Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease.

on behalf of the WELCOME Study InvestigatorsThere is no licensed treatment for nonalcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes, and cardiovascular disease. We tested whether 15-18 months of treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA; Omacor/Lovaza, 4 g/day) decreased liver fat and improved two histologically validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomized in a double-blind, placebo-controlled trial (DHA1EPA, n 5 51; placebo, n 5 52). We quantified liver fat percentage by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA; placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of (1) DHA1EPA treatment (intention-to-treat analyses) and (2) erythrocyte DHA and EPA enrichment (secondary analysis). Median (interquartile range) baseline and end-of-study liver fat percentage were 21.7 (19.3) and 19.7 (18.0) (placebo) and 23.0 (36.2) and 16.3 (22.0) (DHA1EPA). In the fully adjusted regression model, there was a trend toward improvement in liver fat percentage with DHA1EPA treatment (b 5 23.64; 95% confidence interval [CI]: 28.0, 0.8; P 5 0.1), but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat percentage (for each 1% enrichment: b 5 21.70; 95% CI: 22.9, 20.5; P 5 0.007). No improvement in fibrosis scores occurred. Conclusion: Erythrocyte DHA enrichment with DHA1EPA treatment is linearly associated with decreased liver fat percentage. Substantial decreases in liver fat percentage can be achieved with high-percentage erythrocyte DHA enrichment in NAFLD. (HEPATOLOGY 2014;60:1211-1221

*WELCOME, Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy.

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Background/ObjectiveTreatment of subjects with non-alcoholic fatty liver disease (NAFLD) with omega-3 polyunsaturated fatty acids (PUFA) suggests high levels of docosahexaenoic acid (DHA) tissue enrichment decrease liver fat content. We assessed whether changes in erythrocyte DHA enrichment (as a surrogate marker of changes in tissue enrichment) were associated with alterations in hepatic de novo lipogenesis (DNL), postprandial fatty acid (FA) partitioning, and hepatic and peripheral insulin sensitivity in a sub-study of the WELCOME* trial.Subjects/MethodsSixteen participants were randomized to 4 g/day EPA+DHA (n=8) or placebo (n=8) for 15-18 months and underwent pre- and post-intervention measurements. Fasting and postprandial hepatic FA metabolism was assessed using metabolic substrates labelled with stable-isotope tracers (2H2O and [U13C]palmitate). Insulin sensitivity was measured by a stepped hyperinsulinaemic-euglycaemic clamp using deuterated glucose. Participants were stratified according to change in DHA erythrocyte enrichment (< or ≥2% post-intervention).ResultsNine participants were stratified to DHA≥2% (8 randomised to EPA+DHA and 1 to placebo) and seven to the DHA<2% group (all placebo). Compared to individuals with erythrocyte <2% change in DHA abundance, those with ≥2% enrichment had significant improvements in hepatic insulin sensitivity, reduced fasting and postprandial plasma triglyceride concentrations, decreased fasting hepatic DNL, as well as greater appearance of 13C from dietary fat into plasma 3-hydroxybutyrate (all P<0.05).ConclusionsThe findings from our pilot study indicate that individuals who achieved a change in erythrocyte DHA enrichment ≥2% show favourable changes in hepatic FA metabolism and insulin sensitivity, which may contribute to decreasing hepatic fat content.*(Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD (non-alcoholic fatty liver disease) with OMacor thErapy)

Although accumulating evidence points to NAFLD emerging as a novel cardiovascular risk factor, more research is needed to find suitable noninvasive biomarkers of NAFLD severity to allow better risk-stratification based on cardiovascular outcomes. Furthermore, with no established pharmacological treatment option for NAFLD currently available, any potential treatment must show efficacy not only in slowing liver disease progression, but also in ameliorating adverse cardiovascular outcomes.

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We report the case of an elderly lady with Parkinson's tremor whose electrocardiographic (ECG) appearance simulated ventricular tachycardia. As a result she underwent unnecessary clinical intervention. We also highlight the difficulty in correctly identifying a tremor-induced ECG artefact with regard to Parkinson's disease, due to the diverse range of possible clinical scenarios presented by patients with this condition.