Diagnostic performance of controlled attenuation parameter for predicting steatosis grade in chronic hepatitis B.

BACKGROUND & AIMS: A novel controlled attenuation parameter (CAP) using the signals acquired by the FibroScan® has been developed as a method for evaluating steatosis. The aim of this study is to assess the performance of the CAP for the detection and quantification of steatosis in patients with chronic hepatitis B (CHB). MATERIAL AND METHODS: 136 subjects with CHB underwent liver biopsy and FibroScan® within 60 days. CAP was evaluated retrospectively using raw FibroScan® data. Steatosis was graded as follows: S0 (steatosis < 10% of hepatocytes), S1 (10 to < 30%), S2 (30 to < 60%) or S3 (≥ 60%). Performance was evaluated by area under the receiver operating characteristic (AUROC) curve. RESULTS: Proportions of each steatosis grade (S0-S3) were 78, 10, 9 and 3%, respectively. Using univariate analysis, liver stiffness measurement (LMS) significantly correlated with fibrosis (τ = 0.43; P < 10-10), sex, necro-inflammatory activity, steatosis, age, NASH, and perisinusoidal fibrosis, and with liver fibrosis (P < 10-8) and perisinusoidal fibrosis (P = 0.008) using multivariate analysis. CAP correlated with steatosis (τ = 0.38, P < 10-7), body mass index, NASH, fibrosis and perisinusoidal fibrosis using univariate analysis, but only steatosis (P < 10-10) and perisinusoidal fibrosis (P = 0.002) using multivariate analysis. AUROCs for LSM were: 0.77 (0.69-0.85), 0.87 (0.80-0.95), and 0.93 (0.83-1.00), respectively, for fibrosis stages F ≥ 2, F ≥ 3 and F = 4. AUROCs for CAP were: 0.82 (0.73-0.92), 0.82 (0.69-0.95), and 0.97 (0.84-1.00) for ≥ S1, ≥ S2 and S3 steatosis, respectively. CONCLUSIONS: In conclusión CAP is a novel, accurate non-invasive tool and may be suitable for detecting and quantifying steatosis in CHB patients.

Non-invasive assessment of liver graft fibrosis by transient elastography after liver transplantation.

BACKGROUND: Liver stiffness measurement (LSM) by transient elastography (TE) (FibroScan) is a validated method of quantifying liver fibrosis in non-transplanted patients with hepatitis C virus (HCV). It could be useful in follow-up after liver transplantation (LT). The aim of this study was to assess the diagnostic accuracy of LSM in evaluating liver fibrosis after LT in patients with and without recurrent HCV. PATIENTS AND METHODS: Forty-three patients (mean age 57.6 ± 9.9 years), 28 (65.1%) HCV-positive patients and 15 (34.9%) HCV-negative patients underwent gold standard liver biopsy and TE 55.8 ± 4.9 months after transplantation. Liver fibrosis was scored on biopsy specimens according to METAVIR (F0-F4). Accuracy of TE and optimal stiffness cut-off values for fibrosis staging were determined by a receiver-operating characteristics (ROC) curve analysis. RESULTS: Median stiffness values were significantly different for METAVIR score less than 2 (5.8 kPa) vs. METAVIR score greater to equal to 2 (9.6 kPa) (P<0.001). The area under the ROC curve was 0.83 for METAVIR score greater to equal to 2 (95%CI: 0.71-0.95). The optimal stiffness cut-off value was 7 kPa for METAVIR scores greater to equal to 2. The results were similar whether the patients had recurrent HCV infection or not. CONCLUSIONS: These results indicate that transient elastography accurately identifies LT recipients with significant fibrosis, irrespective of HCV status. It is a promising non-invasive tool to assess graft fibrosis progression after LT in patients with HCV recurrence, as well as for screening of late graft fibrosis of other etiologies. Transient elastography could reduce the use of invasive protocol biopsies.

Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes.

There is a need for noninvasive methods to detect liver steatosis, which can be a factor of liver fibrosis progression. This work aims to evaluate a novel ultrasonic controlled attenuation parameter (CAP) devised to target, specifically, liver steatosis using a sophisticated process based on vibration control transient elastography (VCTE™). CAP was first validated as an estimate of ultrasonic attenuation at 3.5 MHz using Field II simulations and tissue-mimicking phantoms. Performance of the CAP was then appraised on 115 patients, taking the histological grade of steatosis as reference. CAP was significantly correlated to steatosis (Spearman ρ = 0.81, p < 10(-16)). Area under receiver operative characteristic (ROC) curve (AUC) was equal to 0.91 and 0.95 for the detection of more than 10% and 33% of steatosis, respectively. Furthermore, results show that CAP can efficiently separate several steatosis grades. These promising results suggest that CAP is a noninvasive, immediate, objective and efficient method to detect and quantify steatosis.

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

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Assessment of liver fibrosis using transient elastography in patients with alcoholic liver disease.

BACKGROUND/AIMS: The aim of this study was to assess the accuracy of liver stiffness measurement (LSM) for the diagnosis of extensive fibrosis and cirrhosis in patients with alcoholic liver disease (ALD). METHODS: One hundred and seventy-four patients with ALD were enrolled in four liver units and underwent concomitant liver biopsy and LSM. Fibrosis was assessed using the Brunt et al. and the Chevallier et al. scoring systems. Steatosis and histological alcoholic hepatitis (HAH) were quoted in classes. RESULTS: Twenty-seven patients had inadequate biopsy or LSM. Distribution in 147 patients according to the Brunt score (median LSM) was: F1: n=13 (5.7kPa); F2: n=24 (8.3kPa); F3: n=31 (17.5kPa) and F4: n=79 (40.9kPa) (P<0.0001). LSM was correlated with the amount of fibrosis according to the Chevallier score (r=0.70, P<0.0001). LSM was correlated to fibrosis stage (tau beta, 0.53; P<0.0001) and HAH (tau beta, 0.30; P<0.0001). In multivariate analysis, fibrosis was the only parameter correlated with LSM. The areas under the ROC curve were 0.94 and 0.87 for the diagnosis of extensive fibrosis (Brunt et al. score > or =3) and cirrhosis, respectively (threshold-values: 12.9 and 22.6kPa). CONCLUSIONS: LSM accurately assesses extensive fibrosis and cirrhosis in alcoholic patients.

Safety and efficacy of combination therapy with peginterferon alfa-2a (40kD) and ribavirin in the outpatient setting: prospective analysis of 197 patients with chronic hepatitis C viral infection.

OBJECTIVES: Combination therapy using peginterferon alfa-2a (40 kD) plus ribavirin achieves viral eradication in nearly 60% of patients with chronic hepatitis C viral infection. However, because of the numerous side effects, use of the combination regimen might be restricted for patients consulting private practitioners specialized in hepatogastroenterology. PATIENTS AND METHOD: Conducted in this specific context, this prospective clinical trial investigated the safety and efficacy of combination therapy in 197 patients. Therapy was given in compliance with the recommendations of the French consensus conference on hepatitis C treatment. RESULTS: Commonly reported adverse effects were noted in 90% of patients, most occurring during the first three months, with a stable prevalence thereafter and resolution after treatment end. The most frequent adverse events were asthenia (35 to 37.5% according to the treatment group pruritus (25 to 26.3%) and flu-like syndrome (19 to 21.7%). A depressive syndrome was reported in 20 to 21% of patients. Grade 4 neutropenia was exceptional and never led to severe infections. At intent-to-treat analysis, the rate of sustained virological response was 54.8% for the entire population. It was 71.1% for patients with genotypes 2 or 3 (mainly treated for 24 weeks) and 44.6% for patients with genotype 1 (all treated 48 weeks). CONCLUSION: The characteristic features of combination therapy observed in the context of private hepatogastroenterology consultations are similar to those observed in randomized clinical trials.

Features associated with success rate and performance of FibroScan measurements for the diagnosis of cirrhosis in HCV patients: a prospective study of 935 patients.

BACKGROUND/AIMS: FibroScan, a non-invasive procedure for the diagnosis of cirrhosis, benefits only patients for which at least 10 valid shots are acquired. We investigated features associated with success rate of shots, and performance of FibroScan for the diagnosis of cirrhosis. METHODS: Liver biopsy and stiffness measurement were performed in HCV patients. AUROCs and mixed logistic models evaluated the influence of patient and operator features on the success of shots and the performance for the diagnosis of cirrhosis. RESULTS: Nine hundred and thirty five (935) patients were included. Success rate of shots decreased with age, and was lower in obese than in other patients. After adjusting for age and obesity, an operator with at least 50 prior FibroScan exams had a higher success rate in shots. FibroScan performance for the diagnosis of cirrhosis was not influenced by the number of valid shots taken into account and by operator skills. CONCLUSIONS: After a rapid training, FibroScan provides a reasonable performance for the diagnosis of cirrhosis that is not influenced substantially by any other feature. More patients will benefit from this procedure with no significant loss in performance if only 5 valid shots are requested. These results should emphasize the use of FibroScan even in non-specialized units.

Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases.

A proper diagnosis of cirrhosis is essential for the management of patients with chronic liver diseases. We assessed the accuracy of liver stiffness measurement by Fibroscan for the diagnosis of cirrhosis in 1,257 patients with chronic liver diseases of various causes enrolled in a prospective multicenter study as well as clarified causes of discrepancies between liver histology and Fibroscan. One hundred thirty-two patients had unsuitable biopsy specimens, and 118 had unreliable liver stiffness measurements. Because 232 patients overlapped with a previous study, analysis was performed in the 775 new patients then derived in the whole population (1,007; 165 cirrhosis). Diagnostic accuracy was assessed by receiver operator curve (ROC) analysis. Liver samples were re-analyzed in case of discrepancies. The area under the ROC (AUROC) was 0.95 (95% CI, 0.93-0.96) for the diagnosis of cirrhosis in either 775 or 1,007 patients. The cutoff value with optimal diagnosis accuracy was 14.6 kPa in 1,007 patients (positive and negative predictive values, 74% and 96%) with discrepancies among the etiological groups. Eighty patients were misclassified: (1) among 45 patients without cirrhosis with liver stiffness 14.6 kPa or greater, 27 (60%) had extensive fibrosis and 10 (22%) significant perisinusoidal fibrosis; and (2) among 35 patients with cirrhosis and liver stiffness less than 14.6 kPa, 10 (29%) had a macronodular pattern and 25 (71%) either none or mild activity. In conclusion, Fibroscan is a reliable method for the diagnosis of cirrhosis in patients with chronic liver diseases, better at excluding than at predicting cirrhosis using a threshold of 14.6 kPa. False-negatives are mainly attributable to inactive or macronodular cirrhosis.

Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients.

BACKGROUND: Chronic hepatitis C in HIV-infected patients is an increasing cause of death dependent on the development of liver fibrosis, which is currently assessed by liver biopsy despite its limitations. Liver stiffness measurement, a new noninvasive method, allows the evaluation of liver fibrosis. The aim of this prospective study was to assess the accuracy of liver stiffness measurement for the detection of fibrosis and cirrhosis in HIV/hepatitis C virus (HCV)-coinfected patients and to compare its accuracy with other noninvasive methods. METHODS: We studied 72 consecutive HIV patients with chronic hepatitis C who had a simultaneous liver biopsy and liver stiffness measurement by transient elastography (FibroScan; Echosens, Paris, France) for the assessment of liver fibrosis. RESULTS: Liver stiffness values ranged from 3.0 to 46.4 kilopascal. Liver stiffness was significantly correlated to fibrosis stage (Kendall tau-b = 0.48; P < 0.0001). The area under the receiver operating characteristic (AUROC) curve of liver stiffness measurement was 0.72 for F > or = 2 and 0.97 for F = 4. For the diagnosis of cirrhosis, AUROC curves of liver stiffness measurement were significantly higher than those for platelet count (P = 0.02), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (P = 0.0001), Aspartate aminotransferase-to-Platelet Ratio Index (APRI) (P = 0.01), and FIB-4 (P = 0.004). CONCLUSION: Liver stiffness measurement is a promising noninvasive method for the assessment of fibrosis in HIV-infected patients with chronic HCV infection. Its use for the follow-up of these patients should be further evaluated.