Wassil Merrouche

Pitfalls of liver stiffness measurement: A 5-year prospective study of 13,369 examinations†

Liver stiffness measurement (LSM) based on transient elastography (TE, FibroScan) is gaining in popularity for noninvasive assessment of liver fibrosis. However, LSM has limitations, which have not yet been thoroughly evaluated. We prospectively investigated the frequency and determinants of LSM failure and unreliable results over a 5‐year period, based on 13,369 examinations (134,239 shots). LSM failure was defined as zero valid shots, and unreliable examinations were defined as fewer than 10 valid shots, an interquartile range (IQR)/LSM greater than 30%, or a success rate less than 60%. LSM failure occurred in 3.1% of all examinations (4% at first examination [n = 7261]) and was independently associated at first examination with body mass index (BMI) greater than 30 kg/m2 (odds ratio [OR], 7.5; 95% confidence interval [CI], 5.6‐10.2; P = 0.0001), operator experience fewer than 500 examinations (OR 2.5 [1.6‐4.0]; P = 0.0001); age greater than 52 years (OR 2.3 [1.6‐3.2]; P = 0.0001), and type 2 diabetes (OR 1.6 [1.1‐2.2]; P = 0.009). Unreliable results were obtained in a further 15.8% of cases (17% at first examination) and were independently associated at first examination with BMI greater than 30 kg/m2 (OR 3.3 [2.8‐4.0]; P = 0.0001), operator experience fewer than 500 examinations (OR 3.1 [2.4‐3.9]; P = 0.0001), age greater than 52 years (OR 1.8 [1.6‐2.1]; P = 0.0001), female sex (OR 1.4 [1.2‐1.6], P = 0.0001), hypertension (OR 1.3 [1.1‐1.5]; P = 0.003), and type 2 diabetes (OR 1.2 [1.0‐1.5]; P = 0.05). When metabolic syndrome and waist circumference were taken into account in a subgroup of 2835 patients, waist circumference was the most important determinant of LSM failure and unreliable results. Conclusion: In our experience, liver stiffness measurements are uninterpretable in nearly one in five cases. The principal reasons are obesity, particularly increased waist circumference, and limited operator experience. These results emphasize the need for adequate operator training and for technological improvements in specific patient subpopulations. (HEPATOLOGY 2010.)

Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient elastography and histology. Two hundred forty‐six consecutive patients from two ethnic groups had successful liver stiffness measurement and satisfactory liver biopsy specimens. The area under the receiver‐operating characteristics curve (AUROC) of transient elastography for F3 or higher and F4 disease was 0.93 and 0.95, respectively, and was significantly higher than that of the aspartate aminotransferase–to–alanine aminotransferase ratio, aspartate aminotransferase–to–platelet ratio index, FIB‐4, BARD, and NAFLD fibrosis scores (AUROC ranged from 0.62 to 0.81, P < 0.05 for all comparisons). At a cutoff value of 7.9 kPa, the sensitivity, specificity, and positive and negative predictive values for F3 or greater disease were 91%, 75%, 52%, and 97%, respectively. Liver stiffness was not affected by hepatic steatosis, necroinflammation, or body mass index. Discordance of at least two stages between transient elastography and histology was observed in 33 (13.4%) patients. By multivariate analysis, liver biopsy length less than 20 mm and F0‐2 disease were associated with discordance. Conclusion: Transient elastography is accurate in most NAFLD patients. Unsatisfactory liver biopsy specimens rather than transient elastography technique account for most cases of discordance. With high negative predictive value and modest positive predictive value, transient elastography is useful as a screening test to exclude advanced fibrosis. Liver biopsy may be considered in NAFLD patients with liver stiffness of at least 7.9 kPa. (HEPATOLOGY 2010;51:454–462.)

Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C : Comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores

BACKGROUND/AIMS To assess prospectively the accuracy of transient elastography (TE, FibroScan) for the detection of cirrhosis and oesophageal varices (OV) in chronic hepatitis C (CHC), as compared with currently available non-invasive methods (AST/ALT ratio (AAR), APRI, prothrombin index (PI), platelet count (PC), FibroTest (FT) and Lok index). METHODS All tests were performed the day of liver biopsy (LB), taken as reference, in 298 consecutive CHC patients (cirrhosis: 70; Child-Pugh A: 70; OV: 25). RESULTS TE had the best diagnostic accuracy for detection of cirrhosis (AUROCs: TE 0.96 vs. FT 0.82, Lok and APRI 0.80, PC 0.79, PI 0.73, AAR 0.61, respectively; p < 0.0001). Overall, the percentage of saved LB was: TE (cut-off: 12.5 kPa) 90%, PC 82%, FT 79%, PI 77%, AAR 76%, APRI 70%, and Lok 45%, respectively. At a cut-off of 21.5 kPa, TE predicted the presence of OV with 76% sensitivity and 78% specificity and correctly classified 73% of patients vs. AAR 81%, Lok 77%, FT, PI 70%, PC 69%, and APRI 66%, respectively. CONCLUSIONS TE is currently the most accurate non-invasive method for early detection of cirrhosis in CHC (cut-off: 12.5 kPa), as compared with other available methods, but cannot replace endoscopy for OV screening.

Noninvasive Tests for Fibrosis and Liver Stiffness Predict 5-Year Outcomes of Patients With Chronic Hepatitis C

BACKGROUND & AIMS Liver stiffness can be measured noninvasively to assess liver fibrosis in patients with chronic hepatitis C. In patients with chronic liver diseases, level of fibrosis predicts liver-related complications and survival. We evaluated the abilities of liver stiffness, results from noninvasive tests for fibrosis, and liver biopsy analyses to predict overall survival or survival without liver-related death with a 5-year period. METHODS In a consecutive cohort of 1457 patients with chronic hepatitis C, we assessed fibrosis and, on the same day, liver stiffness, performed noninvasive tests of fibrosis (FibroTest, the aspartate aminotransferase to platelet ratio index, FIB-4), and analyzed liver biopsy samples. We analyzed data on death, liver-related death, and liver transplantation collected during a 5-year follow-up period. RESULTS At 5 years, 77 patients had died (39 liver-related deaths) and 16 patients had undergone liver transplantation. Overall survival was 91.7% and survival without liver-related death was 94.4%. Survival was significantly decreased among patients diagnosed with severe fibrosis, regardless of the noninvasive method of analysis. All methods were able to predict shorter survival times in this large population; liver stiffness and results of FibroTest had higher predictive values. Patient outcomes worsened as liver stiffness and FibroTest values increased. Prognostic values of stiffness (P<.0001) and FibroTest results (P<.0001) remained after they were adjusted for treatment response, patient age, and estimates of necroinflammatory grade. CONCLUSIONS Noninvasive tests for liver fibrosis (measurement of liver stiffness or FibroTest) can predict 5-year survival of patients with chronic hepatitis C. These tools might help physicians determine prognosis at earlier stages and discuss specific treatments, such as liver transplantation.

Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease.

OBJECTIVES:Liver stiffness measurement (LSM) by transient elastography is a noninvasive test of liver fibrosis, but cannot be performed in a significant proportion of obese patients. The aim of this study was to evaluate the performance of the new XL probe in patients with nonalcoholic fatty liver disease (NAFLD).METHODS:Liver biopsy and paired LSM by both the original M probe and XL probe were performed on 193 consecutive NAFLD patients in France and Hong Kong.RESULTS:Compared with M probe, XL probe was more likely to achieve 10 valid measurements (95% vs. 81%; P<0.001) and a success rate of over 60% (90% vs. 74%; P<0.001). The areas under receiver operating characteristics curves of XL probe for F2, F3, and F4 disease were 0.80, 0.85, and 0.91, respectively. XL probe tended to generate lower LSM than M probe in the same patient. At a cutoff of 7.2 kPa, the sensitivity, specificity, positive, and negative predictive values for F3 or greater disease were 78%, 78%, 60%, and 89%, respectively. Discordance of at least two stages between XL probe and histology was observed in 16 (9%) patients. Body mass index (BMI) over 35 kg/m2 was independently associated with discordance (adjusted odds ratio 9.09; 95% confidence interval 1.10–75.43). Reliable measurements by XL probe were obtained in 75% of the overall population and 65% of patients with BMI over 30 kg/m2.CONCLUSIONS:LSM by XL probe can be performed successfully in most NAFLD patients, but obesity is associated with less accurate and reliable measurements.

Liver Stiffness Measurement in Children Using FibroScan: Feasibility Study and Comparison With Fibrotest, Aspartate Transaminase to Platelets Ratio Index, and Liver Biopsy

Objective: Transient elastography (FibroScan) is a novel, noninvasive, rapid bedside method to assess liver fibrosis by measuring liver stiffness in adult patients. The usefulness of FibroScan in children with chronic liver diseases is unknown. The aim of this prospective study was to evaluate the feasibility of liver stiffness measurement and to compare FibroScan, Fibrotest, and aspartate transaminase to platelets ratio index (APRI) with liver biopsy for the diagnosis of cirrhosis in children with chronic liver diseases. Patients and Methods: Between February 2004 and October 2005, 116 consecutive children with chronic liver diseases were prospectively included. All except 1 child (58 boys, mean age 10.7 years) could have noninvasive tests for fibrosis: FibroScan, Fibrotest, and APRI, and, when necessary, a liver biopsy (n = 33). Results: FibroScan, Fibrotest, and APRI were correlated with clinical or biological parameters of chronic liver diseases, but the FibroScan marker correlated most with all parameters. By histology, the METAVIR fibrosis category score was F1 in 7 cases, F2 in 8 cases, F3 in 6 cases, and F4 in 12 cases. FibroScan, Fibrotest, and APRI were significantly correlated with the METAVIR fibrosis score. For the diagnosis of cirrhosis, the area under the receiver operating characteristic curve was 0.88, 0.73, and 0.73 for FibroScan, Fibrotest, and APRI, respectively. Conclusions: These results indicate that liver stiffness measurement is feasible in children and is related to liver fibrosis. A specific probe dedicated to children and slender patients has thus been developed and is currently under evaluation. The FibroScan equipped with this specific probe could become a useful tool for the management of chronic liver diseases in children.

Non-invasive diagnosis of liver steatosis using controlled attenuation parameter (CAP) and transient elastography

Recently, a study showed that Controlled Attenuation Parameter (CAP), evaluated with transient elastography, could efficiently separate steatosis grades. The aim of this study was to prospectively evaluate the performance of CAP for the diagnosis of steatosis in patients with chronic liver disease.

Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: Comparison between M and XL probe of FibroScan

BACKGROUND & AIMS Unreliable results of liver stiffness measurement are obtained in 16% of cases and are independently associated with body mass index (BMI) greater than 30 kg/m(2). A new FibroScan® probe (XL probe) was designed specifically for obese patients. The aim of this study was to evaluate the accuracy of liver stiffness measurement using M and XL probes of Fibroscan® for the diagnosis of fibrosis and cirrhosis in a large cohort of patients. METHODS Consecutive patients undergoing liver biopsies for chronic liver disease were prospectively recruited. Liver stiffness measurement was performed within 1 week before liver biopsy using both M and XL probes of FibroScan®. RESULTS A total of 286 patients were evaluated. A reliable liver stiffness measurement using M probe was obtained in 79.7% of cases. In the other 21.3%, liver stiffness measurement using XL probe was obtained in 56.9% of patients. A strong correlation was found between M and XL values, regardless of BMI. In all groups, median liver stiffness measurement using the XL probe was significantly lower than liver stiffness measurement using the M probe. By multivariate analysis, unsuccessful liver stiffness examination with M probe was independently associated with age >50 years and BMI >30 kg/m(2). By univariate analysis, only BMI >30 kg/m(2) was associated with unsuccessful liver stiffness measurement with XL probe. No significant difference was observed between the M and XL probes for the diagnosis of liver fibrosis. CONCLUSIONS Liver stiffness measurement with either M or XL probe is possible in 91.2% of patients with comparable diagnostic accuracy. In clinical practice, the M probe could be used as first step for liver stiffness measurement. In case of no valid shot or unreliable measurement, the XL probe could be used. This result could be useful for the assessment of liver fibrosis in NAFLD and/or obese patients.

Feasibility of liver transient elastography with FibroScan using a new probe for obese patients.

Background & Aims: Liver stiffness measurement (LSM) failure when using transient elastography occurs in 2–10% of patients, and is generally related to obesity. The aim of this prospective study was to assess the feasibility of LSM when using a new XL probe on patients with a body mass index (BMI)≥30 kg/m2.

Controlled attenuation parameter (CAP) for the diagnosis of steatosis: A prospective study of 5323 examinations

BACKGROUND & AIMS Controlled attenuation parameter (CAP) evaluated with transient elastography (FibroScan®) is a recent method for non-invasive assessment of steatosis. Its usefulness in clinical practice is unknown. We prospectively investigated the determinants of CAP failure and the relationships between CAP and clinical or biological parameters in a large cohort of consecutive patients. METHODS All CAP examinations performed in adult patients with suspected chronic liver disease were included. CAP failure was defined as zero valid shot. The following factors were analyzed for their influence on CAP value and the relationships between CAP and clinico-biological parameters: age, gender, body mass index, waist circumference, hypertension, diabetes, metabolic syndrome, alcohol use, liver stiffness measurement, indication, and different biological parameters. RESULTS CAP failure occurred in 7.7% of 5323 examinations. By multivariate analysis, factors independently associated with CAP measurement failure were female gender, BMI, and metabolic syndrome. By multivariate analysis, factors significantly associated with elevated CAP were BMI [25-30]kg/m(2), BMI >30kg/m(2), metabolic syndrome, alcohol >14 drink/week and liver stiffness >6kPa. CAP increased with the number of parameters of metabolic syndrome, BMI, waist circumference, the presence of diabetes or hypertension, and the cause of the disease. In the 440 patients with liver biopsy, for the diagnosis of steatosis >10%, steatosis >33%, and steatosis >66%, AUROCs of CAP were 0.79 (95% CI 0.74-0.84, p<0.001), 0.84 (95% CI 0.80-0.88, p<0.001), 0.84 (95% CI 0.80-0.88, p<0.001), respectively. CONCLUSIONS CAP provides an immediate assessment of steatosis simultaneously with liver stiffness measurement. The strong association of CAP with the metabolic syndrome and alcohol use could be of interest for the follow-up of NAFLD or alcoholic patients.