الفهرس 
Insulin ResistanceOnly 14 pages are availabe for public view
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Abstract
Large community-based studies have shown that hepatitis C virus (HCV) infection is strongly associated with insulin resistance(IR) In addition, a high prevalence of both diabetes and impaired fasting glucose has been reported in HCV-infected patients in comparison with other chronic liver diseases .
Although the specific mechanisms involved in the pathogenesis of diabetes associated with HCV remain to be elucidated, it seems that insulin resistance plays an essential role . High levels of proinflammatory cytokines have been found in HCV-infected patients and, thereby, they could be involved in the pathogenesis of insulin resistance associated with HCV. Insulin resistance and type 2 DM are closely associated with a chronic inflammatory state resulting from abnormal cytokine production, increased acute phase proteins and other mediators, and activation of a network of inflammatory signalling pathways.
Our study is one of the few studies in which insulin secretion, insulin resistance, and proinflammatory cytokines have been measured in HCV-infected patients with chronic hepatitis in comparison with HCV negative patients with chronic liver disease of other etiologies. Our study included 90 patients with chronic liver disease divided into 3 groups according to the etiology of liver disease.
Group I included 30 HCV positive patients,
Group II included 30 HBV positive patients
Group III included 30 bilharsial patients
All participants were subjected to detailed history taking, thorough clinical examination, BMI calculation as well as laboratory investigations (complete blood picture, liver function tests, hepatitis markers, fasting glucose,fasting insulin and abdominal ultrasonography).
Insulin resistance was evaluated using the HOMA-IR index and insulin secretion was evaluated according to the HOMA- ß index.
In our current study, we evaluated the prevalence of insulin resistance in patients with HCV infection and compared it with patients infected with HBV and bilharziasis. Furthermore, we measured the levels of CRP, TNF_αand IL-6 as markers of the innate immunity to observe the possible association between activation of the innate immune system and the development of insulin resistance in patients with chronic liver disease .
Our results demonstrated an increase in prevalence of insulin resistance among all the three groups and especially in HCV infected patients. Mean level of Homa-IR in the 3 groups was 4.6, 2.7 and 2.6 in groups I, II and III respectively. Additionally, the incidence of insulin resistance in the 3 studied populations was highest (86.7%) among group I (HCV) in comparison to 46.7% in group II (HBV) and 63.3% in group III (bilharsiasis) .
We also demonstrated an increased levels of pro-inflammatory cytokines (CRP, TNF_α and IL_6) suggesting that the overproduction of pro-inflammatory cytokines could play a crucial role in the pathogenesis of insulin resistance in chronic liver disease. Mean levels of high sensitivity CRP in groups I, II and III were 5776.66, 5103.33 and 6416.66 respectively. Mean level of TNF-α in group I was 367.13, in group II was 262.97 and in group III was 308.43 The mean level of IL-6 in group I was 313.63, in group II was 230.64 and in group III was 294.40.These findings suggest an important role of the innate immunity in the development of insulin resistance in patients with chronic liver disease irrespective of its etiology.
On the other hand, insulin secretion was higher in HBV infected patients in comparison to HCV and bilharsial patients. This is explained by the fact that early-stage insulin-resistance and related mild glucose intolerance may be compensated for by increased insulin secretion. When combined with impaired insulin secretion, insulin resistance plays an important role in type 2 diabetes. Thus insulin resistance in HCV infected patients indicates a later stage than insulin resistance in HBV and bilharsiasis. Insulin resistance in HCV should be considered an alarming sign as it is associated with a decline in insulin secretion therefore indicating a pre-diabetic stage.
from this aspect, we can conclude that insulin resistance is more correlated to HCV infection than to HBV infection and bilharsiasis.
Investigating the association between HCV and DM is highly important. It represents a major public health problem that probably affects hundreds of thousands of patients. Many more HCV-infected patients may have impaired glucose tolerance before becoming overtly diabetic. DM may also adversely affect the course of chronic hepatitis C and be associated with increased liver steatosis and fibrosis, and recent evidence suggests that steatosis and diabetes may also significantly enhance the risk of hepatocellular cancer.
These patients may be less responsive to interferon therapy and may show an increased prevalence of hepatocellular cancer . Finally, elucidating the risk factors and associated features of the HCV-diabetes association may shed a light on novel and intriguing mechanisms of disease. The HCV-DM association may constitute an example in which an exaggerated TNF response is deleterious to the host . Future research should focus on reaffirming this conclusion and defining effective interventions and strategies to block the local TNF response.
In conclusion, IR should be assessed in patients with CHC, since IR is a risk factor for fibrosis progression. Antiviral treatment of the patients at risk is recommended as soon as possible, to selectively improve treatment outcome in these patients and thus prevent fibrosis progression while specific pharmaceutical treatment of insulin resistance is not yet established. Towards the future, HCV infection needs to be viewed not only as a liver disease but also as a metabolic disease