Association of Vitamin D Serum Levels and Its Common Genetic Determinants, With Severity of Liver Fibrosis in Genotype 1 Chronic Hepatitis C Patients

S. Petta; S. Grimaudo; V. D. Marco; C. Scazzone; F. S. Macaluso; C. Cammà; D. Cabibi; R. Pipitone; A. Craxì


J Viral Hepat. 2013;20(7):486-493. 

In This Article


Patient Features and Histology

The baseline features of the 260 patients are shown in Table 1. Most of our patients were in the overweight to obesity range. One patient in four had fibrosis of at least three by Scheuer score, with a high prevalence of moderate/severe necroinflammation (grading 2–3). One patient in three had histological evidence of steatosis of moderate/severe grade.

Mean serum values of 25(OH)D were 24.5 ± 8.4 μg/L. Accordingly, vitamin D deficiency, insufficiency and normality were observed in 0.4%, 75% and 24.6% of G1 CHC patients, respectively.

DHCR7 rs12785878 TT genotype was present in 114 (43.8%) patients, compared to 133 (51.2%) and 13 (5%) with TG and GG variants, respectively. The CYP2R1 rs10741657 AA genotype was observed in 29 patients (11.1%) compared with 109 (41.9%) and 122 (46.9%) with AG and GG variants, respectively. Finally, GC rs7041 TT genotype was present in 149 patients (57.3%) compared with 94 (36.2%) and 17 (6.5%) with TG and GG variants, respectively.

Serum 25(OH)D Levels

Older age (P = 0.002), female sex (P = 0.03), DHCR7 GG (P = 0.003), GC GG (P = 0.05) and the severity of fibrosis (P = 0.001) were associated with lower 25(OH)D levels in G1 CHC, although only DHCR7 GG (P = 0.003) (P = 0.008) and the severity of fibrosis (P = 0.03) were independent factors in multiple linear regression analysis (Table 2). Figure 1 shows the distribution of serum 25(OH)D levels in relation to DHCR7 genotype.

Figure 1.

25(OH)D serum levels according to DHCR7 genotype, in 260 patients with genotype 1 chronic hepatitis C.

Accordingly, all patients with DHCR7 GG genotype had vitamin D insufficiency/deficiency, compared to 74% with DHCR7 TT/TG genotype (P = 0.03).

Variables Related to Severe Fibrosis

The univariate and multivariate comparison of variables between patients with and without severe fibrosis (F3–F4) are reported in Table 3. Older age, male sex, high baseline values of ALT, low cholesterol, high triglycerides, high blood glucose, high HOMA, diabetes, low 25(OH)D, vitamin D insufficiency/deficiency, DHCR7 GG genotype, moderate–severe steatosis and moderate–severe necroinflammatory activity were associated with severe fibrosis (P < 0.10). Multivariate logistic regression analysis showed that the following features were independently linked to severe fibrosis (Scheuer score ≥3): older age (OR, 1.056; 95% CI, 1.023–1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974–0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002–1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919–0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106–16.120; P = 0.03), moderate–severe steatosis (OR, 2.588; 95% CI, 1.355–4.943; P = 0.004) and moderate–severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307–4.763; P = 0.001). The overall area under the curve (AUC) of this model was good (AUC, 0.870). Figure 2 showed the prevalence of severe fibrosis, according to DHCR7 genotype.

Figure 2.

Prevalence of severe liver fibrosis according to DHCR7 genotype, in 260 patients with genotype 1 chronic hepatitis C.