Transient Elastography Liver Stiffness Research Articles

Abstract MP13: Association Between Visceral Adiposity Index and Non-Alcoholic Liver Fibrosis Among United States Adults With Prediabetes

Background: Although type 2 diabetes is a well-established risk factor for non-alcoholic fatty liver disease (NAFLD) and downstream liver fibrosis, little is known about the risk factors associated with NAFLD fibrosis in adults with prediabetes. We aimed to understand whether visceral adiposity was associated with liver fibrosis, independent of insulin resistance, among participants with prediabetes. Methods: In this nationally representative, cross-sectional study, we selected non-pregnant adults ≥20 years from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 with prediabetes, defined as HbA1c of 5.7-6.4%, fasting blood glucose of 100-125 mg/dl, or a self-reported diagnosis of prediabetes. We excluded those with acute transaminitis (aspartate or alanine aminotransferase >500 IU/L), excessive alcohol consumption (>1 drinks/day for females, > 2 drinks/day for males), iron overload (transferrin saturation >50%), and positive hepatitis serology. Visceral adiposity was estimated using the validated Visceral Adiposity Index (VAI) and categorized into tertiles (<1.17, 1.17-2.19, >2.19). Our primary outcome was clinically significant liver fibrosis, defined dichotomously as median Fibroscan vibration controlled transient elastography liver stiffness measurements of 7.9 kPa or greater (≥F2). We used survey design-adjusted logistic regression, adjusting for covariates determined a priori (age, sex, race/ethnicity, income, education, smoking status, physical inactivity, hypertension, hemoglobin A1c (HbA1c), total caloric intake, and Homeostatic Model Assessment for Insulin Resistance [HOMA]) to estimate odds of fibrosis. Results: Among 1,290 prediabetic adults (mean age 62y [SD, 10], 44% female, 62% non-Hispanic White, representing 37,401,474 adults across the U.S.), 121 (10%) had NAFLD fibrosis. Participants in the highest tertile of VAI were more likely to be female, older, have higher waist circumference, and have comorbid cardiac conditions. The highest tertile of VAI was associated with three times higher odds of fibrosis (highest vs. lowest tertile; OR [95% CI], 3.81 [1.65, 8.79], middle vs. lowest tertile: 4.93 [1.74, 13.34]). There was no significant multiplicative interaction between VAI and HOMA (p=0.44). The highest tertile was also associated with 170% higher odds of F1 (mild) liver fibrosis (2.70 [1.10, 6.63], middle vs. lowest tertile: 2.69 [1.26, 5.77]). Conclusion: Nearly 1 in 10 adults with prediabetes have clinically significant liver fibrosis. High visceral adiposity was associated with more than 3 times the likelihood of fibrosis, independent of insulin resistance and traditional risk factors.

Correlation of Transient Elastography with Liver Iron Concentration and Serum Ferritin Levels in Patients with Transfusion-Dependent Thalassemia Major from Oman.

In a longitudinal study, we aimed to assess the correlation between ultrasound transient elastography (TE), serum ferritin (SF), liver iron content (LIC) by magnetic resonance imaging (MRI) T2* along with the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis among chronically transfusion-dependent beta-thalassemia (TDT) patients. The study was conducted at a tertiary health center treating TDT patients. Transient elastography was performed within 3 months of Liver MRI T2* examinations at the radiology department over a median of one-year duration. T-test for independent data or Mann-Whitney U test was used to analyze group differences. Spearman correlation with linear regression analysis was used to evaluate the correlation between TE liver stiffness measurements, Liver MRI T2* values, and SF levels. In this study on 91 patients, the median age (IQR) of the subjects was 33 (9) years, and the median (IQR) body mass index was 23.8 (6.1) kg/m2. Median (IQR) TE by fibroscan, MRI T2*(3T), Liver iron concentration (LIC) by MRI Liver T2*, and SF levels were 6.38 (2.6) kPa, 32.4 (18) milliseconds, 7(9) g/dry wt., and 1881 (2969) ng/mL, respectively. TE measurements correlated with LIC g/dry wt. (rS =0.39, p=0.0001) and with SF level (rS =0.43, P=0.001) but not with MRI T2* values (rS =-0.24; P=0.98). In TDT patients, liver stiffness measured as TE decreased significantly with improved iron overload measured as LIC by MRI and SF levels. However, there was no correlation of TE with the fibrosis-4 (FIB-4) score.

Increasing liver stiffness is associated with higher incidence of hepatocellular carcinoma in hepatitis C infection and non-alcoholic fatty liver disease-A population-based study.

Both non-alcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection commonly result in hepatic fibrosis and may lead to cirrhosis. This study aims to determine the incidence of HCC in patients with HCV or NAFLD complicated by advanced fibrosis, inferred from measurements of liver stiffness. Using Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), we identified a nationwide cohort of patients with an existing diagnosis of HCV or NAFLD with liver transient elastography (TE) testing from 2015 to 2019. HCC cases, along with a random sample of non-HCC patients, were identified and validated, leading to calculation of incidence rates for HCC after adjustment for confounders. 26,161 patients carried a diagnosis of HCV and 13,629 were diagnosed with NAFLD at the time of testing. In those with HCV, rates of HCC increased with liver stiffness with incidences of 0.28 (95% CI 0.24, 0.34), 0.93 (95% CI 0.72, 1.17), 1.28 (95% CI 0.89, 1.79), and 2.79 (95% CI 2.47, 3.14)/100,000 person years for TE score ranges <9.5 kPa, 9.5-12.5 kPa, 12.5-14.5 kPa and >14.5 kPa, respectively, after a median follow-up of 2.3 years. HCC incidence also increased with higher TE liver stiffness measures in NAFLD after a median follow-up of 1.1 years. In this retrospective cohort, the incidence of HCC in HCV and NAFLD increases with higher TE liver stiffness measures, confirming that advanced fibrosis portends risk in viral and non-viral fibrotic liver diseases. Additional comparative studies are needed to determine the optimal cut point of TE liver stiffness to inform HCC screening guidelines and approaches.

Variability of noninvasive MRI and biological markers in compensated cirrhosis: insights for assessing disease progression

BackgroundWe annually monitored stable compensated cirrhosis (CC) patients to evaluate serial variation in blood serum, liver stiffness, and multiparametric magnetic resonance imaging (mpMRI) measures to provide reference change values (RCV) and sample size measures for future studies.MethodsPatients were recruited from a prospectively followed CC cohort, with assessments at baseline and annually over three years. We report on blood markers, transient elastography liver stiffness measures (LSM) and noninvasive mpMRI (volume, T1 mapping, blood flow, perfusion) of the liver, spleen, kidneys, and heart in a stable CC group and a healthy volunteer (HV) group. Coefficient of variation over time (CoVT) and RCV are reported, along with hazard ratio to assess disease progression. Sample size estimates to power future trials of cirrhosis regression on mpMRI are presented.ResultsOf 60 CC patients enrolled, 28 with stable CC were followed longitudinally and compared to 10 HVs. CoVT in mpMRI measures was comparable between CC and HV groups. CoVT of Enhanced Liver Fibrosis score was low (< 5%) compared to Fibrosis-4 index (17.9%) and Aspartate Aminotransferase-to-Platelet-Ratio Index (19.4%). A large CoVT (20.7%) and RCV (48.3%) were observed for LSM. CoVT and RCV were low for liver, spleen, and renal T1 values (CoVT < 5%, RCV < 8%) and volume (CoVT < 10%, RCV < 16%); haemodynamic measures were high (CoVT 12–25%, RCV 16–47%).ConclusionsEvidence of low CoVT and RCV in multiorgan T1 values. RCV and sample size estimates are provided for future longitudinal multiorgan monitoring in CC patients.Trial registrationClinicalTrials.gov identifier: NCT02037867, Registered: 05/01/2013.

FRI063 - Correlations of 2D-Shear wave and transient elastography liver stiffness measurements in patients with non-alcoholic fatty liver disease

FRI063 - Correlations of 2D-Shear wave and transient elastography liver stiffness measurements in patients with non-alcoholic fatty liver disease

Predicting NAFLD prevalence in the United States using National Health and Nutrition Examination Survey 2017-2018 transient elastography data and application of machine learning.

This cohort analysis investigated the prevalence of nonalcoholic fatty liver disease (NAFLD) and NAFLD with fibrosis at different stages, associated clinical characteristics, and comorbidities in the general United States population and a subpopulation with type 2 diabetes mellitus (T2DM), using the National Health and Nutrition Examination Survey (NHANES) database (2017–2018). Machine learning was explored to predict NAFLD identified by transient elastography (FibroScan®). Adults ≥20 years of age with valid transient elastography measurements were included; those with high alcohol consumption, viral hepatitis, or human immunodeficiency virus were excluded. Controlled attenuation parameter ≥302 dB/m using Youden’s index defined NAFLD; vibration‐controlled transient elastography liver stiffness cutoffs were ≤8.2, ≤9.7, ≤13.6, and >13.6 kPa for F0–F1, F2, F3, and F4, respectively. Predictive modeling, using six different machine‐learning approaches with demographic and clinical data from NHANES, was applied. Age‐adjusted prevalence of NAFLD and of NAFLD with F0–F1 and F2–F4 fibrosis was 25.3%, 18.9%, and 4.4%, respectively, in the overall population and 54.6%, 32.6%, and 18.3% in those with T2DM. The highest prevalence was among Mexican American participants. Test performance for all six machine‐learning models was similar (area under the receiver operating characteristic curve, 0.79–0.84). Machine learning using logistic regression identified male sex, hemoglobin A1c, age, and body mass index among significant predictors of NAFLD (P ≤ 0.01). Conclusion: Data show a high prevalence of NAFLD with significant fibrosis (≥F2) in the general United States population, with greater prevalence in participants with T2DM. Using readily available, standard demographic and clinical data, machine‐learning models could identify subjects with NAFLD across large data sets.

The Roles of Fibrosis Index Based on Four Factors and Aspartate Transaminase-to-Platelet Ratio Index Scoring Systems as an Alternative to Transient Elastography Liver Stiffness in Liver Fibrosis Staging in Human Immunodeficiency Virus and Hepatitis C Virus Co-Infected Patients.

BackgroundLiver biopsy used to be the gold standard to assess liver fibrosis in patients infected with hepatitis C virus (HCV). Nonetheless, due to its invasive nature, techniques such as transient elastography liver stiffness (TE-LS), fibrosis index based on four factors (FIB-4) and aspartate transaminase-to-platelet ratio index (APRI) scores are currently being used. FIB-4 and APRI scores have the advantage of low cost and are readily available, compared with TE-LS. Herein, we evaluated the diagnostic performance of these scoring systems as compared to TE-LS in assessing liver fibrosis in patients with human immunodeficiency virus (HIV) and HCV co-infection.MethodsThe medical records of patients with HIV and HCV co-infection who had TE-LS done at our facility between August 1, 2013 and January 1, 2020 were extracted and analyzed. Exclusion criteria include: 1) patients co-infected with hepatitis B virus; 2) invalid TE-LS assessment; 3) have ≥ 10th upper limit of normal (ULN) alanine aminotransferase (ALT) levels; and 4) excessive alcohol use. Patient demographics, medical history, biochemical and clinical data were retrieved. For each patient, we calculated the FIB-4 and APRI score. Descriptive analysis was performed and correlation of FIB-4 and APRI with TE-LS was assessed with GraphPad Prism statistical software.ResultsFive hundred forty-seven patients underwent TE-LS during the study period. After excluding those without complete laboratory parameters, the total study population was 344. Their age was 56 ± 10.4 years and 234 (68%) were male. The average aspartate aminotransferase (AST) and ALT were 27.95 and 30.73. The average platelet count was 224 and the average TE-LS was 7.29. Fourteen patients (4.1%) had TE-LS values between 9 and 11.9 kPa and were classified as F3, while 29 (8.5%) had TE-LS ≥ 12 kPa and were classified as F4. With the correlation analysis, both APRI (correlation coefficient, r = 0.1097, 95% confidence interval (CI) 0.0403 - 0.2130; P = 0.042) and FIB-4 (r = 0.0424, 95% CI -0.0634 - 0.1474; P = 0.4335) were not correlated with TE-LS stages of fibrosis.ConclusionIn our cohort, we failed to demonstrate that APRI and FIB-4 are reliable alternatives for screening liver fibrosis in patients with HIV and HCV co-infection. Nonetheless, APRI score still has a potential role as a screening tool instead of TE-LS measurement, which is costly and not readily available. It will be important to corroborate these findings in another large cohort, since this may have an important impact on patient management.

S1049 Characteristics of a Hispanic Cohort With Non-Alcoholic Fatty Liver Disease in South Texas

INTRODUCTION: In the US, the prevalence and characteristics of Non-alcoholic Fatty Liver Disease (NAFLD) in the Latino population have been poorly described in the literature, with few epidemiological data in a strictly Hispanic cohort. The aim of our study was to further characterize a cohort of patients in South Texas and to assess the predictive value of using vibration controlled transient elastography (TE) to determine histologic diagnosis of non-alcoholic steatohepatitis (NASH) with liver fibrosis. METHODS: This retrospective study cohort analysis was conducted on patients seen at the Gastroenterology/Liver Institute at DHR in South Texas from January 2015 to March 2019. Patients were included if they were ages 18-85, with no alcohol abuse, or other etiology of liver disease, who had high-risk TE results, defined as controlled attenuation parameter(CAP) > 280 and TE Liver stiffness measurement (LSM) > 8.5 kPa. RESULTS: We included 178 patients in our study (mean age 52, 59% women). Hispanic ethnicity made up 94% of the cohort. Mean BMI of 35, 53.4% had diabetes mellitus type 2, and 63% hypertension. Notably, the mean AST was 48.4 IU/L. All patients had clinical diagnosis of NAFLD after excluding other liver disease; because of their risk factors, they underwent TE. TE findings showed a mean LSM was 19.3kPa and a mean CAP of 336.5db/M. Secondary analysis was done for 60 patients who had liver biopsy. Liver biopsies were read by a single GI-trained pathologist to avoid inter-observer variability. We used a NAFLD activity score (NAS) of > 3 to be diagnostic of steatohepatitis, 47% of patients with liver biopsy had a NAS > 3. Fibrosis staging review reported 88% of patients with at least F1-F4 disease. Those with advanced fibrosis (F2-F4) made up 61% of biopsied patients. Interestingly, 29% of patients had F4 correlating to a diagnosis of compensated NASH cirrhosis. CONCLUSION: In our cohort of patients in South Texas, a high-risk TE result was clinically successful in identifying patients with NASH and some fibrosis. The mean LSM in our cohort of 19.3 kPa suggest that obesity affecting TE results and high-risk disease play a role in our results. When looking at a Hispanic cohort of patients with diabetes and obesity, prevalence of NASH was close to 50% and prevalence of advanced fibrosis was 61%. These data further expand our understanding of high-risk disease in our region. To our knowledge this is the first retrospective NAFLD cohort analysis strictly from Texas-based cohort of Hispanics in the US.

Assessment of native liver fibrosis using ultrasound elastography and serological fibrosis indices in children with biliary atresia after the Kasai procedure

Validated non-invasive examinations are necessary to monitor liver fibrosis in children with biliary atresia (BA) after the Kasai procedure. To evaluate the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE), transient elastography (TE), and the serologic biomarkers of aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for evaluating native liver fibrosis in children with BA. We retrospectively reviewed same-day 2D-SWE and TE liver stiffness (LS) measurements of 63 patients with BA who underwent the Kasai procedure. The APRI and FIB-4 score were computed. Hepatic fibrosis was categorized into three clinical categories based on the ultrasound (US) hepatic morphology and clinical manifestations of liver cirrhosis: I, pre-cirrhotic liver state (n = 15); II, US and/or clinical signs of liver cirrhosis with compensated liver function (n = 27); and III, liver cirrhosis with decompensated liver function (n = 21). We compared area under the receiver operating characteristic curve (AUC) data among 2D-SWE, TE, APRI, and FIB-4 score. Combined evaluation of serologic fibrosis indices and US elastography was conducted and AUCs of combinations were analyzed. 2D-SWE, TE, APRI, and FIB-4 score showed good to excellent diagnostic accuracy for differentiating clinical categories (AUCs 0.779-0.955). AUC values were significantly increased after adding TE to FIB-4 score for detecting liver cirrhosis (P = 0.02). 2D-SWE, TE, APRI, and FIB-4 score are accurate non-invasive markers for monitoring native liver fibrosis in patients with BA. Combined use of serologic markers and US elastography could yield more accurate diagnoses of liver fibrosis than serologic markers alone.

Sarcopenia assessed using bioimpedance analysis is associated independently with significant liver fibrosis in patients with chronic liver diseases.

Sarcopenia is common in patients with advanced fibrosis or cirrhosis. We investigated the correlation between sarcopenia and other clinical variables, in particular, significant liver fibrosis in patients with chronic liver diseases (CLDs). Patients with CLDs who underwent transient elastography (TE) and bioelectrical impedance analysis between 2015 and 2017 were retrospectively recruited. The sarcopenia index (SI) was calculated as follows: SI = total appendicular skeletal muscle mass (kg)/ body mass index (BMI) (kg/m). Sarcopenia was defined as SI less than 0.789 for men and less than 0.521 for women. Significant liver fibrosis and fatty liver were defined using TE liver stiffness value more than 7 kPa and controlled attenuation parameter more than 250 dB/m, respectively. Of 2168 patients recruited, 218 (10.1%) had sarcopenia. Age, BMI, diabetes, hypertension, fasting glucose, aspartate aminotransferase, and liver stiffness value were correlated positively with sarcopenia (all P < 0.05), whereas male sex, viral etiology, obesity (BMI > 25 kg/m), total bilirubin, and serum albumin were correlated negatively with sarcopenia (all P < 0.05). On multivariate analysis, TE-defined significant liver fibrosis was associated independently with sarcopenia (odds ratio = 1.597; 95% confidence interval: 1.174-2.172; P = 0.003), together with age, male sex, viral etiology, and TE-defined fatty liver (all P < 0.05). Among the subgroups with ultrasonography-defined nonalcoholic fatty liver disease (n = 957), sarcopenia was also associated independently with TE-defined significant liver fibrosis (odds ratio = 1.887; 95% confidence interval: 1.261-2.823; P < 0.001). Sarcopenia is associated independently with significant liver fibrosis in patients with CLDs. Further studies are required to determine whether interventions to improve muscle mass can improve liver fibrosis.

A study of diagnostic performance of MR elastography in liver fibrosis with chronic hepatitis B

Objective To explore the diagnostic value of MR elastography and diffusion-weighted imaging in patients with liver fibrosis in the context of chronic hepatitis B. Methods Twenty-four patients with chronic hepatitis B, whose course of liver disease was more than 6 months and hepatitis B surface antigen was positive, were prospectively enrolled in the First Affiliated Hospital of Soochow University from July to December 2017. All of the patients underwent abdominal transient elastography (TE), routine MRI, magnetic resonance elastography (MRE) and DWI examination, TE and MRI were performed within one week. TE liver stiffness was measured, the MRE liver stiffness and ADC value were measured on MR imagings. All patients were divided into three groups: mild and non fibrosis (F0 to 1), significant fibrosis(F2 to 3) and cirrhosis (F4), according to the recommended standard of FibroTouch. Correlation between TE liver stiffness, MRE liver stiffness and ADC values were identified by using Spearman correlation test. The difference of the MRE liver stiffness and ADC value among the three groups was tested using independent sample t test. The overall predictive ability of MRE and DWI in assessment of liver fibrosis and cirrhosis was analyzed by constructing ROC curve. Results TE and MRI were successfully performed in all subjects, and the image quality was good. The MRE liver stiffness in mild and non fibrosis, significant fibrosis and cirrhosis was (2.32±0.31),(3.43±1.05),(4.77±0.68) kPa with statistically significant difference (F=61.690, P<0.01). The ADC values in three groups were (1.31±0.14)×10-3, (1.23±0.15)×10-3,(1.22±0.12)×10-3mm2/s without significant difference (F=1.074,P=0.360). The TE liver stiffness in three groups was (5.61±1.05), (9.56±0.57), (17.25±3.55)kPa, respectively, there was significant correlation between the MRE liver stiffness and the TE liver stiffness(t=0.858, P<0.01), but no significant correlation between the TE liver stiffness and the ADC value was found (r=-0.326,P=0.120). The area under ROC of MRE liver stiffness in diagnosing liver fibrosis grade (≥ F2 and F4) was 0.96 and 1.00 respectively, while the AUC of ADC value was less than 0.70, which were 0.67 and 0.62 respectively. Conclusion MRE is a non-invasive promising tool for assessing liver fibrosis with chronic hepatitis B, while DWI has limited role. Key words: Liver fibrosis; Magnetic resonance elastography; Diffusion weighted imaging

High Kynurenine:Tryptophan Ratio Is Associated With Liver Fibrosis in HIV-Monoinfected and HIV/Hepatitis C Virus-Coinfected Women.

BackgroundTryptophan catabolism, measured by the kynurenine:tryptophan (kyn/trp) ratio, is associated with gut microbiota alterations in people with HIV (PWH). We examined the association of the kyn/trp ratio with liver fibrosis in women with/without HIV infection.MethodsThe plasma kyn/trp ratio was measured in 137 HIV-monoinfected, HIV/hepatitis C virus (HCV)–coinfected, and uninfected women in the Women’s Interagency HIV Study. Fibrosis was estimated using FIB-4 in all participants and vibration-controlled transient elastography liver stiffness measurement (LSM) in a subset (n = 83). We used multivariable linear regression to evaluate the associations of infection status and kyn/trp ratio with relative differences in fibrosis estimates.ResultsThe median kyn/trp ratio (interquartile range) was 0.056 (0.045–0.066) in HIV/HCV-coinfected, 0.038 (0.032–0.046) in HIV-monoinfected, and 0.031 (0.025–0.034) in uninfected women (P < .001). After adjustment for sociodemographic, lifestyle, and metabolic factors, HIV monoinfection and HIV/HCV coinfection were associated with 37% (95% confidence interval [CI], 9% to 73%) and 164% (95% CI, 100% to 250%) greater FIB-4, respectively. When kyn/trp ratio was included, higher kyn/trp ratio was associated with greater FIB-4 (27% per kyn/trp doubling; 95% CI, 5% to 53%), and the associations of HIV monoinfection (29% per kyn/trp doubling; 95% CI, 2% to 63%) and HIV/HCV coinfection (123% per kyn/trp doubling; 95% CI, 63% to 203%) with greater FIB-4 were attenuated. Among those with LSM, higher kyn/trp ratio was associated with greater LSM (43% per kyn/trp doubling; 95% CI, 15% to 79%) in multivariable analysis.ConclusionsThe kyn/trp ratio is elevated in PWH and is associated with greater liver fibrosis. Tryptophan catabolism may modify the relationships between HIV, HCV, and fibrosis.

Liver fibrosis staging with combination of APRI and FIB-4 scoring systems in chronic hepatitis C as an alternative to transient elastography.

Background:Liver disease severity must be determined before treatment of chronic hepatitis C (CHC). We evaluated the diagnostic performance of the APRI and FIB-4 scores compared to transient elastography liver stiffness (TE-LS) in detecting significant fibrosis (F3) or cirrhosis (F4).Methods:We retrospectively enrolled 575 patients with CHC who underwent TE-LS between May 2014 and September 2018: 365 (63.5%) male, mean age 51.54±12.4 years. APRI and FIB-4 scores were compared to TE-LS.Results :One hundred patients (17.5%) had TE-LS values between 9 and 11.9 kPa, and were classified as F3, while 265 (46%) were classified as F4 (TE-LS ≥12 kPa). APRI and FIB-4 scores predicted F4 patients adequately using cutoff values of 0.65 (sensitivity 85.5%, specificity 77%) and 1.63 (sensitivity 91%, specificity 77%), respectively. Cutoff values of 0.64 for APRI and 1.46 for FIB-4 predicted F3/F4 patients (sensitivity 72% and 81.5%; specificity 83% and 79%, respectively). The use of these cutoff values with APRI and FIB-4 in combination adequately predicted patients with significant fibrosis or cirrhosis (positive predictive value 91.5%), while cutoff values of 0.3 and 0.98, respectively, predicted F1/F2 patients with specificity 94.5% and sensitivity 26.5%, suggesting that in 58.5% of patients TE-LS could possibly be avoided.Conclusions:The APRI/FIB-4 combination performed well in predicting significant fibrosis, while FIB-4 performed well in predicting cirrhosis. These noninvasive biochemical markers could be used as screening tools instead of LS measurement, which is not widely available. Further prospective validation studies are required to confirm this finding.

Transient elastography reliably estimates liver fibrosis in autoimmune hepatitis.

Aim of the studyAutoimmune hepatitis (AIH) may result in liver fibrosis and cirrhosis. While the gold standard for staging fibrosis is biopsy, transient elastography (TE) represents a non-invasive alternative. TE has been validated in several chronic liver diseases, but no data exist to establish an association between histologic fibrosis on biopsy and TE liver stiffness measurements among a United States cohort of AIH patients.Material and methodsWe conducted a retrospective cohort study of 53 AIH patients who received TE assessment and liver biopsy. Histologic fibrosis was classified as advanced (F3-F4) or mild/moderate (F0-F2). Liver stiffness by TE was measured in kilopascals (kPa). We performed a score test for trend to test the association between histologic fibrosis stage and increasing TE kPa categories. Analyses incorporated probe type (medium or extra-large) and body mass index (BMI). Linear regression was used to generate predicted associations between median kPa and histologic fibrosis score with the medium probe.ResultsThe cohort was primarily female (83%) with median age 56.3 years. Increasing kPa category was associated with worsening fibrosis stage when using the medium probe (p = 0.04), but not the extra-large probe (p = 0.40). BMI, however, differed between these groups (median 25.8 vs. 33.1, respectively, p < 0.001). In adjusted linear regression, increasing median kPa corresponded well to worsening fibrosis stage (p = 0.003).ConclusionsIn a United States AIH cohort, increasing TE kPa measurements are associated with worsening histologic fibrosis staging. While medium probe performance was superior to the extra-large probe, significant variation in BMI between groups may explain this difference.

Association of fetuin B with markers of liver fibrosis in nonalcoholic fatty liver disease.

The liver-derived plasma protein fetuin B is associated with nonalcoholic fatty liver disease (NAFLD) and impaired glucose homeostasis in mice. However, its association with non-invasive ultrasound- and magnetic resonance (MR)-based markers of liver fibrosis and steatosis, the enhanced liver fibrosis (ELF) score, liver biopsy, as well as rs738409 in PNPLA3, has not been elucidated in NAFLD, so far. The association of circulating fetuin B and transient elastography (TE), controlled attenuation parameter (CAP), 1H-MR-spectroscopy, the ELF score, liver biopsy, as well as risk alleles in rs738409 in PNPLA3, was studied in 101 NAFLD patients as compared to 15 healthy controls. Serum fetuin B levels did not differ between NAFLD patients and controls (p = 0.863). Fetuin B was independently and negatively associated with transient elastography liver stiffness measurement (LSM) (p = 0.002), but not with the steatosis markers CAP or 1H-MR-spectroscopy. Fetuin B serum concentrations were significantly lower in individuals with LSM > 7.0 kPa as compared to patients with LSM < 7.0 kPa (p = 0.024). Furthermore, the ELF score and histologically proven fibrosis were independent and negative predictors of circulating fetuin B. Moreover, serum fetuin B significantly depended on number of rs738409 risk alleles (p = 0.026). Fetuin B is independently and negatively associated with non-invasive markers of liver fibrosis and PNPLA3 status in NAFLD patients but does not show a correlation with the hepatic lipid content. Future studies need to elucidate the pathophysiological significance of fetuin B in NAFLD and its potential value as predictor for disease severity.

PWE-111 Non invasive prediction of oesophageal varices based on transient elastography liver stiffness measurement: Abstract PWE-111 Table 1

<h3>Introduction</h3> Transient elastography is a promising noninvasive method for assessing advanced fibrosis in patients with chronic liver disease and has a comparable sensitivity and specificity profile to liver biopsy. Variceal bleeding is the most serious complication of advanced liver disease and early recognition is of prime importance to prevent this life-threatening complication. In cirrhotic patients, liver stiffness measurements range from 12.5 to 75.5 kPa. However, the clinical relevance of these values is unknown. This study was carried out to investigate the reliability of predicting varices using transient elastography liver stiffness measurement. <h3>Method</h3> 1500 patients had liver stiffness measurement (LSM) using transient elastography between January 2011–January 2015 at Macclesfield District General Hospital. Patients who had LSM &gt;12 kPa and underwent gastroscopy were included in the study. Specificity, sensitivity, positive and negative predictive values were calculated for different cut off values of liver stiffness. Variable cut off values were also tested for different aetiologies. <h3>Results</h3> 150 patients were included in the study; 80 males and 70 females. The most common aetiology was alcohol related liver disease (ARLD) representing 39%, followed by non-alcoholic fatty liver disease (NAFLD) 19% and viral hepatitis 11%. Age range of our cohort was 22–90 years (average 61.7). 27 patients (18%) had oesophageal varices. Mean liver stiffness measurement was much higher (51.6 kPa) in the group with varices as compared to the group with no varices (31.9 kPa). LSM cut off value of 25 kPa showed sensitivity of 92.6% and specificity of 56.9% with positive predictive value of 32%. A lower cut off value of 21.5 kPa showed higher sensitivity (100%), but low positive predictive value of 30%. In our study no significant variations were observed between different aetiologies. <h3>Conclusion</h3> Transient elastography is a useful non invasive method for assessing patients with chronic liver disease. It allows us to stratify the degree of liver fibrosis and also to predict the risk of developing oesophageal varices. Patients with advanced fibrosis/cirrhosis with low LSM &lt; 21.5 kPa have a low risk of developing oesophageal varices and may avoid unnecessary endoscopy procedure. We recommend that all patients with LSM &gt; 21.5 kPa should undergo surveillance endoscopy for oesophageal varices. <h3>Disclosure of interest</h3> None Declared.

Nonalcoholic Fatty Liver Disease (NAFLD) And Cardiovascular Risk In Renal Transplant Recipients

Background/Aims: Renal transplant recipients (RTRs) are at high risk for cardiovascular (CVD) mortality. Recently, nonalcoholic fatty liver disease (NAFLD) has been recognized as a new risk factor for adverse CVD events in the general population. We examined whether transient elastography (TE) defined NAFLD was associated with atherosclerosis in RTRs, as measured by ultrasound in the carotid arteries. Methods: Carotid atherosclerosis was assesses in 71 RTRs with a TE proven NAFLD. With the help of TE liver stiffness was used to assess liver fibrosis and Controlled Attenuation Parameter (CAP) was used to detect and quantify liver steatosis. NAFLD was defined by the presence of steatosis with CAP values ≥238 dB.m^-1. Results: RTRs with NAFLD showed more carotid atherosclerosis than RTRs without NAFLD. RTRs-NAFLD patients had the mean intima-media measurements (ITM) of 1.1±0.1 mm and that was statistically significant higher than the mean ITM founded in RTRs without NAFLD (1.1±0.1 vs. 0.9±0.1 mm; p<0.0001). Furthermore, RTRs-NAFLD patients had statistically significant higher prevalence of plaques in comparison with RTRs without NAFLD (p=0.021). Conclusion: We showed for the first time that carotid atherosclerosis is advanced in RTRs with NAFLD. Detection of NAFLD by TE should alert to the existence of an increased cardiovascular risk in RTRs.

Liver Stiffness Is Associated With Monocyte Activation in HIV-Infected Ugandans Without Viral Hepatitis

A high prevalence of liver stiffness, as determined by elevated transient elastography liver stiffness measurement, was previously found in a cohort of HIV-infected Ugandans in the absence of chronic viral hepatitis. Given the role of immune activation and microbial translocation in models of liver disease, a shared immune mechanism was hypothesized in the same cohort without other overt causes of liver disease. This study examined whether HIV-related liver stiffness was associated with markers of immune activation or microbial translocation (MT). A retrospective case-control study of subjects with evidence of liver stiffness as defined by a transient elastography stiffness measurement ≥9.3 kPa (cases=133) and normal controls (n=133) from Rakai, Uganda was performed. Cases were matched to controls by age, gender, HIV, hepatitis B virus (HBV), and highly active antiretroviral therapy (HAART) status. Lipopolysaccharide (LPS), endotoxin IgM antibody, soluble CD14 (sCD14), C-reactive protein (CRP), and D-dimer levels were measured. Conditional logistic regression was used to estimate adjusted matched odds ratios (adjMOR) and 95% confidence intervals. Higher sCD14 levels were associated with a 19% increased odds of liver stiffness (adjMOR=1.19, p=0.002). In HIV-infected individuals, higher sCD14 levels were associated with a 54% increased odds of having liver stiffness (adjMOR=1.54, p<0.001); however, the opposite was observed in HIV-negative individuals (adjMOR=0.57, p=0.001). No other biomarker was significantly associated with liver stiffness, and only one subject was found to have detectable LPS. Liver stiffness in HIV-infected Ugandans is associated with increased sCD14 indicative of monocyte activation in the absence of viral hepatitis or microbial translocation, and suggests that HIV may be directly involved in liver disease.