Impact of combining metformin or lifestyle modifications with direct-acting antivirals on hepatic steatosis and glycemic control in HCV prediabetic patients

Abstract Background Several metabolic disorders have been linked to chronic hepatitis C virus (HCV) infection, especially HCV related hepatic steatosis, insulin resistance, and lipid dysregulation. We aimed at comparing the effects of treatment of HCV direct-acting antivirals (DAAs) alone versus DAAs combined with metformin or lifestyle modifications on improving glycemic control and reducing hepatic steatosis in prediabetic patients chronically infected with HCV. Methods We enrolled 150 chronic HCV-infected patients with confirmed diagnosis of prediabetes [glycosylated hemoglobin (HbA1c) = 5.7–6.4%] and hepatic steatosis as measured by controlled attenuation parameter (CAP). The patients were randomly divided into 3 groups, group 1 received DAAs only, group 2 received DAAs combined with lifestyle modifications, and group 3 received DAAs with metformin. Liver steatosis at baseline and at sustained virological response (SVR) 12, body mass index (BMI), and glycemic parameters were assessed. Results Out of 150 patients, 148 patients completed the study and achieved SVR12. At baseline, no differences in demographic, laboratory, liver steatosis characteristics were seen between the 3 groups. At SVR12, glycemic parameters improved significantly in all 3 groups while steatosis significantly decreased in groups 2 ( p < 0.001) and 3 ( p = 0.014) only. Comparing the delta change of CAP, BMI, HbA1c, and fasting blood sugar (FBS) among the 3 groups showed significant differences ( p = 0.004, p < 0.001, p = 0.007, p = 0.006 respectively). Pairwise group comparison showed superiority of groups 2 and 3 in improving glycemic state while liver steatosis improvement was maximum in group 2. Conclusion Combining DAAs with lifestyle modifications or metformin in HCV-infected patients with prediabetes and hepatic steatosis can significantly improve glycemic control and steatosis compared to DAAs alone.