Riccardo Scaglioni

MR quantitative biomarkers of non-alcoholic fatty liver disease: technical evolutions and future trends

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis as the earliest manifestation and hallmark, and ranges from benign fatty liver to non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is considered the reference standard for NAFLD diagnosis, grading and characterization, but it is limited by its invasiveness and observer-dependence. Among imaging surrogates for the assessment of hepatic steatosis, MR is the most accurate. (1)H MR spectroscopy (MRS) provides a quantitative biomarker of liver fat content (LFC) called proton density fat fraction (PDFF), but it is time-consuming, not widely available and limited in sample size. Several MR imaging (MRI) techniques, in particular fat suppression and in-opposed phase techniques, have been used to quantify hepatic steatosis, mainly estimating LFC from water and fat signal intensities rather than proton densities. Several technical measures have been introduced to minimize the effect of confounding factors, in particular a low flip angle, a multiecho acquisition and a spectral modeling of fat with multipeak reconstruction to address respectively T1 effect, T2* effect, and the multifrequency interference effects of fat protons, allowing to use MRI to estimate LFC based on PDFF. Tang et al. evaluated MRI-estimated PDFF, obtained by applying the above-mentioned technical improvements, in the assessment of hepatic steatosis, using histopathology as the reference standard. The identification of PDFF thresholds, even though to be further explored and validated in larger and more diverse cohorts, is useful to identify steatosis categories based on MRI-based steatosis percentages. MRI, with the new refined techniques which provide a robust quantitative biomarker of hepatic steatosis (PDFF) evaluated on the whole liver parenchyma, is a promising non-invasive alternative to LB as the gold standard for steatosis diagnosis and quantification.

The Burden of Image Based Emphysema and Bronchiolitis in HIV-Infected Individuals on Antiretroviral Therapy

Background With the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown. Methods Thoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning. Findings Nearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction <.0001). The most significant risk factors for both phenotypes were cigarette smoking, intravenous drug use and peripheral leucocytosis. Together, the area-under-the curve statistics was 0.713 (p = 0.0037) for discriminating those with and without these phenotypes. There were no significant changes in lung volumes or flow rates related to these phenotypes, though the carbon monoxide diffusion capacity was reduced for the emphysema phenotype. Interpretation Emphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning.

Lung and Heart Diseases Are Better Predicted by Pack-Years than by Smoking Status or Duration of Smoking Cessation in HIV Patients

Background The objective of this study was to assess the relationship of pack-years smoking and time since smoking cessation with risk of lung and heart disease. Methods We investigated the history of lung and heart disease in 903 HIV-infected patients who had undergone thoracic computed tomography (CT) imaging stratified by smoking history. Multimorbidity lung and heart disease (MLHD) was defined as the presence of ≥ 2 clinical or subclinical lung abnormalities and at least one heart abnormality. Results Among 903 patients, 23.7% had never smoked, 28.7% were former smokers and 47.6% were current smokers. Spirometry indicated chronic obstructive pulmonary disease in 11.4% of patients and MLHD was present in 53.6%. Age, male sex, greater pack-years smoking history and smoking cessation less than 5 years earlier vs. more than 10 years earlier (OR 2.59, 95% CI 1.27–5.29, p = 0.009) were independently associated with CT detected subclinical lung and heart disease. Pack-years smoking history was more strongly associated with MLHD than smoking status (p<0.001). Conclusions MLHD is common even among HIV-infected patients who never smoked and pack- years smoking history is a stronger predictor than current smoking status of MLHD. A detailed pack-years smoking history should be routinely obtained and smoking cessation strategies implemented.

Epicardial adipose tissue and coronary artery calcium predict incident myocardial infarction and death in HIV-infected patients

BACKGROUND Epicardial adipose tissue (EAT) and coronary artery calcium (CAC) have been associated with incident coronary artery disease (CAD) and all-cause mortality in the general population. Their prognostic impact in HIV is unknown. METHODS Observational study of 843 consecutive HIV-infected patients receiving antiretroviral therapy for at least 6 months. Risk stratification was performed with coronary artery calcium (CAC) scoring and EAT screening. Patients were followed for CAD and all-cause mortality for a median of 2.8 years accounting for a total of 2572 patient-year follow-up. RESULTS Mean patient age was 50 ± 8 years and 69% were men. At baseline EAT was associated with male gender, age, waist circumference, visceral adipose tissue, and lipodystrophy, while CAC score ≥ 100 was associated with male gender, age and total cholesterol. During follow-up 33 patients suffered an event (15 incident myocardial infarctions and 18 deaths); the EAT volume was larger and the CAC score was higher in patients with events (p = 0.038 and p = 0.001 respectively). Multivariable regression analyses demonstrated that the upper tertile of EAT (≥ 93 cc; OR 2.15, 95% CI 1.06 - 4.39, p = 0.034), and CAC score ≥ 100 (OR 3.37, 95% CI 1.49 - 7.60, p = 0.003) were independent predictors of events after adjusting for age and sex. CONCLUSIONS In this observational cohort of HIV patients, EAT and CAC were independent predictors of hard outcomes after a median follow-up of approximately 3 years.

Emphysema Distribution and Diffusion Capacity Predict Emphysema Progression in Human Immunodeficiency Virus Infection

Background Chronic obstructive pulmonary disease (COPD) and emphysema are common amongst patients with human immunodeficiency virus (HIV). We sought to determine the clinical factors that are associated with emphysema progression in HIV. Methods 345 HIV-infected patients enrolled in an outpatient HIV metabolic clinic with ≥2 chest computed tomography scans made up the study cohort. Images were qualitatively scored for emphysema based on percentage involvement of the lung. Emphysema progression was defined as any increase in emphysema score over the study period. Univariate analyses of clinical, respiratory, and laboratory data, as well as multivariable logistic regression models, were performed to determine clinical features significantly associated with emphysema progression. Results 17.4% of the cohort were emphysema progressors. Emphysema progression was most strongly associated with having a low baseline diffusion capacity of carbon monoxide (DLCO) and having combination centrilobular and paraseptal emphysema distribution. In adjusted models, the odds ratio (OR) for emphysema progression for every 10% increase in DLCO percent predicted was 0.58 (95% confidence interval [CI] 0.41–0.81). The equivalent OR (95% CI) for centrilobular and paraseptal emphysema distribution was 10.60 (2.93–48.98). Together, these variables had an area under the curve (AUC) statistic of 0.85 for predicting emphysema progression. This was an improvement over the performance of spirometry (forced expiratory volume in 1 second to forced vital capacity ratio), which predicted emphysema progression with an AUC of only 0.65. Conclusion Combined paraseptal and centrilobular emphysema distribution and low DLCO could identify HIV patients who may experience emphysema progression.

Independent association of subclinical coronary artery disease and emphysema in HIV‐infected patients

Chronic obstructive pulmonary disease (COPD) and coronary artery disease are inflammatory states with a significant clinical impact. The relationship between them has not been investigated in patients with HIV infection. We assessed the presence of subclinical emphysema and coronary artery disease using chest computed tomography (CT) imaging in a cohort of HIV‐infected patients receiving antiretroviral therapy.

Predictors of emphysema progression in HIV-positive patients

The aim of the study was to find factors associated with emphysema progression (EP), assessed on sequential thoracic CT scans, in a large cohort of HIV‐positive patients.