Chronic HCV infection is a major health-related burden in Egypt which affects 14.7% of the Egyptian population. Moreover, the incidence rate of HCV infection was reported to range between 2 and 6 per 1000 every year; this leads to an estimated 170,000 new cases every year to add to the 11.5 million patients suffering from the disease. Chronic infection with HCV is the leading cause of end-stage liver disease, HCC, and liver-related death in Egypt [12]. However, with a recent introduction of genotype 4 effective DAAs to the treatment protocol, there was a revolutionary reduction HCV epidemic in Egypt; DAAs combinations were reported to show high rates of SVR and pan-genotypic clinical efficacy in HCV genotypes 1–6 [13].
On the other hand, the current body of evidence shows a higher prevalence of T2DM among patients with chronic HCV infection, it was proposed that HCV proteins increase serine and threonine phosphorylation of insulin receptor substrate-1, which contributes to insulin resistance. In addition, HCV proteins enhance the release of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, which then upregulate gluconeogenesis and enhance lipid accumulation in the liver [14].
Therefore, it is presumed that effective HCV management would result in improved glycemic control in diabetic patients. A growing body of evidence has shown a promising role of effective HCV eradication on glycemic control of diabetic patients; previous reports showed that the change in HbA1c was greater in those who achieved SVR (0.98%) with DAAs than in those who sustained treatment failure. Also, the use of anti-diabetic medications decreased more in patients who achieved SVR than in those who failed to achieve SVR [15].
This was further confirmed by recent studies focusing on the association of SVR achievement and the glycemic improvement in HCV patients who received DAAs regimen [15, 16]. Meanwhile, we conducted our study only on patients who achieved SVR, in order to verify whether this suggested improvement is occurring to all patients who achieved SVR with DAAs or not.
The drop in average HbA1c level after treatment was greater in 37.6% of our included patients, from 7.98 to 6.88% (yielding a mean HA1C difference more than 1%), than in those for whom glycemic control failed (from 8.24 to 8.34%). Moreover, our results revealed that those who achieved a significant glycemic improvement were less likely to have hepatic fibrosis as presented by the FIB-4 score. In agreement with our findings, Abdel Alem and his colleagues reviewed the clinical records of 65 diabetic HCV patients; there were statistically significant declines in fasting plasma glucose and HbA1c values at SVR24. Notably, whatever the degree of hepatic fibrosis, the level of fasting plasma glucose and HbA1c decreased at SVR24 in comparison to the baseline level. The improvement rate of HbA1c was as high as 78% of the included patients [17].
Another report from Egypt by Dawood and his colleagues who included 460 T2DM patients with chronic HCV genotype 4 infection in order to evaluate the role of DAAs therapy on glycemic status. Their results showed that almost 77% of the patients achieved the improved glycemic control status after HCV-eradication by DAAs; moreover, the HbA1c and fasting blood glucose levels changed significantly 6 months following treatment [18].
In concordance with our findings, Pavone and his colleagues reported a statistically significant reduction in HbA1c, with a reduction of the mean value of 1.95%, during the DAAs treatment [11]. The impact of HCV eradication on the glycemic control was also evaluated by Gilad and his colleagues who studied the clinical characteristics of 122 diabetic patients with chronic HCV infection; the authors reported that HbA1c at the nearest time point before treatment was 8.4% ± 1.9%, compared with 7.8% ± 1.7% after treatment, a mean difference of 0.6% [9].
As regards to our patients who did not achieve the expected glycemic improvement at the end of therapy, this may be explained by two factors as proposed by Hashim et al. (2018); first, the etiology of T2DM in HCV-infected individuals has been postulated to result from either hepatogenous T2DM or classical T2DM due to virally mediated IR. Second explanation, HCV infection may affect glucose level by an autoimmune mechanism on β cells and is not related to IR [19].
However, it should be noted that there were limitations in the present study; the sample size and the duration of follow-up, it is well established that the micro-vascular complications of diabetes, including nephropathy, neuropathy, and retinopathy, improve with lowered HbA1c level. Therefore, early treatment of HCV could potentially slow the onset and progression of micro-vascular complications of diabetes. Given the study period, we were unable to evaluate whether improved glycemic control was durable beyond 3 months. Therefore, larger studies with a longer duration of follow-up are recommended to validate these findings.
