Comparison of point-shear wave elastography (ElastPQ) and transient elastography (FibroScan) for liver fibrosis staging in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: ElastPQ is a point shear wave elastography technique used to non-invasively assess liver fibrosis. We compared liver stiffness measurements (LSM) by ElastPQ and fibroscan transient elastography (F-TE) in a cohort of patients with non-alcoholic fatty liver disease (NAFLD). We further evaluated the performance of ElastPQ in a subgroup of patients with available liver histology. MATERIALS AND METHODS: We included patients with NAFLD who presented in a dedicated multidisciplinary clinic. Anthropometric parameters, blood tests and elastography measurements were obtained using F-TE and ElastPQ as part of routine clinical care. RESULTS: We enrolled 671 patients with NAFLD, mean age 55.8 ± 13 years, body mass index (BMI) 31.5 ± 5.7 kg/m2 , 56.6% males, 41% diabetes, 53.7% hypertension, 68% dyslipidaemia. ElastPQ showed an excellent correlation with F-TE (Spearman's r = 0.80, p < .001), which was better for mild/moderate stages of fibrosis. Independent predictors of a >2 kPa discrepancy between the two techniques were a larger waist circumference and F-TE ≥10 kPa. In the subgroup of 159 patients with available histology, ElastPQ showed similar diagnostic accuracy with F-TE in staging liver fibrosis (ElastPQ area under the curves 0.84, 0.83, 0.86 and 0.95, for F ≥ 1, F ≥ 2, F ≥ 3 and F = 4 respectively). Optimal cut-off values of ElastPQ for individual fibrosis stages were lower than those of F-TE. CONCLUSIONS: ElastPQ shows an excellent correlation with F-TE in patients with NAFLD, which was better for lower LSM. The optimal cut-off values of ElastPQ are lower than those of F-TE for individual stages of fibrosis. ElastPQ has similar diagnostic accuracy to F-TE for all stages of fibrosis.

Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria.

BACKGROUND: Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. METHOD: Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3 months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. RESULTS: Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3 months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8 months (IQR: 0.77-2.67). The median follow-up period was 5.1 95% CI [4.7-5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51-10.59], P < 0.001) and body mass index (0.74 95% CI [0.59-0.89], P < 0.001) were significant. Univariable survival analysis of patients with sarcopenia versus patients without sarcopenia showed a significant difference in OS (HR 1.44 95% CI [1.07 - 1.94], P = 0.018). Also the SMI was significant (HR 0.98 95% CI [0.96-0.99], P = 0.014). The survival difference between the lowest SMI quartile versus the highest SMI quartile was significant (log-rank: P = 0.005) with 5 year OS of 57% and 71%, respectively. Data from 423 patients, describing 139 deaths, was used for multivariate analysis. Both sarcopenia (HR 1.45 95% CI [1.02 - 2.05], P = 0.036) and SMI were (HR 0.98 95% CI [0.95-0.99], P = 0.035) significant. On the survival scale this translates to a 5 year OS difference of 11% between sarcopenia and no sarcopenia. Whereas for SMI, this translates to a survival difference of 8% between first and third quartiles for both genders. CONCLUSIONS: Overall, we can conclude that higher muscle mass contributes to a better long-term survival. However, for individual patients, low muscle mass should not be considered an absolute contra-indication for LT as its discriminatory performance was limited.

Predictors of adverse prognosis in COVID-19: A systematic review and meta-analysis.

BACKGROUND: Identification of reliable outcome predictors in coronavirus disease 2019 (COVID-19) is of paramount importance for improving patient's management. METHODS: A systematic review of literature was conducted until 24 April 2020. From 6843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587 790 and 602 234 cases. Two endpoints were defined: (a) a composite outcome including death, severe presentation, hospitalization in the intensive care unit (ICU) and/or mechanical ventilation; and (b) in-hospital mortality. We extracted numeric data on patients' characteristics and cases with adverse outcomes and employed inverse variance random-effects models to derive pooled estimates. RESULTS: We identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR) = 3.15, 95% confidence intervals (CIs) 2.26-4.41), acute cardiac (OR = 10.58, 5.00-22.40) or kidney (OR = 5.13, 1.78-14.83) injury, increased procalcitonin (OR = 4.8, 2.034-11.31) or D-dimer (OR = 3.7, 1.74-7.89), and thrombocytopenia (OR = 6.23, 1.031-37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D-dimer conferred an increased risk of in-hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR = 3.61, 95% CI 1.934-6.73), but not with mortality. CONCLUSIONS: Advanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in-hospital mortality.

Cardiovascular Disease in Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA), is a term used to describe a group of inflammatory disorders beginning before the age of 16 years. Although for the majority of children remission is achieved early, those with systemic or polyarticular form of the disease may present persistent symptoms in adulthood. Considering that there is overlap in the pathogenesis of JIA with adult rheumatic diseases, concerns have been raised as to whether JIA patients could be at increased cardiovascular (CV) risk in the long-term. In this review, we summarize evidence for CV involvement in JIA and present data on CV risk factors and surrogate markers of arterial disease. We also provide information on beneficial and harmful CV effects of anti-inflammatory medications in the context of JIA and suggest strategies for CV screening. Overall, patients with systemic forms of JIA demonstrate an adverse lipid profile and early arterial changes relevant to accelerated arterial disease progression. Although there is paucity of data on CV outcomes, we recommend a holistic approach in the management of JIA patients, which includes CV risk factor monitoring and lifestyle modification as well as use, when necessary, of antiinflammatory therapies with documented CV safety.

Direct-acting antiviral treatment for chronic hepatitis C in people who use drugs in a real-world setting.

BACKGROUND: Direct-acting antivirals (DAAs) offer high cure rates in people who inject drugs (PWID) with hepatitis C virus (HCV) infection. There are concerns regarding lower response rates among PWID in real life. We evaluated the outcome of DAA therapy in PWID in a real-world setting and the factors that affect it. METHODS: We performed a retrospective analysis of 174 PWID with chronic hepatitis C who started DAAs in a Greek liver clinic in collaboration with an addiction program. Patients who did not return for reassessment were considered as lost to follow up (LTFU). A logistic regression model was used to assess factors associated with a sustained virological response 12 weeks after treatment completion (SVR12) and LTFU. RESULTS: Patients' mean age was 48±9.2 years and 91/174 (52.3%) were attending opioid substitution treatment programs. Overall, 144/174 (82.8%) patients completed therapy and presented for SVR12 testing, 8/174 (4.6%) did not complete treatment and 22/174 (12.6%) were LTFU. Overall SVR12 was 79.9% (139/174). For those with an available SVR12 test the response rate reached 96.5% (139/144). Regression analysis did not indicate any significant association between patient characteristics and SVR12. Age <45 years and genotype 3 were independent predictors of LTFU. Parallel use was found to have a trend towards LTFU. CONCLUSIONS: HCV treatment by hepatologists and addiction specialists is feasible, effective and safe in a real-world setting. However, as 12% of patients appear to be LTFU, more emphasis should be placed on interventions guaranteeing follow up for SVR testing and general care.

Liver fibrosis staging with combination of APRI and FIB-4 scoring systems in chronic hepatitis C as an alternative to transient elastography.

BACKGROUND: Liver disease severity must be determined before treatment of chronic hepatitis C (CHC). We evaluated the diagnostic performance of the APRI and FIB-4 scores compared to transient elastography liver stiffness (TE-LS) in detecting significant fibrosis (F3) or cirrhosis (F4). METHODS: We retrospectively enrolled 575 patients with CHC who underwent TE-LS between May 2014 and September 2018: 365 (63.5%) male, mean age 51.54±12.4 years. APRI and FIB-4 scores were compared to TE-LS. RESULTS: One hundred patients (17.5%) had TE-LS values between 9 and 11.9 kPa, and were classified as F3, while 265 (46%) were classified as F4 (TE-LS ≥12 kPa). APRI and FIB-4 scores predicted F4 patients adequately using cutoff values of 0.65 (sensitivity 85.5%, specificity 77%) and 1.63 (sensitivity 91%, specificity 77%), respectively. Cutoff values of 0.64 for APRI and 1.46 for FIB-4 predicted F3/F4 patients (sensitivity 72% and 81.5%; specificity 83% and 79%, respectively). The use of these cutoff values with APRI and FIB-4 in combination adequately predicted patients with significant fibrosis or cirrhosis (positive predictive value 91.5%), while cutoff values of 0.3 and 0.98, respectively, predicted F1/F2 patients with specificity 94.5% and sensitivity 26.5%, suggesting that in 58.5% of patients TE-LS could possibly be avoided. CONCLUSIONS: The APRI/FIB-4 combination performed well in predicting significant fibrosis, while FIB-4 performed well in predicting cirrhosis. These noninvasive biochemical markers could be used as screening tools instead of LS measurement, which is not widely available. Further prospective validation studies are required to confirm this finding.

Free androgen index as a determinant of arterial stiffness in menopause: a mediation analysis.

OBJECTIVE: Associations of endogenous androgens in menopause with blood pressure (BP) and indices of arterial stiffness are reported, but directional relationships are not clear. Structural equation modeling is a contemporary statistical method, which allows assessment of such relationships and improves pathway understanding. METHODS: We recruited 411 consecutive apparently healthy postmenopausal women who underwent noninvasive vascular evaluation. This included pulse wave analysis (aortic pressures and arterial wave reflections [augmentation index]), measurement of aortic stiffness by pulse wave velocity (PWV), stiffness index (SI), and flow-mediated dilatation. A cumulative marker combining PWV and SI (combined local and aortic arterial stiffness [CAS]) was also assessed. Free androgen index (FAI) was calculated from circulating total testosterone and sex hormone-binding globulin. RESULTS: FAI was an independent determinant of systolic BP (SBP) (P = 0.032), SI (P = 0.042), and PWV (P = 0.027). Under structural equation modeling analysis, FAI was a direct predictor for PWV (beta = 0.149, P = 0.014), SI (beta = 0.154, P = 0.022), and CAS (beta = 0.193, P = 0.02), whereas SBP was a parallel mediator of androgen's vascular effects on PWV (beta = 0.280, P < 0.001) and CAS (beta = 0.248, P = 0.004), but not SI (beta = 0.024, P = 0.404). FAI-induced increase in arterial stiffness via flow-mediated dilatation was not established. FAI was not a determinant of augmentation index. CONCLUSIONS: In healthy postmenopausal women, FAI was directly associated with PWV, SI, and CAS. FAI also directly correlated with SBP, which in turn concurrently increased PWV and CAS. The directional correlations found herein, imply that endogenous androgens may be causally associated with indices of arterial stiffness both directly and indirectly. This hypothesis should be confirmed in further studies with causal design.

Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study.

BACKGROUND: Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). METHODS: Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. RESULTS: AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. CONCLUSION: Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research.