Cut-off Values Of Liver Stiffness Measurement Research Articles

Prognostic value of liver stiffness measurement for the liver-related surgical outcomes of patients under hepatic resection: A meta-analysis.

BackgroundPrevious studies have discussed the liver stiffness measurement (LSM) performance on predicting liver-related surgical outcomes for patients of hepatocellular carcinoma (HCC) under hepatic resection, yet there is much variation in reporting and consistency of findings. Therefore, we report a meta-analysis on this issue.MethodsWe comprehensively searched PubMed, Embase, and Web of science to find the eligible cohort studies. The pooled Odds Ratios (OR) and 95% confidence intervals (CIs) were calculated to evaluate effect. The weighted mean LSM value was calculated as the optimal LSM cut-off value among studies.Results12 prospective cohort studies and one retrospective cohort study, including a total of 1942 cases were identified. The pooled results showed that preoperative LSM is significantly associated with the occurrence of overall postoperative complications (OR 1.76, 95% CI 1.46–2.11). In addition, a weighted mean LSM value of 14.2 kPa and 11.3KPa were suggested as the optimal LSM cut-off value reference using transient elastoqraphy (TE) for predicting overall postoperative complications in Asia countries and European countries, respectively.ConclusionsPreoperative LSM should be taken into account cautiously in the management of patients undergoing hepatectomy of HCC. Future studies could focus on setting a prognostic model integrated with LSM in predicting post-hepatectomy outcomes.

Transient Elastography (FibroScan) Performs Better Than Non-Invasive Markers in Assessing Liver Fibrosis and Cirrhosis in Autoimmune Hepatitis Patients.

BackgroundAutoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that can lead to severe fibrosis and cirrhosis. Transient elastography (TE, FibroScan) can assess the fibrotic stages of chronic liver diseases by liver stiffness measurement (LSM). Studies on the diagnostic accuracy of FibroScan for the detection of fibrosis in AIH patients are still limited.Material/MethodsThis study enrolled 108 AIH patients who underwent liver biopsies. Using the METAVIR scoring system as the reference, Spearman’s rank correlation was performed to explore the relationship between the markers and stages of fibrosis. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic accuracy. The optimal LSM cut-off values for predicting the stages of fibrosis were calculated.ResultsLSM was superior to other non-invasive markers in differentiating the stages of fibrosis in AIH patients. AUROC value of LSM was 0.885 for stage F2, 0.897 for stage F3, and 0.878 for stage F4. The optimal LSM cut-off value was 6.27 kPa for stage F2, 8.18 kPa for F3, and 12.67 kPa for F4.ConclusionsFibroScan is a valuable non-invasive method for the evaluation of liver fibrosis of AIH patients.

Risk Assessment of Hepatocellular Carcinoma in General Population by Liver Stiffness in Combination with Controlled Attenuation Parameter using Transient Elastography: A Cross Sectional Study

Hepatocellular carcinoma (HCC) in patients without hepatitis B (HBV) and -C virus (HCV) infection are increasing in Japan. Method for detecting high-risk liver diseases of HCC in general population has still not been established. Liver stiffness measurement (LSM) and Controlled Attenuation Parameter (CAP) using transient elastography (TE; FibroScan System) are useful for detecting liver fibrosis and steatosis. The aim of this study is to clarify TE for risk assessment of HCC in general population. This cross-sectional study was performed for residents aged ≥ 40 years in an intermountain town in Japan with a population of 3,493. Blood laboratory testing included tumor markers, abdominal ultrasound (AUS), and TE was performed. Among 175 subjects (64 men, 111 women), TE was evaluated and three patients with HCC were detected by AUS. For detecting HCC, the cut-off value of LSM was 5.3 kPa sensitivity 100%, specificity 75%, AUROC 0.88). The combination of LSM and CAP (LSM > 5.3 kPa with any CAP and CAP > 248 dB/m with any LSM) could detect the high-risk liver diseases of HCC (HCC, nonalcoholic fatty liver/steatohepatitis, HBV or HCV related chronic viral hepatitis with alanine transaminase (ALT) > 30 IU/L for men or > 19 IU/L for women or cirrhosis of any cause) with high sensitivity (sensitivity 90%, specificity 55%, positive predictive value 10%, negative predictive value 99%, P = 0.006). The combination of LSM and CAP can be useful in detecting high-risk liver diseases of HCC out of general population.

Assessment of transient elastography in Japanese patients with non-alcoholic fatty liver disease.

Transient elastography (TE) is a non-invasive method for predicting liver fibrosis. However, there are limited data regarding the performance of TE in Japanese patients with non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association between liver stiffness measurement (LSM) by TE and liver fibrosis stage, and define a cut-off value for predicting liver fibrosis. A total of 171 Japanese patients with biopsy-proven NAFLD underwent LSM using TE with FibroScan. The area under the receiver operating characteristic curve of LSM and other non-invasive markers of liver fibrosis were compared to determine the most accurate method of predicting liver fibrosis. Liver stiffness measurement significantly correlated with fibrosis stage (P <0.001). The areas under the receiver operating characteristic curve of LSM for fibrosis stage ≥1 and ≥3 was 0.85 and 0.91, respectively and were higher than those of the aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, fibrosis-4 index, and NAFLD fibrosis score. The best cut-off values of LSM fibrosis stage ≥1 and ≥3 were 7.2kPa (sensitivity 78.5%, specificity 78.3%) and 10.0kPa (sensitivity 89.5%, specificity 87.6%), respectively. The combination of LSM (≥10kPa) and type IV collagen 7 s (≥6.0ng/mL) had a specificity of 97.6% for advanced fibrosis. The LSM in patients with high alanine aminotransferase levels or high body mass index was associated with false positive results regarding advanced fibrosis. In NAFLD patients, TE has excellent utility for the assessment of liver fibrosis, particularly for advanced stage cases. The cut-off value of LSM by TE for predicting liver fibrosis stage ≥3 is 10.0kPa in Japanese NAFLD patients.

The Acoustic Radiation Force Impulse Elastography Evaluation of Liver Fibrosis in Posttransplantation Dysfunction of Living Donor Liver Transplantation

BackgroundThe acoustic radiation force impulse elastography (ARFI) is a new technology of elastography integrated into B-mode ultrasonography. It has been a reliable method to evaluate liver fibrosis of chronic liver disease in recent years, but less applied in the posttransplantation liver. The aim of the study was to evaluate liver fibrosis by the ARFI with correlation of pathological stages in living donor liver transplantation (LDLT). Materials and MethodsFrom August 2010 to August 2012, there were 57 LDLT patients with liver biopsy (LB) due to posttransplantation dysfunction; all patients also received posttransplantation ARFI liver stiffness measurement (LSM) after transplantation for liver fibrosis staging. The ARFI elastography was performed using a Siemens Acuson S2000 ultrasound system with 4V1 transducers (Acusion, Siemens Medical Systems Co. Ltd. Erlangen, Germany). The ARFI LSM value was presented by shear wave velocity (SWV, m/s). The fibrosis staging as F0 to F4 was in accordance with the Metavir scoring system. ResultsA total of 57 patients had both posttransplantation LB and effective ARFI fibrosis staging for correlation. The ARFI LSM value increased with severity of liver fibrosis and had significant linear correlation with the results of histological fibrosis staging. The ARFI LSM sensitivities (Se), specificities (Sp), and cutoff values based on receiver-operator characteristic curve were F0: 0.75 m/s (Se: 93.8%, Sp: 4%), F1: 1.06 m/s (Se: 95.5%, Sp: 25.7%), F2: 1.81 m/s (Se: 50%, Sp: 83.6%) and F3: 2.33 m/s (Se: 100%, Sp: 92.9%). Predictive value of ARFI LSM reported a significant difference between early fibrosis stage (F0–F1) and advanced fibrosis stage (F ≧ 2) (P < .05). ConclusionIn this study, ARFI demonstrated a strong linear correlation and severity of liver fibrosis with LB pathologic staging. ARFI can be an alternative and compensatory method for frequent LB in the posttransplantation liver.

Baseline Values and Changes in Liver Stiffness Measured by Transient Elastography Are Associated With Severity of Fibrosis and Outcomes of Patients With Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that leads to extensive liver fibrosis and cirrhosis, which are associated with poor outcome. However, there are no validated noninvasive markers of liver fibrosis in patients with PSC. We assessed the diagnostic performance, reproducibility, longitudinal changes, and prognostic value of liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE). In a prospective study, we analyzed percutaneous liver biopsy specimens from 73 consecutive patients with PSC from January 2005 to December 2010. Patients underwent VCTE no more than 6 months after the biopsy specimens were collected. The biopsy specimens were analyzed by a pathologist blinded to the results of VCTE for the stage of fibrosis, and LSM was associated with the stage of fibrosis and other variables using the Kruskal-Wallis and Spearman correlation tests. The cutoff values of LSM were selected based on the accuracy with which they identified the stage of fibrosis on receiver-operating characteristic analysis. The rates of LSM progression were assessed using a linear mixed model, and the association between LSM values and clinical outcomes were evaluated using Cox regression analysis in 168 patients with PSC treated with ursodeoxycholic acid and followed up from November 2004 to July 2013 (mean follow-up period, 4 years). LSM was independently linked to the stage of fibrosis. Cutoff values for fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 7.4 kPa, 8.6 kPa, 9.6 kPa, and 14.4 kPa, respectively. The adjusted diagnostic accuracy values for severe fibrosis and cirrhosis were 0.83 and 0.88, respectively. The diagnostic performance of LSM was comparable to that of hyaluronic acid measurement but superior to the aspartate aminotransferase/platelet ratio index, FIB-4 score, and Mayo risk score in differentiating patients with significant or severe fibrosis from those without. LSM had a high level of reproducibility between operators for the same measurement site and for the same operator between 2 adjacent sites. LSM increased significantly and exponentially over time. Baseline measurements and rate of LSM progression were strongly and independently linked with patients' outcomes. VCTE is able to differentiate severe from nonsevere liver fibrosis with high levels of confidence in patients with PSC. Baseline measurements of LSM and longitudinal changes are prognostic factors for PSC.

Performance of transient elastography (TE) and factors associated with discordance in non‐alcoholic fatty liver disease

To determine the accuracy of transient elastography (TE) and factors associated with discordance between TE and liver histology in patients with non-alcoholic fatty liver disease (NAFLD). The accuracy of TE was assessed and compared with the aspartate aminotransferase-to-platelet ratio index (APRI) in patients with histologically proven NAFLD. Factors associated with discordance between liver histology and TE were analyzed. Altogether 131 patients with a mean age of 49.9 years, including 69 men and 62 women, with NAFLD underwent liver stiffness measurement (LSM) by TE. Among all patients, 120 (91.6%) had a successful LSM with an interquartile to median ratio of 0.15. The accuracy of TE in detecting ≥F3 and F4 fibrosis, assessed by the area under the receiver operating characteristic curve, were 0.77 and 0.95, respectively. The sensitivity and specificity of the optimal LSM cut-off values for detecting ≥F3 fibrosis (sensitivity 70.4% and specificity 66.6%) and F4 (sensitivity 87.5% and specificity 89.3%) were modest, but better than those of APRI. Discordance between TE and histology for fibrosis grading was observed in 22.5% of patients, but it could not be explained by body mass index, alanine aminotransferase level, the length of the biopsied specimens or the grade of steatosis. TE plays an important role in the detection of advanced fibrosis and cirrhosis in patients with NAFLD and its accuracy does not appear to be influenced by components of the disease.

Liver stiffness measurement: Is it a non-invasive substitution for HVPG?

Liver stiffness measurement: Is it a non-invasive substitution for HVPG?

Efficacy of transient elastography in screening for large esophageal varices in patients with suspicious or proven liver cirrhosis

To evaluate the liver stiffness measurement (LSM) using transient elastography (TE) to predict the risk of esophageal varices (EVs) in Chinese patients. In total, 46 patients with suspicious or proven liver cirrhosis underwent TE and liver biopsy. All participants were endoscopically screened for the presence of EVs and large EVs by two endoscopists who were blinded to the LSM status. Large EVs were defined as more than 5 mm in diameter. Receiver operating characteristic (ROC) curves for both TE and the platelet count/spleen diameter (PC/SD) ratio in predicting the presence of EVs or large EVs were calculated. Of the 46 patients, 30 (65%) had EVs including 19 (41%) with large EVs. The area under the ROC curve (AUROC) of LSM was 0.85 for the presence of EVs and 0.83 for large EVs, respectively. The cut-off values of LSM were ≥13.4 kPa for the presence of EVs and ≥14.6 kPa for large EVs. Notably, the AUROC of the PC/SD ratio was 0.92 for the presence of EVs but only 0.69 for large EVs. LSM using TE can predict the presence of EVs or large EVs in Chinese patients with suspicious or proven cirrhosis and may identify patients who require endoscopic surveillance.

A Meta-analysis of Transient Elastography for the Detection of Hepatic Fibrosis

The use of transient elastography to assess liver stiffness measurement (LSM) has now become widely available for the diagnosis of liver fibrosis as a rapid, noninvasive test (it is still not approved for use in the United States). It has previously been showed as an accurate method of representing the state of liver fibrosis with concomitant evaluation of liver biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to further assess its use in comparison with liver biopsy. Studies from the literature were analyzed with a median liver stiffness value in kilopascal given for fibrosis stages according to histopathologic findings on biopsy and best discriminant cutoff levels in kilopascals for significant fibrosis (>or=F2) and cirrhosis (F4). A total of 22 studies were selected comprising 4,430 patients; chronic hepatitis C infection was the most common etiology of fibrosis. The pooled estimates for significant fibrosis (>or=F2) measured 7.71 kPa (LSM cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%-72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4) the results showed a cutoff of 15.08 kPa with a sensitivity of 84.45% (95% CI: 84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). Further evaluation of transient elastography to assess LSM is required in prospective studies to potentially increase the sensitivity and establish its clinical utility.

Insulin resistance is a major determinant of liver stiffness in nondiabetic patients with HCV genotype 1 chronic hepatitis

In patients with chronic hepatitis C (CHC), liver stiffness measurement (LSM) by transient elastography (TE), is closely related to the stage of fibrosis, but may be affected by necroinflammation. Other factors, such as insulin resistance (IR), might influence the performance of LSM. To evaluate in a cohort of nondiabetic patients with genotype 1 CHC, whether IR and other anthropometric, biochemical, metabolic and histological factors contribute to LSM and to identify the best cut-off values of LSM for predicting different stages of fibrosis. Nondiabetic patients with genotype 1 CHC (n = 156) were evaluated by liver biopsy (Metavir score), anthropometric, biochemical and metabolic features including IR. Furthermore, all subjects underwent LSM by TE. Severe fibrosis (F3-F4) was associated with LSM (OR 1.291; 95%CI 1.106-1.508). LSM was also independently correlated with low platelets (P = 0.03), high gammaGT (P < 0.001) and high HOMA (P = 0.004) levels. A stiffness value > or =8 KPa was identified as the best cut-off for predicting severe fibrosis (AUC 0.870); yet this cut-off still failed to rule out F3-F4 fibrosis in 22.7% of patients (false-negative rate) or rule in F3-F4 in 19.6% (false-positive rate). Platelets <200 x 10(3)/mmc and a HOMA of >2.7 were the major determinants of these diagnostic errors in predicting severe fibrosis. Conclusions In nondiabetic patients with genotype 1 CHC, insulin resistance, gammaGT and platelet levels contribute to LSM independently of liver fibrosis. The identification of these three factors contributes to a more correct interpretation of LSM.

FibroScan and ultrasonography in the prediction of hepatic fibrosis in patients with chronic viral hepatitis

The aim of this study was to assess the diagnostic performances of liver stiffness measurement (LSM), ultrasonography (US) and their combined use in predicting the extent of hepatic fibrosis. Consecutive patients with chronic hepatitis B (HBV) or hepatitis C virus (HCV) infections, with indications for liver biopsy, were prospectively enrolled. LSM was performed on the same day as biopsy. US scores, including assessment of liver surface, liver parenchyma, intrahepatic vessels and spleen index, were used to assess the degree of hepatic fibrosis. The pathological findings were used as a reference standard and diagnostic accuracy was assessed and compared. Three-hundred and twenty patients, including 199 men and 121 women, with a mean age of 50.8 years, were analyzed. There were 214 (66.9%) HCV patients, 88 (27.5%) HBV patients and 18 (5.6%) patients with both HCV and HBV. LSM correlated significantly with the hepatic fibrosis (F) scores, necro-inflammatory activity and US scores in multivariate analysis. The diagnostic accuracy of LSM is significantly superior to US, and equal to combined LSM with US, in the prediction of all HCV-related fibrosis scores. The cut-off value of LSM is 6 kPa for diagnosing F > =1, with a positive predictive value of 91%. Also, the cut-off value is 12 kPa for the prediction of cirrhosis, with a negative predictive value of 94%. LSM is useful for predicting hepatic fibrosis and excluding cirrhosis. A combination of LSM and US does not improve the accuracy in assessing hepatic fibrosis.

Non‐invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B

The need for new non-invasive tools to assess liver fibrosis in chronic liver diseases has been largely advocated. Liver stiffness measurement (LSM) using transient elastography (FibroScan), Echosens) has been shown to be correlated to liver fibrosis in various chronic liver diseases. This study aims to assess its diagnosis accuracy in patients with chronic hepatitis B. We prospectively enrolled 202 patients with chronic hepatitis B in a multicentre study. Patients underwent liver biopsy (LB) and LSM. METAVIR and Ishak liver fibrosis stages were assessed by two pathologists. LSM or LB was considered unreliable in 29 patients. Statistical analysis was conducted in 173 patients. LSM was significantly (P<0.001) correlated with METAVIR (r=0.65) and Ishak fibrosis stage (0.65). The area under receiver-operating characteristic curves were 0.81 (95% confidence intervals, 0.73-0.86) for F>/=2, 0.93 (0.88-0.96) for F>/=3 and 0.93 (0.82-0.98) for F=4. Optimal LSM cut-off values were 7.2 and 11.0 kPa for F>/=2 and F=4, respectively, by maximizing the sum D of sensitivity and specificity, and 7.2 and 18.2 kPa by maximizing the diagnosis accuracy. In conclusion, LSM appears to be reliable for detection of significant fibrosis or cirrhosis in HBV patients and cut-off values are only slightly different from those observed in HCV patients.

Alanine aminotransferase‐based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.

Comparison of Liver Biopsy and Transient Elastography based on Clinical Relevance

Liver stiffness measurement (LSM) by transient elastography has recently been validated for the evaluation of liver fibrosis in chronic liver diseases. The present study focused on cases in which liver biopsy and LSM were discordant. Three hundred eighty-six patients with chronic hepatitis C who underwent a liver biopsy between December 2004 and April 2007 were studied. First, the optimal cut-off value of LSM was selected for the determination of cirrhosis based on the receiver operating characteristic curve. Then, the cases in which liver histology and evaluation by LSM were discordant were selected. Laboratory test results such as serum total bilirubin concentration, prothrombin activity, albumin concentration, platelet count and the aspartate aminotransferase to platelet ratio index, together with the presence of esophageal varices, were analyzed. The optimal cut-off value was chosen to be 15.9 kPa for cirrhosis (fibrosis stage [F] 4) determination to maximize the sum of sensitivity (78.9%) and specificity (81.0%). There were 78 discordant cases: 51 patients showed an LSM of 15.9 kPa or higher and a fibrosis stage of F1 to F3 (high LSM group), and 27 patients had an LSM lower than 15.9 kPa and a fibrosis stage of F4 (low LSM group). Esophageal varices were seen in 11 patients in the high LSM group (n=51) and in no patients in the low LSM group (n=27) (P=0.0012). The aspartate aminotransferase to platelet ratio index was significantly higher in the high LSM group (1.49 versus 0.89, P=0.019). Other parameters did not differ significantly. However, platelet count, prothrombin activity and albumin concentration tended to be lower in the high LSM group. Patients with a high LSM need proper attention for cirrhosis, even if liver biopsy does not reveal cirrhosis.

Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C

Liver fibrosis is the main predictor of the progression of chronic hepatitis C, and its assessment by liver biopsy (LB) can help determine therapy. However, biopsy is an invasive procedure with several limitations. A new, noninvasive medical device based on transient elastography has been designed to measure liver stiffness. The aim of this study was to investigate the use of liver stiffness measurement (LSM) in the evaluation of liver fibrosis in patients with chronic hepatitis C. We prospectively enrolled 327 patients with chronic hepatitis C in a multicenter study. Patients underwent LB and LSM. METAVIR liver fibrosis stages were assessed on biopsy specimens by 2 pathologists. LSM was performed by transient elastography. Efficiency of LSM and optimal cutoff values for fibrosis stage assessment were determined by a receiver-operating characteristics (ROC) curve analysis and cross-validated by the jack-knife method. LSM was well correlated with fibrosis stage (Kendall correlation coefficient: 0.55; P < .0001). The areas under ROC curves were 0.79 (95% CI, 0.73-0.84) for F > or =2, 0.91 (0.87-0.96) for F > or =3, and 0.97 (0.93-1) for F=4; for larger biopsies, these values were, respectively, 0.81, 0.95, and 0.99. Optimal stiffness cutoff values of 8.7 and 14.5 kPa showed F > or =2 and F=4, respectively. In conclusion, noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to detect significant fibrosis or cirrhosis in patients with chronic hepatitis C.