Non-Alcoholic Fatty Liver in Patients with Chylomicronemia

Abstract

Non-alcoholic fatty liver disease (NAFLD) is frequent in patients with features of the metabolic syndrome (MetS), obesity, or type 2 diabetes. Lipoprotein lipase (LPL) is the main driver of triglyceride (TG) hydrolysis in chylomicrons and very-low density lipoproteins (VLDL). In some patients with MetS, dysfunction of this pathway can lead to plasma TG values > 10 mmol/L (multifactorial chylomicronemia or MCS). Chylomicronemia also characterizes LPL deficiency (LPLD), a rare autosomal recessive disease called familial chylomicronemia syndrome (FCS), which is associated with an increased risk of recurrent pancreatitis. This study aims to investigate the expression of NAFLD, as assessed by transient elastography, in MCS and FCS subjects. Data were obtained from 38 subjects with chylomicronemia; 19 genetically confirmed FCS and 19 sex- and age-matched MCS. All participants underwent liver ultrasonography and stiffness measurement after a 4-h fast using transient elastography (FibroScan®, Echosens, Waltham, MA, USA). NAFLD (controlled attenuation parameter (CAP) > 280 dB/m) was observed in 42.1% of FCS and 73.7% of MCS subjects (p = 0.05). FCS subjects had lower body mass index (BMI) than MCS. Only 25% of FCS subjects with NAFLD had a BMI ≥ 30 compared to 64.3% in MCS (p = 0.004). In FCS, NAFLD occurred even in the presence of very low (≤18 kg/m2) BMI. In both FCS and MCS, CAP was negatively associated with acute pancreatitis risk. In this study, NAFLD was commonly observed in both FCS and MCS subjects and occurred independently of the BMI and fasting glucose values in FCS; NAFLD was associated with a lower occurrence of acute pancreatitis episodes.

Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease

“…32 In the present study, we found a potentially causal inverse association between genetically predicted LPL expression in subcutaneous adipose tissue and NAFLD. These results are in line with the recent study of Maltais et al, 33 who reported that 4 in 10 patients with familial chylomicronemia syndrome and almost 3 in 4 patients with multifactorial chylomicronemia syndrome (2 disorders of impaired LPL function) met the criteria of NAFLD independently of their BMI. It should be noted that although the variant at the LPL locus linked with higher NAFLD was associated with higher liver enzymes levels in the UK Biobank, it was not associated with liver fat accumulation in the UK Biobank or with NAFLD in the Mass General Brigham Biobank.…”

Identifying Patients with Familial Chylomicronemia Syndrome Using FCS Score-Based Data Mining Methods

“…These findings might be due to the common presence of insulin resistant conditions as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) among hospital goers and are concordant with the recent report of Paquette et al, who found higher activities of gamma-glutamyl transferase (GGT) in MFCS compared to FCS [ 7 ]. Of note, although occurring in both FCS and MFCS patients, NAFLD was observed to be significantly less frequent in patients with familial chylomicronemia syndrome [ 26 ].…”

The Evolving Story of Multifactorial Chylomicronemia Syndrome

“…Indeed, FCS patients are typically within the normal BMI range, whereas the average BMI in MCS patients is mostly between 28 and 30 kg/m 2 . A higher frequency of NAFLD has also been reported in MCS (74%) compared with FCS (42%) ( 22 ). However, conflicting results have been obtained concerning differences in prevalence or incidence of CVD, diabetes, and hypertension ( 11 , 26 , 28 ).…”

“…In a recent study, the prevalence of NAFLD in patients affected by MCS was studied for the first time using transient elastography (FibroScan). The authors observed that the prevalence of NAFLD was 74% in 19 MCS subjects, which is three times more prevalent than in the general population ( 22 ). Interestingly, the authors observed a negative correlation between liver fat accumulation and AP risk in these patients.…”

“…Interestingly, the authors observed a negative correlation between liver fat accumulation and AP risk in these patients. This may suggest that if more TG accumulates in the liver, a lower quantity would be available to contribute to the pathophysiology of AP ( 22 ). However, because of the small sample size of this study, these results need to be replicated in a larger cohort of MCS patients.…”