Ultrasound-based steatosis grading system using 2D-attenuation imaging: An individual patient data meta-analysis with external validation.

BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

Liver Fat Quantification With Ultrasound: Depth Dependence of Attenuation Coefficient.

OBJECTIVES: The primary aim was to estimate the influence of various depths on ultrasound attenuation coefficient (AC) of multiple vendors in the liver. The secondary aim was to evaluate the impact of region of interest (ROI) size on AC measurements in a subset of participants. METHODS: This Institutional Review Board (IRB)-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study was carried out in two centers using AC-Canon and AC-Philips algorithms and extracting AC-Siemens values from ultrasound-derived fat fraction algorithm. Measurements were performed positioning ROI upper edge (3 cm size) at 2, 3, 4, 5 cm from the liver capsule with AC-Canon and AC-Philips and at 1.5, 2, 3 cm with Siemens algorithm. In a subset of participants, measurements were obtained with 1 and 3 cm ROI size. Univariate and multivariate linear regression models and Lin's concordance correlation coefficient (CCC) were used for statistical analysis as appropriate. RESULTS: Three different cohorts were studied. Sixty-three participants (34 females; mean age: 51 ± 14 years) were studied with AC-Canon, 60 (46 females; mean age: 57 ± 11 years) with AC-Philips, and 50 (25 females; 61 ± 13 years) with AC-Siemens. There was a decrease in AC values per 1 cm increase in depth in all. In multivariable analysis, the coefficient was -0.049 (-0.060; -0.038 P < .001) with AC-Canon, -0.058 (-0.066; -0.049 P < .001) with AC-Philips and -0.081 (-0.112; -0.050 P < .001) with AC-Siemens. AC values with 1 cm ROI were significantly higher than those obtained with 3 cm ROI at all depths (P < .001) but the agreement between AC values obtained with different ROI size was excellent (CCC 0.82 [0.77-0.88]). CONCLUSIONS: There is depth dependence in AC measurement that affects results. A standardized protocol with fixed ROI's depth and size is needed.

Point Shear Wave Elastography by ElastPQ for Fibrosis Screening in Patients with NAFLD: A Prospective, Multicenter Comparison to Vibration-Controlled Elastography.

BACKGROUND: 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. METHOD: In this prospective, European multinational study we assessed the diagnostic accuracy of EPQ using vibration-controlled transient elastography (VCTE) as a reference standard. RESULTS: 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; p<0.0001) 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). CONCLUSION: The point shear wave elastography technique EPQ shows excellent correlation to and concordance with VCTE. EPQ can reliably exclude NAFLD fibrosis <6.0 kPa (<1.41 m/s) and indicate a high risk of advanced fibrosis ≥10.4 kPa (≥1.86 m/s).

Is a radiological score needed to define the severity of Nontuberculous mycobacteria lung disease?

High-resolution CT-scan (HRCT) plays a major role in the diagnosis of Nontuberculous mycobacteria lung disease (NTM-LD), but its role in follow-up is controversial. Our aim was first to conceive a radiological score able to quantify the severity of pulmonary involvement by NTM infection and, second, to check its association with the NTM-LD clinical burden. We also intended, if possible, to verify the potential influence of NTM specific treatment on the radiological score. We retrospectively collected the clinical, microbiological and radiological data of all patients who were admitted to our hospital from 1 January 2012 to 1 January 2020 with a confirmed diagnosis of NTM-LD. A radiological score was applied to evaluate lung involvement on HRCT at diagnosis and at 6-18 months follow-up. Twenty-eight patients with NTM-LD performed follow-up HRCT. No association was found between radiological and clinical score (Spearman R -0.05, 95%CI -0.41 to 0.33). Repeated measures analysis showed a significant increase in radiological score over time (change 1.11, 95%CI 0.10 to 2.11; p-value 0.032), while Mann-Whitney test did not show any difference between treated and untreated patients (p value 0.922). Further studies are needed to assess the usefulness of routine radiological follow-up in patients with NTM-LD.

Performance of the Attenuation Imaging Technology in the Detection of Liver Steatosis.

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.

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020.

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21-28 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age > 65 years, antiviral treatment and for severe disease, lactate dehydrogenase > 300 mg/dL.

Evaluation of Inter-System Variability in Liver Stiffness Measurements.

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Noninvasive assessment of liver steatosis in children: the clinical value of controlled attenuation parameter.

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 clinical value of controlled attenuation parameter for the noninvasive assessment of liver steatosis.

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.

Two-dimensional shear wave elastography (ElastQ) accurately rules out liver fibrosis and rules in advanced chronic liver disease across liver disease etiologies: a prospective multicenter study.

PURPOSE: This study evaluated ElastQ, a two-dimensional shear wave elastography (2D-SWE) technique, for the non-invasive assessment of liver fibrosis risk using liver stiffness measurement (LSM). The aim was to determine its diagnostic accuracy and establish LSM cutoffs for clinical risk stratification. METHODS: A prospective multicenter study was conducted, employing vibration-controlled transient elastography (VCTE) as a reference standard. The statistical analysis utilized Pearson correlations and Lin concordance correlation coefficients, diagnostic areas under the curve (AUCs), and 90%-specific rule-in and 90%-sensitive rule-out ElastQ cutoffs. RESULTS: The study included 875 patients at risk for liver disease, of whom 816 (376 women, 46.1%; median age, 57.0 years [interquartile range, 19.0]) had successful and reliable VCTE- and ElastQ-LSMs. The median LSM was 13.0 kPa (range, 2.0 to 75.0 kPa) for VCTE and 6.6 kPa (range, 2.9 to 26.5 kPa) for ElastQ. The correlation between VCTE-LSM and ElastQ-LSM was adequate for VCTE-LSM <15 kPa (Pearson r=0.63) but lower for VCTE-LSM ≥15.0 kPa (Pearson r=0.27). VCTE-LSM indicated no fibrosis risk (<5.0 kPa) in 178 cases (21.8%), gray zone (5.0-9.9 kPa) in 347 cases (42.5%), and advanced chronic liver disease (ACLD; ≥10.0 kPa) in 291 cases (35.7%). The diagnostic AUC for ElastQ-LSM was 0.82 for fibrosis risk and 0.90 for ACLD. The clinically relevant ElastQ cutoffs for ruling out fibrosis risk and ruling in compensated ACLD (cACLD) were <5.0 kPa and ≥9.0 kPa, respectively. CONCLUSION: ElastQ 2D-SWE enables accurate, non-invasive assessments of liver fibrosis and cACLD risk. In clinical practice, ElastQ-LSM <5.0 kPa rules out fibrosis, while ElastQ-LSM ≥9.0 kPa rules in cACLD.

Dynamic NLR and PLR in Predicting COVID-19 Severity: A Retrospective Cohort Study.

INTRODUCTION: The hyperinflammation phase of severe SARS-CoV-2 is characterised by complete blood count alterations. In this context, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) can be used as prognostic factors. We studied NLR and PLR trends at different timepoints and computed optimal cutoffs to predict four outcomes: use of continuous positive airways pressure (CPAP), intensive care unit (ICU) admission, invasive ventilation and death. METHODS: We retrospectively included all adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia admitted from 23 January 2020 to 18 May 2021. Analyses included non-parametric tests to study the ability of NLR and PLR to distinguish the patients' outcomes at each timepoint. Receiver operating characteristic (ROC) curves were built for NLR and PLR at each timepoint (minus discharge) to identify cutoffs to distinguish severe and non-severe disease. Their statistical significance was assessed with the chi-square test. Collection of data under the SMACORE database was approved with protocol number 20200046877. RESULTS: We included 2169 patients. NLR and PLR were higher in severe coronavirus disease 2019 (COVID-19). Both ratios were able to distinguish the outcomes at each timepoint. For NLR, the areas under the receiver operating characteristic curve (AUROC) ranged between 0.59 and 0.81, and for PLR between 0.53 and 0.67. From each ROC curve we computed an optimal cutoff value. CONCLUSION: NLR and PLR cutoffs are able to distinguish severity grades and mortality at different timepoints during the course of disease, and, as such, they allow a tailored approach. Future prospects include validating our cutoffs in a prospective cohort and comparing their performance against other COVID-19 scores.

Performance of real-time strain elastography, transient elastography, and aspartate-to-platelet ratio index in the assessment of fibrosis in chronic hepatitis C.

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 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. CONCLUSION: 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.

Quantification of Liver Fat Content with the iATT Algorithm: Correlation with Controlled Attenuation Parameter.

Background: The primary aim of our study was to assess the correlation between an improved version of the attenuation coefficient available on the Arietta 850 ultrasound system (iATT, Fujifilm Healthcare, Tokyo, Japan) and controlled attenuation parameter (CAP). The secondary aim was to assess whether focusing only on iATT acquisition without following the strict protocol for liver stiffness measurements would affect iATT measurement. Methods: Consecutive individuals were enrolled. Pearson's r was used to test the correlation between ATT and CAP values. The concordance between iATT and CAP was tested using Lin's concordance correlation coefficient (CCC). Results: 354 individuals (203 males, 151 females) were studied. The overall Pearson correlation between CAP and iATT values obtained following or not following the liver stiffness measurement protocol, respectively, were r = 0.73 and r = 0.71. The correlation was affected by the interquartile range/median (IQR/M) of the 10 measurements: it was r = 0.75 for IQR/M ≤ 15% and r = 0.60 for IQR/M > 15%. CCC showed that there was a moderate to good concordance between iATT and CAP values. Conclusion: iATT shows a strong correlation with CAP that does not decrease when the protocol for liver stiffness acquisition is not followed. The correlation between iATT and CAP values is higher when the IQR/M ≤ 15%.

Mortality due to COVID-19 during the pandemic: A comparison of first, secondo and third SMAtteo COvid19 REgistry (SMACORE).

COVID-19 tide had shattered on European countries with three distinct and tough waves, from March and April, 2020; October and November, 2020 and March and April, 2021 respectively. We observed a 50% reduction in the hazard of death during both wave II and III compared with wave I (HR 0.54, 95%CI 0.39-0.74 and HR 0.57, 95%CI 0.41-0.80, respectively). Sex and age were independent predictors of death. We compare in-hospital mortality of COVID-19 patients admitted at our Referral Hospital of Northern Italy during the different waves, discuss the reasons of the observed differences and suggest approaches to the challenges ahead.

Performance and cutoffs for liver fibrosis staging of a two-dimensional shear wave elastography technique.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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, P < 0.0001). 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, were > 7 and > 9 kPa. Shear-wave-speed dispersion showed a high correlation with fibrosis (r = 0.85, P < 0.0001), whereas there was a very weak correlation with steatosis. CONCLUSIONS: 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.

COVID vaccination and asthma exacerbation: might there be a link?

INTRODUCTION: There is ongoing debate regarding the role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in asthma exacerbation, and its long-term impact on the lung function of individuals with asthma. In contrast, the potential impact of coronavirus disease 2019 (COVID-19) vaccination on asthma is entirely unexplored. CASE STUDY: This study examined a challenging case of severe asthma exacerbation in a 28-year-old female following two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech) at IRCCS Policlinico San Matteo in Pavia, Italy. The patient, a fourth-year resident at the hospital, was vaccinated in early 2021. She was an occasional smoker with a 10-year history of asthma and seasonal allergic rhinitis. She tested negative for SARS-CoV-2 on several molecular swabs and serology tests. RESULTS: After receiving the second dose of vaccine, the patient started to experience worsening of respiratory symptoms. Following several episodes and a severe asthma attack, the patient required treatment with mepolizumab, a biologic drug (interleukin-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 at present, this case is a valuable prompt for further investigation. This is particularly true from the perspective of mass vaccination of adolescents and children currently underway across the globe.

Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection.

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

Patients with chronic hepatitis C receiving treatment with direct acting antivirals: How is this population changing?

BACKGROUND AND AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: In the study were included 2565 patients. During the study period, the yearly proportion of men and cirrhotic patients decreased (p<0.001) 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 (p<0.001). Instead, the yearly number of experienced patients decreased significantly (p<0.001) as well as the mean MELD score of cirrhotic patients from 9 to 7.6 (p<0.001). SVR rates increased significantly, from 93.4% in 2015 to 97.1% in 2018 (P<0.05). CONCLUSIONS: The population of patients with CHC receiving DAAs is becoming older and with more comorbidities. Nevertheless, this did not impact SVR rates.

Competing-risk analysis of coronavirus disease 2019 in-hospital mortality in a Northern Italian centre from SMAtteo COvid19 REgistry (SMACORE).

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.

Pathogenesis of liver damage in HCV-HIV patients.

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.