Association of non-alcoholic steatohepatitis with subclinical myocardial dysfunction in non-cirrhotic patients

Abstract

Background & aims: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk. Among categories of NAFLD, hepatic fibrosis is most likely to affect mortality. Myocardial function and its energy metabolism are tightly linked, which might be altered by an insulin resistant condition such as NAFLD. We investigated whether hepatic steatosis and fibrosis were associated with myocardial dysfunction relative to myocardial glucose uptake.

Methods: A total of 308 patients (190 without NAFLD, 118 with NAFLD) were studied in a tertiary care hospital. Myocardial glucose uptake was evaluated at fasted state using [¹⁸F]-fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET). Hepatic steatosis and fibrosis were assessed by transient liver elastography (Fibroscan®) with controlled attenuation parameter, which quantifies hepatic fat and by surrogate indices (fatty liver index and NAFLD fibrosis score). Cardiac structure and function were examined by echocardiogram.

Results: Compared to those without NAFLD, patients with NAFLD had alterations in cardiac remodeling, manifested by increased left ventricular mass index, left ventricular end-diastolic diameter, and left atrial volume index (all p <0.05). Hepatic steatosis was significantly associated with left ventricular filling pressure (E/e' ratio), which reflects diastolic dysfunction (p for trend <0.05). Those without NAFLD were more likely to have higher myocardial glucose uptake compared to those with NAFLD. Significant hepatic fibrosis was also correlated with diastolic dysfunction and impaired myocardial glucose uptake. Using multivariable linear regression, E/e' ratio was independently associated with hepatic fibrosis (standardized β = 0.12 to 0.27; all p <0.05). Association between hepatic steatosis and E/e' ratio was also significant (standardized β = 0.10 to 0.15; all p <0.05 excluding the model adjusted for adiposity).

Conclusions: Hepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction. This association is linked with myocardial glucose uptake evaluated by ¹⁸FDG-PET.

Lay summary: Non-alcoholic fatty liver disease is associated with an increased risk of cardiovascular disease. More severe forms of non-alcoholic fatty liver disease, where hepatic fibrosis occurs, are linked to increased mortality. In this study, we have shown that hepatic steatosis and fibrosis are associated with subclinical myocardial dysfunction. This association is linked to altered myocardial glucose uptake.

Keywords: Diastolic heart dysfunction; Insulin resistance; Liver fibrosis; Non-alcoholic fatty liver disease; Obesity; Positron emission tomography.