Correlation between vitamin D levels and apoptosis in geriatric patients infected with hepatitis C virus genotype 4

Abstract

BackgroundVitamin D levels play a pivotal role in most biological processes and differ according to age. A deficiency of vitamin D in chronic hepatitis C (CHC) patients has been shown to be linked with the severity of liver fibrosis, but little is known about the mechanism of this association.ObjectiveIn this study, we evaluate the potential interrelation between vitamin D levels, oxidative stress, and apoptosis, based on liver fibrosis in geriatric patients infected with hepatitis C virus (HCV) genotype 4.Subjects and methodsA total of 120 adult individuals aged 30–68 years were recruited in this study. Of these, 20 healthy subjects (15 men and five women) with a mean age of 48.3±6.1 years were selected as controls, and 100 patients with a mean age of 47.8±4.9 years with chronic HCV (CHC) who had undergone liver biopsy (80 men and 20 women) were included in this study. Based on liver radiographic (computed tomography, magnetic resonance imaging) and histological Metavir system analyses, the CHC patients were classified into three groups: asymptomatic CHC carriers (n=30), fibrosis (n=25), and cirrhosis (n=45). HCV RNA, HCV genotypes, inflammatory cytokines AFP and TNFα, 25-hydroxyvitamin D (25[OH]D) levels, apoptotic markers single-stranded DNA (ssDNA) and soluble Fas (sFas), and oxidative stress markers nitric oxide (NO) and total antioxidant capacity (TAC) were estimated by using molecular, immunoassay, and colorimetric techniques.ResultsApproximately 30% of the study population (n=30) were diagnosed as asymptomatic CHC carriers, and 70% of the study population (n=70) had severe fibrosis; these were classified into fibrosis and cirrhosis. There was a significant reduction in 25(OH)D levels and TAC activity, along with an increase in levels of NO, AFP, TNFα, ssDNA, and sFas in fibrosis and cirrhosis subjects compared with those of asymptomatic CHC carriers and health controls. The deficiency in 25(OH)D levels correlated positively with sFas, ssDNA, AFP, TNFα, NO, and TAC, and negatively with age, sex, liver function, body mass index, homeostatic model assessment – insulin resistance, HCV RNA, and viral load. Significant intercorrelation was reported between serum 25(OH)D concentrations and apoptotic and oxidative markers, which suggested progression of liver pathogenesis and fibrogenesis via oxidative and apoptotic mechanisms.ConclusionThe data showed that vitamin D status was significantly correlated with pathogenesis and fibrogenesis of the liver in geriatric patients infected with HCV genotype 4. The deficiency in 25(OH)D levels was shown to have a pivotal role in the pathogenesis of liver via apoptotic, oxidative stress, and inflammatory mechanistic pathways. The data point to adequate vitamin D levels being recommended for a good response to treatment strategies, especially in older CHC patients.

The interplay between vitamin D and viral infections

“…106,135 Apoptosis is another mechanism by which vitamin D is suggested to play a role in EBV and KSHV infections ( Figure 5). 117,127,[136][137][138] It has been reported that EBNA-3 is capable of blocking the expression of VDR-dependent genes involved in growth inhibition and apoptosis. 117 Similarly, vitamin D treatment of endothelial cells and cells transformed by the vGPCR of KSHV was shown to increase the proapoptotic protein Bim through a caspase-3-dependent mechanism.…”

“…Apoptosis is another mechanism by which vitamin D is suggested to play a role in EBV and KSHV infections (Figure ) . It has been reported that EBNA‐3 is capable of blocking the expression of VDR‐dependent genes involved in growth inhibition and apoptosis .…”

Changes in the human transcriptome upon vitamin D supplementation

“…PLS analysis showed clustering of the two study groups (Figure 2), which could not be observed previously when considering all 94 patients (as mentioned in 3.2). For further evaluation, we filtered the data with a log2 fold change of minimum |0.2| and used the resulting 41 genes ( Figure S4 and S5, supplementary information) for analysis of pathways and biological processes (Table 4) both pathways has been implied [40][41][42][43], but its role is not fully understood.…”

Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes

“…Chronic liver inflammation and the subsequent progression to liver cirrhosis and hepatocellular carcinoma (HCC) are typical clinical symptoms of chronic HCV infection. A significant inverse relationship between the severity of inflammatory fibrosis and cirrhosis and serum 25(OH)D 3 levels was observed in HCV patients [32,33,37,40,[62][63][64]. This implies VD deficiency as an independent predictor and risk factor for inflammatory liver complications in HCV patients [38,39,[65][66][67].…”