomarkers and possibly biopsy.     

Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease

Background & AimsPatients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events.MethodsWe performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3–F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19–63 months).ResultsBased on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04; P < .001), HCC (HR, 1.03; 95% CI, 1.00–1.04; P = .003), and liver-related death (HR, 1.02; 95% CI, 1.02–1.03; P = .005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05–2.51; P = .04), HCC (HR, 1.72; 95% CI, 1.01–3.02; P = .04), overall mortality (HR, 1.73; 95% CI, 1.11–2.69; P = .01), and liver-related mortality (HR, 1.96; 95% CI, 1.10–3.38; P = .02).ConclusionsIn patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality.     

FibroScan对慢性乙型肝炎肝纤维化患者的应用价值及ALT、AST对其诊断的影响

目的探讨瞬时弹性探测仪(FS)在慢性乙型肝炎肝纤维化患者中应用价值及ALT、AST对其诊断纤维化的影响。方法应用FS对90名慢性乙型肝炎肝纤维化患者进行肝穿前肝脏弹性测量值(LSM)的测定,同时进行血清ALT、AST的检测。以肝脏活检病理结果为金标准,对肝纤维化进行分期。结果 LSM在肝纤维化病理S1～4之间逐渐增高,组间差异有统计学意义(P<0.01);相邻两分期间LSM组间差异均有统计学意义(P<0.01)。肝脏LSM与病理分期呈正相关(r=0774,P<0.01)。S1～4各期的LSM与相应分期的ALT呈正相关,相关系数分别为0.672(P=0.000)、0.790(P=0.000)、0.845(P=0.001)和0.797(P=0.003),S1～4各期LSM与相应分期的AST呈正相关,相关系数分别为0.593(P=0.000)、0.762(P=0.001)、0.743(P=0.009)和0.872(P=0.000)。结论 FS在慢性乙型肝炎肝纤维化程度评估中有较好的应用价值,但是血清ALT和AST水平对其有一定影响。     

Serum levels of soluble dipeptidyl peptidase-4 in type 2 diabetes are associated with severity of liver fibrosis evaluated by transient elastography (FibroScan) and the FAST (FibroScan-AST) score,a novel index of non-alcoholic steatohepatitis with significant fibrosis

AimTo investigate the relationship in people with type 2 diabetes between serum soluble dipeptidyl peptidase-4 (sDDP-4) and degree of liver fibrosis assessed as the liver stiffness measurement (LSM) and FAST (FibroScan-AST) score, both of which were measured by transient elastography (FibroScan).Subjects and methodsIn this cross-sectional study, we examined 115 patients with type 2 diabetes. With transient elastography (FibroScan), we assessed the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) as measures of hepatic steatosis and liver fibrosis, respectively. We calculated the FAST score, which identifies progressive non-alcoholic steatohepatitis (NASH), from CAP, LSM, and the serum aspartate aminotransferase level. Significant hepatic steatosis was defined as CAP ≥280 dB/m; and significant liver fibrosis, as LSM ≥ 8.0 kPa. LSM was divided into 3 severity levels: significant fibrosis (8.0 to <9.7 kPa); advanced fibrosis, (9.7 to <13.0 kPa); and liver cirrhosis (≥ 13.0 kPa).ResultsSerum sDPP-4 correlated positively with liver enzymes, CAP, LSM, and FAST score. Multivariate analysis showed that LSM remained to be an independent factor for serum sDDP-4. Serum sDPP-4 was significantly higher in patients with LSM ≥ 8.0 kPa than in those with LSM <8.0 kPa and was significantly elevated in patients who are at risk for non-alcoholic steatohepatitis (NASH) with fibrosis (FAST score ≥ 035 or 0.67). Patients with both hepatic steatosis and liver fibrosis had the highest serum sDPP-4.ConclusionSerum sDPP-4 was strongly associated with severity of liver fibrosis evaluated by LSM and the FAST score and was markedly elevated in diabetic patients with LSM ≥ 13.0 kPa indicating probable cirrhosis.     

肝组织炎症对FibroScan诊断慢性乙型肝炎患者肝纤维化的影响

目的探讨肝组织学炎症对瞬时弹性扫描仪（FS）诊断慢性乙型肝炎患者肝纤维化的影响。方法应用FS对124名慢性乙型肝炎患者进行肝穿刺前肝脏弹性测量值（LSM）的测定,采用肝穿刺活组织病理诊断技术进行肝纤维化分期（S）和炎症分级（G）。对同一肝纤维化分期不同肝组织炎症分级组间LSM进行比较,并对各肝纤维化分期中LSM与肝组织炎症分级进行相关性分析。结果肝组织纤维化逐渐发展伴随肝炎症程度加重,如肝纤维化S1期患者中以G1为主（81.8%）,S2期以G2为主（54.2%）,S3期以G3为主（47.4%）,S4期以G3、G4为主（40%,33.4%）,S1～S4每一纤维化分期水平上,不同炎症分级LSM差异均具有统计学意义（P〈0.05）,且LSM与不同炎症分级之间均呈显著正相关（P〈0.01）。结论肝组织炎症程度是影响FS诊断的一个重要因素,炎症活动程度加重可使LSM增加。     

Effects of a one-week treatment with acid gastric inhibitors on Helicobacter pylori-infected mice

Abstract

Background: Obesity is one of the main factors of transient elastography (TE) failure, considering body mass index (BMI) ≥28?kg/m² as a limiting factor. The XL probe was designed to overcome this limitation.

Aim: To compare the feasibility of the M and XL probes in patients with BMI ≥ 28?kg/m², to evaluate differences in mean values of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) between the two probes and find predictive factors of TE failure.

Material and methods: Prospective study, including all patients with BMI ≥ 28?kg/m² consecutively admitted for TE.

Results: Included 161 patients. Measurements with M probe were reliable in 69.6% of the patients, with 68.2% of valid measurements in obese population and 58.9% in patients with skin-capsule distance (SCD) >25?mm. In 40 patients (81.6%) with an invalid M probe measurement, a reliable result was obtained with XL probe. We found that SCD >25?mm was the only predictor of M probe failure (OR: 4.9, CI: 1.64–14.63, p?=?.004). In those patients in which TE was possible with both probes (n?=?112), mean CAP was 304?±?49?dB/m² with M probe and 301?±?50?dB/m² with XL probe (p?=?.59). Regarding liver stiffness, a mean value of 7.58?±?3.47?kpas was obtained with the M probe and 6.21?±?3.44?kpas with the XL probe (p?Conclusion: There is a reliable applicability of the M probe in a high number (68.2%) of patients with a BMI ≥30?kg/m². A SCD >25?mm was the only predictive factor of M probe failure. Mean values of LSM with XL probe were lower than those obtained with M probe.     

Prevalence in vulnerable population of liver fibrosis identified by transient elastography

Background. Transient elastography (TE) is a useful tool for the assessment of hepatic fibrosis as an alternative to liver biopsy, but it has not been validated as a screening procedure in apparently healthy people.Aim. To determine the prevalence of advanced liver fibrosis diagnosed by TE in a socioeconomically challenged rural population.Material and methods. We enrolled 299 participants aged over 18 years old from a vulnerable population in Mexico who responded to an open invitation. All participants had their history recorded and underwent a general clinical examination and a liver stiffness measurement, performed by a single operator according to international standards.Results. Overall, 7.35% participants were found to be at high risk for cirrhosis. Three variables correlated with a risk for a TE measure ≥ 9 kPa and significant fibrosis: history of alcohol intake [7.95 vs. 92.04%, odds ratio (OR) 4.47, 95% confidence interval (CI) 1.45-13.78, P = 0.0167], body mass index (BMI) ≥ 30 kg/m² (30.87 vs. 69.12%, OR 4.25, 95%CI 1.04-6.10, P = 0.049), and history of diabetes mellitus (14.87 vs. 85.12%, OR 2.76, 95%CI 1.002-7.63, P = 0.0419). In the multivariate analyses BMI ≥ 30 kg/m² was the only significant risk factor for advanced liver fibrosis or cirrhosis (OR 2.54, 95%CI 1.02-6.3, P = 0.0460).Conclusion. TE could be useful as a screening process to identify advanced liver fibrosis in the general and apparently healthy population.     

Noninvasive methods,including transient elastography,for the detection of liver disease in adults with cystic fibrosis

BACKGROUND:

Liver disease is the third leading cause of mortality in patients with cystic fibrosis (CF). However, detection of CF-associated liver disease (CFLD) is challenging.

OBJECTIVE:

To evaluate the diagnostic performance of noninvasive methods for the detection of CFLD with a focus on transient elastography (TE).

METHODS:

Patients at the Adult CF Clinic of Calgary and Southern Alberta (n=127) underwent liver stiffness measurement (LSM) by TE using the FibroScan (FS, Ecosens, France) M probe; aspartate amino-transferase to platelet ratio index (APRI) and FibroTest (FT) scores were also calculated. The diagnostic performance of these tools for the detection of CFLD (defined as two or more the following criteria: abnormal liver biochemistry, hepatomegaly or sonographic abnormalities other than steatosis) were compared using the area under ROC curves.

RESULTS:

Forty-seven percent of the cohort was male. The median age was 27 years (interquartile range [IQR] 22 to 37 years) and body mass index 21 kg/m² (IQR 19 kg/m² to 23 kg/m²); 25% of patients were on ursodeoxycholic acid and 12% had undergone lung transplantation. The prevalence of CFLD was 14% (n=18). FS was successful in all patients; one (0.8%) patient had poorly reliable results (IQR/M >30% and LSM ≥7.1kPa). Compared with patients without CFLD (n=109), individuals with CFLD had higher median LSM according to FS (3.9 kPa [IQR 3.4 to 4.9 kPa] versus 6.4 kPa [IQR 4.4 to 8.0 kPa]), APRI (0.24 [IQR 0.17 to 0.31] versus 0.50 [IQR 0.22 to 1.18]) and FT scores (0.08 [IQR 0.05 to 1.5] versus 0.18 [IQR 0.11 to 0.35]; all P<0.05). Area under ROC curve for FS, APRI and FT for the detection of CFLD were 0.78 (95% CI 0.65 to 0.92), 0.72 (95% CI 0.56 to 0.87) and 0.76 (95% CI 0.62 to 0.90) (P not significant). At a threshold of >5.2 kPa, the sensitivity, specificity, positive and negative predictive values of LSM according to FS for detecting CFLD were 67%, 83%, 40% and 94%, respectively.

CONCLUSIONS:

FS, APRI and FT were useful noninvasive methods for detecting CFLD in adults.     

Dynamic evaluation of liver stiffness measurement to improve diagnostic accuracy of liver cirrhosis in patients with chronic hepatitis B acute exacerbation

Summary. To investigate the dynamic changes of liver stiffness measurement (LSM) by FibroScan^® and improve its diagnostic accuracy, we studied patients with chronic hepatitis B undergoing acute exacerbation. Eighty‐nine treatment naïve patients were enrolled, and Fibroscan^® was performed every 7–10 days during hospitalization and every 1～3 months for follow‐up. Haematology and liver functions were tested in parallel. Liver biopsies were performed in 23 patients. A total of 282 LSMs were performed. LSM was positively correlated with both alanine aminotransferase (ALT) (r = 0.321, P < 0.001) and bilirubin levels (r = 0.626, P < 0.001). Mean reduction in LSMs in patients along with ALT or bilirubin normalization was significantly greater than those without ALT or bilirubin nomalization(P = 0.001, P = 0.038, respectively). In 23 patients with initial LSMs in the range usually defined as indicating cirrhosis (i.e.>18.2 kPa), only 5 were diagnosed with cirrhosis by histopathology or ultrasonography. As ALT normalized, LSMs remained over 12.0 kPa in all these 5 patients. However, in 18 other patients without cirrhosis at baseline, LSMs still remained above 12.0kPa in 10 patients and decreased to below 12.0 kPa in the other 8 patients. LSMs decreased in parallel with ALT and bilirubin normalization. LSM performed after ALT and bilirubin nomalization may improve the accuracy in diagnosing cirrhosis in patients with exacerbations of hepatitis B.     

Effect of liver inflammation on accuracy of FibroScan device in assessing liver fibrosis stage in patients with chronic hepatitis B virus infection

BACKGROUND Transient elastography(FibroScan)is a new and non-invasive test,which has been widely recommended by the guidelines of chronic hepatitis B virus(HBV)management for assessing hepatic fibrosis staging.However,some confounders may affect the diagnostic accuracy of the FibroScan device in fibrosis staging.AIM To evaluate the diagnostic value of the FibroScan device and the effect of hepatic inflammation on the accuracy of FibroScan in assessing the stage of liver fibrosis in patients with HBV infection.METHODS The data of 416 patients with chronic HBV infection who accepted FibroScan,liver biopsy,clinical,and biological examination were collected from two hospitals retrospectively.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic performance of FibroScan for assessing the stage of liver fibrosis.Any discordance in fibrosis staging by FibroScan and pathological scores was statistically analyzed.Logistic regression and ROC analyses were used to analyze the accuracy of FibroScan in assessing the stage of fibrosis in patients with different degrees of liver inflammation.A non-invasive model was constructed to predict the risk of misdiagnosis of fibrosis stage using FibroScan.RESULTS In the overall cohort,the optimal diagnostic values of liver stiffness measurement(LSM)using FibroScan for significant fibrosis(≥F2),severe fibrosis(≥F3),and cirrhosis(F4)were 7.3 kPa[area under the curve(AUC)=0.863],9.7 kPa(AUC=0.911),and 11.3 kPa(AUC=0.918),respectively.The rate of misdiagnosis of fibrosis stage using FibroScan was 34.1%(142/416 patients).The group of patients who showed discordance between fibrosis staging using FibroScan and pathological scores had significantly higher alanine aminotransferase and aspartate aminotransferase levels,and a higher proportion of moderate to severe hepatic inflammation,compared with the group of patients who showed concordance in fibrosis staging between the two methods.Liver inflammation activity over 2(OR=3.53)was an independent risk factor for misdiagnosis of fibrosis stage using FibroScan.Patients with liver inflammation activity≥2 showed higher LSM values using FibroScan and higher rates of misdiagnosis of fibrosis stage,whereas the diagnostic performance of FibroScan for different fibrosis stages was significantly lower than that in patients with inflammation activity<2(all P<0.05).A non-invasive prediction model was established to assess the risk of misdiagnosis of fibrosis stage using FibroScan,and the AUC was 0.701.CONCLUSION Liver inflammation was an independent risk factor affecting the diagnostic accuracy of FibroScan for fibrosis stage.A combination of other related noninvasive factors can predict the risk of misdiagnosis of fibrosis staging using FibroScan.     

Applicability and variability of liver stiffness measurements according to probe position

AIM： TO investigate the liver stiffness measurement （LSM） applicability and variability with reference to three probe positions according to the region of liver biopsy.
METHODS： The applicability for LSM was defined as at least 10 valid measurements with a success rate greater than 60% and an interquartile range/median LSM 〈 30%. The LSM variability compared the inter-position concordance and the concordance with FibroTest.
RESULTS： Four hundred and forty two consecutive patients were included. The applicability of the anterior position （81%） was significantly higher than that of the reference （69%） and lower positions （68%）, （both P = 0.0001）. There was a significant difference （0.5 kPa, 95% CI 0.13-0.89; P 〈 0.0001） between mean LSM estimated at the reference position （9.3 kPa） vs the anterior position （8.8 kPa）. Discordance between positions was associated with thoracic fold （P = 0.008）. The discordance rate between the reference position result and FibroTest was higher when the 7.1 kPa cutoff was used to define advanced fibrosis instead of 8.8 kPa （33.6% vs 23.5%, P = 0.03）.
CONCLUSION： The anterior position of the probe should be the first choice for LSM using Fibroscan, as it has a higher applicability without higher variability compared to the usual liver biopsy position.     

Transient elastography for the noninvasive assessment of liver fibrosis: a multicentre Canadian study

BACKGROUND

Liver stiffness measurement (LSM) using transient elastography (TE) is a promising tool for the noninvasive assessment of hepatic fibrosis.

OBJECTIVES

To determine the feasibility and performance of TE in a North American cohort of patients with chronic liver disease.

METHODS

LSMs were obtained using TE in 260 patients with chronic hepatitis B or C, or nonalcoholic fatty liver disease from four Canadian hepatology centres. The accuracy of TE compared with liver biopsy for the prediction of significant fibrosis (Metavir fibrosis score of F2 or greater), bridging fibrosis (Metavir fibrosis score of F3 or greater) and cirrhosis (Metavir fibrosis score of F4 ) was assessed using area under ROC curves (AUROCs), and compared with the aspartate aminotransferase-to-platelet ratio index. The influence of alanine aminotransferase (ALT) levels and other factors on liver stiffness was determined using linear regression analyses.

RESULTS

Failure of TE occurred in 2.7% of patients, while liver biopsies were inadequate for staging in 0.8%. Among the remaining 251 patients, the AUROCs of TE for Metavir fibrosis scores of F2 and F3 or greater, and F4 were 0.74 (95% CI 0.68 to 0.80), 0.89 (95% CI 0.84 to 0.94), and 0.94 (95% CI 0.90 to 0.97), respectively. LSM was more accurate than the aminotransferase-to-platelet ratio index for bridging fibrosis (AUROC 0.78) and cirrhosis (AUROC 0.88), but not significant fibrosis (AUROC 0.76). At a cut-off of 11.1 kPa, the sensitivity, specificity, and positive and negative predictive values for cirrhosis (prevalence 11%) were 96%, 81%, 39% and 99%, respectively. For significant fibrosis (prevalence 53%), a cut-off of 7.7 kPa was 68% sensitive and 69% specific, and had a positive predictive value of 70% and a negative predictive value of 65%. Liver stiffness was independently associated with ALT, body mass index and steatosis. The optimal LSM cut-offs for cirrhosis were 11.1 kPa and 11.5 kPa in patients with ALT levels lower than 100 U/L and 100 U/L or greater, respectively. For fibrosis scores of F2 or greater, these figures were 7.0 kPa and 8.6 kPa, respectively.

CONCLUSIONS

The major role of TE is the exclusion of bridging fibrosis and cirrhosis. However, TE cannot replace biopsy for the diagnosis of significant fibrosis. Because liver stiffness may be influenced by significant ALT elevation, body mass index and/or steatosis, tailored liver stiffness cut-offs may be necessary to account for these factors.