Chronic HCV infection is the leading cause of hepatocellular carcinoma and the leading indication for liver transplantation in developed countries [9]. Newer combination of DAAs offers cure rates exceeding 90%. However, achieving SVR does not immediately reverse HCV related liver fibrosis or cirrhosis [10].
In addition to causing liver disease, CHC infection is associated with wide metabolic disarrangements. HCV interacts with lipid metabolism leading to steatosis, causing wide adipocytokine changes and impairs glucose metabolism leading to increased prevalence of insulin resistance and type 2 diabetes [11]. This association is important because the presence of insulin resistance is associated with increased rates of fibrosis [12] and lower rates of rapid and sustained response to antiviral therapy [13].
The mechanism of how metabolic factors influence disease progression is not clearly understood. Adipose tissue secretes bioactive proteins known as adipokines, including leptin, adiponectin, and resistin. These proteins exert different effects on insulin resistance and inflammation [14].
The behavior of circulating resistin during liver disease owing to viral hepatitis is still under investigation. The current study aimed at determining the value of assessment of serum resistin in prediction of insulin resistance among chronic HCV infected patients and their potential prognostic value in CHC patients under new direct-acting antiviral therapy.
On applying a non-invasive scoring to identify liver cirrhosis among the studied patients, pretreatment FIB -4 was statistically significantly higher in naïve group than in relapse group which could be attributed to decline in steatosis index among relapse group as a result of previous treatment regimen and this was in agreement with Tada et al who stated that viral eradication reduces both liver stiffness and steatosis [15].
In this study, we found that baseline fasting insulin level, HOMA-IR were statistically significantly higher in naïve and relapse chronic HCV patients in comparison to control with P-value <0.001 and these results were in agreement with El Sebaey et al who proved that there is strong link between hepatitis C virus infection and the insulin resistance panel & concluded that Insulin sensitivity improved markedly in patients who achieved SVR [16].
Also in agreement with Adinolfi et al. who stated that the prevalence of insulin resistance & type 2 diabetes in HCV-infected patients is significantly higher than that observed in hepatitis B virus infection & the general population with a direct correlation between viremia and IR levels and the development of type 2 diabetes [3].
Insulin Resistance in HCV patients has been reported to be mediated by the HCV core protein, which interferes with glucose metabolism and insulin signaling by inhibiting the expression of insulin receptor substrate (IRS)1 and IRS2 [17]. HCV-induced IR in the tissue of HCV-infected patients and animal models has also been indicated to be mediated via several cytokines, including tumor necrosis factor-α [18].
The current study results also showed that there was a statistically significant decline in FBS, Fasting Insulin, HOMA-IR in Both naïve and relapse groups of patients after treatment with DAA in relation to their pre-treatment levels And This goes in agreement with previous data that showed that interferon-based treatment improves insulin resistance and blood glucose levels in patients who clear HCV [19].
Another meta-analysis evaluated data from 8 studies comparing the reduction in IR between SVR and non-SVR groups of HCV patients treated with IFN-based therapy indicated no significant difference in the reduction of IR between the SVR and non-SVR groups. However, patients who achieved SVR had a significantly higher mean reduction in HOMA-IR compared to patients in the non-SVR group [18].
The current study results also showed that pre-treatment serum resistin level was statistically significantly higher in naïve and relapse groups in comparison to control group with a statistically significant decline in its post-treatment level in both groups in relation to pre-treatment level.
Concerning the role of resistin in liver damage associated with viral hepatitis, Resistin expression in human liver was found to be increased in alcoholic liver disease, HCV-induced hepatitis or non-alcoholic steato-hepatitis (NASH). Its expression during liver damage positively correlated with infiltration of inflammatory cells, which represent the principal source of intrahepatic resistin [20].
Regarding this, our results matched with Tiftikci et al. who stated that patients with chronic HCV infection had elevated levels of adipocytokines, such as leptin and resistin, in their sera compared to healthy subjects, although low levels of resistin were associated with the presence of fibrosis in the patient group [21].
Although the possible relationship between resistin and anti-viral treatment has been scarcely studied, Our results go in agreement with Durrazzo et al. who found a significant reduction in resistin levels after anti-viral treatment in a group of CHC patients [22]. On the contrary, the analysis by Lo Iacono et al. found no changes in resistin level in a cluster of chronic HCV patients before and after the anti-viral therapy [23].
Nevertheless, it is yet unclear whether the presence of logistic state stresses the action of resistin as a mediator of IR and moreover its real patho-physiological role is still debated in chronic hepatitis [24].
Resistin may play an important role in the regulation of glucose homeostasis and adipogenesis [25] thereby influencing the development of insulin resistance, type 2 diabetes, and endothelial dysfunction, thrombosis, and angiogenesis [5].
The present study showed that baseline resistin level was found to have significant positive correlation with baseline Fasting insulin in both Naïve and relapser group with r value equal 0.756 and 0.725 with P-value <0.001, and with baseline HOMA-IR with r-value 0.877 and 0.789 respectively and P-value <0.001. These results agreed with Makni et al who highlighted a significant correlation between resistin and HOMA-IR through Multiple regression models [26].
Possible explanation could be attributed to the important role of resistin in the inflammatory response associated with chronic liver inflammation, such as hepatitis C and NASH [27]. Resistin presents a directed pro-inflammatory activity or mediated by other cytokines such as interleukin (IL)1, IL6 and the TNFα, through nuclear factor-κB pathway. In the course of chronic liver disease, elevated serum levels have been associated with IR, disease progression, severity, clinical complications, and a more severe prognosis [28].
Finally, the present study revealed the best cutoff value of serum resistin in predicting absence of liver cirrhosis based on FIB-4 score among patients with CHC to be greater than 1800 ng/L. This value had 38.89% sensitivity, 86.36% specificity and an overall accuracy of 57.1%.
It also revealed that the best cutoff value of serum resistin in prediction of presence of significant insulin resistance among CHC patients to be greater than 2400ng/L. This value had 93.55% sensitivity, 33.33% specificity and an overall accuracy of 62.4%.