Abstract
Ketone body production, an alternative fuel upon low glucose availability, reduces hepatic fat accumulation. However, its clinical implications have not been established in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the association between spontaneous fasting ketonuria and liver fibrosis in patients with NAFLD without prediabetes and diabetes mellitus (DM). A total of 6202 patients with ultrasound confirmed NAFLD without prediabetes and DM were enrolled in the study. Using low cut off values of NAFLD fibrosis score (NFS) and fibrosis-4, liver fibrosis was defined as an intermediate–high probability of advanced liver fibrosis. Of the 6202 NAFLD patients, 360 (5.8%) had ketonuria. Compared to the patients without ketonuria, patients with ketonuria were younger (41.1 vs. 44.6 years, p < 0.001), had lower levels of glucose (87.2 vs. 91.0 mg/dL, p < 0.001), and homeostatic model assessment for insulin resistance (1.0 vs. 1.5, p < 0.001). The presence of ketonuria had an inverse association with liver fibrosis, assessed using both NFS (final adjusted odds ratio [aOR], 0.67; 95% confidence interval [CI], 0.45–1.01) and fibrosis-4 (aOR, 0.58; 95% CI, 0.40–0.84). The presence of ketonuria in NAFLD patients without prediabetes and DM may have favorable metabolic effects compared to the absence of ketonuria, independent of traditional metabolic factors.
Highlights
Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic fat infiltration without a secondary cause of fatty liver, is closely associated with diabetes mellitus (DM), obesity, and metabolic syndrome due to insulin resistance (IR) [1,2]
Using low cut off values (COVs) by two fibrosis scoring systems, the ketonuria group had a lower percentage of an intermediate–high probability of advanced liver fibrosis compared to the nonketonuria group (7.5 vs. 10.5% for NAFLD fibrosis score (NFS); 14.7 vs. 20.7% for Fib-4, p < 0.05) (Figure 3)
We demonstrated the association between spontaneous fasting ketonuria and an intermediate–high probability of advanced liver fibrosis using low COVs of NFS and Fib-4 in NAFLD patients without prediabetes and DM
Summary
Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic fat infiltration without a secondary cause of fatty liver, is closely associated with diabetes mellitus (DM), obesity, and metabolic syndrome due to insulin resistance (IR) [1,2]. Ketosis, characterized by the increased serum levels of ketone bodies, is divided into pathological and nutritional ketosis [9,12]. Nutritional ketosis, associated with prolonged fasting and low carbohydrate or ketogenic diets (KD), has been shown to be metabolically favorable in recent studies [13,14,15,16]. KD was shown to have hepatic antisteatotic effects by the activation of mitochondrial beta oxidation in patients with NAFLD [17]
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