We’re Going to Be Hearing a Whole Lot More About NAFLD

SOURCE: Rinella ME. Nonalcoholic fatty liver disease: A systematic review. JAMA 2015;313:2263-2273.

Epidemiologic insights about disease prevalence might sometimes be perceived as belaboring the obvious. After all, who doesn’t know that obesity has become an epidemic, that diabetes prevalence continues to rise unabated, and that hepatitis C is currently the most common cause of end-stage liver disease. Nevertheless, new epidemiologic sirens may sometimes awaken our motivation to address what might otherwise remain silent health burdens, with nonalcoholic fatty liver disease (NAFLD) being an excellent case-in-point.

Even the moniker “NAFLD” presumes we might automatically consider alcohol to be the default cause of fatty liver disease. While that might have been the case decades ago, the dual burdens of obesity and diabetes — both of which are direct antecedents to NAFLD — have changed the map of fatty liver disease on a global basis.

NAFLD portends important downstream consequences. Up to 30% of people with NAFLD have steatohepatitis, among whom approximately 20% will ultimately progress to cirrhosis. Since as many as 75 million to 100 million U.S. adults have NAFLD, this presents an epidemiologically compelling burden. Lifestyle intervention, when it leads to weight loss, is successful in improving liver pathology. There is some suggestion that independent of weight loss, a Mediterranean diet may have particular advantage.

Although no medication has been FDA approved to treat nonalcoholic steatohepatitis, some clinical data are supportive of pioglitazone (30 mg/d) or vitamin E (800 IU/d). Clinicians should maintain vigilance as recommendations for identification and management of NAFLD evolve.

Dietary Fat Used to Be the ‘Bad Guy’

SOURCE: Mozaffarian D, Ludwig DS. The 2015 U.S. Dietary Guidelines: Lifting the ban on total dietary fat. JAMA 2015;313:2421-2422.

In March 2015, the Dietary Guidelines Advisory Committee (DGAC) released its report for review by the secretaries of Agriculture and Health and Human Services. The 2015 Dietary Guidelines for Americans will be derived from the DGAC report, and some clinicians may be surprised at new directions suggested by the DGAC.

For instance, dietary cholesterol has been eliminated as a “nutrient of concern” based on recent data clarifying the lack of a relationship between dietary cholesterol and cardiovascular (CV) events. Similarly, previous guidance suggested an upper limit on total dietary fat consumption; in contrast, the current DGAC report neither restricts dietary fat nor lists fat as a “nutrient of concern,” based on the observation that reducing total fat has not been shown to improve CV outcomes.

Earlier guidance, which suggested limiting fat in the diet, often resulted in substitutions with increased amounts of carbohydrates, resulting in dietary modifications that commonly contained highly processed carbohydrates (such as added sugar.)

The new report includes advice that Americans consume excessive amounts of refined grain produces, such as white bread chips, white rice, crackers, and bakery goods. The U.S. populace has had more than a decade to ingrain the concept that dietary fats are “the bad guy.” It will likely take a substantial amount of additional effort to clarify that replacement of fats with refined carbohydrates is not a healthful
tradeoff.

Risks of Digoxin Use in Atrial Fibrillation

SOURCE: Washam JB, et al. Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: A retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Lancet 2015;385:2363-2370.

Beta-blockers, calcium channel blockers, and digoxin are among the commonly used choices for rate control in patients with atrial fibrillation (AF). The role of digoxin is based on limited data, most of which is not recent. Large clinical trials of novel anticoagulants for patients with AF have been completed within the last decade. Since a substantial minority of patients enrolled in AF anticoagulant trials were receiving digoxin as part of their therapeutic regimen, these data provide a window of observation about associations of digoxin with outcomes.

The Rivaroxaban Once Daily Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) enrolled more than 14,000 patients with AF to compare rivaroxaban with warfarin. More than 5000 AF patients were being treated with digoxin at baseline (37% of total ROCKET-AF participants).

At a median follow-up of approximately 2 years, digoxin treatment was associated with increased all-cause mortality (17% relative increase), vascular death (19% relative increase), and sudden death (36% relative increase).

Because these results have been obtained from a post-hoc analysis of a clinical trial, they cannot be regarded as definitive. Nonetheless, the results should prompt reconsideration of the various choices available for rate control in AF, and hopefully will stimulate performance of a randomized trial to provide more conclusive evidence.