Non-alcoholic fatty liver disease and heart failure with preserved ejection fraction: from pathophysiology to practical issues

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) in heart failure (HF) preserved left ventricular ejection fraction (HFpEF) patients could reach 50%. Therefore, NAFLD is considered an emerging risk factor. In 20% of NAFLD patients, the condition progresses to non-alcoholic steatohepatitis (NASH), the aggressive form of NAFLD characterized by the development of fibrosis in the liver, leading to cirrhosis. The purpose of this review is to provide an overview of the relationships between NAFLD and HFpEF and to discuss its impact in clinical setting. Based on international reports published during the past decade, there is growing evidence that NAFLD is associated with an increased incidence of cardiovascular diseases, including impaired cardiac structure and function, arterial hypertension, endothelial dysfunction, and early carotid atherosclerosis. NAFLD and HFpEF share common risk factors, co-morbidities, and cardiac outcomes, in favour of a pathophysiological continuum. Currently, NAFLD and NASH are principally managed with non-specific therapies targeting insulin resistance like sodium-glucose co-transporter-2 inhibitors and liraglutide, which can effectively treat hepatic and cardiac issues. Studies including HFpEF patients are ongoing. Several specific NAFLD-oriented therapies are currently being developed either alone or as combinations. NAFLD diagnosis is based on a chronic elevation of liver enzymes in a context of metabolic syndrome and insulin resistance, with fibrosis scores being available for clinical practice. In conclusion, identifying HF patients at risk of NAFLD is a critically important issue. As soon as NAFLD is confirmed and its severity determined, patients should be proposed a management focused on symptoms and co-morbidities.

Keywords: Atherosclerosis; Fibrosis; Heart failure with preserved ejection fraction; Insulin resistance; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis.

Figure 1

Pathophysiological relationship and common co‐morbidities in NAFLD and HFpEF. The scheme summarizes the main pathophysiological pathways resulting from NAFLD or NASH reported to enhance (thunderlights) heart dysfunctions associated with HFpEF. The part below indicates common co‐morbidities shared by both conditions.

Figure 2

Proposed algorithm for the screening of NAFLD in patients with HFpEF.

Figure 3

Fibrosis scores available for clinical practice. Values are from the EASL‐ALEH Clinical Practice Guidelines ²⁰ and Boursier et al. (2016) ²¹ .