1 23
European Journal of Nutrition
ISSN 1436-6207
Volume 50
Number 7
Eur J Nutr (2011) 50:499-506
DOI 10.1007/s00394-010-0156-1
Vitamins B status and antioxidative
defense in patients with chronic hepatitis
B or hepatitis C virus infection
Chun-che Lin, Wen-hu Liu, Zhi-hong
Wang & Mei-chin Yin
1 23
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O R I G I N A L C O N T R I B U T I O N
Vitamins B status and antioxidative defense in patients
with chronic hepatitis B or hepatitis C virus infection
Chun-che Lin•Wen-hu Liu• Zhi-hong Wang• Mei-chin Yin
Received: 18 August 2010 / Accepted: 3 December 2010 / Published online: 24 December 2010 Ó Springer-Verlag 2010
Abstract
Background & Aims The impact of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection upon B vita-mins status and antioxidative defense in infected patients was examined.
Methods Dietary record and blood levels of B vitamins and oxidative stress–associated biomarkers were deter-mined for 195 healthy controls, 132 HBV, and 114 HCV patients.
Results HBV-infected patients had significantly higher levels of total cholesterol, free fatty acids (FFA), and lower ghrelin level (p \ 0.05); and HCV-infected patients had significantly higher Ishak inflammation score and lactate
dehydrogenase activity (p \ 0.05). HBV patients had sig-nificantly lower red blood cell (RBC) vitamins B2and B6 levels, and HCV infection significantly decreased vitamins B2,B6and folate levels in RBC and/or plasma (p \ 0.05). Correlation coefficients of RBC vitamin B2 versus serum FFA in HBV patients, RBC vitamins B2 and B6 versus HCV RNA and Ishak inflammation score, and plasma vitamin B6 vs Ishak inflammation score in HCV patients were \-0.5. HBV-infected patients had significantly higher oxidized glutathione level and lower glutathione peroxidase activity (p \ 0.05), but HCV patients had significantly lower superoxide dismutase and catalase activities (p \ 0.05).
Conclusion HBV or HCV infection enhanced oxidative stress and lowered B vitamins in circulation. In order to avoid other healthy risk, nutrition status should be moni-tored and limitation or supplementation of certain nutrients might be helpful for HBV- or HCV-infected patients. Keywords Hepatitis B virus Hepatitis C virus B vitamins Oxidative stress Lipid metabolism
Abbreviations
ALT Alanine aminotransferase AST Aspartate aminotransferase GPX Glutathione peroxidase GSH Glutathione GSSG Oxidized glutathione Hb Hemoglobin HBV Hepatitis B virus HCV Hepatitis C virus HDL High density lipoprotein LDH Lactate dehydrogenase LDL Low density lipoprotein
C. Lin
Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung City, Taiwan
C. Lin
Institute of Medicine, Chung Shan Medical University, Taichung City, Taiwan
W. Liu
Radiation Safety Office, Chung Shan Medical University, Taichung City, Taiwan
Z. Wang
Department of Nutritional Science, Chung Shan Medical University, Taichung City, Taiwan
M. Yin (&)
Department of Nutrition, China Medical University, 91, Hsueh-shih Rd., Taichung City, Taiwan, ROC e-mail: mcyin@mail.cmu.edu.tw
M. Yin
Department of Health and Nutrition Biotechnology, Asia University, Taichung County, Taiwan
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Eur J Nutr (2011) 50:499–506 DOI 10.1007/s00394-010-0156-1
MDA Malondialdehyde SOD Superoxide dismutase XO Xanthine oxidase
Introduction
Hepatitis B, resulted from hepatitis B virus (HBV) infec-tion, and hepatitis C, resulted from hepatitis C virus (HCV) infection, are two major etiologies of liver diseases in many countries including Taiwan [1, 2]. Both HBV and HCV infections are often chronic and able to progress into liver fibrosis, cirrhosis, and hepatocellular carcinoma [2,3].
B vitamins including vitamin B1(thiamine), vitamin B2 (riboflavin), vitamin B6(pyridoxine), vitamin B12, and folic acid are involved in many important physiological func-tions such as energy metabolism, protein biosynthesis, and cell reproduction. So far, less attention is paid to the influence of HBV or HCV infection upon the status of B vitamins in circulation. On the other hand, ghrelin is an important metabolism-associated hormone and favors a positive energy balance [4]. Our previous study found that liver cancer patients had lower ghrelin and higher choles-terol levels in circulation than healthy controls [5]. How-ever, the variation of ghrelin level and lipid metabolism in HBV- or HCV-infected patients (without cirrhosis or cancer) remains unknown.
It has been proposed that oxidative stress contributes to the progression and deterioration of viral hepatitis [6,7]. The study of Chrobot et al. [8] reported that HBV or HCV infection increased oxidative stress via decreasing SOD and catalase activities. However, that study included chil-dren only and did not examine the impact of HBV or HCV upon the variation of other non-enzymatic antioxidants such as glutathione and vitamin C. Hepatic oxidative DNA damage in liver biopsy samples from HBV- and HCV-infected patients has been investigated [9]. However, liver biopsy examination for patients with viral infection may not be always practical or feasible. In order to enhance understanding regarding the impact of HBV and HCV infection upon oxidative stress and antioxidant defense, both HBV- and HCV-infected patients were included, and oxidative stress–associated biomarkers in circulation from HBV- or HCV-infected patients were examined in this study.
The purpose of this study was to examine the status of B vitamins, lipid profile, and antioxidative defense in HBV-or HCV-infected patients. This study provided several novel clinical findings to elucidate the possibility of nutritional intervention for virus-infected patients in order
to prevent the prevalence and complications of advanced liver diseases.
Materials and methods Patients and healthy subjects
This study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was proved by Ethical Committee of the Medicine Faculty at Chung Shan Medical University. From January 2008 to February 2009, 132 patients with chronic hepatitis B and 114 patients with chronic hepatitis C who had not previously been treated were eligible to enter this study. Patients co-infected with both HBV and HCV and patients with habitual alcohol intake, and any other liver diseases (alcohol-, drug-, or obesity-induced liver disease, autoimmune hepatitis, hemochromatosis, alfa-1 antitrypsin deficiency, Wilson disease or cirrhosis) were excluded. Patients with serum creatinine [1.5 mg/dL, absolute neutrophil count \1,000/ lL, platelet count \50,000/lL, or hemoglobin \10 g/dL were also excluded. One hundred and ninety-five healthy subjects were recruited in Chung Shan Medical University Hospital between January and September 2008. These subjects, confirmed by blood and ultrasound examination, did not suffer from HBV, HCV, or other liver diseases and were included as control group for comparison. The baseline characteristics of healthy controls, HBV and HCV patients are presented in Table1. Informed consent for study par-ticipation was obtained from 132 HBV, 114 HCV patients, and 195 healthy control subjects.
Clinical evaluation
Chronic HBV infection was confirmed by the presence of serum hepatitis B virus surface antigen (HBsAg), HBeAg, and HBV DNA. HBsAg and HBeAg were measured by radioimmunoassay (Abbott Laboratories, Chicago, IL, USA) and electrochemiluminescence immunoassay (Roche Diagnostics, Indianapolis, IN, USA), respectively. After DNA extraction, plasma HBV DNA level was analyzed by the real-time TaqMan polymerase chain reaction with an ABI Prism 7,900 HT sequence detection system (Applied Biosystems, Foster City, CA, USA). Quantitative HCV RNA was measured by Cobas Monitor HCV v 2.0 (Roche Diagnostics, Branchburg, NJ, USA) and qualitative HCV RNA by Amplicor HCV v 2.0 (Roche Diagnostics, Branchburg, NJ, USA). HCV genotypes were determined by a linear probe assay (Inno-Lipa HCV, Innogenetics, Belgium). Percutaneous liver biopsy was performed for patients, and liver necro-inflammation and fibrosis were assessed according to the Ishak scoring system [10].
500 Eur J Nutr (2011) 50:499–506
Dietary record and nutrients analyses
A 3-day dietary record including meal, snack, and drink was obtained from control subjects, HBV, and HCV patients. Nutrient composition in diet was calculated based on Taiwan Nutrient Databases [11]. All subjects did not take vitamins and minerals supplement.
Blood sampling
A peripheral blood sample, 15 mL, from each subject was drawn after an overnight fasting. One ml whole blood was used for vitamin B1analysis. The other 14 mL blood samples was treated to separate plasma or serum from erythrocyte. Biochemical measurements
Blood level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, albumin, red blood cell
(RBC) count, hemoglobin (Hb), total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipo-protein (LDL) cholesterol, triglyceride, creatinine, and uric acid was determined by an autoanalyzer (Dr. Lange LP 420, Berlin, German). Serum free fatty acid (FFA) content was determined by using a commercial kit (Wako Chem-icals, Richmond, VA, USA). Lactate dehydrogenase (LDH) activity in serum was determined using photometric method by an automated instrument (Shimadzu CL-7300, Tokyo, Japan). Plasma immunoreactive ghrelin concen-tration was measured using a commercial radioimmuno-assay kit (Phoenix Pharmaceuticals, Belmont, CA, USA). Plasma level of Se, Cu, and Zn was determined by flame atomic absorption spectrometry (Perkin-Elmer Model 5000; Norwark, CT, USA). The plasma level of a-tocopherol and b-carotene was quantified by a reverse-phase HPLC method [12]. Plasma level of total vitamin C (ascorbic acid and dehydroascorbic acid) was determined by an HPLC method, in which monolithic column and UV detector were equipped [13]. Glutathione (GSH) and oxi-dized glutathione (GSSG) concentrations in plasma were determined by commercial colorimetric GSH and GSSG assay kits (OxisResearch, Portland, OR, USA). The activity of catalase, Cu–Zn superoxide dismutase (SOD) and glu-tathione peroxidase (GPX) in plasma was determined by catalase, SOD, and GPX assay kits (Calbiochem, EMD Biosciences, Inc. San Diego, CA, USA), respectively. Xanthine oxidase (XO) activity was measured spectro-photometrically by the formation of uric acid from xan-thine through the increase in absorbance at 293 nm [14].
B vitamins analyses
The level of vitamins B1, B2, and B6 in whole blood, plasma, or RBC was determined by HPLC methods [15–17]. The status of vitamins B1, B2, and B6was deter-mined as thiamine diphosphate, flavin adenine dinucleo-tide, and pyridoxal-50-phosphate, respectively. Folate and vitamin B12 (cobalamin) were analyzed by radioprotein-binding assays (Bio-Rad Laboratories, Richmond, CA, USA). For folate determination, folic acid as pteroylglu-tamic acid was used for calibration, and its 125I-labeled analog was used as the tracer. For cobalamin determina-tion, cyanocobalamin was used for calibradetermina-tion, and its 57Co-labeled analog was the tracer for cobalamin assay. Lipid oxidation determination
Malondialdehyde (MDA) level in plasma was measured via an HPLC method [18]. Briefly, 0.1 mL plasma was mixed with thiobarbituric acid and phosphoric acid. After heating to 95°C for 1 h, sample was cooled down and mixed with 0.1 mL methanol. HPLC equipped with a Nova-Pak C18
Table 1 Baseline characteristics in healthy subjects (control), HBV, and HCV patients
Parameters Control HBV HCV n = 195 n = 132 n = 114 Gender, M/F 100/95 72/60 59/55 Age 51.4 ± 8.5 48.7 ± 7.3 45.9 ± 9.0 Body mass index
(kg/m2)
25.3 ± 3.0a 24.5 ± 2.8a 23.9 ± 3.4a
Serum ALT (U/L) 33 ± 7a 311 ± 38b 304 ± 47b
Serum AST (U/L) 28 ± 6a 241 ± 30b 260 ± 36b
HBeAg Negative Positive Negative HBsAg Negative Positive Negative HBV DNA, 9 105 –c 5.7 ± 2.2 – HCV RNA, 9 105 – – 6.3 ± 1.9 HCV genotype
1a/1b/2a/2b
NA NA 15/42/37/20 Ishak fibrosis score NA 2.17 ± 1.12a 2.58 ± 1.34a Ishak inflammation score NA 4.28 ± 1.61a 7.05 ± 2.04b
Bilirubin (mg/dL) 0.45 ± 0.18a 0.50 ± 0.17a 0.39 ± 0.22a
Alpha fetal protein (ng/L) 17 ± 3a 34 ± 15a 29 ± 10a Albumin (g/dL) 3.35 ± 0.49a 3.58 ± 0.53a 3.77 ± 0.41a Other diseases COPD 1 4 1 Gout 0 3 4 Diabetes 2 4 3 Renal insufficiency 0 0 1 Hypertension 5 7 3 Values are means ± SD
NA not available
ab In a row without a common letter differ, p \ 0.05 c Too low to be detected
Eur J Nutr (2011) 50:499–506 501
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column (Waters, Millipore, Milford, MA, USA) was used to quantify MDA level. Plasma level of 8-isoprostane was determined via a method described in Konishi et al. [19]. Briefly, 0.5 mL plasma was diluted with a phosphate buffer and applied to an 8-isoprostane affinity column (Cayman Chemical, Ann Arbor, MI, USA). The 8-isoprostane was eluted from this column by adding 1.5 mL of 95% etha-nol and further evaporated under nitrogen. The level of 8-isoprostane was measured by an EIA kit (Cayman Chemical, Ann Arbor, MI, USA) according to the manu-facturer’s protocol.
Statistical analysis
Each measurement was analyzed from 132 HBV, 114 HCV patients, and 195 healthy subjects. Data were assessed for normality using the Shapiro–Wilk test. Skewed data were logarithmically transformed before statistical analysis. Data were subjected to analysis of variance (ANOVA), and difference with p \ 0.05 was considered to be significant. All data presented in this study were mean ± SD. Corre-lation between two variables was calculated by simple regression analysis (Minitab Inc., State College, Philadel-phia, PA, USA).
Results
HBV or HCV infection significantly increased ALT and AST levels, and Ishak fibrosis and inflammation scores (Table1, p \ 0.05). HCV-infected patients had signifi-cantly higher Ishak inflammation score than HBV-infected patients (p \ 0.05). HBV patients had significantly lower dietary fiber and calcium intake than other two groups (Table2, p \ 0.05). The dietary intake of vitamin B6, folic acid, and Se in HCV groups was similar as healthy controls (p [ 0.05), but with greater SD values. As shown in Table3, when compared with healthy controls, HBV patients had significantly higher levels of total cholesterol, LDL cholesterol, FFAs, uric acid, and LDH activity as well as lower plasma ghrelin level (p \ 0.05), and HCV patients had significantly higher levels of FFAs, uric acid, and LDH activity (p \ 0.05).
Blood levels of B vitamins are shown in Table4. HBV patients had significantly lower RBC vitamins B2 and B6 levels than healthy controls (p \ 0.05). HCV infection significantly decreased vitamin B2, vitamin B6, and folate levels in plasma and RBC (p \ 0.05). As shown in Table5, the correlation coefficients of RBC vitamin B2vs serum FFA in HBV patients, RBC vitamins B2and B6vs HCV RNA and Ishak inflammation score in HCV patients, and plasma vitamin B6vs Ishak inflammation score were \-0.5.
Compared with healthy controls, plasma levels of MDA and 8-isoprostane in HBV or HCV patients were signifi-cantly increased (p \ 0.05, Fig. 1), in which HCV infec-tion led to more producinfec-tion of 8-isoprostane than HBV infection (p \ 0.05). As shown in Table6, HBV or HCV infection resulted in significantly lower levels of vitamin C and GSH and higher XO activity (p \ 0.05). Furthermore, HBV patients had significantly higher GSSG level and lower GPX activity than healthy controls and HCV patients (p \ 0.05), but HCV patients had significantly lower SOD and catalase activities than other two groups (p \ 0.05). Plasma level of Se, Cu, and Zn was not significantly dif-ferent among controls, HBV, and HCV patients (p [ 0.05).
Discussion
Elevated serum uric acid in HCV-infected patients has been reported [20]. Our present study found that increased cir-culating uric acid also occurred in HBV-infected patients, which could be explained by enhanced XO activity in those infected patients. In addition, we found that LDH activity was markedly elevated in HBV- or HCV-infected patients.
Table 2 Daily dietary intake in healthy subjects (control), HBV, and HCV patients Parameters Control HBV HCV n = 195 n = 132 n = 114 Energy, kcal 1,732 ± 231a 1,808 ± 187a 1,590 ± 284a Protein, g 73 ± 19a 70 ± 26a 68 ± 16a Carbohydrate, g 214 ± 48a 237 ± 36a 220 ± 51a Fat, g 68 ± 20a 75 ± 32a 61 ± 25a Cholesterol, mg 190 ± 42a 214 ± 29a 208 ± 30a Dietary fiber, g 15.1 ± 3.7b 12.7 ± 2.3a 16.0 ± 3.1b Vit A, lg REc 774 ± 72a 801 ± 64a 735 ± 80a Vit D, lg 7.08 ± 1.42a 8.13 ± 0.75a 6.71 ± 1.68a Vit E, mg 11.3 ± 2.8a 12.2 ± 2.3a 11.0 ± 3.1a Vit C, mg 62 ± 11a 71 ± 14a 66 ± 9a Vit B1, mg 1.16 ± 0.24a 1.10 ± 0.19a 1.32 ± 0.25a Vit B2, mg 1.21 ± 0.17a 1.03 ± 0.31a 1.17 ± 0.20a Vit B6, mg 1.79 ± 0.31a 1.66 ± 0.28a 1.59 ± 0.75a Vit B12, lg 3.57 ± 0.66a 3.61 ± 0.58a 3.48 ± 0.70a Folic acid, lg 342 ± 36a 367 ± 24a 354 ± 72a Ca, mg 730 ± 154b 514 ± 126a 697 ± 181b Fe, mg 11.2 ± 3.3a 12.1 ± 1.8a 10.9 ± 3.1a Zn, mg 9.3 ± 2.1a 10.8 ± 3.0a 10.2 ± 2.5a Cu, mg 3.8 ± 1.0a 3.6 ± 1.2a 4.1 ± 1.5a Se, lg 109 ± 17a 121 ± 14a 115 ± 43a
Values are means ± SD
ab In a row without a common letter differ, p \ 0.05 c Retinol equivalent
502 Eur J Nutr (2011) 50:499–506
Table 3 Metabolic profile in healthy subjects (control), HBV, and HCV patients
Values are means ± SD
abc In a row without a common
letter differ, p \ 0.05
Parameters Control HBV HCV n = 195 n = 132 n = 114 Plasma glucose (mg/dL) 103 ± 14a 99 ± 18a 92 ± 5a HOMA-IR 1.98 ± 0.81a 2.27 ± 1.03a 2.05 ± 0.74a Serum total cholesterol (mg/dL) 128 ± 21a 178 ± 30b 133 ± 23a
HDL cholesterol (mg/dL) 47 ± 7a 44 ± 9a 50 ± 6a
LDL cholesterol (mg/dL) 61 ± 11a 99 ± 21b 67 ± 16a Serum triglyceride (mg/dL) 101 ± 17a 121 ± 21a 109 ± 14a Serum FFA (lmol/L) 267 ± 19a 360 ± 31c 306 ± 22b Serum creatinine (mg/dL) 0.53 ± 0.14a 0.59 ± 0.17a 0.60 ± 0.24a Serum uric acid (lmol/L) 178 ± 23a 237 ± 19b 251 ± 30b LDH activity (U/L) 155 ± 13a 266 ± 25b 304 ± 19c Plasma ghrelin (pmol/L) 141 ± 20b 102 ± 18a 132 ± 14b
Table 4 B vitamins in whole blood, plasma or red blood cell (RBC) from healthy subjects (control), HBV, and HCV patients
Values are means ± SD
abc In a row without a common
letter differ, p \ 0.05
Parameters Control HBV HCV n = 195 n = 132 n = 114 Whole blood vitamin B1(nmol/L) 107 ± 12a 98 ± 15a 91 ± 19a
RBC vitamin B1(ng/g Hb) 425 ± 21a 413 ± 25a 408 ± 19a
Plasma vitamin B2(nmol/L) 66.3 ± 2.2b 67.1 ± 1.8b 57.0 ± 3.1a
RBC vitamin B2(nmoL/g Hb) 2.82 ± 0.30c 2.41 ± 0.26b 1.97 ± 0.33a
Plasma vitamin B6(nmol/L) 20.8 ± 1.4b 21.5 ± 1.0b 16.6 ± 2.0a
RBC vitamin B6(pmoL/g Hb) 332 ± 20c 298 ± 24b 260 ± 18a
Plasma vitamin B12(pmol/L) 328 ± 22a 323 ± 19a 311 ± 27a
Plasma folate (nmol/L) 32.4 ± 2.6b 30.7 ± 3.1b 27.2 ± 2.3a Table 5 Correlation coefficients of B vitamins versus clinical and metabolic features in HBV- and HCV-infected patients
RBC vitamin B1 Plasma vitamin B2 RBC vitamin B2 Plasma vitamin B6 RBC vitamin B6 Plasma folate
HBV infected HBV DNA load -0.055 -0.037 -0.405 0.016 -0.318 -0.102 ALT -0.094 -0.058 -0.319 -0.063 -0.285 -0.205 AST -0.103 -0.091 -0.241 -0.025 -0.206 -0.153 Fibrosis score -0.021 -0.082 -0.258 0.022 -0.224 -0.092 Inflammation score -0.100 -0.095 -0.306 -0.066 -0.351 -0.140 Serum FFA -0.118 -0.084 -0.529* -0.050 -0.451 -0.075 Serum LDL cholesterol -0.070 -0.067 -0.463 -0.018 -0.389 -0.039 Serum uric acid -0.062 -0.071 -0.212 -0.087 -0.194 -0.116 Plasma ghrelin -0.078 0.049 0.389 -0.029 0.268 0.119 HCV infected HCV RNA -0.073 -0.361 -0.646* -0.436 -0.624* -0.314 ALT -0.086 -0.290 -0.378 -0.378 -0.462 -0.280 AST -0.109 -0.214 -0.267 -0.304 -0.321 -0.205 Fibrosis score -0.064 -0.138 -0.274 -0.186 -0.210 -0.146 Inflammation score -0.142 -0.395 -0.605* -0.504* -0.537* -0.259 Serum FFA -0.077 -0.205 -0.323 -0.189 -0.280 -0.182 Serum LDL cholesterol -0.045 -0.096 -0.089 -0.104 -0.106 -0.041 Serum uric acid -0.095 -0.173 -0.286 -0.202 -0.303 -0.142 Plasma ghrelin 0.060 0.033 -0.077 -0.047 -0.106 -0.108 * Correlation coefficient was higher than 0.5 or lower than -0.5
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Because increased uric acid level and LDH activity may impair cardiac or hepatic functions, monitoring the varia-tion of uric acid and LDH for patients with viral hepatitis could benefit understanding their hepatitis progression.
Viral infection is a cause of lipid metabolism distur-bance [21,22]. Kim et al. [22] further indicated that HBV expression promoted lipid accumulation in hepatic cells by mediating sterol regulatory element–binding protein 1. In our present study, HBV patients had similar dietary lipid
intake as healthy controls, but higher circulating levels of total cholesterol, LDL cholesterol, and free fatty acids than healthy controls. These findings agreed that HBV infection was a contributor toward abnormal lipid metabolism. Furthermore, we found that RBC vitamin B2 level was negatively correlated with serum free fatty acids in HBV patients. It is reported that the administration of vitamin B2, via acting as precursors of flavin adenine dinucleotide and flavin mononucleotide, could enhance activity of flavin-dependent acyl-CoA dehydrogenases and ameliorate lipid storage myopathies [23,24]. Thus, it is possible that vita-min B2was used to modify HBV-induced lipid metabolism disorder in these patients, which caused vitamin B2 depletion. Therefore, limiting dietary lipid intake or sup-plying vitamin B2 might be helpful for these patients to minimize the disturbance of lipid metabolism. In addition, we notified that HBV patients had lower plasma ghrelin level. Ghrelin is an appetite stimulant, and its function is to cause a positive energy balance by decreasing fat utiliza-tion through growth hormone independent mechanisms [25]. Decreased plasma ghrelin level has been observed in patients with advanced cancer, cachexia, and weight loss [26]. The lower ghrelin level as we observed in HBV patients might favor the development of catabolic status (or so called negative energy balance) in these patients. Thus, in order to avoid the occurrence of negative energy bal-ance, appropriate nutritional intervention should be con-sidered for these HBV patients, especially when lipid intake is restricted.
In our present study, HBV patients had lower RBC vitamins B2 and B6 levels, but HCV patients had lower plasma and RBC levels of vitamins B2, B6, and folate. The
a a b b c b 0 5 10 15 20 25 30 e n a t s o r p o s i -8 A D M pg/ m L control HBV HCV
Fig. 1 Plasma level of malondialdehyde (MDA) and 8-isoprostane in healthy subjects (control), HBV and HCV patients. Data are mean ± SD.abcAmong bars without a common letter differ, p\ 0.05
Table 6 Plasma level of a-tocopherol, b-carotene, vitamin C, glutathione (GSH), oxidized glutathione (GSSG), selenium, copper, zinc, activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), and xanthine oxidase (XO) in healthy sub-jects (control), HBV and HCV patients
Parameters Control HBV HCV n = 195 n = 132 n = 114 a-tocopherol (lmol/L) 17.4 ± 2.3a 16.8 ± 3.0a 17.1 ± 2.5a b-carotene (lmol/L) 0.59 ± 0.17a 0.76 ± 0.29a 0.63 ± 0.25a Vitamin C (lmol/L) 31.5 ± 3.7b 26.2 ± 2.4a 25.9 ± 3.1a GSH (lmol/L) 15.6 ± 1.0c 11.5 ± 1.8a 13.4 ± 1.6b GSSG (lmol/L) 0.25 ± 0.07a 0.79 ± 0.16b 0.33 ± 0.10a Se (lg/L) 217 ± 9a 214 ± 11a 202 ± 13a Cu (lg/L) 570 ± 38a 596 ± 45a 608 ± 40a Zn (lg/L) 603 ± 56a 611 ± 42a 608 ± 51a GPX (U/L) 267 ± 32b 209 ± 17a 251 ± 24b SOD (U/mL) 20.5 ± 0.28b 19.4 ± 0.17b 15.3 ± 0.23a CAT (U/mL) 14.0 ± 0.38b 13.1 ± 0.45b 10.2 ± 0.26a XO (U/L) 1.65 ± 0.45a 2.53 ± 0.78b 2.66 ± 0.61b
Values are means ± SD
abc In a row without a common letter differ, p \ 0.05
504 Eur J Nutr (2011) 50:499–506
greater SD values for dietary B6 and folic acid levels in HCV patients implied that some of these HCV patients had insufficient B6 and folic acid intake, which partially explained the lower B6and folic acid levels in circulation of HCV patients. However, the observed folate, vitamins B2, and B6 reduction in circulation of these infected patients should be mainly ascribed to viral infection. Especially, HCV infection caused more severe impairment upon host’s B vitamins status. The greater correlation coefficients between HCV RNA load vs vitamins B2and B6 also indicated that HCV played a crucial role in decreasing these two vitamins in circulation. In addition, we found that RBC vitamins B2 and B6 levels in HCV patients were negatively correlated with inflammation score in HCV patients. Gori et al. [27] reported that patients with low concentration of vitamin B6 and high concentration of homocysteine had greater inflammatory injury and a high risk of developing cardiovascular dis-eases. The study of Ullegaddi et al. [28] found that B vitamins supplementation provided both antioxidant and antiinflammatory effects for patients with stroke disease. Thus, the observed lower levels of vitamins B2and B6in HCV patients might be due to host use these vitamins to attenuate hepatic inflammatory stress.
It is known that vitamin B2affects epithelial integrity and rate of prostaglandin biosynthesis [29], and vitamin B6 is a cofactor for many enzymes involved in metabolism [30]. The insufficiency of these vitamins in circulation of HBV- or HCV-infected patients might further impact many physiological functions and induce other complications. Hence, it is important for these patients, especially HCV patients, to obtain sufficient dietary B vitamins intake in order to maintain normal B vitamins associated physio-logical functions. B vitamins supplement based on their water-soluble property should be safe and could benefit infected patients to counteract the impairment caused by viral infection and delay the development of advanced liver diseases such as cirrhosis and cancer. However, it remains unknown that vitamin B6 and other B vitamins could facilitate the replication of HBV or HCV or not. Therefore, the extra supplementation of B vitamins for these patients should be carefully considered.
It has been documented that HBV or HCV infection induced oxidative stress in host [31,32]. The increase in MDA, 8-isoprostane, and GSSG, and decrease in GSH and vitamin C in circulation as we observed agreed that HBV or HCV infection markedly enhanced oxidative injury in these patients. Particularly, the circulating 8-isoprostane was a more sensitive indicator for HCV-induced oxidative stress. Furthermore, we found that blood GPX, SOD, and catalase activities in these infected patients were markedly reduced, which revealed that HBV or HCV diminished antioxidative defense in these infected patients. On the
other hand, we notified that HBV patients had lower cir-culating GSH level and GPX activity; however, HCV patients had lower SOD and catalase activities. These findings suggested that HBV and HCV infection caused different oxidative features. Although HBV and HCV patients involved in our present study already had sufficient dietary intake of Se and vitamin C, these patients still suffered from severe oxidative injury. Thus, the supple-ment of nutrients with antioxidant property or foods rich in antioxidant compounds may benefit these patients to alle-viate oxidative stress caused by viral infection.
In conclusion, this study provided novel clinical findings regarding B vitamins status and oxidative features in HBV-and HCV-infected patients. Both HBV HBV-and HCV infection enhanced oxidative injury. HBV infection promoted lipid metabolism disorder, and HCV infection accelerated B vitamins depletion. In order to avoid other healthy risk, nutrition status should be monitored and limitation or supplementation of certain nutrients might be helpful for HBV- or HCV-infected patients.
Acknowledgments Authors, Lin CC, Liu WH, Wang ZH and Yin MC, would like to thank all subjects participated in this study. Conflict of interest None of the authors reports a conflict of interest.
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