Liver Stiffness Cutoff Research Articles

Magnetic resonance elastography as a preoperative assessment for predicting intrahepatic recurrence in patients with hepatocellular carcinoma

PurposeMagnetic resonance elastography (MRE) is a noninvasive tool for diagnosing hepatic fibrosis with high accuracy. We investigated the preoperative clinical and imaging predictors of intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC), and evaluated MRE as a predictor of intrahepatic recurrence. MethodsWe retrospectively evaluated 80 patients who underwent preoperative contrast-enhanced magnetic resonance imaging (MRI) with two-dimensional MRE and curative resection for treatment-naïve HCC between May 2019 and December 2021. Liver stiffness (LS) was measured on the elastograms, and the optimal cutoff of LS for predicting intrahepatic recurrence was obtained using receiver operating characteristic (ROC) analysis. An LS above this cutoff was defined as MRE-recurrence. Preoperative imaging features of the tumor were assessed on MRI, including features in the Liver Imaging Reporting and Data System and microvascular invasion (MVI). Recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method, and differences were compared using the log-rank test. Using a Cox proportional hazards model, we conducted a multivariable analysis to investigate the factors affecting recurrence-free survival. ResultsDuring a median follow-up period of 32 months (range, 4–52 months), thirteen patients (16.3%) developed intrahepatic recurrence. ROC analysis determined an LS cutoff of ≥4.35 kPa to define MRE-recurrence. The 4-year RFS rate was significantly higher in patients without MRE-recurrence than in those with MRE-recurrence (93.4% vs. 48.9%; p = 0.001). In multivariable analysis, MRE-recurrence (Hazard ratio [HR], 5.9; 95% confidence interval [CI], 1.5–23.1) and MVI (HR, 3.4; 95% CI, 1.0–11.3) were independent predictors of intrahepatic recurrence. ConclusionsPatients without MRE-recurrence had significantly higher RFS rates than those with MRE-recurrence. MRE-recurrence and MVI were independent predictors of intrahepatic recurrence in patients after curative resection for HCC.

Liver Stiffness Values to Predict Occurrence and Recurrence of Hepatocellular Carcinoma.

Globally, liver cancer is the third most frequent etiology of cancer death, with the rates of occurrence of both new cases and mortality estimated to increase. Given the availability of multiple treatments, interdisciplinary management of the patient is crucial. Moreover, the diagnostic assessment of patients with severe liver fibrosis is essential for the staging of HCC and liver cirrhosis and early diagnosis of HCC. In this context, non-invasive evaluation plays a critical role in identifying prognostic factors of clinical application for the surveillance of the occurrence or recurrence of HCC. The new frontiers of transient elastography have become a useful tool to assess the risk of HCC occurrence and recurrence. There has been a major increase in studies investigating the cutoff liver stiffness value that best predicts the need for monitoring for the onset of HCC. Therefore, this review discusses the new advances that have occurred in the last four years on HCC, highlighting the new frontiers of non-invasive evaluation of HCC subjects, with particular attention regarding the clinical application of liver stiffness assessment for de novo HCC and predicting recurrence in patients with chronic HCV achieving sustained virological response after treatment with direct antiviral agents.

Baveno VII Criteria Is an Accurate Risk Stratification Tool to Predict High-Risk Varices Requiring Intervention and Hepatic Events in Patients with Advanced Hepatocellular Carcinoma.

The Baveno VII criteria are used in patients with liver cirrhosis to predict high-risk varices in patients with liver cirrhosis. Yet its use in patients with advanced hepatocellular carcinoma (HCC) has not been validated. HCC alone is accompanied with a higher variceal bleeding risk due to its association with liver cirrhosis and portal vein thrombosis. The use of systemic therapy in advanced HCC has been thought to further augment this risk. Upper endoscopy is commonly used to evaluate for the presence of varices before initiation of treatment with systemic therapy. Yet it is associated with procedural risks, waiting time and limited availability in some localities which may delay the commencement of systemic therapy. Our study successfully validated the Baveno VI criteria with a 3.5% varices needing treatment (VNT) missed rate, also with acceptable <5% VNT missed rates when considering alternative liver stiffness (LSM) and platelet cut-offs. The Baveno VII clinically significant portal hypertension rule-out criteria (LSM < 15 kPa and platelet >150 × 109/L) also revealed a low frequency (2%) of hepatic events, whilst the rule-in criteria (LSM > 25 kPa) was predictive of a higher proportion of hepatic events (14%). Therefore, our study has successfully validated the Baveno VII criteria as a non-invasive stratification of the risk of variceal bleeding and hepatic decompensation in the HCC population.

Association between Liver Stiffness and Liver-Related Events in HCV-Infected Patients after Successful Treatment with Direct-Acting Antivirals

Background and Objectives: Direct-acting antivirals (DAAs) are highly effective for the treatment of chronic hepatitis C virus (HCV) infection, but the risk of liver-related events and hepatocellular carcinoma (HCC) remains after successful therapy. We aimed to evaluate post-treatment changes in liver stiffness (LS) and identify a cut-off LS value for predicting such events in chronic HCV-infected patients receiving DAA. Materials and Methods: A total of 185 patients who had achieved sustained virologic response (SVR) after DAA therapy were included. Baseline characteristics and laboratory results were retrospectively abstracted. LS was measured by transient elastography at baseline, 12, 24, 48, and 96 weeks after SVR. FIB-4 index was assessed at baseline and 48 weeks after SVR. Development of liver-related events (hepatocellular carcinoma (HCC), portal-hypertension-related decompensation, listing for transplantation, and mortality) after SVR were identified. The association between liver fibrosis and the occurrence of liver-related events was analyzed using Cox regression analysis. Results: Significant differences in LS values were observed between baseline and 24, 48, 72, and 96 weeks after SVR. FIB-4 index at 48 weeks after SVR was significantly lower than the FIB-4 index at baseline. During the 41.6-month follow-up time, the incidence rates of all liver-related events and HCC were 2.36 and 1.17 per 100 person-years, respectively. Age, LS ≥8 kPa, and FIB-4 ≥1.35 at 48 weeks post-SVR were significantly associated with the occurrence of any liver-related events. By multivariate analysis, LS ≥8 kPa at 48 weeks post-SVR remained significantly associated with any liver-related events, with an adjusted hazard ratio (95%CI) of 5.04 (1.01-25.26), p = 0.049. Conclusions: Despite a significant reduction in LS after SVR, patients with LS ≥8 kPa at 48 weeks after SVR should be regularly monitored for liver-related complications, particularly HCC development.

Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice

Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings. A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas. There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median= 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of <1.3 (range <1.0 to <1.45) and 21% reported using age-specific cut-offs. For Fibroscan®, 21% of respondents used a single liver stiffness cut-off: 8kPa in 50%, while the rest used 7.2kPa, 7.8kPa and 8.7kPa. Among the 63% of respondents who used lower and upper liver stiffness cut-offs, there were variations in both values (<5 to <10kPa and >7.5 to >20kPa, respectively). The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management. Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.

Diagnostic accuracy of transient elastography in diagnosing clinically significant portal hypertension in patients with chronic liver disease: a systematic review and meta-analysis.

Liver stiffness measurement using transient elastography (TE-LSM) is a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for diagnosing clinically significant portal hypertension (CSPH). However, previous studies have yielded conflicting results. We evaluated the correlation between TE-LSM and HVPG and the performance of TE-LSM in diagnosing CSPH (HVPG ≥ 10mmHg). We conducted a systematic review and meta-analysis by searching PubMed and Scopus databases for relevant literature evaluating the clinical usefulness of TE for diagnosing CSPH in patients with chronic liver disease. Twenty-six studies (4337 patients with valid TE and HVPG) met our inclusion criteria. The median correlation coefficient of TE with HVPG was 0.70 (range 0.36-0.86). The weighted mean of optimal cut-off of liver stiffness value for diagnosing CSPH was 22.8kPa (95% CI 22.7-23.0kPa). The summary sensitivity and specificity were 79% (95% CI 74-84%) and 88% (95% CI 84-91%), respectively. The area under the hierarchical summary receiver operating characteristic (HSROC) curve was 0.91 (95% CI 0.88-0.93) according to the bivariate model. One limitation of the study was significant heterogeneity in the results of summary sensitivity and specificity (I2 83 and 74%, respectively). The heterogeneity could be explained by the variable liver stiffness cut-offs used in studies. The meta-regression plot revealed that as the optimal cut-off increased, the sensitivity decreased, the specificity increased, and vice versa. Liver stiffness measurement using TE correlates well with HVPG, and a liver stiffness cut-off value of 22.8kPa shows a high accuracy for diagnosing CSPH. Thus, use of TE should be integrated into clinical practice for noninvasive diagnosis of CSPH.

Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia.

Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune intervention. We performed a cross-sectional analysis of ultrasound-based transient elastography (TE) in patients with CVID to evaluate liver stiffness and compared this between patients with (N = 12) and without (N = 6) biopsy-proven NRH. Additionally, these data were compared to a cohort followed at our institution for non-alcoholic fatty liver disease (NAFLD) (N = 527), a disease for which TE has routine diagnostic use. Clinical and pathologic features of NRH were evaluated as correlates of liver stiffness, and receiver operating characteristic curves were used to define a liver stiffness cutoff with diagnostic utility for NRH among CVID patients. CVID patients with NRH had a more severe disease presentation compared to those without. This included increased autoinflammatory disease comorbidities, combined B-cell and T-cell dysfunction, and abnormal liver biochemistries (specifically an increased mean alkaline phosphatase level [proximal to TE, 250 vs. 100 U/L; p = 0.03; peak, 314 vs. 114 U/L; p = 0.02). Results of TE demonstrated a significantly elevated liver stiffness in CVID patients with NRH (mean 13.2 ± 6.2 kPa) as compared to both CVID patients without NRH (mean 4.6 ± 0.9 kPa) and non-CVID patients with NAFLD (mean 6.9 ± 5.5 kPa) (p < 0.01). No single or composite histopathologic feature of NRH correlated with liver stiffness including nodule size, nodule density, sinusoidal dilation, fibrosis, and/or lymphocytosis. In contrast, liver stiffness by TE was significantly correlated with clinical parameters of portal hypertension, including an elevated hepatic venous pressure gradient, an increased splenic longitudinal diameter, presence of varices, and presence of peripheral edema. A liver stiffness of greater than or equal to 6.2 kPa was a clinically significant cutoff for NRH in CVID patients. We propose that TE has diagnostic utility in CVID, particularly in the presence of immunophenotypic features such as combined B-cell and T-cell dysfunction, autoinflammatory comorbidities, and/or abnormal liver tests. Elevated liver stiffness by TE should raise suspicion for NRH in patients with CVID and prompt expedited evaluation by hepatology.

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.

Clinical predictive score for detecting nonalcoholic fatty liver disease with significant fibrosis in patients with metabolic syndrome.

Patients with metabolic syndrome are at a higher risk of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis than the general population. Still, accessibility of screening method for NAFLD with significant fibrosis, such as transient elastography (FibroScan) are limited in some settings. This study aimed to develop a simple clinical predictive score for detecting NAFLD with significant fibrosis in patients with metabolic syndrome.A cross-sectional study was designed to obtain the data from medical records of all relevant patients who underwent transient elastography between January 2011 and December 2020 at Siriraj Hospital, Thailand. A liver stiffness cutoff value of 7.0 kilopascal was used to define the presence of significant liver fibrosis. To examine potential predictors, medical history and clinical data commonly assessed in routine practice were selected by following expert opinions and univariable statistical analysis. Backward and forward stepwise logistic regression was performed to acquire a final prediction model. To simplify the model, a weighted score was assigned for each categorized predictor. In addition, eligible cutoff values of the score and their predictive performances were determined.A total of 745 medical records were reviewed. The prevalence of NAFLD with significant fibrosis in patients with metabolic syndrome was 12.6%. Most clinical characteristics of patients with NAFLD with significant fibrosis and those non-NAFLD and NAFLD with no/mild fibrosis were quite disparate. The most practical model comprised globulin, aspartate transaminase, platelet count, and type 2 diabetes. It provided a good predictive performance with an area under the receiver operating characteristic curve of 0.828 (95% confidence interval [CI]: 0.782, 0.874). At the proper cutoff value, sensitivity and specificity were 76.6% (95% CI: 66.7%, 84.7%) and 72.4% (95% CI: 68.7%, 75.8%), respectively. The likelihood ratio of testing positive for NAFLD with significant fibrosis was 2.8 (95% CI: 2.34, 3.27) among patients with scores above the cutoff value.The first score for detecting of NAFLD with significant fibrosis in patients with metabolic syndrome was developed. This practical score, providing a good predictive performance, should be useful to help clinicians prioritize needs for further investigations among high-risk patients, especially in resource-limited settings.

Association between serum tumor necrosis factor-α and sarcopenia in liver cirrhosis.

Background/AimsSarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear.MethodsSprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease.ResultsLC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues.ConclusionsThese results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

The Prognostic Role of On-Treatment Liver Stiffness for Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B.

BackgroundDynamic changes in fibrosis markers occur under long-term antiviral treatment (AVT) for chronic hepatitis B. We evaluated prognostic values of on-treatment liver stiffness (LS) compared to ultrasonography findings and determined its optimal cutoff.MethodsThe cumulative probability of hepatocellular carcinoma (HCC) was assessed among 880 patients receiving entecavir or tenofovir for ≥2 years. LS was measured using transient elastography.ResultsAfter ≥2 years’ AVT, the proportion of patients with cirrhosis on ultrasonography decreased from 54.7% to 44.9% and the mean LS decreased from 13.6 to 8.2 kPa (both p<0.001). However, unlike cirrhosis on ultrasonography before AVT (p<0.001), that after ≥2 years’ AVT did not discriminate HCC risk (p=0.792). Using the Contal and O’Quigley’s method, pre-AVT and on-treatment LS of 12.0 and 6.4 kPa, respectively, were chosen as optimal cutoffs to successfully discriminate HCC risk (both p<0.001). However, through stratification using both pre-AVT and on-treatment LS, the prognosis was finally determined according to on-treatment LS of 6.4 kPa, regardless of pre-AVT LS of 12.0 kPa. Using on-treatment LS of 12 kPa suggested by Caucasians with CHB receiving long-term AVT, patients with higher LS were more likely to develop HCC than those with lower LS (p=0.017); however, there was no significant difference between those with on-treatment LS of 6.4–11.9 and ≥ 12.0 kPa (p=0.920).ConclusionFor HCC risk stratification in patients receiving long-term AVT, on-treatment LS cutoff should be lowered to 6.4 kPa, which is more predictive than 12 kPa or cirrhosis on ultrasonography. Further studies are required for validation.

Clinical and novel application of FibroScan, FIB-4 and aspartate aminotransferase-to-platelet ratio index in liver fibrosis evaluation in patients with hepatocellular carcinoma and their roles in oesophageal variceal prediction.

Non-invasive techniques for liver fibrosis diagnosis are very important for clinician especially in high-risk patients for liver biopsy. We further explored the diagnostic accuracy of FibroScan, FIB-4 and aminotransferase-to-platelet ratio index (APRI) in identifying liver fibrosis and assess their predictive role for oesophageal varices in patients with hepatocellular carcinoma (HCC). In total, 380 patients who underwent surgery for HCC were included based on retrospective study design. Liver fibrosis was pathologically diagnosed using the Ishak scoring system. Liver stiffness parameters were measured using FibroScan. APRI and FIB-4 were calculated. Among those, 121 patients who received oesophagogastroduodenoscopic examination underwent variceal evaluation. For liver cirrhosis diagnosis with FibroScan, the optimal cut-off values for the patients with HCC overall, left HCC and right HCC were 8.85, 11.75 and 8.70kPa (the accuracy were 78.7%, 78.4% and 79.2%, respectively). They had high areas under the receiver operating characteristic curve of 0.84, 0.84 and 0.85. The combined FibroScan, APRI and FIB-4 had very high specificity (more than 92%) for cirrhosis diagnosis. The optimal cut-off liver stiffness values for the diagnosis of varices were all 11.2kPa. For predicting varices, the optimal cut-off values of FIB-4 and APRI were 2.64 and 0.71, their accuracy were 64.3%-78.4%, 69.4% and 72.7%, respectively. FibroScan, FIB-4 and APRI have moderate accuracy for liver fibrosis diagnosis and oesophageal varices prediction in patients with hepatoma. This is a study of these non-invasive techniques applied in specific hepatoma patients and with inevitable limitations and need future more studies for validation.

2D shear wave elastography is better than transient elastography in predicting post-hepatectomy complication after resection.

Both transient elastography (TE) and 2D shear wave elastography (SWE) are accurate methods to evaluate liver fibrosis. We aimed to evaluate the diagnostic performance of 2D-SWE in predicting post-hepatectomy complication and to compare it with TE. We prospectively enrolled 125 patients with liver tumors. Liver stiffness (LS) (kilopascal [kPa]) was measured using both TE and 2D-SWE before surgery. All post-operative complication was evaluated using the comprehensive complication index (CCI), and CCI ≥ 26.2 was defined as severe complication. Logistic regression analysis was performed to identify predictive factors for severe complication. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of TE/2D-SWE in detecting liver fibrosis and severe complication. Severe complication developed in 18 patients. The median LS in patients with severe complication was significantly higher for both 2D-SWE (11.4kPa vs. 7.0kPa, p < 0.001) and TE (8.9kPa vs. 6.2kPa, p = 0.009). LS obtained from 2D-SWE was a significant factor correlated with severe complication (odds ratio: 1.27 per kPa [1.10-1.46], p = 0.001). The diagnostic performance of 2D-SWE was significantly higher than that of TE in detecting both ≥F3 (p = 0.024) and F4 (p = 0.048). The area under the curve of 2D-SWE to predict severe complication was 0.854, significantly higher than 0.692 of TE (p = 0.004). The optimal cut-off LS from 2D-SWE to predict severe complication was 8.6kPa, with sensitivity of 88.9% (16/18) and specificity of 73.8% (79/107). LS obtained from 2D-SWE was a significant predictive factor for severe complication, and 2D-SWE showed significantly a better diagnostic performance than TE in detecting liver fibrosis and severe complication. • The diagnostic performance of 2D-SWE was significantly higher than that of TE in detecting both ≥ F3 (AUC: 0.853 vs. 0.779, p = 0.024) and F4 (AUC: 0.929 vs. 0.872, p = 0.048). • Liver stiffness value obtained from 2D-SWE was a significant factor correlated with the development of severe complication defined as CCI ≥ 26.2 after hepatic resection for liver tumors (odds ratio: 1.27 per kPa [1.10-1.46], p = 0.001). • 2D-SWE provided significantly a better diagnostic performance in predicting severe complication after hepatic resection than TE (AUC for 2D-SWE: 0.853 vs. AUC for TE: 0.692, p = 0.004).

The cut-off value of transient elastography to the value of hepatic venous pressure gradient in alcoholic cirrhosis.

Background/AimsThe hepatic venous pressure gradient (HVPG) reflects portal hypertension, but its measurement is invasive. Transient elastography (TE) is a noninvasive method for evaluating liver stiffness (LS). We investigated the correlation between the value of LS, LS to platelet ratio (LPR), LS-spleen diameter-to-platelet ratio score (LSPS) and HVPG according to the etiology of cirrhosis, especially focused on alcoholic cirrhosis.MethodsBetween January 2008 and March 2017, 556 patients who underwent HVPG and TE were consecutively enrolled. We evaluated LS, LPR, and LSPS according to the etiology of cirrhosis and analyzed their correlations with HVPG.ResultsThe LS value was higher in patients with alcoholic cirrhosis than viral cirrhosis based on the HVPG (43.5 vs. 32.0 kPa, P<0.001). There were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups, and the areas under the curves for the LPR and LSPS in subgroups according to HVPG levels were not superior to that for LS. In alcoholic cirrhosis, the LS cutoff value for predicting an HVPG ≥10 mmHg was 32.2 kPa with positive predictive value (PPV) of 94.5% and 36.6 kPa for HVPG ≥12 mmHg with PPV of 91.0%.ConclusionsThe LS cutoff value should be determined separately for patients with alcoholic and viral cirrhosis. In alcoholic cirrhosis, the LS cutoff values were 32.2 and 36.6 kPa for predicting an HVPG ≥10 and ≥12 mmHg, respectively. However, there were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups.

Quantification of Hepatic and Splenic Stiffness After Fontan Procedure in Children and Clinical Implications.

We aimed to investigate Fontan associated liver disease in children by shear wave elastography (SWE). This is a single-center, prospective case-control study included 41 patients with Fontan physiology and 30 healthy controls. Hepatic and splenic shear wave elasticity values were exhibited both as kPa and m/s. The mean hepatic SWE values of Fontan patients (n = 41; 15.8 ± 3.2 kPa or 2.5 ± 1.8 m/s) were significantly higher than the control group (n = 30; 5.59 ± 0.6 kPa or 1.37 ± 0.07 m/s) (P < 0.001). The mean splenic SWE values of Fontan patients were (25.6 ± 4.61 kPa or 2.85 ± 0.22 m/s) significantly higher than the control group (15.9 ± 1.44 kPa or 2.29 ± 0.1 m/s) (P < 0.001). There were statistically significant positive correlations among the follow-up duration after the Fontan procedure with NT-proBNP (P = 0.008, r = 1) and prothrombin time (P = 0.009, r = 0.4) as well as the hepatic SWE values with alanine aminotransferase (P = 0.039, r = 0.32), gamma-glutamyl transferase (P = 0.045, r = 0.31), and PT (P = 0.011, r = 0.39). There has been statistically significant moderate positive correlations of splenic stiffness values with PT (P = 0.047, r = 0.34), and INR (P = 0.038, r = 0.35). The sensitivity and specificity of liver stiffness cutoff value as 11.1 kPa for detection of Fontan associated liver disease were 95% and 100%, respectively. The hepatic and splenic stiffness increase independently in Fontan patients due to parenchymal disease. Hepatic SWE is a reliable and noninvasive predictor of early hepatic alterations that could not be detected only by biochemical results or routine ultrasound examinations.

Modified AST to platelet ratio index improves APRI and better predicts advanced fibrosis and liver cirrhosis in patients with non-alcoholic fatty liver disease

AimsAdvanced fibrosis (AF) and liver cirrhosis (LC) are important milestones in non-alcoholic fatty liver disease (NAFLD). FIB-4, NFS and BARD are validated scores with good accuracy in detecting AF and LC. APRI does not have similar predictive accuracy. While a modification (m-APRI) improves its use in viral hepatitis, this has yet to be evaluated in NAFLD. This study compares diagnostic performance of aforementioned scores in predicting AF and LC in NAFLD. MethodsConsecutive NAFLD patients undergoing Transient Elastography (TE) using Echosens® Fibroscan® for fibrosis staging were included. Cut-off liver stiffness measurements for AF and LC were 7.9 kPa and 11.5 kPa respectively. Anthropometric and laboratory tests done within 3 months were used. Diagnostic performances of scores were analyzed by standard statistical tests. Results161 patients qualified for the study. Mean age was 60.2 ± 14 years, BMI 26.8 ± 4.6 kg/m2. M-probe was used in 113, XL in 48. Optimal cut-offs of m-APRI for AF and LC were 5.84 and 9 respectively. Area under receiver operator characteristic curves (AUROC) for prediction of AF at optimal cut-off points were m-APRI 0.84, APRI 0.80, FIB-4: 0.77, NFS 0.77 and BARD 0.65. For prediction of LC, AUROC were m-APRI: 0.83, APRI: 0.76, FIB-4: 0.81, NFS: 0.77 and BARD: 0.66. m-APRI was significantly superior to all scores compared in detecting AF (p < 0.05 for all) and superior to APRI (p = 0.008) and BARD (p = 0.007) in predicting LC. There was no significant difference between m-APRI and FIB-4 or NFS in prediction of LC. ConclusionsFor prediction of AF in NAFLD, m-APRI outperforms BARD, APRI, NFS and FIB-4, while for the prediction of cirrhosis, m-APRI is superior to APRI and BARD but comparable to NFS and FIB-4.

The Performance of a 2-Dimensional Shear-Wave Elastography Technique for Predicting Different Stages of Liver Fibrosis Using Transient Elastography as the Control Method.

The aim was to evaluate the performance of 2-dimensional (2D) shear-wave elastography from general electric (2D SWE-GE), implemented on the new LOGIQ S8 system, for the noninvasive assessment of liver fibrosis, and to identify liver stiffness (LS) cutoff values for predicting different stages of fibrosis using transient elastography (TE) as the control method. We included 179 consecutive subjects, with or without chronic hepatopathies, in whom LS was evaluated in the same session using 2 elastographic techniques: TE (FibroScan, EchoSens) and 2D SWE-GE (LOGIQ S8; GE Healthcare, Chalfont St Giles, United Kingdom). Reliable LS measurements were defined for TE: the median value of 10 measurements with a success rate of 60% or greater and an interquartile range/median ratio (IQR/M) < 0.30; for 2D SWE-GE: the median value of 10 measurements acquired in a homogenous area and IQR/M < 0.30. To discriminate between fibrosis stages by TE, we used the following cutoffs: F2-7; F3-9.5 and F4-12 kPa. Reliable LS measurements were obtained in 97.2% subjects by 2D SWE-GE and in 98.3% by TE (P = 0.72), so that 171 subjects were included for the final analysis. A good correlation was found between the LS values obtained by the 2 methods (r = 0.72, P < 0.0001). The best 2D SWE-GE cutoff value for F ≥ 2 was 6.9 kPa (areas under receiver operating characteristic [AUROC], 0.93; sensitivity, 85.8%; specificity, 90.2%), for F of 3 or greater, it was 8.2 kPa (AUROC, 0.93; sensitivity, 87.5%; specificity, 86.8%) and for F value of 4, it was 9.3 kPa (AUROC, 0.91; sensitivity, 85.7%; specificity, 81.2%). In conclusion, the best 2D SWE-GE (S8) cutoff values for predicting F2, F ≥ 3 and F = 4 were 6.9, 8.2, and 9.3 kPa.

Liver Stiffness Measured by Either Magnetic Resonance or Transient Elastography Is Associated With Liver Fibrosis and Is an Independent Predictor of Outcomes Among Patients With Primary Biliary Cholangitis.

We aimed to describe the diagnostic and prognostic performance of transient elastography (TE) and magnetic resonance elastography (MRE) in patients with primary biliary cholangitis (PBC). The diagnostic performance of TE and MRE in detecting advanced fibrosis in PBC and in predicting outcomes independent of existing serologic prognostic markers is incompletely understood. Five hundred thirty-eight consecutive patients with PBC at 3 centers with liver stiffness (LS) measurements by TE (n=286) or MRE (n=332) were reviewed. LS cutoffs for predicting fibrosis stages were determined by receiver operating characteristic curves among those with a liver biopsy (TE, n=63; MRE, n=98). Cox proportional hazard regression modeling was used to identify associations between covariates and hepatic decompensation. The optimal LS thresholds for predicting histologic stage F4 were 14.40 kPa (area under the curve=0.94) for TE and 4.60 kPa (area under the curve=0.82) for MRE. Both TE and MRE outperformed biochemical markers for the prediction of histologic advanced fibrosis. Optimal LS thresholds to predict hepatic decompensation were 10.20 kPa on TE and 4.30 kPa on MRE. LS by TE and MRE (respectively) remained predictors of hepatic decompensation after adjusting for ursodeoxycholic acid responsiveness [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.24 and HR, 1.68; 95% CI, 1.28-2.19] and the GLOBE score (HR, 1.13; 95% CI, 1.07-1.19 and HR, 2.09; 95% CI, 1.57-2.78). LS measurement with either TE or MRE can accurately detect advanced fibrosis and offers additional prognostic value beyond existing serologic predictive tools.

Controlled attenuation parameter value-based diagnostic algorithm improves the accuracy of liver stiffness measurement in chronic hepatitis B patients.

Liver stiffness measurement (LSM) frequently overestimates the severity of liver fibrosis because of steatosis. However, the impact of the controlled attenuation parameter (CAP) on liver stiffness cutoff values remains unknown; CAP was used to quantify and diagnose the severity of hepatic steatosis. The study was conducted to determine the effect of CAP on liver stiffness cutoff values in chronic hepatitis B (CHB) patients. A retrospective cross-sectional study was performed in liver biopsy-proven CHB patients. The median LSM (kPa) in the elevated CAP group was higher than that in the normal CAP group at the same fibrosis stage. For S2-4, the area under the receiver operating characteristic (AUROC) curve of LSM was 0.78 and 0.72 in the normal and elevated CAP groups, respectively. When a cutoff value of 8.9 kPa was used, the diagnostic accuracy was 77.82% and 63.41% in the normal and elevated CAP groups, respectively. Compared with the alanine transaminase (ALT)-based LSM algorithm, the CAP-based LSM algorithm had a similar correct diagnosis rate (33.64% vs. 33.94%, respectively) but a lower misdiagnosis rate (16.97% vs. 20.30%, respectively). The new CAP-based LSM diagnostic algorithm will improve the diagnostic accuracy of liver fibrosis in CHB patients.

Diagnostic Performance of Vibration-Controlled Transient Elastography in Liver Transplant Recipients

Vibration-controlled transient elastography (VCTE) is a non-invasive tool for detecting hepatic steatosis and fibrosis in patients who have not received liver transplants. We aimed to evaluate the diagnostic performance of VCTE in detection of hepatic steatosis and fibrosis in patients who have undergone liver transplantation. We performed a prospective study of 99 liver transplant recipients assessed by VCTE using a standard protocol. Controlled attenuation parameter cutoff values for pairwise steatosis grade and liver stiffness measurements (LSM) and cutoff values for pairwise fibrosis stage were determined using cross-validated area under the receiver operating characteristics (AUROC) curve analyses. We calculated sensitivity (fixed at 90%) and specificity (fixed at 90%) values. A controlled attenuation parameter cutoff value of 270 dB/m detected any hepatic steatosis with an AUROC of 0.88 (95% CI, 0.78-0.93). VCTE detected steatosis grades 2-3 vs 0-1 with an AUROC of 0.94 (95% CI, 0.89-0.99) and steatosis grade 3 vs 0-2 was similar and AUROC of 0.89 (95% CI, 0.83-0.96). When we used an LSM cutoff value of 10.5 kPa, VCTE identified patients with advanced fibrosis (fibrosis stages≥3) with an AUROC of 0.94 (95% CI, 0.88-0.99). At fixed sensitivity, the cutoff LSM value of 10.5k Pa excluded advanced fibrosis with a negative predictive value of 0.99. At fixed specificity, the cutoff LSM value of 16.9 kPa detected advanced fibrosis with a sensitivity of 0.86, a positive predictive value (PPV) of 0.40, and a negative predictive value of 0.99. VCTE accurately detects hepatic steatosis and fibrosis in recipients of liver transplants. This non-invasive method might be used to identify patients in need of confirmatory liver biopsy analysis.