Giulia Besutti

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.

Post-transplantation hepatocellular carcinoma recurrence: Patterns and relation between vascularity and differentiation degree

AIM To evaluate the relationship between hepatocellular carcinoma (HCC) vascularity and grade; to describe patterns and vascular/histopathological variations of post-transplantation recurrence. METHODS This retrospective study included 165 patients (143 men, 22 women; median age 56.8 years, range 28-70.4 years) transplanted for HCC who had a follow-up period longer than 2 mo. Pre-transplantation dynamic computed tomography or magnetic resonance examinations were retrospectively reviewed, classifying HCC imaging enhancement pattern into hypervascular and hypovascular based on presence of wash-in during arterial phase. All pathologic reports of the explanted livers were reviewed, collecting data about HCC differentiation degree. The association between imaging vascular pattern and pathological grade was estimated using the Fisher exact test. All follow-up clinical and imaging data were reviewed for evidence of recurrence. Recurrence rate was calculated and imaging features of recurrent tumor were collected, classifying early and late recurrences based on timing (< or ≥ 2 years after transplantation) and intrahepatic, extrahepatic and both intrahepatic and extrahepatic recurrences based on location. All intrahepatic recurrences were classified as hypervascular or hypovascular and the differentiation degree was collected where available. The presence of variations in imaging enhancement pattern and pathological grade between the primary tumor and the intrahepatic recurrence was evaluated and the association between imaging and histopatholgical variations was estimated by using the χ(2) test. RESULTS Of the 163 patients with imaging evidence of viable tumor, 156 (95.7%) had hypervascular and 7 (4.3%) hypovascular HCC. Among the 125 patients with evidence of viable tumor in the explanted liver, 19 (15.2%) had grade 1, 56 (44.8%) grade 2, 40 (32%) grade 3 and 4 (3.2%) grade 4 HCC, while the differentiation degree was not assessable for 6 patients (4.8%). A significant association was found between imaging vascularity and pathological grade (P = 0.035). Post-transplantation recurrence rate was 14.55% (24/165). All recurrences occurred in patients who had a hypervascular primary tumor. Three patients (12.5%) experienced late recurrence; the location of the first recurrence was extrahepatic in 14 patients (58.3%), intrahepatic in 7 patients (29.2%) and both intrahepatic and extrahepatic in 3 patients (12.5%). Two patients had a variation in imaging characteristics between the primary HCC (hypervascular) and the intrahepatic recurrent HCC (hypovascular), while 1 patient had a variation of histopathological characteristics (from moderate to poor differentiation), however no association was found between imaging and histopathological variations. CONCLUSION A correlation was found between HCC grade and vascularity; some degree of variability may exist between the primary and the recurrence imaging/histopathological characteristics, apparently not correlated.

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.

Magnetic resonance for quantitative assessment of liver steatosis: a new potential tool to monitor antiretroviral-drug-related toxicities

BACKGROUND There is an increasing need for new diagnostic tools to monitor antiretroviral drug-related toxicities. Magnetic resonance (MR) imaging and MR spectroscopy are non-invasive diagnostic methods used in the detection and quantification of liver fat. The aim of this study was to compare sensitivity and specificity of different MR techniques in the quantitative assessment of liver steatosis, using liver biopsy as the reference standard, in patients with and without HIV infection. METHODS Sequentially evaluated patients with suspected steatosis who were referred for liver biopsy at our tertiary care site were eligible. MR liver fat content (LFC) was estimated by T2-weighted and fat-suppressed T2-weighted spin-echo, dual-phase T1-weighted gradient-echo, multiecho gradient-echo and (1)H spectroscopy. Association between LFC and histological steatosis percentage was calculated by using univariate linear regressions and Pearsons coefficient. Respective receiver operating characteristic (ROC) curves were used to compare specificity and sensitivity of MR methods in diagnosis (cutoff 5%) and in quantitative evaluation (cutoff 33%) of steatosis. RESULTS A total of 28 patients were identified: 12 refused or had contraindications for liver biopsy and 16 had biopsies plus MR. LFC and histological steatosis percentage were strongly associated (fat-suppressed r=0.86 [P<0.001], dual-phase r=0.88 [P<0.001], multiecho r=0.95 [P<0,001] and spectroscopy r=0.84 [P=0.01]). MR techniques had high sensitivity and specificity in diagnosis and quantitative assessment of steatosis (areas under ROC curves ranging from 0.88 to 0.98). CONCLUSIONS This pilot study confirms that MR may be a sensitive non-invasive alternative to biopsy for the quantitative assessment of liver fat and a potential end point to monitor antiretroviral-drug-related toxicities.

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.

Burden of subclinical heart and lung disease detected on thoracic CT scans of HIV patients on HAART

The aim was to determine the prevalence of lung and heart abnormalities on thoracic CT scans in HIV‐infected patients who were treated with antiretroviral therapy (ART).

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.