Arai T, et al. PLoS One. 2019 Nov 13; 14(11):e0224184.
Arai T, et al., conducted a study to specify the components linked to sub-clinical arteriosclerosis which comprises the histopathological intensity of the disease and patatin-like phospholipase domain containing 3 gene (PNPLA3) gene polymorphisms, in patients with NAFLD.
Approximately, 153 Japanese patients with biopsy-confirmed NAFLD were included in the study. By utilizing brachial-ankle pulse wave velocity (baPWV) in this study, arterial stiffness was estimated as well as components affecting arterial stiffness which includes histological findings and the PNPLA3 single nucleotide polymorphisms (SNPs), were also evaluated. Additionally, by using clinical parameters, a risk assessment for arteriosclerosis was conducted.
No association was observed for inflammation and ballooning with baPWV. Conversely, significant reduction was observed in baPWV with development of liver steatosis (p = 4.16 × 10−2) and improvement with development of liver fibrosis (p = 7.52 × 10−3) (Figure 1).
Figure 1: Box and whisker plots of baPWV values according to the severity of each histological component in NAFLD patients. baPWV, brachial-ankle pulse wave velocity; NAFLD, nonalcoholic fatty liver disease. *, p < 0.05.
Whilst stages of fibrosis were classified into fibrosis groups with less advanced (F0-2) and advanced (F3-4) group, it was observed that in the advanced fibrosis group, baPWV was significantly superior (p = 5.49 × 10−4) (Figure 2).
Figure 2: baPWV values in NAFLD patients according to fibrosis stage.
By using multiple logistic regression analysis it was observed that the following three variables: older age (≥55 years) (p = 8.57 × 10−3; OR = 3.03; 95% CI = 1.33–6.91), hypertension (p = 1.05 × 10−3; OR = 3.46; 95% CI = 1.65– 7.28), and advanced fibrosis (p = 9.22 × 10−3; OR = 2.94; 95% CI = 1.31–6.63) were irrespectively associated to baPWV ≥1600 cm/s.
The prevalence of baPWV ≥1600 cm/s was observed in 7.1% (3/42) in the low-risk group, 30.8% (12/39) in the intermediate-risk group, and 63.9% (46/72) in the high risk group, respectively (p = 9.44 × 10−10) (Figure 3).
Figure 3: The prevalence of baPWV≥1600 cm/s according to risk groups based on the number of risk factors including older age, hypertension, and advanced fibrosis; low-risk group (number of risk factors = 0), intermediate-risk group (= 1), and high-risk group (≥2).
For the diagnosis of advanced fibrosis, by using ROC analyses, the area under the curve (AUC) of the fibrosis markers and scores were as follows: FIB-4 index (cut-off value = 2.49, AUC = 0.836), NFS (9.47 × 10−2, 0.874), hyaluronic acid (62.3 ng/mL, 0.871), WFA+-M2BP (0.95 C.O.I, 0.816), and type IV collagen 7s (5.2 ng/mL, 0.842) (Figure 4).
Figure 4: Receiver-operating characteristic (ROC) curves of FIB4-index (A), NFS (B), hyaluronic acid (C), WFA+-M2BP (D), and type IV collagen 7s (E) for predicting advanced fibrosis (F3-4). FIB-4, fibrosis-4; NFS, NAFLD (nonalcoholic fatty liver disease) fibrosis score; WFA+-M2BP, Wisteria floribunda agglutinin positive Mac-2-binding protein.
Thus, independent association was observed between older age, hypertension, and advanced liver fibrosis with arterial stiffness in Japanese patients with biopsy-proven NAFLD. Additionally, the combination of these three factors such as older age, hypertension, and advanced liver fibrosis may anticipate the arteriosclerosis risk development in patients with NAFLD in clinical practice based on non-invasive fibrosis markers and scores.
