XL Probe Research Articles

Prospective comparison of transient elastography, MRI and serum scores for grading steatosis and detecting non-alcoholic steatohepatitis in bariatric surgery candidates

Background & AimsTools for the non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) in morbidly obese patients with suspected non-alcoholic fatty liver disease (NAFLD) are an unmet clinical need. We prospectively compared the performance of transient elastography, MRI, and 3 serum scores for the diagnosis of NAFLD, grading of steatosis and detection of NASH in bariatric surgery candidates.MethodsOf 186 patients screened, 152 underwent liver biopsy, which was used as a reference for NAFLD (steatosis [S]>5%), steatosis grading and NASH diagnosis. Biopsies were read by a single expert pathologist. MRI-based proton density fat fraction (MRI-PDFF) was measured in an open-bore, vertical field 1.0T scanner and controlled attenuation parameter (CAP) was measured by transient elastography, using the XL probe. Serum scores (SteatoTest, hepatic steatosis index and fatty liver index) were also calculated.ResultsThe applicability of MRI was better than that of FibroScan (98% vs. 79%; p <0.0001). CAP had AUROCs of 0.83, 0.79, 0.73 and 0.69 for S>5%, S>33%, S>66% and NASH, respectively. Transient elastography had an AUROC of 0.80 for significant fibrosis (F0-F1 vs. F2-F3). MRI-PDFF had AUROCs of 0.97, 0.95, 0.92 and 0.84 for S>5%, S>33%, S>66% and NASH, respectively. When compared head-to-head in the 97 patients with all valid tests available, MRI-PDFF outperformed CAP for grading steatosis (S>33%, AUROC 0.97 vs. 0.78; p <0.0003 and S>66%, AUROC 0.93 vs. 0.75; p = 0.0015) and diagnosing NASH (AUROC 0.82 vs. 0.68; p = 0.0056). When compared in “intention to diagnose” analysis, MRI-PDFF outperformed CAP, hepatic steatosis index and fatty liver index for grading steatosis (S>5%, S>33% and S>66%).ConclusionMRI-PDFF outperforms CAP for diagnosing NAFLD, grading steatosis and excluding NASH in morbidly obese patients undergoing bariatric surgery.Lay summaryNon-invasive tests for detecting fatty liver and steatohepatitis, the active form of the disease, have not been well studied in obese patients who are candidates for bariatric surgery. The most popular tests for this purpose are Fibroscan, which can be used to measure the controlled attenuation parameter (CAP), and magnetic resonance imaging, which can be used to measure the proton density fat fraction (MRI-PDFF). We found that, when taking liver biopsy as a reference, MRI-PDFF performed better than CAP for detecting and grading fatty liver as well as excluding steatohepatitis in morbidly obese patients undergoing bariatric surgery.

P-111 FREQUENCY OF LIVER STEATOSIS AND FIBROSIS DETERMINED BY FIBROSCAN AND CAP IN A SCREENING PROGRAM

Nonalcoholic fatty liver disease represents a worldwide public health problem, in Latin America a prevalence of around 30% is estimated, however in Peru we do not have large epidemiological studies about this. To evaluate the frequency of liver steatosis determined by CAP (Controlled Attenuation Parameter) and liver fibrosis by hepatic elastography in a population of patients who participated in a screening campaign. Descriptive and cross-sectional study. During the period September-December 2019, the ALEH Screening Fibroscan program was carried out in 4 reference hospitals in Lima and Callao. Patients were evaluated with a Fibroscan 530 device with M and XL probes. Those examinations that met the quality parameters were included for the study: 10 valid measurements, IQR <30% for liver stiffness, IQR <40 dB / m for CAP. The study population was people aged 18 and older who voluntarily attended the screening campaigns. 1978 patients were included, with an average age of 54.22 +/- 14.36 years, the distribution by sex was 1342 women (67.8%) and 636 men (32.2%). The distribution according to the degree of liver steatosis determined by CAP was S0: 1198 (60.6%), S1: 335 (16.9%), S2: 59 (3%), S3: 386 (19.5%). The distribution according to the degree of fibrosis was F0-1: 1662 (84%), F2: 97 (4.9%), F3: 98 (5%), F4: 121 (6.1%). In the studied population a frequency of hepatic steatosis of 39.4% and advanced hepatic fibrosis of 11.1% was found.

Feasibility of Fibroscan in Assessment of Hepatic Steatosis and Fibrosis in Obese Patients: Report From a General Internal Medicine Clinic.

In metabolic associated fatty liver disease (MAFLD) vibration controlled transient elastography (VCTE) by Fibroscan has emerged as a non-invasive diagnostic tool for the measurement of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), which are surrogate markers for hepatic steatosis and fibrosis, respectively. However, obesity constitutes a limitation in terms of creating unreliable examinations due to increased skin to liver capsule distance. Here, we aimed to investigate the feasibility of VCTE in the evaluation of hepatic steatosis and fibrosis in obese individuals. A total of 126 consecutive obese patients (body mass index ≥30 kg/m2) without a known history of MAFLD enrolled in the study. We performed CAP and LSM measurements and calculated Fibrosis-4 Index for each patient and included data of those patients to the analysis, from whom valid measurements were able to be taken. Reliable VCTE measurements were able to be obtained in 122 patients (97%), from those in 34 patients with M and 88 patients in XL probe (median age: 50 [18-75], 45 males and 77 females). In 1 patient VCTE failed to take any measurements and in 3 the measurements were classified as unreliable. The mean CAP value was 323 ± 48 dB/m and the median LSM value 5.3 [1.8-34.3] kPa. CAP and LSM assessments by Fibroscan are reliable diagnostic tools for the early diagnosis of hepatic steatosis and fibrosis in obese individuals.

Inducing and Probing Localized Excitons in Atomically Thin Semiconductors via Tip‐Enhanced Cavity‐Spectroscopy

AbstractIn atomically thin semiconductors, localized exciton (XL) coupled to light provides a new class of optical sources for potential applications in quantum communication. However, in most studies, XL photoluminescence (PL) from crystal defects has mainly been observed in cryogenic conditions because of their sub‐wavelength emission region and low quantum yield at room temperature. Hybrid‐modality of cavity‐spectroscopy to induce and probe the XL emissions at the nanoscale in atomically thin semiconductors is presented. By placing a WSe2 monolayer on the two extremely sharp Au tips in a bowtie antenna with a radius of curvature of &lt;1 nm, tensile strain of ≈0.3% is effectively induced in a &lt;30 nm region to create robust XL states. The Au tip then approaches the strained crystal region to enhance the XL emissions and probe them with tip‐enhanced photoluminescence (TEPL) spectroscopy at room temperature. Through this triple‐sharp‐tips cavity‐spectroscopy with &lt;15 nm spatial resolution, TEPL enhancement as high as ≈4.0 × 104 by the Purcell effect is achieved, and peak energy shifts of XL up to ≈40 meV are observed. This approach combining nano‐cavity and ‐spectroscopy provides a systematic way to induce and probe the radiative emission of localized excitons in 2D semiconductors offering new strategies for dynamic quantum nano‐optical devices.

Transient Versus Two-Dimensional Shear-Wave Elastography in a Multistep Strategy to Detect Advanced Fibrosis in NAFLD.

The combination of laboratory and elastography tests allows the accurate diagnosis of advanced liver fibrosis in patients with NAFLD. In this study, we compared the diagnostic performances of a two-step strategy (laboratory tests and vibration-controlled transient elastography [VCTE] or two-dimensional shear-wave elastography with SuperSonic Imagine [2D-SWE-SSI]) and the added value of a three-step strategy (laboratory tests and two elastography methods). From a prospective registry, we retrospectively selected 577 consecutive patients with suspicion of NAFLD who underwent laboratory tests to calculate the Fibrosis-4 (FIB-4) score, liver stiffness evaluation by VCTE (M and XL probes) and 2D-SWE-SSI, and liver biopsy. The diagnostic performances and need for liver biopsy in unclassified patients for the diagnosis of advanced fibrosis (F≥3) in multistep strategies were compared. The area under the curve of FIB-4, VCTE, and 2D-SWE-SSI was 0.74, 0.82, and 0.88, respectively. Using the same thresholds, the FIB-4/2D-SWE-SSI and FIB-4/VCTE diagnostic performances were comparable (sensitivity, 71.4% and 66%; specificity, 91.4% and 91.5%; and accuracy, 83.7% and 81.4%; all P=not significant). Conversely, more patients required liver biopsy after 2D-SWE-SSI (24.6% versus 15.3%, P<0.001). Performing a second elastography technique in patients with unreliable or gray zone (between 8 and 10kPa) results greatly decreased the need for liver biopsy (42/577, 7.3%). The diagnostic performances (accuracy, sensitivity, and specificity) of FIB-4/2D-SWE-SSI/VCTE and FIB-4/VCTE/2D-SWE-SSI were comparable (81.1%, 71.5%, and 87.9% versus 81.3%, 69.7%, and 89.5%, respectively; all P=not significant). Using the same cutoff values, 2D-SWE-SSI is as accurate as VCTE for advanced liver fibrosis diagnosis in NAFLD. The three-step strategy in selected patients strongly decreased the need for liver biopsy while maintaining excellent accuracy.

Interplay between non-alcoholic fatty liver disease and cardiovascular risk in an asymptomatic general population.

Non-alcoholic fatty liver (NAFLD) is a major cause of liver disease worldwide leading also to a higher risk of cardiovascular events. We aimed to evaluate the impact of fatty liver and fibrosis on cardiovascular risk in a general population. Five hundred and forty-two subjects included in the community-based ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study were recruited. Steatosis (controlled attenuation parameter>288dB/m) and severe fibrosis (low risk, liver stiffness measurement [LSM]<7.9KPa with M probe and <5.7KPa with XL probe; intermediate risk, LSM 7.9-9.5KPa with M probe and 5.7-9.2KPa with XL probe; high risk, LSM≥9.6KPa with M probe and ≥9.3KPa with XL probe) were assessed with FibroScan. Cardiovascular risk was evaluated by the atherosclerotic cardiovascular disease (ASCVD) risk estimator and defined low if <5%, borderline if 5-7.4%, intermediate if 7.5-19.9% and high if ≥20%. Intima-media thickness (IMT) was measured with ultrasound. Prevalence of steatosis and of severe fibrosis in this cohort was 31.7% and 4.8%, respectively. ASCVD score was evaluated in patients with and without steatosis and according to the risk of severe fibrosis. By ordinal regression analysis, both steatosis (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.13-2.33, P=0.009) and severity of fibrosis (OR 1.67, 95% CI 1.18-2.36, P=0.003) were independent risk factors for a higher ASCVD risk after adjusting for obesity. Subjects with NAFLD, when compared with those without, did not differ for IMT (0.75 vs 0.72mm; P=0.11) and IMT≥1mm (15.6% vs 12.1%; P=0.24). Higher prevalence of IMT≥1mm was found in patients at high or intermediate risk of severe fibrosis (24% and 28.6%, respectively) compared with those at low risk (12.1%) (P=0.03); this association was maintained after adjusting for confounders (OR 2.70, 95% CI 1.01-2.86, P=0.04). In the setting of a general adult population, the presence of NAFLD and severe fibrosis are associated with to a higher cardiovascular risk profile, pointing towards the need for specific preventive measures.

Validation of the FibroScan-aspartate aminotransferase score by vibration-controlled transient and B-mode ultrasound elastography.

The FibroScan-aspartate aminotransferase (FAST) score comprises an easy and feasible method for identifying advanced non-alcoholic steatohepatitis. Recently, shear-wave elastography and attenuation coefficient measurement on B-mode ultrasound (US) have become widely utilized. We investigated the diagnostic accuracy of the FAST score as calculated using US-elastography compared with that using vibration-controlled transient elastography (VCTE). Patients with chronic liver disease who underwent VCTE, point-shear-wave elastography with attenuation coefficient measurement, and liver biopsy on the same day between January 2015 and September 2020 were retrospectively reviewed. Of 189 patients, 94 underwent VCTE using both M and XL probes. The C-statistics were similar for VCTE (0.846) and US-elastography (0.814; p=0.251), and for M (0.857) and XL probes (0.833; p=0.412). Scatter and Bland-Altman plots showed good reproducibility for the FAST score. For VCTE, a cut-off of ≤0.35 had a sensitivity of 92.3%, negative predictive value of 85.5%, and negative likelihood ratio of 0.14, and a cut-off of ≥0.67 had a specificity of 90.6%, positive predictive value of 88.1%, and positive likelihood ratio of 6.03, for ruling out and in advanced non-alcoholic steatohepatitis, respectively. For US-elastography, a cut-off of ≤0.35 had a sensitivity of 90.4%, negative predictive value of 83.3%, and negative likelihood ratio of 0.16, and a cutoff of ≥0.67 had a specificity of 91.8%, positive predictive value of 85.1%, and positive likelihood ratio of 4.67, for ruling out and in advanced non-alcoholic steatohepatitis, respectively. The FAST score is highly reproducible, even when different echo equipment or probes are used.

FIB-4 Improves LSM-Based Prediction of Complications in Overweight or Obese Patients With Compensated Advanced Chronic Liver Disease

Liver stiffness measurement (LSM) by transient elastography (TE) is able to stratify the risk of decompensation in patients with compensated advanced chronic liver disease (cACLD).1 Recently, we demonstrated that this holds true also in overweight or obese patients with cACLD due to nonalcoholic steatohepatitis (NASH) studied by the XL probe. An LSM cutoff of ≥21 kPa remained associated with a high risk of complications in this population.2.

Diagnostic value of serological biomarkers for detection of non-alcoholic fatty liver disease (NAFLD) and/or advanced liver fibrosis in people living with HIV.

We aimed to evaluate the accuracy of serological biomarkers for non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis (METAVIR-F3F4) in HIV mono-infected individuals. In all, 674 participants from the PROSPEC-HIV study (NCT02542020), who had blood sample tests and transient elastography (TE) performed on the same day, were eligible. Exclusion criteria were viral hepatitis co-infection (n=90), abusive alcohol intake (n=61), missing data (n=47) or unreliable TE (n=39). NAFLD was defined by controlled attenuation parameter≥248dB/m and advanced fibrosis by liver stiffness measurement≥8.7kPa with M probe or ≥7.2kPa with XL probe. Biomarkers for NAFLD [Steato-ELSA, Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), NAFLD-Liver Fat Score (NAFLD-LFS)] and fibrosis [Fibrosis-4 score (FIB-4), Aspartate-to-Platelet Ratio Index (APRI) and NAFLD Fibrosis Score (NFS)] were calculated. A total of 437 patients [57% female, age=44 (interquartile range: 35-52)years, body mass index (BMI)=26.1 (23.4-29.3)kg/m2 , CD4=660 (427-901)cells/μL] were included. The prevalence [95% confidence interval (CI)] of NAFLD and advanced fibrosis were 38.2% (33.8-42.9) and 10.5% (8.0-13.8), respectively. The areas (95% CI) under the receiver operator curve (AUROCs) for diagnosis of NAFLD were 0.854 (0.818-0.889), 0.840 (0.804-0.877), 0.805 (0.762-0.847) and 0.793 (0.750-0.836) for Steato-ELSA, FLI, HSI and NAFLD-LFS (P<0.001), respectively. All tests yielded satisfactory sensitivities, specificities and negative predictive values (NPVs). The AUROCs (95% CI) for diagnosis of advanced fibrosis were 0.736 (0.659-0.814), 0.700 (0.614-0.7851) and 0.795 (0.726-0.864) for FIB-4, APRI and NFS (P=0.077), respectively. These tests yielded high specificities and negative predictive values (NPVs)>90%. Biomarkers for NAFLD had a good accuracy and those for fibrosis had high specificities and NPVs. These tests should be integrated to HIV care to detect NAFLD and to exclude advanced liver fibrosis.

Assessment of hepatic steatosis by controlled attenuation parameter using the M and XL probes: an individual patient data meta-analysis

Diagnostic tools for liver disease can now include estimation of the grade of hepatic steatosis (S0 to S3). Controlled attenuation parameter (CAP) is a non-invasive method for assessing hepatic steatosis that has become available for patients who are obese (FibroScan XL probe), but a consensus has not yet been reached regarding cutoffs and its diagnostic performance. We aimed to assess diagnostic properties and identify relevant covariates with use of an individual patient data meta-analysis. We did an individual patient data meta-analysis, in which we searched PubMed and Web of Science for studies published from database inception until April 30, 2019. Studies reporting original biopsy-controlled data of CAP for non-invasive grading of steatosis were eligible. Probe recommendation was based on automated selection, manual assessment of skin-to-liver-capsule distance, and a body-mass index (BMI) criterion. Receiver operating characteristic methods and mixed models were used to assess diagnostic properties and covariates. Patients with non-alcoholic fatty liver disease (NAFLD) were analysed separately because they are the predominant patient group when using the XL probe. This study is registered with PROSPERO, CRD42018099284. 16 studies reported histology-controlled CAP including the XL probe, and individual data from 13 papers and 2346 patients were included. Patients with a mean age of 46·5 years (SD 14·5) were recruited from 20 centres in nine countries. 2283 patients had data for BMI; 673 (29%) were normal weight (BMI <25 kg/m2), 530 (23%) were overweight (BMI ≥25 to <30 kg/m2), and 1080 (47%) were obese (BMI ≥30 kg/m2). 1277 (54%) patients had NAFLD, 474 (20%) had viral hepatitis, 285 (12%) had alcohol-associated liver disease, and 310 (13%) had other liver disease aetiologies. The XL probe was recommended in 1050 patients, 930 (89%) of whom had NAFLD; among the patients with NAFLD, the areas under the curve were 0·819 (95% CI 0·769-0·869) for S0 versus S1 to S3 and 0·754 (0·720-0·787) for S0 to S1 versus S2 to S3. CAP values were independently affected by aetiology, diabetes, BMI, aspartate aminotransferase, and sex. Optimal cutoffs differed substantially across aetiologies. Risk of bias according to QUADAS-2 was low. CAP cutoffs varied according to cause, and can effectively recognise significant steatosis in patients with viral hepatitis. CAP cannot grade steatosis in patients with NAFLD adequately, but its value in a NAFLD screening setting needs to be studied, ideally with methods beyond the traditional histological reference standard. The German Federal Ministry of Education and Research and Echosens.

Accuracy of Controlled Attenuation Parameter and Liver Stiffness Measurement in Patients with Non-alcoholic Fatty Liver Disease

We evaluated the diagnostic accuracy of the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) measured with either an M or XL probe against liver biopsy (LB) in patients with non-alcoholic fatty liver disease (NAFLD). This study was a cross-sectional prospective study that included 179 NAFLD patients. With a cutoff value for CAP ≥345, we can exclude significant steatosis in 87% (79.4%–92.5%) of our population. With respect to the LSM, the highest accuracy was obtained for F ≥ F3 (area under the receiver operating characteristic curve [AUROC] = 0.98) and F = F4 (AUROC = 0.98). In a multivariable linear regression model, significant predictors influencing LSM were fibrosis stage (β = 2.6, p < 0.001) as a positive predictor and lobular inflammation (β = –0.68, p = 0.04) as a negative predictor, without significant influence after adjustment for CAP and probe type. We found that CAP is a satisfactory method for excluding advanced steatosis, while LSM is a good non-invasive marker for the exclusion of fibrosis.

High Prevalence of Advanced Liver Fibrosis Assessed by Transient Elastography Among U.S. Adults With Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is an important risk factor for the progression of metabolic liver disease to advanced fibrosis. Here, we provide an estimate of the prevalence of steatosis and fibrosis in U.S. adults with T2DM on the basis of transient elastography (TE) and identify factors associated with these conditions. This is a cross-sectional study of U.S. adults with T2DM participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey who were evaluated by TE. Hepatic steatosis and fibrosis were diagnosed by the median value of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Among the 825 patients with reliable TE examination results, 484 (53.7%) were assessed using the M probe and 341 (46.3%) using the XL probe. Liver steatosis (CAP ≥274 dB/m), advanced fibrosis (LSM ≥9.7 kPa), and cirrhosis (LSM ≥13.6 kPa) were present in 73.8% (95% CI 68.5%-78.5%), 15.4% (95% CI 12.2%-19.0%), and 7.7% (95% CI 4.8%-11.9%) of patients, respectively. The mean ± SE age of patients with advanced fibrosis and cirrhosis was 63.7 ± 2.2 years and 57.8 ± 1.6 years, respectively. In the multivariable logistic regression model, BMI, non-Black race, and ALT levels were independent predictors of steatosis; and BMI, non-Black race, and AST and γ-glutamyltranspeptidase levels were independent predictors of advanced fibrosis. Prevalence of both liver steatosis and fibrosis is high in patients with T2DM from the United States and obesity is a major risk factor. Our results support the screening of these conditions among patients with diabetes.

Diagnostic Accuracy of FibroScan and Factors Affecting Measurements.

Evaluating liver steatosis and fibrosis is important for patients with non-alcoholic fatty liver disease. Although liver biopsy and pathological assessment is the gold standard for these conditions, this technique has several disadvantages. The evaluation of steatosis and fibrosis using ultrasound B-mode imaging is qualitative and subjective. The liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) determined using FibroScan are the evidence-based non-invasive measures of liver fibrosis and steatosis, respectively. The LSM and CAP measurements are carried out simultaneously, and the median values of more than ten valid measurements are used to quantify liver fibrosis and steatosis. Here, we demonstrate that the reliability of the LSM depends on the interquartile range to median ratio (IQR/Med), but CAP values do not depend on IQR/Med. In addition, the LSM is affected by inflammation, congestion, and cholestasis in addition to fibrosis, while CAP values are affected by the body mass index in addition to steatosis. We also show that the M probe provides higher LSM values but lower CAP values than the XL probe in the same population. However, there was no statistically significant difference between the diagnostic accuracies of the two probes. These findings are important to understand the reliability of FibroScan measurements and the factors influencing measurement values for all patients.

Optimal Threshold of Controlled Attenuation Parameter for Detection of HIV-Associated NAFLD With Magnetic Resonance Imaging as the Reference Standard.

Controlled attenuation parameter (CAP) is an ultrasound-based point-of-care method to quantify liver fat; however, the optimal threshold for CAP to detect pathologic liver fat among persons living with human immunodeficiency virus (HIV; PLWH) is unknown. Therefore, we aimed to identify the diagnostic accuracy and optimal threshold of CAP for the detection of liver-fat among PLWH with magnetic resonance imaging proton-density fat fraction (MRI-PDFF) as the reference standard. Patients from a prospective single-center cohort of PLWH at risk for HIV-associated nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRI-PDFF and CAP assessment were included. Subjects with other forms of liver disease including viral hepatitis and excessive alcohol intake were excluded. Receiver operatic characteristic (ROC) curve analysis were performed to identify the optimal threshold for the detection of HIV-associated NAFLD (liver fat ≥ 5%). Seventy PLWH (90% men) at risk for NAFLD were included. The mean (± standard deviation) age and body mass index were 48.6 (±10.2) years and 30 (± 5.3) kg/m2, respectively. The prevalence of HIV-associated NAFLD (MRI-PDFF ≥ 5%) was 80%. The M and XL probes were used for 56% and 44% of patients, respectively. The area under the ROC curve of CAP for the detection of MRI-PDFF ≥ 5% was 0.82 (0.69-0.95) at the cut-point of 285 dB/m. The positive predictive value of CAP ≥ 285 dB/m was 93.2% in this cohort with sensitivity of 73% and specificity of 78.6%. The optimal cut-point of CAP to correctly identify HIV-associated NAFLD was 285 dB/m, is similar to previously published cut-point for primary NAFLD and may be incorporated into routine care to identify patients at risk of HIV-associated NAFLD.

Applicability and Results of Liver Stiffness Measurement and Controlled Attenuation Parameter Using XL Probe for Metabolic-Associated Fatty Liver Disease in Candidates to Bariatric Surgery. A Single-Center Observational Study.

Patients with morbid obesity are at high risk of liver fibrosis due to metabolic-associated fatty liver disease. Data on liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by vibration-controlled transient elastography (VCTE, FibroScan®) XL probe for liver fibrosis and steatosis assessment in morbid obesity are needed. LSM and CAP were measured in candidates to bariatric surgery at a single center during 12months. In patients who underwent an intraoperative liver biopsy, we compared LSM and CAP with histology findings. Comorbidities, body mass index, type of surgery, and infections after surgery were collected and analyzed. Of the eighty-three patients assessed by XL probe, 49 (59%; female in 63%, BMI 42.6 ± 5.1kg/m2) had a valid LSM and CAP measurement. LSM was 7.0 ± 3.9kPa and CAP 329 ± 57dB/m. In the 14 patients undergoing intraoperative liver biopsy, all had steatosis (severe in 50%), 6 (43%) had NASH (NAS ≥ 5), and 4 (29%) showed significant or bridging fibrosis. LSM accurately discriminated between patients with and without significant or severe fibrosis (AUROC 0.833) and CAP well-identified patients with or without ≥S2 steatosis (AUROC 0.896). Nine of 49 patients (18%) tested positive for significant/severe fibrosis by LSM (cut-off 8.9kPa). Applicability of LSM and CAP by XL probe in patients candidate to bariatric surgery was moderate. However, when technically successful, their reliability to diagnose severe steatosis and fibrosis related to MAFLD was good.

Modest alcohol intake not associated with significant hepatic steatosis or more severe liver disease among patients with diabetes mellitus.

The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear. This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤21units/week in men and ≤14units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter>263dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement≥9.6kPa using M probe or ≥9.3kPa using XL probe. Patients with liver stiffness measurement≥8.0kPa were offered liver biopsy. Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease. Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM.

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.

Diagnostic accuracy of FibroScan-AST score to identify non-alcoholic steatohepatitis with significant activity and fibrosis in Japanese patients with non-alcoholic fatty liver disease: Comparison between M and XL probes.

Recently, FibroScan-AST (FAST) score was reported to be effective for identifying non-alcoholic steatohepatitis (NASH) with significant activity and fibrosis in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to confirm the diagnostic accuracy of FAST score of Japanese patients and compare the cut-off values and diagnostic accuracy between the FibroScan M and XL probes. Eighty-two and 84 patients were included the verification and validation sets, respectively. All patients were diagnosed with NAFLD by biopsy by two central expert pathologists. Liver stiffness measurements and controlled attenuation parameter were carried out, and diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. No significant difference existed in FAST score between the M and XL probes (0.489 vs. 0.483, P = 0.187). No significant difference existed in the area under the ROC between the two probes (M, 0.7598; XL, 0.7614; P = 0.958). According to the Youden index, the cut-off value using the M probe was 0.57 with 68.2% sensitivity and 78.3% specificity. For the XL probe, the cut-off value was 0.56 with 68.2% sensitivity and 73.3% specificity. To obtain sensitivity and specificity values higher than 90%, cut-off values of 0.35 and 0.66 were chosen for the M probe and 0.32 and 0.63 were chosen for the XL probe. There was no significant difference in diagnostic accuracy of FAST score between the FibroScan M and XL probes. The FAST score can be used to identify NASH with significant risk in Japanese patients regardless of probe selection.

Exam 2: Prospective, Same-Day, Direct Comparison of Controlled Attenuation Parameter With the M vs the XL Probe in Patients With Nonalcoholic Fatty Liver Disease, Using Magnetic Resonance Imaging—Proton Density Fat Fraction as the Standard

Exam 2: Prospective, Same-Day, Direct Comparison of Controlled Attenuation Parameter With the M vs the XL Probe in Patients With Nonalcoholic Fatty Liver Disease, Using Magnetic Resonance Imaging—Proton Density Fat Fraction as the Standard

Noninvasive Markers of Portal Hypertension Detect Decompensation in Overweight or Obese Patients With Compensated Advanced Chronic Liver Disease

Some patients with compensated advanced chronic liver disease (cACLD) require use of an extralarge probe for liver stiffness measurement (LSM), owing to overweight or obesity. However, the ability of noninvasive markers of portal hypertension and the controlled attenuation parameter (CAP) to determine which of these patients are at risk for decompensation has not been fully assessed. We collected data from 272 patients with cACLD (LSM ≥10 kPa by XL probe; 57% with nonalcoholic steatohepatitis; mean body mass index, 33.8 ± 6.5 kg/m2; median Child-Pugh score, 5; median LSM, 16.8 kPa; mean CAP, 318 ± 66 dB/m) evaluated at 2 academic centers from 2015 through 2018. We collected clinical data on decompensation (ascites, portal hypertension bleeding, jaundice, hepatic encephalopathy) and severe bacterial infections; patients were followed up for a median of 17 months (interquartile range, 11-24 mo). We evaluated associations between these events and LSM, CAP, LSM∗spleen size/platelet count (LSPS), and portal hypertension risk scores. Decompensation occurred in 12 patients and severe bacterial infections developed in 5 patients. LSM, LSPS, and the portal hypertension risk score identified patients with decompensation with area under the receiver operating characteristic curve values of 0.848 (95% CI, 0.720-0.976; P < .0001), 0.881 (95% CI, 0.798-0.954; P < .0001), and 0.890 (95% CI, 0.814-0.966; P < .0001), respectively. In multivariate Cox regression analysis, in patients with nonalcoholic steatohepatitis, LSM and CAP were associated independently with decompensation and severe bacterial infection; CAP ≥ 220 dB/m was associated with a reduced risk of decompensation (hazard ratio, 0.043, 95% CI, 0.004-0.476; P= .01). LSM, LSPS, and the portal hypertension risk score identify obese or overweight patients with cACLD who are at increased risk of decompensation and severe bacterial infection.