To assess the clinical validity of controlled attenuation parameter (CAP) in the diagnosis of hepatic steatosis in a series of overweight or obese children by using the imperfect gold standard methodology. Consecutive children referred to our institution for auxological evaluation or obesity or minor elective surgery were prospectively enrolled. Anthropometric and biochemical parameters were recorded. Ultrasound (US) assessment of steatosis was carried out using ultrasound systems. CAP was obtained with the FibroScan 502 Touch device (Echosens, Paris, France). Pearson’s or Spearman’s rank correlation coefficient were used to test the association between two study variables. Optimal cutoff of CAP for detecting steatosis was 249 dB/m. The diagnostic performance of dichotomized CAP, US, body mass indexes (BMI), fatty liver index (FLI) and hepatic steatosis index (HSI) was analyzed using the imperfect gold standard methodology. Three hundred five pediatric patients were enrolled. The data of both US and CAP were available for 289 children. Steatosis was detected in 50/289 (17.3%) children by US and in 77/289 (26.6%) by CAP. A moderate to good correlation was detected between CAP and BMI (r = 0.53), FLI (r = 0.55) and HSI (r = 0.56). In obese children a moderate to good correlation between CAP and insulin levels (r = 0.54) and HOMA-IR (r = 0.54) was also found. Dichotomized CAP showed a performance of 0.70 (sensitivity, 0.72 [0.64–0.79]; specificity, 0.98 [0.97–0.98], which was better than that of US (performance, 0.37; sensitivity, 0.46 [0.42–0.50]; specificity, 0.91 [0.89–0.92]), BMI (performance, 0.22; sensitivity, 0.75 [0.73–0.77]; specificity, 0.57 [0.55–0.60]) and FLI or HSI. For the evaluation of liver steatosis in children CAP performs better than US, which is the most widely used imaging technique for screening patients with a suspicion of liver steatosis. A cutoff value of CAP of 249 dB/m rules in liver steatosis with a very high specificity.

The two available pegylated interferon formulations, peginterferon alpha-2a and peginterferon alpha-2b, have different pharmacokinetic profiles; as a result they may have differing abilities to suppress the hepatitis C virus. A recently reported study by Formann and colleagues assessing early viral kinetics among 20 patients receiving peginterferon alpha-2b either once or twice weekly suggests that once-weekly administration of peginterferon alpha-2b is not sufficient for continuous exposure to interferon over 160 h. Twice-weekly administration is recommended to avoid increases in viral load as interferon levels decline prior to the end of the one-week dosing period. The objective of this study was to compare viral dynamics and pharmacokinetics between peginterferon alpha-2a and peginterferon alpha-2b in interferon-naive chronic hepatitis C patients. Patients were randomized to receive peginterferon alpha-2a 180 μg ( n=10) or peginterferon alpha-2b 1.0 μg/kg ( n=12) once weekly. Serum peginterferon concentrations were measured at baseline, 24, 48, 120 and 168 h. Hepatitis C virus (HCV) RNA was measured at baseline, 24, 48, 120 and 168 h during week 1 and then at 4 and 12 weeks. Peginterferon alpha-2b achieved maximal serum levels at 24 h, and then decreased rapidly. Of the 12 patients who received peginterferon alpha-2b, no drug was detectable in seven (58%) patients at 120 h and in 11 (92%) at 168 h. In contrast, peginterferon alpha-2a concentrations increased continuously over time, reaching maximal serum levels from 48 to 168 h. Drug was detectable in all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed in mean HCV RNA between the groups. However, at week 12, mean HCV RNA was significantly lower in the peginterferon alpha-2a group versus the peginterferon alpha-2b group (2.8126 vs 3.8726; P<0.01). The differences in mean HCV RNA values at 12 weeks may be related to the different absorption and distribution profiles of the two drugs. In conclusion, once-weekly administration of peginterferon alpha-2b (1.0 μg/kg/wk) may be insufficient for continuous interferon exposure; twice-weekly administration may help avoid increases in viral replication as interferon levels decline. Larger-scale studies assessing both viral kinetics and sustained virological responses are needed to confirm these observations.

OBJECTIVE. The purpose of this article is to evaluate the diagnostic performance of transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index in assessing fibrosis in patients with chronic hepatitis C by using histologic Metavir scores as reference standard. SUBJECTS AND METHODS. Consecutive patients with chronic hepatitis C scheduled for liver biopsy were enrolled. Liver biopsy was performed on the same day as transient elastography and real-time strain elastography. Transient elastography and real-time strain elastography were performed in the same patient encounter by a single investigator using a medical device based on elastometry and an ultrasound machine, respectively. Diagnostic performance was assessed by using receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) analysis. RESULTS. One hundred thirty patients (91 men and 39 women) were analyzed. The cutoff values for transient elastography, real-time strain el...

Background & Aims: Noninvasive assessment of liver stiffness has been increasingly used to evaluate fibrosis instead of liver biopsy, especially in patients with chronic viral hepatitis. The aim of this study was to assess the performance in staging liver fibrosis of the updated ElastPQ® technique (EPIQ7 ultrasound system, Philips Healthcare, Bothell, WA, USA) in the “real life” setting by using the FibroScan as the reference standard and to understand whether the use of the quality criteria improves the performance of the technique. Methods: This was a cross-sectional study: 278 patients affected by chronic hepatitis C referred for liver stiffness measurement with the FibroScan® 502 Touch device (Echosens, Paris, France) underwent measurements also with the ElastPQ® technique. For the assessment of significant fibrosis (F≥2), advanced fibrosis (F≥3) and cirrhosis (F=4), respectively, we used the cutoffs of 7.0, 9.5 and 12.0 kPa. The diagnostic performance of ElastPQ® was assessed using the area under the ROC (AUROC) curve analysis and was evaluated overall and for cases with (a) 10 measurements and IQR/M≤30%, (b) 5 measurements and IQR/M ≤30%, (c) 10 measurements and IQR/M>30%, (d) 5 measurements and IQR/M>30%. Results: The optimal cutoffs of ElastPQ® for significant fibrosis, advanced fibrosis and cirrhosis were 6.43, 9.54 and 11.34 kPa, respectively. For measurements with an IQR/M≤30%, there was no statistically significant decrease in sensitivity between 10 and 5 measurements (p=0.26, p=0.09, p=0.71, for F≥2, F≥3, and F=4, respectively). Conclusion: The ElastPQ® technique is reliable and accurate for staging liver fibrosis. The number of measurements does not affect the performance. Abbreviations: ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; AUROC: area under the ROC curve; BMI: body mass index; GGT: gamma-glutamyl transferase; LR: likelihood ratio; LSM: liver stiffness measurement; pSWE: point shear wave elastography; ROC: receiver operating characteristic; VCTE: vibration controlled transient elastography; VTQ®: virtual touch quantification.

Background Peginterferon alfa‐2a and alfa‐2b, the two commercially available pegylated interferons, have different pharmacokinetic properties that produce differing abilities to suppress replication of the hepatitis C virus. Aim To compare the pharmacodynamics of peginterferon alfa‐2a and peginterferon alfa‐2b in interferon‐naive patients with chronic hepatitis C. Methods Patients were randomized to receive peginterferon alfa‐2a, 180 μg (n = 10) or peginterferon alfa‐2b 1.0 μg/kg (n = 12) once weekly. The enzymatic activity of 2′5′‐oligoadenylate synthetase and levels of neopterin and β₂‐microglobulin were measured at baseline and at 24, 48, 120 and 168 h. Results Oligoadenylate synthetase activity and serum neopterin and β₂‐microglobulin concentrations did not differ significantly between the two patient groups at any time point, nor was there a significant correlation between the serum area under the concentration‐time curve of either peginterferon and the area under the concentration‐time curve for 2′,5′‐oligoadenylate synthetase, neopterin and β₂‐microglobulin. The area under the concentration‐time curves calculated for these three markers did not correlate with body mass index stratified at <25 and ≥25 kg/m² for either peginterferon. Conclusions Despite pharmacokinetic differences between peginterferon alfa‐2a and peginterferon alfa‐2b, the pharmacodynamic profiles of the two formulations appear to be comparable.