Introduction
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.
Patients and methods
Consecutive patients with chronic liver disease had steatosis diagnosis using CAP, blood sample and liver biopsy. Steatosis was graded as the percentage of hepatocytes with fat: S0 ≤ 10%, S1: 11 ~ 33%, S2: 34 ~ 66%, S3 ≥ 67%.
Results
Characteristics of the 112 patients included were as follows: age 54 years, BMI 26 kg m−², HCV 36%, NAFLD 25%. Steatosis repartition was: S0 52%, S1 19%, S2 14%, S3 15%. CAP was significantly correlated with SteatoTest, Fatty Liver Index (FLI), percentage of steatosis on liver biopsy, steatosis grade and slightly with liver stiffness, but not with fibrosis and activity grade on liver biopsy. Using CAP vs SteatoTest vs FLI score, Area Under the Receiver‐Operating Characteristics (ROC) curves (AUROC)s were 0.84 vs 0.72 vs 0.72 for the diagnosis of steatosis ≥ S1, 0.86 vs 0.73 vs 0.71 for the diagnosis of steatosis ≥ S2, and 0.93 vs 0.73 vs 0.75 for the diagnosis of steatosis S3 respectively. For a sensitivity ≥ 90%, cut‐offs of CAP were 215 dB m−1 for S ≥ 1, 252 dB m−1 for S ≥ 2, and 296 dB m−1 for S3.
Conclusion
CAP is very efficient to detect even low grade steatosis. CAP being implemented on FibroScan® (Echosens, Paris, France), both steatosis and fibrosis can be evaluated simultaneously, enlarging the spectrum of non‐invasive techniques for the management of chronic liver diseases.
No data are available about the prediction of long‐term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3‐year ...liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB‐4) evolution in CHC. CHC patients with two LSM (1,000‐1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB‐4 were calculated the day of baseline (bLSM) and follow‐up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow‐up‐baseline results)/duration. Date and cause of death were recorded during follow‐up that started the day of fLSM. In all, 1,025 patients were included. Median follow‐up after fLSM was 38.0 months (interquartile range IQR: 27.7‐46.1) during which 35 patients died (14 liver‐related death) and seven had liver transplantation. Prognostic accuracy (Harrell C‐index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB‐4 (P ≥ 0.24), whereas FIB‐4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7‐14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥1 kPa/year) in 7‐14 kPa bLSM, or decrease (≤0 kPa/year) in ≥14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥14 kPa bLSM had the worst prognosis. Baseline and delta FIB‐4 also identified patient subgroups with significantly different prognosis. Conclusion: Three‐year evolution of noninvasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. (Hepatology 2014;60:65‐76)
Background & Aims
Several non‐invasive tests (NITs) have been developed to diagnose oesophageal varices (EV), including the recent Baveno VI criteria to rule out high‐risk varices (HRV). Spleen ...stiffness measurement (SSM) with the standard FibroScan® (SSM@50Hz) has been evaluated. However, the EV grading could be underestimated because of a ceiling threshold (75 kPa) of the SSM@50Hz. The aims were to evaluate SSM by a novel spleen‐dedicated FibroScan® (SSM@100Hz) for EV diagnosis compared with SSM@50Hz, other validated NITs and Baveno VI criteria.
Methods
This prospective multicentre study consecutively enrolled patients with chronic liver disease; blood data, endoscopy, liver stiffness measurement (LSM), SSM@50Hz and SSM@100Hz were collected.
Results
Two hundred and sixty patients met inclusion criteria. SSM@100Hz success rate was significantly higher than that of SSM@50Hz (92.5% vs 76.0%, P < .001). SSM@100Hz accuracy for the presence of EV (AUC = 0.728) and HRV (AUC = 0.756) was higher than in other NITs. SSM@100Hz AUC for large EV (0.782) was higher than SSM@50Hz (0.720, P = .027). AUC for HRV with SSM@100Hz (0.780) was higher than with LSM (0.615, P < .001). The spared endoscopy rate of Baveno VI criteria (8.1%) was significantly increased by the combination to SSM@50Hz (26.5%) or SSM@100Hz (38.9%, P < .001 vs others). The missed HRV rate was, respectively, 0% and 4.7% for combinations.
Conclusions
SSM@100Hz is a new performant non‐invasive marker for EV and HRV providing a higher accuracy than SSM@50Hz and other NITs. The combination of Baveno VI criteria and SSM@100Hz significantly increased the spared endoscopy rate compared to Baveno VI criteria alone or combined with SSM@50Hz. Clinical trial number: NCT02180113.
Iron dysmetabolism has long been identified as a primary key factor involved in Restless Legs Syndrome (RLS) pathophysiology and may account for the high prevalence of RLS observed in chronic liver ...diseases (CLD). Prevalence of RLS was also reported to be high in genetic hemochromatosis (GH) but whether this is due to the unique iron metabolism disorder and to treatment procedure in GH remains unknown. If this assumption is true, then one would hypothesize that RLS prevalence is higher in GH than in another CLD such as chronic hepatitis B (CHB).
We conducted a prospective questionnaire-based survey to assess the prevalence of RLS symptoms in consecutive patients with either GH or CHB. Patients who were screened positive for RLS based on the criteria of the International RLS Study Group were further interviewed by telephone and if needed by face to face assessment to confirm RLS diagnosis.
Symptoms of confirmed RLS were confirmed in 8.9% of the 101 participants with CHB and in 10% of the 105 patients with GH. Low ferritin levels were not associated with the presence of RLS in both groups nor were the severity of the liver disease.
GH is not a risk factor for RLS occurrence as any other cause of CLD, as RLS prevalence in both GH and CHB is within the range of RLS prevalence in the general Caucasian population.
•Genetic hemochromatosis is not a risk factor for RLS.•Chronic hepatitis B is not a risk factor for RLS.•Ferritin levels are not associated with RLS occurrence in genetic hemochromatosis.•Severity of liver disease is not associated with RLS occurrence in chronic hepatitis B and in genetic hemochromatosis.
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.)
The aim of this work was to develop an individualized score for predicting hepatocellular carcinoma (HCC) in patients with hepatitis C (HCV)‐compensated cirrhosis. Among 1,323 patients with HCV ...cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, 720 and 360 were randomly assigned to training and validation sets, respectively. Cox's multivariate model was used to predict HCC, after which a nomogram was computed to assess individualized risk. During follow‐up (median, 51.0 months), 103 and 39 patients developed HCC in the training and validation sets, respectively. Five variables were independently associated with occurrence of HCC: age > 50 years (hazard ratio HR, 1.94; 95% confidence interval CI, 1.16; 3.25; P = 0.012); past excessive alcohol intake (HR, 1.55; 95% CI, 1.02; 2.36; P = 0.041); low platelet count (<100 Giga/mm3: HR, 2.70; 95% CI, 1.62; 4.51; P < 0.001; 100; 150 Giga/mm3: HR, 1.87; 95% CI, 1.10; 3.18; P = 0.021); gamma‐glutamyl transpeptidase above the upper limit of normal (HR, 1.96; 95% CI, 1.11; 3.47; P = 0.021); and absence of a sustained virological response during follow‐up (HR, 3.02; 95% CI, 1.67; 5.48; P < 0.001). An 11‐point risk score was derived from the training cohort and validated in the validation set. Based on this score, the population was stratified into three groups, in which HCC development gradually increased, from 0% to 30.1% at 5 years for patients with the lowest (≤3) and highest (≥8) scores (P < 0.001). Using this score, a nomogram was built enabling individualized prediction of HCC occurrence at 1, 3, and 5 years. Conclusion: This HCC score can accurately predict HCC at an individual level in French patients with HCV cirrhosis. (Hepatology 2016;64:1136‐1147)
Two‐dimensional shear wave elastography (2D‐SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate‐sized clinical trials. We aimed at running a larger‐scale ...meta‐analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D‐SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D‐SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D‐SWE was 0.022‐0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003‐0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. Conclusion: 2D‐SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head‐to‐head comparison between 2D‐SWE and other imaging modalities to establish disease‐specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260‐272).
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.)
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/m2 , BMI >30 kg/m2 , metabolic syndrome, alcohol >14 drink/week and liver stiffness >6 kPa. 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.
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