Musa Nima Mezher, Dhuhah Hayder Abdul Jawad
College of Science-Kufa University-Iraq
*Corresponding Author E-mail: musan.alabbasi@uokufa.edu.iq
ABSTRACT:
This study was conducted to detect the role Tumor Necrosis Factor- Alpha in Hepatitis C virus infected patients and type 2 diabetes mellitus induction. The study included 150 hepatitis C virus suspected patients attending Al-Hakeem Hospital/Central Laboratory in Al-Najaf province, over a period of 7 months from August (2014) to 7 February (2015), there ages ranged from (14-67) years old from both genders. Hepatitis C virus infection and diabetes mellitus detected based on clinical and laboratory investigations e, sixty four patients were found to be seropositive result to Hepatitis C virus , fourteen of HCV infected patients have type 2 diabetes mellitus and Eighteen individuals without any signs or symptoms of disease were selected as normal control group.
Serum level of tumor necrosis factor- alpha was measured through enzyme linked immunosorbant assay technique, the level of tumor necrosis factor- alpha showed a high significance (P<0.05) elevation in the serum of all patients than control. Also the hepatitis C virus with type 2 diabetes mellitus patients have an increased level of tumor necrosis factor-alpha (194.4pg/ml) than HCV patients without diabetes(124.6pg/ml), but these increase not significantly .Statistical analysis showed a positive association between HCV seropositive and tumor necrosis factor- alpha. Increment of serum level in HCV infected patients may lead to developed type 2 diabetes mellitus.
KEYWORDS: Hepatitis C Virus; Mellitus; Diabetes.
1. INTRODUCTION:
Hepatitis C is infectious disease caused by hepatotropic virus that attacks the liver cells and leads to scaring of the liver which is generally apparent after many years called Hepatitis C Virus (HCV)1. Several studies show the relationship between HCV and type 2 diabetes mellitus (T2DM), also reported that HCV infection may increase the probability of diabetic development specially type 2, T2DM is one of most complication of liver infection, independently of the etiology, especially at the advanced stage.2
However, clinical and experimental information suggest an very essential role of HCV in the defect of glucose metabolism, the observation of T2DM in cirrhotic patients have HCV infection more often than patients with cirrhosis of other etiology occurred in 1994 by Allison.3
Tumor necrosis factor- alpha (TNF-α) has a pivotal role in the inflammatory processes of HCV infection and it is level related with the inflammation degree, also it can induce insulin resistance by diverse mechanisms, both direct and indirect.4
last study has been recommended that chronic sub-clinical inflammation is related with insulin resistance, then leads the type 2 DM development, Furthermore, in many researches, levels bio-markers of inflammation like, TNF-α linked with insulin sensitivity and with syndrome characters of insulin resistance.5 TNF-α may even decrease β-cell role by direct inhibiting the tyrosine "phosphorylation of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2(IRS-2)" further contributing to its role in the development of diabetes .6 Excessive TNF-α response in patients with HCV has been submitted as a potential mechanism of increased progress of T2DM in this patient community.7
2. MATERIALS AND METHODS:
The blood samples were collected from AL-Hakeem Hospital in AL-Najaf City, during the period from 23 August (2014) to 7 February (2015). The anti-HCV-IgG measured depending up on commercial kit(Third Generation HCV enzyme linked immunosorbent assay kit from DALAB, Austria), fasting serum glucose test was assayed at clinical biochemistry laboratory by automated laboratory method and Tumor necrosis factor alpha level was determined by enzyme linked immunosorbent assay (Ray Bio ,USA), .Patients with diabetes mellitus only , having end stage renal disease , and patients with other viral infection or under viral therapy are excluded . Data were analyzed by using the software Statistical Package social sciences (SPSS) version 16.Values of p < 0.05 were considered to be statistically significant and results were expressed as means ± standard error (SE).
3. RESULTS:
Total of 150 patients were suspected with hepatitis C virus their age are ranged between (14-67) years both male and female, 64cases of chronic hepatitis C virus from which 14cases only were diabetic , 18 healthy individuals without any signs or symptoms of disease and diagnosed by some serological tests were selected as normal control groups .The patients were distributed to four groups based on age (A1-6), gender( M and F), T2DM (A and B), and residency (R and U).
The results revealed that an increase in the specific anti-HCV IgG antibody level in all groups of patients in comparison to healthy control groups. The seropositive hepatitis C according to the age showed high significant increased (p> 0.05) in all groups reached to (2.041 IU/ml ) in (A4) group, while in male revealed to (1.746 IU/ml ), in patients with T2DM (1.961 IU/ml ) and in rural group (1.761 IU/ml) are recorded a highest mean as compared to other patients groups and health control group (0.2862 IU/ml) as shown in table 1.
Table 1: Mean ± SE serum level of IgG in patients and healthy control groups .
|
Para meters |
Control (n=18) |
Patients groups |
P value |
|||||||||||
|
Age patients |
Gender |
T2DM |
Residency |
|||||||||||
|
A1 (n=16) |
A2 (n=3) |
A3 n=6)) |
A4 (n=9) |
A5 (n=6) |
A6 (n=24) |
M (n=30) |
F (n=34)) |
A (n=50)) |
B (n=14)) |
R (n=35) |
U (n=29) |
|||
|
IgG (IU/ml) |
0.2862 ± 0.014 |
**1.663 ± 0.160 |
***1.893 ± 3.596 |
**1.668 ± 0.135 |
***2.041 ± 0.194 |
**1.783 ± 0.212 |
**1.681 ± 0.121 |
**1.746 ± 0.104 |
**1.718 ± 0.098 |
**1.666 ± 0.070 |
***1.961 ± 0.170 |
**1.706 ± 0.096 |
**1.761 ± 0.107 |
<0.05 |
A1: the group of patients with the age (≤25) years ; A2: the group of patients with the age (26- 30) years; A3: the group of patients with the age (31- 35) years; A4: the group of patients with the age (36- 40) years; A5: the group of patients with the age (41- 45) years; A6: the group of patients with the age (> 45) years; M :Males with HCV infection ; F :Females with HCV infection; A :Patients with HCV only; B :Patients with HCV-T2DM; R :Patients how life in Rural; U :Patients how life in Urban.
The results revealed that an increase in TNF- α level in groups of patients in comparison to healthy control group (7.411 pg/ml ), The results revealed that an increase in TNF- α level in all groups of patients in comparison to healthy negative control group, hepatitis C patients group with age (31-35) years perform high significant(881.4pg/ml), where is male (375.2pg/ml), T2DM (194.4pg/ml), and urban (387.7pg/ml) as shows in table 2 .
Table-2: Mean ± SE of TNF-α (pg/ml) in the patients and healthy groups .
|
Para meters |
Control (n=18) |
Patients groups |
P value |
|||||||||||
|
Age patients |
Gender |
T2DM |
Residency |
|||||||||||
|
A1 (n=16) |
A2 (n=3) |
A3 n=6)) |
A4 (n=9) |
A5 (n=6) |
A6 (n=24) |
M (n=30) |
F (n=34)) |
A (n=50)) |
B (n=14)) |
R (n=35) |
U (n=29) |
|||
|
TNF-α (pg/ml |
7.411 ± 1.141 |
*169.7 ± 41.29 |
***78.27 ± 49.37 |
*881.4 ± 611.4 |
*130.6 ± 47.34 |
*96.87 ± 30.22 |
*114.3 ± 36.55 |
**375.2 ± 187.8 |
*136 ± 23.51 |
*128.2 ± 33.5 |
*194.4 ± 31 |
*132.4 ± 23.11 |
**387.7 ± 193.9 |
<0.05 |
*Statistically significant p value<0.05 .
4. DISCUSSION:
Hepatitis C virus is a one main cause of disease and death rate in the world, it is responsible for about twenty-five percent of both Chronic liver disease and Hepatocellular carcinoma, although HCV is hepatotrophic virus, it has also been associated with many extra-hepatic manifestation one of which is T2DM .8,9 Diabetes mellitus are common worldwide disease with a significant influence on population, a great incidence of type 2 diabetic mellitus among patients who were infected with hepatitis C have been reliably recorded and there is many evidence and studies support the concept "that HCV infection is a risk factor for developing T2DM".10
The present study has found that HCV infection rate at the general population was 64 /150(42.6 %) were HCV infection suspected individual by using specific anti-HCV IgG third generation of ELISA technique. However the age group ( > 45) years old has a highest percentage (37.5%), high prevalence of HCV infection was recorded in aged group more than 45 years old as in table 1.This result compatible with results of Amjad et al.,(2010)in Pakistan concluded that the prevalence of HCV increased with increases of individual and people with aged more than 41 years old have highest prevalence. 11Likewise, a highest prevalence of HCV among patients with age (31-40) years and males group was reported by Kolawole et al.(2013),12 also Hanan et al.(2014)in Baghdad noted that an increase chance of infection in older age and males.13 The prevalence T2DM in HCV general population of the current study was constituted 14 (21.9 %) patients .The incidence of T2DM in HCV patients was attributed to two reason, firstly, pathophysiology of HCV-associated type 2 diabetes mellitus consists of a defect in insulin secretion, increased hepatic tumor necrosis factor alpha, excessive hepatic glucose production, and insulin resistance, because the core-encoding region of HCV is sufficient to induce IR by the previously defined mechanism via either direct or indirect way.14 Secondly, a major contribution of already present risk factors of diabetes such as positive family history and advancing age also plays an important role among HCV infected patients .15
Muhammad et al., (2013) in Southeast Asian reported that the prevalence of T2DM as 31.5%(114/361) in HCV seropositive patients whose age was < 40 years.16 Also recent data also suggest three times higher prevalence of type 2 diabetes in HCV seropositive patients as compared to non-HCV-infected control group .17
The study of Aslam et al., (2014) in Pakistan, observed that the prevalence of T2DM as (28%) is more common in patients with CHC than those without hepatitis and of the 28 diabetic patients, 18 (68.28%) were over 45 years of age, so increasing in age is a one of many risk factors for its development.18
Knobler and Schattner, (2005) reported that HCV patients have elevated serum TNF-α and the activation of this cytokine has a crucial role in the inflammatory immune process of CHC also suggested that a possible link between HCV infection and diabetes.4 In fact , in chronic HCV patients , an increased intrahepatic TNF-α response, which results in IR and a high risk of developing T2DM has been described.19
The results of this study demonstrated that the level of TNF-α in serum was increased significantly in all aged groups. The HCV patient with T2DM were recorded a high TNF-α level (194.4 pg/ml)as contrast HCV- non diabetes patient (128.2 pg/ml) but no significant difference in two patients groups (p <0.0001) .
The present study also, showed a significant increase in TNF–α level in HCV-T2DM patients group when compared with control group, figure 2
Knobler et al., (2003) reported that TNF-a receptors were increased in HCV+DM patients compared with HCV and controls and the increase TNF-α response characterize HCV seropositive patients who develop DM , Moreover the control of excessive synthesis and response to TNF-α can delay the development of T2 DM.20
Laila et al., (2010) reported that TNF-α level may be considered as a biomarker for T2DM and critical stage in chronic HCV infected patients.21 Another study by May et al.,(2011) who showed that TNF-α level was elevated in HCV-T2DM patients as compared healthy controls with and explained the role of over production of TNF-α inflammatory cytokine that result from HCV infection in development of T2DM via insulin resistance.22
Unlike our results, lower serum level of TNF – α was assessed in HCV patients in comparison with healthy control group, They revealed that serum level of TNF – α increased in the hepatic inflammation fibrosis process in HBV and HCV.23
Another studies reported that the HCV patients group have a higher level of TNF-α compared with HCV-T2M patients and diabetes mellitus alone, but this increase was not significant .24
5. CONCLUSIONS AND RECOMMENDATIONS:
This study concludes that the HCV infected patients have a high risk to developed diabetes mellitus type II due to abnormal glucose metabolism also high concentration of inflammatory cytokines (TNF-α) play crucial role in pathogensis of HCV that lead to T2DM,therefore, the early detection and control of HCV infects and other liver viruses necessary. Through our study, we Recommend finding a relationship between insulin secretion and TNF- α activity in HCV infection.
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Received on 08.09.2017 Modified on 25.09.2017
Accepted on 19.10.2017 © RJPT All right reserved
Research J. Pharm. and Tech 2017; 10(10):3260-3263.
DOI: 10.5958/0974-360X.2017.00578.9