Anna Russolillo

Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) has been recognized as a major health burden. It is the most important cause of chronic liver disease and a major independent cardiovascular risk factor. Lacking a definite treatment for NAFLD, a specific diet and an increase in physical activity represent the most commonly used therapeutic approaches. In this review, major literature data about the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs) as a potential treatment of NAFLD have been described. n-3 PUFAs, besides having a beneficial impact on most of the cardio-metabolic risk factors (hypertension, hyperlipidemia, endothelial dysfunction and atherosclerosis) by regulating gene transcription factors [i.e., peroxisome proliferator-activated receptor (PPAR) α, PPARγ, sterol regulatory element-binding protein-1, carbohydrate responsive element-binding protein], impacts both lipid metabolism and on insulin sensitivity. In addition to an enhancement of hepatic beta oxidation and a decrease of the endogenous lipid production, n-3 PUFAs are able to determine a significant reduction of the expression of pro-inflammatory molecules (tumor necrosis factor-α and interleukin-6) and of oxygen reactive species. Further strengthening the results of the in vitro studies, both animal models and human intervention trials, showed a beneficial effect of n-3 PUFAs on the severity of NAFLD as expressed by laboratory parameters and imaging measurements. Despite available results provided encouraging data about the efficacy of n-3 PUFAs as a treatment of NAFLD in humans, well-designed randomized controlled trials of adequate size and duration, with histological endpoints, are needed to assess the long-term safety and efficacy of PUFA, as well as other therapies, for the treatment of NAFLD and non-alcoholic steatohepatitis patients. It is worthwhile to consider that n-3 PUFAs cannot be synthesized by the human body and must be derived from exogenous sources (fish oil, flaxseeds, olive oil) which are typical foods of the Mediterranean diet, known for its beneficial effects in preventing obesity, diabetes and, in turn, cardiovascular events. According to these data, it is important to consider that most of the beneficial effects of n-3 PUFAs can also be obtained by an equilibrate nutrition program.

Obesity and the prediction of minimal disease activity: A prospective study in psoriatic arthritis

We prospectively evaluated whether obesity impacts achievement of minimal disease activity (MDA) in subjects with psoriatic arthritis (PsA).

Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumour necrosis factor α blockers

Objectives To evaluate prospectively the effect of weight loss on the achievement of minimal disease activity (MDA) in overweight/obese patients with psoriatic arthritis (PsA) starting treatment with tumour necrosis factor α (TNFα) blockers. Methods Among subjects with PsA starting treatment with TNFα blockers, 138 overweight/obese patients received a concomitant dietary intervention (69 a hypocaloric diet (HD) and 69 a free-managed diet (FD)). Changes in metabolic variables were measured and a complete clinical rheumatological evaluation was made in all patients at baseline and after a 6-month follow-up to define the achievement of MDA. Results 126 subjects completed the study. MDA was more often achieved by HD than by FD subjects (HR=1.85, 95% CI 1.019 to 3.345, p=0.043). A diet was successful (≥5% weight loss) in 74 (58.7%) patients. Regardless of the type of diet, after 6 months of treatment with TNFα blockers, ≥5% of weight loss was a predictor of the achievement of MDA (OR=4.20, 95% CI 1.82 to 9.66, p<0.001). For increasing weight-loss categories (<5%, 5–10%, >10%), MDA was achieved by 23.1%, 44.8% and 59.5%, respectively. A higher rate of MDA achievement was found in subjects with 5–10% (OR=3.75, 95% CI 1.36 to 10.36, p=0.011) and in those with >10% (OR=6.67, 95% CI 2.41 to 18.41, p<0.001) weight loss in comparison with those with <5% weight loss. Conclusions Regardless of the type of diet, a successful weight loss (≥5% from baseline values) is associated with a higher rate of achievement of MDA in overweight/obese patients with PsA who start treatment with TNFα blockers.

Obesity and psoriatic arthritis: from pathogenesis to clinical outcome and management

PsA is an axial and/or peripheral inflammatory arthritis associated with psoriasis, included in the group of spondylarthritides. It has been suggested that PsA could be a systemic disease, involving even coronary arteries and the heart. An increased prevalence of vascular risk factors has been found in PsA subjects as compared with the general population and psoriatic subjects. Moreover, PsA patients exhibit an increased prevalence of liver steatosis, a marker of metabolic syndrome, and of obesity. Interestingly, many reports demonstrate that adipose tissue is metabolically active, representing a source of inflammatory mediators, known as adipokines. The latter include TNF-α, macrophage chemoattractant protein-1, plasminogen activator inhibitor-1 (PAI-1), IL-6, leptin and adiponectin, leading to a pro-inflammatory status in obese subjects. This evidence supports the idea of obesity as a low-grade inflammatory disease. Accordingly, obesity might be associated with some rheumatic diseases. In particular, it seems to affect several features of PsA, such as its development, cardiovascular risk and clinical outcome. Recent data suggest that increased BMI in early adulthood increases the risk of PsA development in psoriatic patients, supporting a link between fat-mediated inflammation and joint involvement. Obesity may represent an additive cardio-metabolic risk factor in PsA subjects. Abdominal obesity may also determine an increased risk of not achieving minimal disease activity in PsA patients, highlighting the role of abdominal fat accumulation as a negative predictor of good clinical response to biologic agents. This review assesses the relationship between obesity and PsA according to the available literature.

Predictors of early minimal disease activity in patients with psoriatic arthritis treated with tumor necrosis factor-α blockers

Objective. To identify predictors of early minimal disease activity in patients with psoriatic arthritis (PsA) receiving tumor necrosis factor-α (TNF-α) antagonists. Methods. In total 146 consecutive patients with PsA eligible for anti-TNF-α therapy were enrolled. At baseline (T0) information about age, sex, PsA subset, disease duration, comorbidities, and treatments was collected. All subjects were tested for metabolic syndrome (MetS) and/or liver steatosis. A clinical and laboratory evaluation was performed at T0 and at 3 months (T3). Changes in all these variables were compared in subjects achieving minimal disease activity (MDA) and those who did not. Results. Among 146 PsA subjects, 10 discontinued therapy before 3-month followup because of adverse events; thus 136 concluded the study. All clinical outcome measures changed significantly from T0 to T3. Erythrocyte sedimentation rate showed a significant reduction (p < 0.001). C-reactive protein (CRP), serum cholesterol, and triglycerides showed no significant variation (p > 0.05). The prevalence of MetS and liver steatosis showed no significant differences between subjects achieving MDA and those who did not (p = 0.347 and 0.053, respectively). Patients achieving MDA at T3 were younger than those not achieving MDA (p = 0.001). A lower baseline tender joint count (p = 0.001), swollen joint count (p = 0.013), Bath Ankylosing Spondylitis Disease Activity Index (p = 0.021), and Ritchie index (p = 0.006) were found in subjects achieving MDA. Age (OR 0.896, p = 0.003) and Bath Ankylosing Spondylitis Functional Index (BASFI) (OR 0.479, p = 0.007) inversely predicted, whereas CRP (OR 1.78, p = 0.018) directly predicted, achievement of MDA at T3. Conclusion. In patients with PsA, age, CRP, and BASFI at the beginning of treatment were found to be reliable predictors of MDA after 3 months of TNF-α blocker therapy.

Cardiovascular risk in rheumatic patients: the link between inflammation and atherothrombosis.

In addition to a high prevalence of the metabolic syndrome and a significant under-diagnosis of vascular risk factors (VRFs), the effect of chronic inflammation also represents the cornerstone of the raised cardiovascular (CV) risk in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Moreover, the finding that among current anti-inflammatory treatments, the use of tumor necrosis factor (TNF)-α blockers is associated with optimal rheumatologic and CV outcomes further supports the impact of inflammation on the CV risk. However, up-to-date treatment guidelines suggest that TNF-α blockers should be used only after the failure of traditional disease-modifying antirheumatic drugs (DMARDs). Early predictors of the therapeutic efficacy of traditional DMARDs are needed to identify candidates for TNF-α blocker treatment. Furthermore, whether the CV risk should be taken into account while choosing antirheumatic treatments is an emerging issue to be addressed. Common educational programs for specialists and general practitioners and appropriate CV prevention programs, taking into consideration traditional VRFs as well as the inflammatory status, should be planned to prevent ischemic events and to achieve optimal inflammation control in rheumatic patients.

Hepatic Steatosis and Disease Activity in Subjects with Psoriatic Arthritis Receiving Tumor Necrosis Factor-α Blockers

Objective. Little is known about tumor necrosis factor-α (TNF-α) blockers, disease activity, and liver steatosis (hepatic steatosis; HS) in subjects with psoriatic arthritis (PsA). We prospectively evaluated changes in HS during treatment with TNF-α blockers. Methods. In 48 patients with PsA who had evidence of HS before the beginning of TNF-α blocker treatment, an ultrasound followup examination was performed after a 12-month treatment period with TNF-α blockers. All subjects were stratified according to minimal disease activity (MDA) or not (n-MDA), during treatment with TNF-α blockers. Changes in grade of HS were evaluated in parallel in 42 controls with HS and without PsA. Results. At baseline, no significant difference in HS score was found between PsA subjects and controls (HS scores 1.46 ± 0.65 vs 1.62 ± 0.66, respectively; p = 0.249). At 12-month followup, a worsening HS score was found in 20 (41.7%) patients with PsA and in 6 (14.3%) controls (p = 0.005). Overall, the grade of HS worsening was higher in patients with PsA (0.37 ± 0.70) than in controls (0.09 ± 0.43; p = 0.028). A significantly lower prevalence of worsening HS was found among patients with PsA with MDA, compared with n-MDA subjects (16.7% vs 66.7%, respectively; p = 0.001). Laboratory measures of liver function behaved similarly. The risk of worsening HS in patients with PsA who had MDA was similar to that in controls (HR 1.20, 95% CI 0.34–4.33, p = 0.77), and higher in patients who did not have MDA (HR 4.46, 95% CI 1.73–11.47, p = 0.001, regression analysis). Conclusion. Compared with patients with MDA, those with active disease after 12-month treatment with TNF-α blockers exhibited significantly higher incidence of worsening liver steatosis.

Hepatic steatosis, carotid plaques and achieving MDA in psoriatic arthritis patients starting TNF-α blockers treatment: a prospective study

IntroductionWe prospectively evaluated whether hepatic steatosis (HS) and the presence of carotid plaques (CPs) impacts on achieving minimal disease activity (MDA) in psoriatic arthritis (PsA) patients starting tumor necrosis factor (TNF)-α blockers treatment.MethodsBefore starting treatment with TNF-α blockers, consecutive PsA subjects with an active disease were evaluated for the presence of the metabolic syndrome (MetS), HS and CPs. The incidence of MDA was evaluated 12 and 24 months later.ResultsAmong 270 PsA subjects, 91 (33.7%) exhibited the MetS, 58 (21.5%) CPs and 76 (28.1%) HS. At the 12-month follow-up, 98 (36.3%) individuals achieved MDA. Compared with those who did, a higher prevalence of the MetS, HS and CPs was found in subjects who did not achieve the MDA (P always < 0.001). After adjusting for the MetS and for all the other demographic/clinical characteristics analyzed, the presence of HS and CPs at baseline independently predicted the risk of not achieving MDA (Hazard Ratio: 1.91, 95% confidence interval (CI): 1.04 to 3.38, P = 0.035 and Hazard Ratio: 3.21, 95%CI: 1.64 to 6.29, P = 0.001, respectively). Separate Kaplan-Meier survival models confirmed this (Log-Rank: 12.894, P < 0.001 and Log-Rank: 12.849, P < 0.001, respectively). Compared with those without, progressively increasing Hazard Ratios of not achieving MDA were found in those with HS, CPs or HS + CPs at baseline. Moreover, the presence of HS and/or CPs predicted the risk of relapse during the additional 12-month follow-up (Hazard Ratio: 2.85, 95%CI: 1.27 to 6.37, P = 0.011 and Hazard Ratio: 3.17, 95%CI: 1.57 to 6.41, P = 0.001 respectively).ConclusionsHS and/or CPs at baseline are negative predictors of achieving and maintaining MDA.

Exploring newer cardioprotective strategies: ω-3 fatty acids in perspective

In the 1980s, observational retrospective studies showed an inverse relation between coronary heart disease (CHD) and consumption of fish containing fatty acids that belong to the omega (ω)-3 family. Large case-control studies and prospective intervention trials consistently showed that ω-3 fatty acids supplementation lowers fatal myocardial infarction (MI) and sudden cardiac death. By analysing the strengths of the results of individual studies and how the meta-analyses agree with them, putting together relevant backgrounds, and identifying open questions, the following findings/directions emerge. (i) Dietary and non-dietary intake of ω-3 fatty acids reduces overall mortality, mortality due to MI, and sudden death in patients with CHD; (ii) Fish oil consumption directly or indirectly affects cardiac electrophysiology. Fish oil reduces heart rate, a major risk factor for sudden death; (iii) Among patients with implantable cardioverter defibrillators, ω-3 fatty acids do not reduce the risk of ventricular tachycardia/ventricular fibrillation and may actually be pro-arrhythmic; (iv) The consumption of ω-3 fatty acids leads to a 10-33% net decrease of triglyceride levels. The effect is dose-dependent, larger in studies with higher mean baseline triglyceride levels, and consistent in different populations (healthy people, people with dyslipidaemia, diabetes, or known cardiovascular risk factors); (v) Outcomes for which a small beneficial effect ω-3 fatty acids is found include blood pressure (about 2 mmHg reduction), re-stenosis rates after coronary angioplasty (14% reduction), and exercise tolerance testing. Major experimental data provide strength (biological plausibility) for these findings, and define directions for newer clinical trials with ω-3 fatty acids.

Antithrombin levels and the risk of a first episode of venous thromboembolism. A case-control study

Antithrombin levels and the risk of a first episode of venous thromboembolism. A case-control study -