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Since nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in the Western world, clinicians need reliable noninvasive tools for the identification of NAFLD-associated fibrosis. Limited evidence on the performance of the novel shear wave elastography technique Elast-PQ (EPQ) in NAFLD is available.In this prospective, European multinational study we assessed the diagnostic accuracy of EPQ using vibration-controlled transient elastography (VCTE) as a reference standard.Among 353 NAFLD patients, 332 (94.1%) fulfilled reliability criteria of VCTE and EPQ (defined by IQR/median ≤0.3; 41.3% female, mean age: 59 [IQR: 16.5], mean BMI: 29.0 (7.1)). 4/353 (1.1%) and 17/353 (4.8%) had unreliable VCTE and EPQ measurements, respectively. VCTE-based NAFLD fibrosis stages were F0/F1: 222(66.9%), F2: 41 (12.3%), F3: 30 (9.1%), F4: 39 (11.7%). We found a strong correlation (Pearson R=0.87; p0.0001) and concordance (Lin's concordance correlation coefficient =0.792) of EPQ with VCTE. EPQ was able to identify NAFLD-fibrosis risk with the following EPQ cutoffs: ≥6.5 kPa for significant fibrosis (≥F2) (≥1.47 m/s; sensitivity: 78%; specificity: 95%; AUROC: 0.94), ≥6.9 kPa for advanced fibrosis (≥F3) (≥1.52 m/s; sens.: 88%, spec.: 89%; AUROC: 0.949), and ≥10.4 kPa for cirrhosis (F4) (≥1.86 m/s; sens.: 87%; spec.: 94%; AUROC: 0.949).The point shear wave elastography technique EPQ shows excellent correlation to and concordance with VCTE. EPQ can reliably exclude NAFLD fibrosis6.0 kPa (1.41 m/s) and indicate a high risk of advanced fibrosis ≥10.4 kPa (≥1.86 m/s).Die nichtalkoholische Fettleber (NAFLD) ist mittlerweile die häufigste Lebererkrankung in der westlichen Welt. Daher besteht ein Bedarf an nichtinvasiven Methoden zur Einschätzung des Fibrose-Risikos bei NAFLD. Über die Aussagekraft der neue Scherwellen-Technologie Elast-PQ (EPQ) liegen nur wenige Daten vor.Diese prospektive, europäische multinationale Studie untersuchte die diagnostische Genauigkeit von EPQ bei NAFLD-PatientInnen im Vergleich zur Vibrations-kontrollierten transienten Elastografie (VCTE).Von 353 NAFLD-Patient*innen erfüllten 332 (94,1%) die Zuverlässigkeitskriterien für VCTE und EPQ (definiert als IQR/median ≤0,3). Die Studienpopulation war zu 41,3% weiblich, mit einem medianen Alter von 59 [IQR: 16,5] Jahren und einem medianen BMI von 29 [IQR: 7] kg/mDie Punkt-Scherwellen-Elastografie-Methode EPQ zeigt eine exzellente Korrektion und Konkordanz mit der VCTE. Bei NAFLD-Patient*innen wird durch EPQ6,0 kPa (1,41 m/s) eine signifikante Fibrose ausgeschlossen und durch EPQ ≥10,4 kPa (≥1,86 m/s) ein hohes Risiko für eine fortgeschrittene Fibrose angezeigt.

Introduction There is an ongoing debate as to the role of acute SARS-CoV-2 infection on asthma exacerbation, and its long-term impact on the lung function of individuals with asthma. In contrast, the potential impact of COVID -19 vaccination on asthma is entirely unexplored. Case Study We are shedding light on this critical topic by examining a challenging case of severe asthma exacerbation that a 28-year-old female patient developed after receiving two doses of mRNA-based vaccine BNT162b2 (Pfizer-BioNTech) at our Hospital, IRCCS Policlinico San Matteo of Pavia, in Northern Italy. The patient is a fourth year resident at the hospital, and like all health care workers at the facility, has been vaccinated since early 2021. She was an occasional smoker with a 10-year history of asthma and seasonal allergic rhinitis. She also tested negative for SARS-CoV-2 on several negative molecular swabs and serology tests. Results After receiving the second vaccine dose, she started experiencing a worsening of respiratory symptoms. Following several episodes, and a severe asthma attack, the patient required treatment with mepolizumab, a biologic drug [interleukin-5 (IL-5)] antagonist monoclonal antibody. Conclusion This single case study is insufficient to draw conclusions about the association between asthma exacerbation and the COVID-19 vaccine. While the cause-effect link between vaccination against SARS-CoV-2 and worsening of asthmatic disease might only be suggested, we consider the present case as a valuable prompt for further investigations. This is particularly true from the perspective of mass vaccination of adolescents and children currently underway across the globe.

Objectives The main aim was to assess the performance and cutoff value for the detection of liver steatosis (grade S > 0) with the Attenuation Imaging–Penetration (ATI‐Pen) algorithm available on the Aplio i‐series ultrasound systems (Canon Medical Systems, Otawara, Japan). The magnetic resonance imaging–derived proton density fat fraction (MRI‐PDFF) was used as the reference standard. Secondary aims were to compare the results to those obtained with the previous ATI algorithm (Attenuation Imaging–General [ATI‐Gen]) and with the controlled attenuation parameter (CAP) and to generate a regression equation between ATI‐Pen and ATI‐Gen values. Methods Consecutive adult patients potentially at risk of liver steatosis were prospectively enrolled. Each patient underwent ultrasound quantification of liver steatosis with ATI‐Pen and ATI‐Gen and a CAP assessment with the FibroScan system (Echosens, Paris, France). The MRI‐PDFF evaluation was performed within a week. The correlations between ATI‐Pen, ATI‐Gen, the CAP, and the MRI‐PDFF were analyzed with the Pearson rank correlation coefficient. The diagnostic performance of ATI‐Pen, ATI‐Gen, and the CAP was assessed with receiver operating characteristic curves and an area under the receiver operating characteristic curve (AUROC) analysis. Results Seventy‐two individuals (31 male and 41 female) were enrolled. Correlation coefficients of ATI‐Pen, ATI‐Gen, and the CAP with the MRI‐PDFF were 0.78, 0.83, and 0.58, respectively. The AUROCs of ATI‐Pen, ATI‐Gen, and the CAP for detecting steatosis (S > 0) were 0.90 (95% confidence interval, 0.81–0.96), 0.92 (0.82–0.98), and 0.85 (0.74–0.92), and the cutoffs were greater than 0.69 dB/cm/MHz, greater than 0.62 dB/cm/MHz, and greater than 273 dB/m. The regression equation between ATI‐Pen and ATI‐Gen was ATI‐Pen = 0.88 ATI‐Gen + 0.13. Conclusions Attenuation Imaging is a reliable tool for detecting liver steatosis, showing an excellent correlation with the MRI‐PDFF and high performance with AUROCs of 0.90 or higher., Access the CME test here and search by article title.

Objectives An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. MethodsAll consecutive hospitalised patients from February 21stto March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge.Results 426 adult patients (median age 68 (IQR, 56 to 77 years) were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4thwere independent risk factors associated with in-hospital mortality.Conclusions Olderage, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19

An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge. 426 adult patients [median age 68 (IQR 56 to 77 years)] were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Among these 46 patients, updated as of 30 May, 2020, 5 (10.9%) had died, 8 (17.4%) were still in ICU, 12 (26.1%) were transferred to lower intensity care units and 21 (45.7%) were discharged. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4th were independent risk factors associated with in-hospital mortality. Older age, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19.

To assess performance and cutoffs of the 2-dimensional shear wave elastography technique available on the Aplio i800 ultrasound system (Canon Medical Systems, Japan), using transient elastography as reference standard, and to assess the correlation of shear-wave-speed dispersion with liver fibrosis or steatosis.This was a single-center cross-sectional study. The correlations between values obtained with transient elastography and 2-dimensional-shear wave elastography, and between shear-wave-speed dispersion and fibrosis or steatosis, were assessed with Pearson's r. The diagnostic performance of the 2-dimensional-shear wave elastography for staging significant fibrosis and severe fibrosis compared to transient elastography was assessed using the area under the receiver operating characteristic curve analysis.Three hundred sixty-seven patients (198 males and 169 females) were studied. There was a high correlation between 2-dimensional-shear wave elastography and transient elastography (r = 0.87, P0.0001). The area under the receiver operating characteristics of 2-dimensional-shear wave elastography for staging significant fibrosis (F2) and severe fibrosis (F3-F4), respectively, were 0.97 (95% confidence interval, 0.91-0.98) and 0.97 (95% confidence interval, 0.95-0.99). The best cutoffs for significant fibrosis and severe fibrosis, respectively, were7 and9 kPa. Shear-wave-speed dispersion showed a high correlation with fibrosis (r = 0.85, P0.0001), whereas there was a very weak correlation with steatosis.The results of this study show that this 2-dimensional-shear wave elastography technique is accurate for staging liver fibrosis. Shear-wave-speed dispersion is highly correlated with liver fibrosis but not with steatosis.

Direct acting antiviral agents (DAAs) have revolutionized the landscape of chronic hepatitis C (CHC) enabling treatment of all those infected. It remains to be determined how the characteristics of those receiving treatment are changing.We retrospectively analysed all the patients with CHC who received treatment with DAAs in a large referral centre since 01/01/2015. We stratified their demographic, clinical and virological characteristics at baseline and the sustained virological response (SVR) rates according to the year of treatment.In the study were included 2565 patients. During the study period, the yearly proportion of men and cirrhotic patients decreased (p0.001) whereas mean age increased from 59.8 to 62.2 years old (p=0.04). An increasing trend was observed in the foreign-born patients from 4.3% to 7.9%, without reaching statistical significance. The prevalence of comorbidities had also increased during the study period (p0.001). Instead, the yearly number of experienced patients decreased significantly (p0.001) as well as the mean MELD score of cirrhotic patients from 9 to 7.6 (p0.001). SVR rates increased significantly, from 93.4% in 2015 to 97.1% in 2018 (P0.05).The population of patients with CHC receiving DAAs is becoming older and with more comorbidities. Nevertheless, this did not impact SVR rates.

BACKGROUND: Assessment of liver stiffness provides important diagnostic and prognostic information in patients with chronic liver disease. AIMS: To investigate whether the use of quality criteria (i) improves the concordance between transient elastography (TE) and a novel point shear wave elastography technique (ElastPQ®) and (ii) impacts on the performance of ElastPQ® for liver fibrosis staging using TE as the reference standard. METHODS: In this multicenter retrospective study, data of patients undergoing liver stiffness measurements (LSM) in five European centers were collected. TE was performed with FibroScan® (Echosens, France) and ElastPQ® with EPIQ® or Affiniti® systems (Philips, The Netherlands). The agreement between TE and ElastPQ® LSMs was assessed with Lin's concordance correlation coefficient (CCC). Diagnostic performance of ElastPQ® was assessed by the area under receiver operating characteristic (AUROC) curves. RESULTS: Overall, 664 patients were included: mean age: 54.8(13.5) years, main etiologies: viral hepatitis (83.1%) and NAFLD (7.5%). CCC increased significantly when LSMs with ElastPQ® were obtained with IQR/M ≤ 30% (p

OBJECTIVES: The primary aim of this study was to investigate the value of attenuation imaging (ATI), a novel ultrasound technique for detection of steatosis, by comparing the results to that obtained with controlled attenuation parameter (CAP) and by using MRI-derived proton density fat fraction (PDFF) as reference standard. METHODS: From March to November 2018, 114 consecutive adult subjects potentially at risk of steatosis and 15 healthy controls were enrolled. Each subject underwent ATI and CAP assessment on the same day. MRI-PDFF was performed within a week. RESULTS: The prevalence of steatosis, as defined by MRI-PDFF ≥ 5%, was 70.7%. There was a high correlation of ATI with MRI-PDFF (r = 0.81, P < 0.0001). The correlation of CAP with MRI-PDFF and with ATI, respectively, was moderate (r = 0.65, P < 0.0001 and r = 0.61, P < 0.0001). The correlation of ATI or CAP with PDFF was not affected by age, gender, or body mass index. Area under the receiver operating characteristics of ATI and CAP, respectively, were 0.91 (0.84–0.95; P < 0.0001) and 0.85 (0.77–0.91; P < 0.0001) for detecting S > 0 steatosis (MRI-PDFF ≥ 5%); 0.95 (0.89–0.98; P < 0.0001) and 0.88 (0.81–0.93; P < 0.0001) for detecting S > 1 steatosis (MRI-PDFF ≥ 16.3%). The cutoffs of ATI and CAP, respectively, were 0.63 dB/cm/MHz and 258 dB/m for detecting S > 0 liver steatosis; 0.72 dB/cm/MHz and 304 dB/m for detecting S > 1 steatosis. ATI performed better than CAP, and this improvement was statistically significant for S > 1 (P = 0.04). DISCUSSION: This study shows that, in patients with no fibrosis/mild fibrosis, ATI is a very promising tool for the noninvasive assessment of steatosis.

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 & aims Ultrasound is the imaging modality most widely utilized in the general population for diagnostic purposes. Controlled attenuation parameter is a novel noninvasive method for assessing steatosis. Our aim was to investigate whether the clinical value of controlled attenuation parameter in patients referred for abdominal ultrasound examinations is affected by liver fibrosis. Methods Consecutive patients referred for abdominal ultrasound examinations were enrolled. Controlled attenuation parameter and liver stiffness were assessed with the FibroScan (Echosens, France). Liver fibrosis was staged according to published cutoffs of liver stiffness measurements. Pearson's or Spearman's rank correlation coefficient was used to test the association between two study variables. Optimal cutoff of controlled attenuation parameter for diagnosing liver steatosis (S≥2) was 256 dB/m. The diagnostic performance and accuracy of dichotomized controlled attenuation parameter, ultrasound and body mass index were analysed using the imperfect gold standard methodology. Results A total of 726 subjects (464 males and 262 females) were studied. Five hundred and eight-nine (81.1%) patients were affected by chronic viral hepatitis. Correlation of controlled attenuation parameter with ultrasound score was 0.48 and 0.57 in patients with and without chronic viral hepatitis respectively. In patients with chronic viral hepatitis, ultrasound, dichotomized controlled attenuation parameter and body mass index showed performance of 58.2%, 82.3% and 46.7%, respectively, whereas in patients without chronic viral hepatitis, the performance was 86.4%, 68.6% and 48.6% respectively. Conclusions In patients with chronic viral hepatitis and advanced liver fibrosis, controlled attenuation parameter performs better than ultrasound for assessing liver steatosis, whereas in patients without viral hepatitis and with nonsignificant liver disease ultrasound shows the best performance.

The primary aim of this study was to determine the inter-system variability of liver stiffness measurements (LSMs) in patients with varying degrees of liver stiffness. The secondary aim was to determine the inter-observer variability of measurements. 21 individuals affected by chronic hepatitis C and 5 healthy individuals were prospectively enrolled. The assessment of LSMs was performed using six ultrasound (US) systems, four of which with point shear wave elastography (p-SWE) and two with 2 D shear wave elastography (2D-SWE) systems. The Fibroscan (Echosens, France) was used as the reference standard. Four observers performed the measurements in pairs (A-B, C-D). The agreement between different observers or methods was calculated using Lin's concordance correlation coefficient. The Bland-Altman limits of agreement (LOA) were calculated as well. There was agreement above 0.80 for all pairs of systems. The mean difference between the values of the systems with 2D-SWE technique was 1.54 kPa, whereas the maximum mean difference between the values of three out of four systems with the pSWE technique was 0.79 kPa. The intra-patient concordance for all systems was 0.89 (95 % CI: 0.83 - 0.94). Inter-observer agreement was 0.96 (95 % CI: 0.94 - 0.98) for the pair of observers A-B and 0.93 (95 % CI: 0.89 - 0.96) for the pair of observers C-D. The results of this study show that the agreement between LSMs performed with different US systems is good to excellent and the overall inter-observer agreement in "ideal conditions" is above 0.90 in expert hands.ZIEL: Das Primärziel dieser Studie war es, die Intersystem-Variabilität von Lebersteifigkeitsmessungen (LSM) bei Patienten mit unterschiedlichen Lebersteifigkeiten zu bestimmen. Das Sekundärziel bestand in der Bestimmung der Inter-Beobachter-Variabilität der Messungen. Einundzwanzig Personen mit chronischer Hepatitis C und fünf gesunde Personen wurden prospektiv aufgenommen. Die Bewertung der LSM erfolgte mit sechs Ultraschallsystemen (US), vier davon verwendeten Punkt-Scherwellen-Elastografie (p-SWE) und zwei 2D-Scherwellen-Elastografie (2D-SWE). Der Fibroscan (Echosens, Frankreich) wurde als Referenzstandard verwendet. Vier Beobachter führten jeweils in Paaren die Messungen durch (A-B, C-D). Die Übereinstimmung zwischen verschiedenen Beobachtern oder Methoden wurde unter Verwendung des Konkordanz-Korrelationskoeffizienten nach Lin berechnet. Die Bland-Altman Übereinstimmungsgrenzen (LOA) wurden ebenfalls bestimmt. Die Übereinstimmung betrug mehr als 0,80 für alle Systempaare. Der mittlere Unterschied zwischen den Werten der Systeme mit 2D-SWE-Technik betrug 1,54 kPa, während der maximale mittlere Unterschied zwischen den Werten von drei der vier Systeme mit pSWE-Technik 0,79 kPa betrug. Die Intra-Patienten-Konkordanz für alle Systeme war 0,89 (95 % CI: 0,83 – 0,94). Die Interobserver-Übereinstimmung betrug 0,96 (95 % CI: 0,94 – 0,98) für das Paar der Beobachter A-B und 0,93 (95 % CI: 0,89 – 0,96) für das Paar der Beobachter C-D. Die Ergebnisse dieser Studie zeigen, dass die Übereinstimmung zwischen LSMs, die mit unterschiedlichen US-Systemen durchgeführt wurden, gut bis hervorragend ist und die globale Übereinstimmung zwischen den Beobachtern, sofern diese Expertise besitzen, unter „idealen Bedingungen“ über 0,90 liegt.

Aims: To prospectively assess the cutoff values of a point shear wave measurement (SWM) method for ruling-in and ruling-out significant fibrosis and cirrhosis using transient elastography (TE) as the reference standard.Method: Consecutive patients with chronic hepatitis C were enrolled. Liver stiffness was assessed with the SWM method implemented on the HI VISION Ascendus ultrasound system (Hitachi Ltd, Japan) and with the TE method of the FibroScan® device (Echosens, France). For staging significant fibrosis (F≥2) and cirrhosis (F=4) we used the TE cutoffs of 7.0 and 12.0 kiloPascal (kPa), respectively. The diagnostic performance of SWM was assessed by calculating the area under the receiver operating characteristic (AUROC) curve. Cutoffs with specificity or sensitivity > 90% were chosen to rule-in or rule-out F≥2 and F=4.Results: 445 individuals [235 males, 210 females; mean age, 61.1 (13.3) years] were studied: 190 (42.7%) individuals had F0-F1 fibrosis stage, 82 (18.4%) F2, 46 (10.3%) F3, and 127 (28.6%) F4 fibrosis stage. For ruling-in F≥2 the SWM cutoff was 6.78 kPa [sensitivity, 76.9%(70.6-82.4); specificity, 90.3% (85.0-94.3)] and for ruling-out it was 5.55 kPa [sensitivity, 90.6% (85.8-94.1); specificity, 72.2% (64.9-78.6)]. For ruling-in F=4 the SWM cutoff was 9.15 kPa [sensitivity, 83.3% (74.4-90.2); specificity, 90.1% (86.0-93.2)] and for ruling-out it was 8.41 kPa [sensitivity, 90.6% (82.9-95.6); specificity, 82.2% (77.3-86.4)]. AUROCs were 0.92 (0.89-0.94) for F≥2 and 0.94 (0.91-0.96) for F=4.Conclusions. In clinical practice, the use of a dual cutoff of SWM may increase the confidence in staging liver fibrosis with a non-invasive shear wave elastography technique.Abbreviations: ARFI: acoustic radiation force impulse; AUROC: area under the ROC curve; CCC: concordance correlation coefficient; IQR/M: interquartile range/median; LSM: liver stiffness measurement; ROC: receiver operating characteristic; pSWE: point shear wave elastography; SWM: shear wave measurement; TE: transient elastography; US: ultrasound.

Background 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. Methods 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. Results 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. Conclusions 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 pharmacokinetics and in dosing regimens of the currently available pegylated interferon (peginterferon) alfa molecules differ greatly, depending on the size and nature of their polyethylene glycol (PEG) moiety. Peginterferon alfa-2a has a branched 40 kDa PEG chain covalently attached to lysine residues and circulates as an intact molecule. On the other hand, peginterferon alfa-2b has a linear 12 kDa PEG chain covalently attached to interferon-a-2b via an unstable urethane bond that is hydrolysed after injection, releasing native interferon alfa-2b. The difference in pegylation between the two peginterferons has a significant impact on their pharmacokinetic properties. Data from comparative and non-comparative studies indicate that peginterferon alfa-2b has a shorter half-life in serum than peginterferon alfa-2a, and a significant proportion of patients receiving peginterferon alfa-2b may have trough concentrations below the limit of detection during the latter part of the 7-day dosing schedule. However, the pharmacodynamic parameters of the two drugs appear to be similar.

Agents that specifically target the replication cycle of the virus direct-acting antiviral agents (DAAs) by directly inhibiting the NS3/4A serine protease, the NS5B polymerase and NS5A are currently in clinical development. The need to achieve serum drug concentrations able to suppress viral replication is a key factor for a successful antiviral therapy and the prevention of resistance. Thus pharmacokinetics parameters became important issues for drugs used in the therapy of hepatitis C. The ratio of C(min)/IC(50) (inhibitory quotient or IQ) can provide a surrogate measure of a drug's ability to suppress HCV replication, by taking into account the relationship between plasma drug levels and viral susceptibility to the drug. Ritonavir boosting may be a useful strategy to improve pharmacokinetic parameters. Characterising resistance to DAAs in clinical trials is essential for the management of a drug regimen to reduce the development of resistance and thereby maximise SVR rate. The lesson of HIV therapy, provide a compelling case for the exploration of combinations of direct-acting antiviral agents.

Introduction: The objective of this study was to evaluate the cost-effectiveness of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin in the treatment of chronic hepatitis C in HIV-HCV co-infection. Methods: We used a pre-existent Markov model of disease progression in which two cohorts of patients received peginterferon α-2a plus ribavirin or peginterferon α-2b plus ribavirin for 48 weeks and were followed for their expected lifetimes. The reference patient was a 40-year-old man or woman. The sustained virological response (SVR) with peginterferon α-2a plus ribavirin and peginterferon α-2b plus ribavirin, were taken from two different publications. Utilities and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs in 2005 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was conducted from the perspective of the Italian National Health Service. Results: For the two cohorts, expected life-years with peginterferon α-2a plus ribavirin versus peginterferon α-2a plus ribavirin were respectively 24.47 and 23.71 years. Quality-adjusted life years for peginterferon α-2a plus ribavirin were 12.93, and 12.49 for peginterferon α-2b plus ribavirin. The expected cost was € 19,858 with peginterferon α-2a plus ribavirin and €19,983 with peginterferon α-2b plus ribavirin. Conclusion: This economic evaluation suggests that peginterferon α-2a plus ribavirin is a dominant strategy versus peginterferon α-2b plus ribavirin for treatment of adults with HIV-HCV co-infection, under some assumptions regarding treatment effectiveness and model structure.

BACKGROUND The natural history of initially compensated cirrhosis in patients with HIV and concurrent hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection is poorly defined. This study was designed to investigate the incidence and type of liver-related complications and mortality in coinfected cirrhotic patients. METHODS We retrospectively identified a cohort of patients coinfected with HIV and HCV or HBV and initially compensated viral cirrhosis. Time to decompensation and mortality from liver-related causes were recorded. RESULTS Between 1999 and 2004, 392 HIV-infected patients underwent a follow-up of > or =6 months. Sixty-nine patients (17.6%) with initially compensated cirrhosis were identified (7 HBV positive, 59 HCV positive, and 3 positive for both HBV and HCV). The most frequent complication was ascites. The mortality was 71.3 per 1000 person-years (95% confidence interval [CI], 47 to 108) in HIV-infected patients with HBV and/or HCV compensated cirrhosis, 8 (95% CI, 4 to 16) in HIV/HCV-coinfected patients without cirrhosis, and 6.5 (95% CI, 2.7 to 15.5) in HIV-monoinfected patients. After the first event of decompensation, the survival rate was 48% at 1 year and 18.1% at 3 years. Treatment with HAART after the first event of decompensation was associated with an increased survival rate (61.1% and 26.2% at 1 and 3 years, respectively, vs. 26.7% and 0%; P < 0.0001). CONCLUSIONS These results indicate significant morbidity and mortality during the 6 years after the diagnosis of compensated cirrhosis due to HBV and/or HCV in HIV-infected patients, identifying ascites as the most frequent complication.

Summary 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

Highly active antiretroviral therapy including protease inhibitors has led to dramatic decrease in the morbidity and mortality resulting from infection with human immunodeficiency virus-1. However, this combination regimen can be associated with the occurrence of serious toxicities, which may reduce patient compliance. In particular, human immunodeficiency virus-1 protease inhibitors and nevirapine among nonnucleoside reverse transcriptase inhibitors, have the potential for producing hepatotoxicity. We summarise current knowledge of the hepatotoxic effects associated with the commercially available human immunodeficiency virus-1 protease inhibitors based on a literature review of the major retrospective and prospective clinical studies designed to elucidate risk factors for developing hepatotoxicity among human immunodeficiency virus-1-infected patients receiving antiretroviral therapy containing protease inhibitors. Coinfection with chronic hepatitis, a common occurrence in human immunodeficiency virus-1-infected patients, is identified as an independent risk factor for developing hepatotoxicity in antiretroviral-treated human immunodeficiency virus-1-infected patients treated with antiretroviral regimens containing protease inhibitors. The importance of other risk factors for developing protease inhibitor-associated hepatotoxicity and the mechanism underlying the drug-related hepatotoxicity are discussed. The data indicate that the potential for producing hepatotoxicity is variable among the protease inhibitors and suggest that based on differences in drug-related hepatotoxicity, certain protease inhibitors may be preferred for the treatment of human immunodeficiency virus–hepatitis C virus coinfected patients.

Patients with AIDS present a wide variety of clinical manifestations through involvement of various organs. Ultrasonography (US) is easy to perform, safe, inexpensive, not invasive and repeatable. Those features are crucial for AIDS patients, who in industrialised countries are now mostly seen on an outpatient basis thanks to the introduction of Highly Active Antiretroviral Therapy. US can investigate most of the organs affected in AIDS and can guide biopsies, allowing the cyto-histological and microbiological investigations needed for a definitive diagnosis. This paper reviews the wide variety of applications of abdominal US and stresses its importance in the management of a complex and changing condition, particularly in settings where other more expensive imaging techniques are not--and will not be for a long time--available. The increasing use of portable/hand-carried scanners further adds to the value of the technique in such settings. With new treatments, prevalence and morbidity/mortality rates change, but new conditions and new side effects appear. US applications to these new conditions are discussed as well.

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.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.One hundred thirty patients (91 men and 39 women) were analyzed. The cutoff values for transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index were 6.9 kPa, 1.82, and 0.37, respectively, for fibrosis score of 2 or higher; 7.3 kPa, 1.86, and 0.70, respectively, for fibrosis score of 3 or higher; and 9.3 kPa, 2.33, and 0.70, respectively, for fibrosis score of 4. AUC values of transient elastography, real-time strain elastography, aspartate-to-platelet ratio index were 0.88, 0.74, and 0.86, respectively, for fibrosis score of 2 or higher; 0.95, 0.80, and 0.89, respectively, for fibrosis score of 3 or higher; and 0.97, 0.80, and 0.84, respectively, for fibrosis score of 4. A combination of the three methods, when two of three were in agreement, showed AUC curves of 0.93, 0.95, and 0.95 for fibrosis scores of 2 or higher, 3 or higher, and 4, respectively.Transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index values were correlated with histologic stages of fibrosis. Transient elastography offered excellent diagnostic performance in assessing severe fibrosis and cirrhosis. Real-time elastography does not yet have the potential to substitute for transient elastography in the assessment of liver fibrosis.

Assessment of liver fibrosis is crucial in HIV/HCV coinfected patients, in whom metabolic disturbances are frequent. Aims of this study were to analyse the association of two non-invasive liver fibrosis evaluation methods, liver stiffness measurement and FIB4, and their correlation with metabolic parameters.This was a single centre cross-sectional study. All patients underwent biochemical and virological assessment, FIB4 score, HOMA and transient elastography.Seventy-five patients were evaluated. Liver stiffness values positively correlated with FIB4 (R = 0.62; p0.0001). By ROC curve analysis the optimal cut-off for liver stiffness to identify high FIB4 was calculated as 10.1 kPa. The area under the ROC curve was 0.78 (95% CI 0.78-0.94, sensitivity 83.3%, specificity 80.7%). Liver stiffness values positively correlated with HOMA score (R = 0.31; p = 0.006).The combination of two non invasive tools provide a useful system for the assessment of fibrosis evolution in patients with HIV-HCV coinfection.

The coinfection of HIV and HCV has become a pathology with several distinctive characteristics. Pathogenesis of liver damage in patients with HIV and HCV coinfection is complex and multifactorial. It derives from a balance of factors which interact among themselves in a dynamic way. The reasons for the accelerated course of HIV/HCV coinfection are mainly related to two principal causes: the persistence of HCV, which depends upon alterations of cell-mediated immunity, and the activation of the immune system towards secretion of proinflammatory and profibrotic cytokines. This review will first focus on the characteristics of both these immune-mediated mechanisms, and then their implication on fibrogenesis as well as on other pathogenetic mechanisms, such as interactions between viruses and the deficit of protective mechanisms. A better knowledge of adaptive immune mechanisms, cytokine alteration, interference with host defense mechanisms, and the "cross-talk" among the viruses will improve the understanding of the pathogenetic mechanism and provide the opportunity to cure this disease.

One reason for dosing a drug by body weight is to reduce interpatient variability in clinical response. This study evaluated the relationship between body weight and drug exposure for peginterferon alpha-2a and peginterferon alpha-2b used in combination with ribavirin for treating patients with chronic hepatitis C. These two products are dosed differently: peginterferon alpha-2a is flat-dosed at 180 microg regardless of body weight, whereas peginterferon alpha-2b is dosed by body weight at 0.5-1.5 microg/kg. Bodyweight dosing of peginterferon alpha-2b is purported to overcome the adverse effect of increased body weight on sustained virological response. To test this hypothesis, we measured the area-under-the-curve (AUC) for both drugs as part of a previously reported pharmacokinetics study. In total, 22 interferon-naive patients with chronic hepatitis C were treated for 12 weeks. Patients were randomly assigned in a 1:1 ratio to receive once-weekly peginterferon alpha-2a 180 microg (n=10) or peginterferon alpha-2b 1.0 microg/kg (n=12). Ribavirin was dosed by body weight at 1000 mg/day (or = 75kg) or 1200 mg/day (75 kg). We found no correlation between body weight and AUC for either peginterferon alpha-2a or peginterferon alpha-2b. Considerable interpatient variability in AUC occurred for peginterferon alpha-2a [coefficient of variation (CV): 37.5%] and, despite dosing by body weight, for peginterferon alpha-2b (CV: 36.8%). Thus, there appears to be no rationale for a body-weight dosing regimen for peginterferon alpha-2a, and such dosing does not achieve more consistent AUC measurements in patients receiving peginterferon alpha-2b.

The development of peginterferon and ribavirin combination therapy has significantly improved the sustained virologic response (SVR) rates in patients with chronic hepatitis C. However, poor patient adherence to therapy negatively influences drug levels and drug exposure, often preventing the development of an inhibitory drug level. To optimize patient adherence, the clinician must recognize factors predicting low adherence and negotiate a treatment plan that the patient understands and to which he or she commits. If adverse effects become intolerable, continuing patients on a reduced dose rather than withdrawing treatment seems to confer considerable advantage in preserving the chance for attaining an SVR. Results of a head-to-head comparison have demonstrated the possibility that, in cases of dose reduction, levels of peginterferon alfa-2a could remain above the limit of detection, whereas those of peginterferon alfa-2b might not.