Liver Stiffness Measurement In Patients Research Articles

Sound Touch Elastography for Noninvasive Assessment of Liver Stiffness in Patients With Chronic Heart Failure

Heart failure (HF) can damage various organs, including the liver, a phenomenon known as "cardiohepatic syndrome." The latter is characterized by liver congestion and hepatic artery hypoperfusion, which can lead to liver damage. In this study, we aimed to assess liver damage quantitatively in chronic HF (CHF) with sound touch elastography (STE). A total of 150 subjects were enrolled, including HF with reduced ejection fraction (HFrEF) groups (left ventricular ejection fraction ≤40%, n=45), HF with mildly reduced ejection fraction (HFmrEF) groups (left ventricular ejection fraction between 41% and 49%, n=40), and right-sided HF (RHF) groups (n=25); normal groups (n=40). Liver stiffness measurement (LSM) was performed in all subjects by STE. The other hepatic parameters were also measured. The LSM was 5.4 ± 1.1 kPa in normal subjects and increased slightly to 5.9 ± 0.7 kPa in patients with HFmrEF. However, the HFrEF and RHF groups had significantly higher LSMs of 8.4 ± 2.0 kPa and 10.3 ± 2.7 kPa, respectively. The LSM of HFrEF was significantly higher than that of HFmrEF, whereas the increase in LSM in patients with RHF was significant relative to HFmrEF and HFrEF. In addition, the other parameters showed abnormal values in only RHF and HFrEF. In conclusion, STE is a useful clinical technique for the noninvasive evaluation of liver stiffness associated with CHF, which could help patients with CHF manage their treatment regimens.

SAT-473 - Correlation between serial Fibrosis-4 scores and liver stiffness measurements in patients with low-risk non-alcoholic fatty liver disease

SAT-473 - Correlation between serial Fibrosis-4 scores and liver stiffness measurements in patients with low-risk non-alcoholic fatty liver disease

Accuracy of FIB-4 to Detect Elevated Liver Stiffness Measurements in Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Referral Centers.

The identification of advanced fibrosis by applying noninvasive tests is still a key component of the diagnostic algorithm of NAFLD. The aim of this study is to assess the concordance between the FIB-4 and liver stiffness measurement (LSM) in patients referred to two liver centers for the ultrasound-based diagnosis of NAFLD. Fibrosis 4 Index for Liver Fibrosis (FIB-4) and LSM were assessed in 1338 patients. A total of 428 (32%) had an LSM ≥ 8 kPa, whereas 699 (52%) and 113 (9%) patients had an FIB-4 < 1.3 and >3.25, respectively. Among 699 patients with an FIB-4 < 1.3, 118 (17%) had an LSM ≥ 8 kPa (false-negative FIB-4). This proportion was higher in patients ≥60 years, with diabetes mellitus (DM), arterial hypertension or a body mass index (BMI) ≥ 27 kg/m2. In multiple adjusted models, age ≥ 60 years (odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.19–3.23)), DM (OR = 2.59, 95% CI 1.63–4.13), body mass index (BMI) ≥ 27 kg/m2 (OR = 2.17, 95% CI 1.33–3.56) and gamma-glutamyltransferase ≥ 25 UI/L (OR = 2.68, 95% CI 1.49–4.84) were associated with false-negative FIB-4. The proportion of false-negative FIB-4 was 6% in patients with none or one of these risk factors and increased to 16, 31 and 46% among those with two, three and four concomitant risk factors, respectively. FIB-4 is suboptimal to identify patients to refer to liver centers, because about one-fifth may be false negative at FIB-4, having instead an LSM ≥ 8 KPa.

FRI058 - Determinants of liver stiffness measurements in patients with NAFLD-an individual patient data meta-analysis

FRI058 - Determinants of liver stiffness measurements in patients with NAFLD-an individual patient data meta-analysis

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

Fibrosis regression following hepatitis C antiviral therapy

Hepatitis C virus (HCV) infection is one of the most common causes of liver pathology. It is a major etiological factor of continuous liver injury by triggering an uncontrolled inflammatory response, causing liver fibrosis and cirrhosis. Liver fibrosis is a dynamic process that can be reversible upon timely cessation of the injurious agent, which in cases of HCV is represented by the sustained virological response (SVR) following antiviral therapies. Direct-acting antiviral therapy has recently revolutionized HCV therapy and minimized complications. Liver fibrosis can be assessed with variable invasive and non-invasive methods, with certain limitations. Despite the broad validation of the diagnostic and prognostic value of non-invasive modalities of assessment of liver fibrosis in patients with HCV, the proper interpretation of liver stiffness measurement in patients after SVR remains unclear. It is also still a debate whether this regression is caused by the resolution of liver injury following treatment of HCV, rather than true fibrosis regression. Regression of liver fibrosis can possess a positive impact on patient's quality of life reducing the incidence of complications. However, fibrosis regression does not abolish the risk of developing hepatocellular carcinoma, which mandates regular screening of patients with advanced fibrosis.

The Ability of Lipoprotein (a) Level to Predict Early Carotid Atherosclerosis Is Impaired in Patients With Advanced Liver Fibrosis Related to Metabolic-Associated Fatty Liver Disease.

Hepatic fibrosis reduces the serum level of lipoprotein (a) (Lp(a)) and may affect its accuracy in cardiovascular disease prediction of metabolic-associated fatty liver disease (MAFLD). We aimed to estimate the association between Lp(a) levels and the risk of carotid atherosclerosis in MAFLD patients with advanced fibrosis. This was a cross-sectional study enrolling 4,348 consecutive individuals (1,346 patients with MAFLD and 3,002 non-MAFLD patients) who were admitted to the First Affiliated Hospital, Sun Yat-sen University, and underwent abdominal and carotid ultrasonography from 2015 to 2021. Lp(a) levels, liver biochemical markers, metabolic indices, and anthropometric parameters were measured. Liver fat content and fibrosis severity were assessed by MRI-PDFF, using the NAFLD fibrosis score (NFS) and liver stiffness measurement (LSM) of two-dimensional shear wave elastography, respectively. There was an L-shaped relationship between Lp(a) levels and LSMs in patients with MAFLD, and Lp(a) levels had a different relationship with liver fat content in MAFLD patients with F1-2 versus those with F3-4. Non-MAFLD patients had higher levels of Lp(a) than MAFLD patients with or without advanced fibrosis (both P < 0.05). Lp(a) levels and degree of liver fibrosis were both positively correlated with carotid atherosclerosis in patients with MAFLD. Lp(a) levels performed well on carotid atherosclerosis risk prediction for non-MAFLD patients with an area under the curve (AUC) of 0.819, which was significantly better than the carotid atherosclerosis risk prediction for MAFLD patients with NFS ≤ -1.836 (AUC: 0.781), NFS > -1.836 (AUC: 0.692), and LSM ≥ 9.0 kPa (AUC: 0.635) (all P < 0.05). Advanced liver fibrosis significantly reduces the predictive value of Lp(a) levels for the risk of carotid atherosclerosis in patients with MAFLD.

Comparison between spleen and liver stiffness measurements by sound touch elastography for diagnosing cirrhosis at different aminotransferase levels: a prospective multicenter study.

To compare the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by sound touch elastography (STE) for the diagnosis of cirrhosis at different alanine aminotransferase (ALT) levels, and to compare the applicability and repeatability of SSM with LSM performed by STE, a new two-dimensional shear wave elastography technology. This prospective multicenter study included 25 centers and recruited chronic hepatitis B (CHB) patients with liver biopsy between May 2018 and November 2019. All patients underwent LSM and SSM by STE. Success and reliability rates were calculated and compared. Intra-observer agreement was assessed using intraclass correlation coefficients (ICCs). Differences between areas under the receiver operating characteristic curves (AUCs) of LSMs and SSMs at different ALT levels were compared using the Delong test. Among 603 CHB patients, the success and reliability rates of SSM were 94.53% (570/603) and 85.74% (517/603), respectively, which were similar to those of LSM (p > 0.05), respectively. The ICC for intra-observer agreements of SSM was 0.964 (p < 0.001). In the total cohort, ALT ≤ 2 × upper limit of normal (ULN) group, and A0-1 group, the AUCs of SSMs were significantly lower than those of LSMs for the diagnosis of cirrhosis (p < 0.001). In the ALT > 2 × ULN group and A2-3 group, the AUC of SSM improved and was not significantly different from that of LSM (p = 0.342, p = 0.510, respectively). SSM by STE achieved applicability and repeatability equivalent to those of LSM. SSM might be a good substitute to LSM in patients with high ALT levels. • Spleen stiffness measurement performed by sound touch elastography was proven to have similar applicability and repeatability to liver stiffness measurement in this prospective multicenter study. • Spleen stiffness measurement demonstrated a poorer diagnostic performance for cirrhosis compared with liver stiffness measurement in the total cohort and low ALT level group, yet it showed a similar diagnostic performance to liver stiffness measurement in patients with high ALT levels.

Role of liver stiffness measurements in patients who develop hepatocellular carcinoma after clearance of the hepatitis C virus

PurposeTo measure changes in liver stiffness over time due to direct-acting antiviral (DAA) therapy in hepatitis C patients using shear wave elastography (SWE).MethodsPatients with hepatitis C treated with DAA therapy in a university medical center between July 2015 and April 2020 were evaluated. Shear wave velocity (Vs) of the liver was measured using SWE. Alanine aminotransferase (ALT), platelet count, and α-fetoprotein (AFP) were measured at the same time, and the FIB-4 index was estimated. Absence of hepatocellular carcinoma was confirmed at baseline and end of therapy. Imaging was then performed every 6 months. Patient characteristics were compared between patients who did and did not develop carcinoma.ResultsThe mean age of the 229 patients (93 men) was 65.6 years. Eight patients developed carcinoma during follow-up (mean 32.6 ± 19.5 months). Significant differences were found between the groups in terms of AFP, platelet count, and Fib-4 index at baseline; the pre-treatment data had the best relationship with hepatocarcinogenesis. Mean Vs decreased significantly during DAA therapy, and then decreased further. Liver stiffness 6 months after treatment ended had the best relationship with hepatocarcinogenesis.ConclusionIn patients with a sustained virological response, risk of developing cancer can be predicted by measuring Vs approximately 6 months after treatment.

Utility of Hepatic 2D Shear-Wave Elastography in Monitoring Response to Image-Guided Intervention in Children With Chronic Budd-Chiari Syndrome: A Prospective Study.

BACKGROUND. Image-guided interventions for Budd-Chiari syndrome (BCS) reduce hepatic congestion, thereby reducing liver stiffness. Liver stiffness measurement (LSM) by means of ultrasound may provide a noninvasive marker for assessing treatment response. OBJECTIVE. The purpose of this study was to assess, with attention to changes in LSMs in patients with disease recurrence, the utility of 2D shear-wave elastography (SWE) for monitoring response to image-guided intervention in children with BCS. METHODS. This prospective study included children with chronic BCS and planned image-guided intervention. Color Doppler ultrasound (CDUS) and 2D SWE were performed at baseline; 24 hours, 1 month, and 3 months after intervention; and every 3 months thereafter or when recurrence was clinically suspected. Eighteen children underwent liver biopsy at intervention for fibrosis staging according to the Metavir criteria. Disease recurrence was diagnosed with CDUS. Statistical evaluation was performed by means of nonparametric tests. RESULTS. A total of 32 children (28 boys, four girls; mean age, 9 years; range, 3-14 years) were included. The median LSM at baseline was 43.7 (interquartile range [IQR], 33.0-65.4) kPa, at 24 hours was 22.5 (IQR, 16.8-32.0) kPa, at 1 month was 18.7 (IQR, 14.2-32.0) kPa, and at 3 months was 16.7 (IQR, 11.5-22.5) kPa (p = .001 for all postintervention time points vs baseline). Nine (28.1%) patients had a recurrence at a mean of 4 months after intervention. In one patient with recurrence, LSM was higher at 24 hours (52.3 kPa) than at baseline (44.2 kPa). In the other eight patients with recurrence, LSM was increased at recurrence compared with the prior postintervention LSM (median absolute increase, 11.0 [IQR, 6.1-24.4] kPa). Fibrosis stage was not significantly correlated with baseline LSM (r = 0.11 [95% CI, -0.37 to 0.54]; p = .51) or LSM 24 hours after intervention (r = 0.39 [95% CI, -0.11, 0.73]; p = .11). CONCLUSION. LSMs decreased significantly after image-guided intervention for chronic BCS in children, exhibiting a maximal decrease 24 hours after intervention. Disease recurrence was typically associated with an increase in LSM compared with the patient's prior measurement. CLINICAL IMPACT. LSM obtained with 2D SWE may serve as a useful quantitative adjunct to CDUS in monitoring children with chronic BCS for disease recurrence after percutaneous interventional treatment.

Effect of liver steatosis on liver stiffness measurement in chronic hepatitis B patients with normal serum alanine aminotransferase levels: A multicentre cohort study.

Liver steatosis is becoming increasingly common in patients with chronic hepatitis B (CHB), and its effect on liver stiffness measurement (LSM), as assessed by transient elastography, remains controversial. Seven hundred and fifty-five patients with CHB and normal serum alanine aminotransferase levels, who underwent vibration-controlled transient elastography and liver biopsy, were included in the study. We examined whether the histological degree of liver steatosis affects the accuracy of transient elastography-assessed LSM in these patients. Among the 755 CHB patients included in the study, 286 (37.9%) had liver steatosis, of whom 156had grade S1, 74had grade S2, and 56had grade S3 on histology. Presence of liver steatosis was independently associated with greater body mass index (BMI, adjusted-odds ratio [OR]=5.786, 95% CI: 3.998-8.373, p=0.018), and higher serum total cholesterol (adjusted-OR=7.944, 95% CI: 4.731-13.339, p<0.001) and triglyceride levels (adjusted-OR=2.777, 95% CI: 2.050-3.761, p<0.001). There was no significant association between liver steatosis and fibrosis stage (OR=1.016, 95% CI: 0.905-1.140, p=0.790). Age (B-coefficient = 0.020, 95% CI: 0.001-0.040, p=0.044), BMI (B-coefficient=0.060, 95% CI: 0.011-0.127, p=0.019), serum gamma-glutamyl-transpeptidase (GGT, B-coefficient=0.015, 95% CI: 0.001-0.029, p=0.032), positivity for HBeAg (B-coefficient=-0.816, 95% CI: -1.568 to -0.064, p=0.034), as well as liver fibrosis stage (B-coefficient=2.796, 95% CI: 2.501-3.090, p<0.001), and inflammation activity grade (B-coefficient=0.648, 95% CI: 0.162-1.135, p=0.009) were all independently associated with higher LSM, while no significant association was found between degree of liver steatosis and LSM. Among patients with the same histological fibrosis stage, LSM values did not show any significant difference among patients with absent, mild, moderate or severe steatosis. We conclude that liver steatosis has no significant effect on transient elastography-measured LSM in CHB patients with normal serum alanine aminotransferase levels.

Non-invasive tests for predicting liver outcomes in chronic hepatitis C patients: A systematic review and meta-analysis.

BACKGROUNDLiver fibrosis leads to liver-related events in patients with chronic hepatitis C (CHC) infection. Although non-invasive tests (NITs) are critical to early detection of the development of liver fibrosis, the prognostic role of NITs remains unclear due to the limited types of NITs and liver outcomes explored in previous studies.AIMTo determine the prognostic value of NITs for risk stratification in CHC patients.METHODSThe protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019128176). The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search was performed using MEDLINE and EMBASE databases under a timeframe from the inception of the databases through February 25, 2020. We restricted our search to CHC cohort studies reporting an association between liver fibrosis assessed by NITs and the development of hepatocellular carcinoma, decompensation, or mortality. Pooled hazard ratios (HR) and area under the receiver operating characteristic (AUROC) for each NIT were estimated using a random effects model. Subgroup analyses were performed for NITs assessed at pre-treatment or post-treatment with sustained virologic response (SVR), treatment with either pegylated interferon and ribavirin or direct acting antiviral, Eastern or Western countries, and different cutoff points.RESULTSThe present meta-analysis included 29 cohort studies, enrolling 69339 CHC patients. Fibrosis-4 (FIB-4) index, aspartate aminotransferase to platelet ratio (APRI) score, and liver stiffness measurement (LSM) were found to have hepatocellular carcinoma predictive potential with pooled adjusted HRs of 2.48 [95% confidence interval (CI): 1.91-3.23, I2 = 96%], 4.24 (95%CI: 2.15-8.38, I2 = 20%) and 7.90 (95%CI: 3.98-15.68, I2 = 52%) and AUROCs of 0.81 (95%CI: 0.73-0.89, I2 = 77%), 0.81 (95%CI: 0.75-0.87, I2 = 68%), and 0.79 (95%CI: 0.63-0.96, I2 = 90%), respectively. Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22 (95%CI: 2.32-4.47, I2 = 80%). Pooled adjusted HRs for post-treatment with SVR FIB-4, APRI, and LSM were 3.01 (95%CI: 0.32-28.61, I2 = 89%), 9.88 (95%CI: 2.21-44.17, I2 = 24%), and 6.33 (95%CI: 2.57-15.59, I2 = 17%), respectively. Pooled adjusted HRs for LSM in patients with SVR following direct acting antiviral therapy was 5.55 (95%CI: 1.47-21.02, I2 = 36%). Pooled AUROCs for post-treatment with SVR FIB-4 and LSM were 0.75 (95%CI: 0.55-0.95, I2 = 88%) and 0.84 (95%CI: 0.66-1.03, I2 = 88%), respectively. Additionally, FIB-4 and LSM were associated with overall mortality, with pooled adjusted HRs of 2.07 (95%CI: 1.49-2.88, I2 = 27%) and 4.04 (95%CI: 2.40-6.80, I2 = 63%), respectively. CONCLUSIONFIB-4, APRI, and LSM showed potential for risk stratification in CHC patients. Cutoff levels need further validation.

Unreliable Estimation of Fibrosis Regression During Treatment by Liver Stiffness Measurement in Patients With Chronic Hepatitis B.

INTRODUCTION:Little reliable evidence has been reported regarding usefulness of liver stiffness measurement (LSM) for monitoring the hepatic fibrosis changes during treatment. We aimed to assess the association between changes in LSM and histological outcomes in patients with chronic hepatitis B.METHODS:In this prospective multicenter study, 727 treatment-naive patients receiving entecavir-based therapy, who underwent paired biopsies at treatment baseline and week 72, were analyzed. Changes in LSM were defined as ≥30% decrease, minor change, and ≥30% increase. Multivariate logistic regression was used to estimate odds ratios (ORs) of changes in LSM on clinical outcomes accounting for regression to the mean. A new on-treatment LSM threshold was established by receiver operating curve.RESULTS:Overall regression of fibrosis, improvement of inflammation, significant histological response, virologic response, alanine aminotransferase normalization, and hepatitis B e antigen seroconversion were 51.2%, 74.4%, 22.0%, 86.0%, 83.5%, and 13.3%, respectively. The association between changes in LSM and improvement of inflammation was nonlinear (P = 0.012). LSM decrease ≥30% was associated with regression of fibrosis (OR 1.501, 95% confidence interval [CI] 1.073–2.099, P = 0.018), significant histological response (OR 1.726, 95% CI 1.124–2.652, P = 0.013), and alanine aminotransferase normalization (OR 2.149, 95% CI 1.229–3.757, P = 0.007). After adjusting for regression to the mean, LSM increase ≥30% became negatively associated with the above 3 outcomes. A new on-treatment LSM cutoff value of 5.4 kPa was established for indicating the significant histological response.DISCUSSION:Changes in LSM are unreliable to estimate regression of fibrosis during treatment; the established cutoff value of on-treatment LSM can optimize monitoring strategy for histological outcomes in patients with chronic hepatitis B.

Clinical application of liver stiffness measurement in patients with cavernous transformation of portal vein.

The clinical outcomes differ between patients with cavernous transformation of the portal vein (CTPV) with and without cirrhosis. Therefore, invasive liver biopsy may be needed for the differential diagnosis of patients with CTPV with or without cirrhosis. The present study aimed to investigate the diagnostic efficacy of liver stiffness measurements (LSM) for the prediction of cirrhosis in patients with CTPV. A total of 20 patients with CTPV, 34 with chronic hepatitis B (CHB)-related cirrhosis and 20 healthy volunteers, were retrospectively recruited in the study. CTPV was diagnosed with contrast-enhanced computed tomography (CT) and ultrasound for the abdomen. LSM values were detected for each patient, while liver biopsy was performed in each patient in the CTPV and cirrhosis groups. The results demonstrated that LSM values were significantly lower in the CTPV group (12.5 kPa; range, 6.8-21.5 kPa) compared with the CHB-related cirrhosis group (21.0 kPa; range, 15.5-27.2 kPa; P=0.017). However, this was still higher compared with healthy volunteers (4.9 kPa; range 4.0-5.8 kPa; P<0.001). In addition, CTPV patients with cirrhosis (17.7 kPa; range, 13.9-30.8 kPa) exhibited significantly increased LSM values compared with those without cirrhosis (6.4 kPa; range, 5.7-7.8 kPa; P<0.001). Furthermore, LSM values in CTPV patients without cirrhosis were slightly higher compared with those of healthy volunteers (P=0.003), while no statistically significant difference was observed in LSM between CTPV patients with cirrhosis and CHB-related cirrhosis group. These findings indicated that LSM values could be used for the differential diagnosis of CTPV patients with or without cirrhosis. However, further validation studies are needed.

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.

Prognostic value of liver stiffness measurement in patients with hepatocellular carcinoma (HCC) treated by radiofrequency ablation: a meta-analysis

Background In patients with stage 0–A (as per Milan criteria) hepatocellular carcinoma (HCC) image-guided ablation is less invasive and requires shorter hospitalization than resection, but long-term prognosis is poorer. This meta-analysis was conducted to investigate whether liver stiffness measurement (LSM) could be used to predict prognosis in HCC patients after tumor ablation. Methods A literature search was conducted for all studies published till July 2020 in PubMed, Web of Science, Cochrane Library and EMBASE. Studies were included if they investigated the association between pretreatment LSM and prognosis in HCC patients treated with ablation. Subgroup analysis, meta-regression, publication bias assessment and sensitivity were conducted. Results Eight studies (with a total of 1276 HCC patients) were included in this meta-analysis. All patients were treated with radiofrequency ablation. Pooled results showed that high pretreatment LSM were associated with poor overall survival (OS) (hazard ratio [HR] = 4.31, 95% confidence interval [CI]: 2.27–8.20, p < .001) and recurrence-free survival (RFS), regardless of whether LSM was considered as a categorical variable (HR = 2.63, 95% CI = 1.63–4.22, p < .001) or as a continuous variable (HR = 1.02, 95% CI = 1.01–1.04, p = .003). Among studies treating LSM value as a categorical variable, liver stiffness measured using acoustic radio force impulse (ARFI) or transient elastography (TE) was significantly associated with RFS, but not liver stiffness measured using two-dimensional shear wave elastography (SWE). Conclusions High baseline LSM value appears to be associated with poor prognosis in HCC patients treated with radiofrequency ablation.

Increased liver stiffness by transient elastography and acoustic radiation force impulse imaging in patients with extrahepatic cholestasis.

Transient elastography and acoustic radiation force impulse (ARFI) imaging are noninvasive tools for liver stiffness measurement (LSM), which may be influenced by cholestasis. The aim of the study was to evaluate the performance of transient elastography and ARFI in extrahepatic cholestasis and correlate changes in LSM with biochemical activity. A total of 38 patients with extrahepatic cholestasis prospectively underwent transient elastography and ARFI. Changes in LSM by transient elastography/ARFI were evaluated after 1 week of ERCP and correlated with biochemical parameters. The optimal ARFI cutoffs according to stages of clinical interest were analyzed. Biliary obstruction was calcular in 21 (55.3%) and noncalcular in 17 (44.7%) (benign n = 15, malignant n = 2). After 1 week, adequate biliary drainage reduced total bilirubin from 7.7 to 2.2 mg/dL (P < 0.001) which significantly correlated with reduction of LSM by transient elastography from 12.38 ± 6.68 kPa to 8.08 ± 3.21 kPa (P < 0.001), and by ARFI from 1.73 ± 0.51 m/s to 1.56 ± 0.70 m/s (P = 0.014). The LSM percentage change showed a decrease (nonsignificant, P = 0.843) by 25.83% using transient elastography and a significant decrease (P < 0.001) by 18.42% using ARFI in the improved patients. At initial visit, transient elastography positively correlated with ARFI, bilirubin and platelets, also, transient elastography had a positive correlation with ARFI, bilirubin, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) in follow-up visit. LSM by ARFI (visit 1) negatively correlated with ALT, while in (visit 2), ARFI positively correlated with bilirubin, ALP, GGT and negatively correlated with albumin. The increased LSM in patients with extrahepatic cholestasis is reduced after adequate biliary drainage, implying that increased values are not solely due to liver fibrosis, but due to biliary congestion leading temporarily to increased elasticity.

Combined alcoholic and non-alcoholic steatohepatitis.

SummaryWhile metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.

Liver stiffness measurement in patients with nodular regenerative hyperplasia undergoing magnetic resonance elastography

Nodular regenerative hyperplasia (NRH) may mimic cirrhosis at imaging. We aim to investigate the effect of NRH on liver stiffness measurement (LSM) obtained with magnetic resonance elastography (MRE). This retrospective, Institutional Review Board-approved study included 37 subjects with NRH (Group 1) and no or minimal fibrosis (F0-F1), a control group (Group 2) made of 30 subjects with non-advanced fibrosis (F0-F2), and a control group (Group 3) made of 30 subjects with advanced fibrosis (F3-F4), all with available MRE. LSM was measured in each subject along with assessment of hepatic morphological features of cirrhosis and signs of portal hypertension. The significance of the difference in mean LSM between Group 1 and 2 and between Group 1 and 3 was evaluated using the Mann-Whitney U test. The difference in distribution of imaging features among groups was assessed using the Pearson χ2 or Fisher exact test. The mean ± SD LSM in Group 1 (3.56 ± 1.10kPa) was significantly higher compared to Group 2 (2.91 ± 0.52kPa, P = 0.019) and significantly lower compared to Group 3 (7.18 ± 2.08kPa, P < 0.001). Twelve (32%) patients with NRH had LSM ≥ 4.11kPa, and 6 (16%) patients had LSM ≥ 4.71kPa. Surface nodularity (P = 0.032) and caudate lobe hypertrophy (P = 0.004) were more commonly visualized in Group 1 than in Group 2. At least one feature of portal hypertension was observed in 16 (43%) NRH subjects. NRH may increase the LSM obtained with MRE and may represent a confounding factor when using liver stiffness for the non-invasive diagnosis of fibrosis.

Low Sensitivity to Thrombomodulin Correlates with Liver Stiffness in Advanced Chronic Liver Disease

Advanced chronic liver disease (ACLD) is characterized by changes in the coagulation system that embrace not only hypo-, but also hyper-coagulability. Global hemostatic tests such as thrombin generation (TG) assays are used to evaluate the hemostatic balance, in order to better assess bleeding and thrombotic risks. In addition, procoagulant state in ACLD patients has been demonstrated using modified TG assays with thrombomodulin (TM), a cofactor for protein C activation. Evaluation of the liver stiffness by transient elastography (Fibroscan) is a reliable method for the diagnosis of cirrhosis and disease staging. Increased liver stiffness is associated with clinically significant portal hypertension (PVT) in patients with ACLD. Here, we aimed to investigate whether TG parameters in patients with ACLD could be associated to liver stiffness. Of 147 enrolled patients with ACLD, we excluded 69 patients (5 patients received anticoagulation, 3 were on chemotherapy, 48 with other liver diseases and 13 had a history of orthotopic liver transplantation), leaving a study sample of 78 patients. Liver stiffness measurement (LSM) was performed by transient elastography in each patient. Cut-offs of 13 and 21 kPa were used to subgroup the studied ACLD patients sample, as a LSM of ≥13 kPa has been associated with the diagnosis of cirrhosis and ≥21 kPa with the development of a clinically significant PVT (Deillon et al., 2019). TG was evaluated by ST Genesia® Thrombin Generation System (STG) using Thromboscreen with/without TM (TS-TM/+TM) assay and the Calibrated Automated Thrombography (CAT) using PPP reagent low (Stago) with/without TM. TG was measured by STG in 50 patients with ACLD. ETP inhibition by TM correlated with LSM (r =-0.339, p=0.0184). The discriminant analysis (ANOVA with multiple comparison) among the study groups showed that ETP inhibition by TM was higher in ACLD patients with LSM &lt;13 kPa than in those with LSM ≥13 but &lt;21 kPa (p=0.003), indicating a lower sensitivity to TM in patients with liver stiffness values ≥13 but &lt;21 kPa. However, there was no difference in ETP inhibition by TM between the group with LSM ≥13 but &lt;21 kPa and the group with LSM ≥21 kPa (p=0.995). TG was measured by CAT in 56 patients with ACLD and ETP inhibition by TM was evaluated using a normalized ETP ratio in presence and in absence of TM. Similarly to STG data, ETP inhibition by TM measured by CAT correlated with LSM (r=0.4108, p=0.0018). The discriminant analysis among the study groups revealed that ETP inhibition by TM was higher in ACLD patients with LSM &lt;13 kPa than in those with ≥13 but &lt;21 kPa (p=0.0098) as well as with the group with LSM ≥21kPa (p=0.0022), indicating a lower sensitivity to TM in patients with liver stiffness values ≥13 kPa. However, there was no difference in ETP inhibition by TM between the group with LSM ≥13 but &lt;21 and the group with LSM ≥21 kPa (p=0.721). In addition, TG was measured by both by STG and CAT in 35 patients with ACLD in order to compare the two methods. ETP inhibition by TM measured by STG correlated with the normalized ETP inhibition determined by CAT (r = -0.61, p&lt;0.0001). Low sensitivity to TM measured in ST Genesia® and CAT, correlated with liver stiffness in patients with ACLD. Sensitivity to TM discriminated between ACLD groups with low (≤13 kPa) and high (≥13 kPa) LSM, confirming a procoagulant state in patients with ALCD. However, it did not differ between patients with ACLD with high LSM (≥13 and &lt;21 kPa) and patients prone to the decompensation defined by higher (≥21 kPa) LSM. Sensitivity to TM measurements determined by ST Genesia® correlated with those obtained with CAT. Further studies are needed to determine whether sensitivity to TM and LSM in patients with ACLD could help to identify patients at higher risk of portal vein thrombosis Disclosures No relevant conflicts of interest to declare.