Results
Our study included 74 patients with HCV infection and 88 individuals
without HCV infection. Demographic characteristics and laboratory
findings of the patient and control groups are summarized in Table1. The
mean HCV-RNA of patients with HCV infection was 1513297.6 ± 2898584
IU/mL, and the distribution of the genotypes (gp) was as follows: gp 1a,
10%; gp 1b, 47%; gp 1, 12%; gp 2, 20%; gp 3, 8%; and gp 5, 3%.
There was no significant difference in age, gender distribution, body
mass index, smoking, or comorbidities (diabetes mellitus, hypertension,
cardiovascular disease, chronic renal failure, hyperlipidemia, and
asthma/chronic obstructive pulmonary disease) between the HCV patients
and controls (p >0.05). ALT, AST, GGT, total protein, total
bilirubin and direct bilirubin levels were significantly higher in the
HCV group compared with the control group, whereas the albumin level was
significantly lower (p <0.05 for all). Leukocyte and platelet
counts, as well as urea, creatinine, PT, and INR values were similar in
the two groups (p >0.05) (Table1).
As shown in Table 2, the NT, TT, and NT/TT levels were significantly
lower in the HCV group than in the control group, whereas the DS, DS/NT,
and DS/TT levels were significantly higher (p <0.05 for all).
The TOS and OSI levels were significantly higher and the TAS levels were
significantly lower in the HCV group than in the control group
(p < 0.001 for all).
In the correlation analysis between oxidative stress markers (TAS, TOS,
OSI and DTDH) and liver function tests (albumin, ALT, AST and bilirubin)
in the HCV group, there was only a negative correlation between OSI and
albumin (r = -0.301, p= 0.009).
DiscussionGrowing evidences suggest that oxidative stress caused by disruption of
the balance between ROS and antioxidants is associated with the
pathogenesis and progression of CHC.2-4 Induction of
NADPH oxidases by HCV proteins, HCV protein-mediated mitochondrial
dysfunction, production of various cytokines, decreased GSH output, iron
overload, induced antioxidant gene expression and increased expression
of HCV core protein and cytochrome P450 2E1 have been reported as the
possible sources of ROS in HCV infection.16Antioxidant defense systems remove increased ROS to maintain the redox
balance in the liver.5 Thiols are one of the
antioxidants that protect cells and tissues against oxidative damage.
Under oxidative stress, thiols can be oxidized by oxidant molecules to
form reversible DS bonds and thereby resulting in altered DTDH.
Therefore, DTDH is an important indicator used to evaluate the presence
and intensity of oxidative stress.8
Many previous studies found that total thiol levels measured using the
Ellmann’s method were significantly lower in patients with HCV infection
than in those without.17-19 However, there were no
data on DTDH in these studies because the level of DS, the thiol
oxidation product, could not be determined with this method. Both
components of the DTDH can be measured simultaneously using the
automated colorimetric method developed by Erel and Neselioglu in 2014,
thereby this balance can be fully evaluated.8 Prior to
the availability of this technique, the thiol and disulfide levels of
low molecular weight thiols (LMWTs), such as glutathione (GSH),
glutathione disulfide (GSSG), cysteine (Cys) and cystine (CySS), were
generally measured to evaluate the status of DTDH.8However, LMWTs constitute only a small part of the plasma thiol pool; a
large part primarily comprises albumin and protein
thiols.20 Therefore, we assume that the low molecular
weight thiol/disulfide homeostasis such as GSG/GSSG and cys/CySS may not
precisely reflect body DTDH.
Lin et al.21 found that the levels of GSH, a
predominant LMWT, were low and GSSG were high in HCV group before
treatment compared with the control group; however, it was observed that
the GSSG level decreased after treatment. Jain et al.4showed that the plasma GSSG/(GSH + GSSG) ratio in patients with HCV
infection was significantly higher than in the controls. Similarly,
another study demonstrated low GSH and high GSSG levels in HCV patients,
suggesting a high GSH turnover.22 Consistent with
these studies, we found that NT level, TT level and NT/TT ratio were
significantly lower and DS level, DS/NT ratio and DS/TT ratio were
significantly higher in HCV group compared to the control group. These
results indicate that DTDH is disturbed and shifts to the DS side in
patients with HCV infection. This shift reveals that patients with HCV
infection are exposed to high oxidative stress. This increased oxidative
stress in CHC may be due to chronic inflammation and continuous
production of ROS in HCV-infected cells.16 Similarly,
researchers have observed that the DTDH shifted to the DS side in other
infectious diseases such as chronic hepatitis B,9 and
Crimean-Congo hemorrhagic fever,10brucellosis.23
In our study, we also found no correlation between DTDH parameters and
albumin, ALT, AST, and bilirubin levels, which is in concordance with
some previous studies.3,17,18 In contrast, some
researchers reported that ALT and AST were negatively correlated with
GSH and positively correlated with GSSG in HCV-infected
patients.24-26 These conflicting results may be due to
differences in the characteristics of the patients with HCV infection
included in the studies, such as disease stage and the presence or
absence of HCV-related liver disease.
Several studies have demonstrated that antioxidant therapy may have a
beneficial effect on normalization of ALT, decrease in viral load and
improvement of liver histology in patients with HCV
infection.27,28 In that aspect, we believe that
compensation for the thiol deficiency with thiol resources such as
N-acetylcysteine and alpha-lipoic acid may improve the efficacy of
treatment in these patients.
To assess oxidative stress, TOS and TAS measurements may provide more
valuable information than individual measurements of each oxidant and
antioxidant molecule.13,14 Therefore, in this study,
TAS, TOS, and OSI values of the HCV and control groups were also
compared. We observed that the TOS and OSI values were higher and the
TAS level was lower in the HCV group compared with the control group, as
in a previous study.19 These results indicate
increased oxidative stress in HCV infected patients.
There are some limitations in this study. It was conducted with a small
number of participants in a single center. Furthermore, the relationship
between the progression of CHC disease and the DTDH status was not
examined.
ConclusionTo the best of our knowledge, the present study is the first to examine
the DTDH status in patients with HCV infection. DTDH shifted toward DS
formation in patients with HCV infection. The TOS and OSI levels were
significantly higher and TAS level was significantly lower in HCV group
compared to the control group. These results indicate that patients with
HCV infection are vulnerable to oxidative stress and have disturbed
status of oxidant- antioxidant. This study supports the view that
oxidative stress plays a role in the pathogenesis of CHC.