Altered serum acylcarnitine profile is associated with the status of nonalcoholic fatty liver disease (NAFLD) and NAFLD-related hepatocellular carcinoma

Abstract

Metabolic disturbance of lipids is a hallmark of nonalcoholic fatty liver disease (NAFLD). In this study, we measured the serum levels of 15 acylcarnitine species of various carbon chain lengths from 2 to 18 in 241 patients with biopsy-proven NAFLD, including 23 patients with hepatocellular carcinoma (HCC), and analyzed the relationship between serum acylcarnitine profile and NAFLD status. Long-chain acylcarnitines AC14:1 and AC18:1 increased gradually with the progression of fibrosis and further increased in patients with HCC, whereas the middle-chain acylcarnitine AC5:0 exhibited the opposite trend. In particular, AC18:1, which we previously showed to possess a tumor promoting effect, was significantly elevated in patients with HCC compared to those without HCC. In addition, long-chain acylcarntines including AC18:1 were positively correlated with serum levels of inflammatory cytokines. Although none of the acylcarnitine species were independently associated with the presence of HCC, (AC16:0 + AC18:1)/AC2:0, an index for the diagnosis of carnitine palmitoyltransferase 2 (CPT2) deficiency, was independently associated with the presence of HCC after adjusting for age and liver fibrosis stage, likely reflecting the downregulation of CPT2 in HCC tissues. Thus, serum acylcarnitine profiles changed significantly according to the status of NAFLD, which may be implicated in the pathogenesis of NAFLD.

Figure 1

Serum levels of acylcarnitine species in nonalcoholic fatty liver disease (NAFLD) patients with and without hepatocellular carcinoma (HCC). Patients without HCC were classified according to their fibrosis stage. The box plot indicates the mean (horizontal line), interquartile range (box), 10^th and 90^th percentiles (whiskers), and outliers outside the 10^th and 90^th percentiles (dots).

Figure 2

The proportion of patients with the AC5:0^low/AC14:1^high/AC18:1^high signature according to NAFLD status.

Figure 3

The values of the (AC16:0 + AC18:1)/AC2:0 index in NAFLD patients with or without HCC. Patients without HCC were classified according to their fibrosis stage (a) and non-classified (b). The box plot indicates the mean (horizontal line), interquartile range (box), 10^th and 90^th percentiles (whiskers), and outliers outside the 10^th and 90^th percentiles (dots).