Background Hepatitis C is associated with metabolic effects and fatty liver disease. The effect of different direct antivirals on the liver steatosis, and the metabolic profile, still needs to be established. The aim of this study is to determine the effect of achieving the sustained virological response after 12 weeks (SVR-12 weeks) with different combinations of direct antiviral drugs, on the hepatic steatosis, and fibrosis presented by laboratory and transient elastography parameters. Our study population is nondiabetic, chronically infected HCV Egyptian patients and naïve to any form of HCV treatment. Methods This cohort study was carried on 100 nondiabetic HCV treatment-naïve patients attending the Hepatology Clinic, in the Gastroenterology and Hepatology Department, Ain Shams University, and Kobry El Koba Military Hospital. The patients were divided into four groups according to their treatment regimens as follows: group A: 25 patients who received sofosbuvir (400 mg) and daclatasvir (60 mg) daily for 12 weeks; group B: 25 patients who received sofosbuvir (400 mg) and ledipasvir (90 mg) daily for 12 weeks; group C: 25 patients who received ombitasvir (12.5 mg), paritaprevir (75 mg), and ritonavir (50 mg) daily for 12 weeks; and group D: 25 patients who received sofosbuvir (400 mg) and simeprevir (150 mg) daily for 12 weeks. All patients were subjected to the following investigations: HCV quantitative PCR before and after 12 weeks of treatment, clinical and laboratory metabolic evaluation including alfa-fetoprotein level, thyroid profile assessment, ferritin level, pelvi-abdominal ultrasound, and FibroScan examination. Results All patients achieved SVR after 12 weeks. FibroScan median decreased (P < 0.001) from 19.29 ± 6.97 kPa at baseline to 14.15 ± 6.48 kPa at SVR12. NAFLD score median increased from 1.88 (1.49–2.22) at baseline to 2.01 (1.61–2.33) after 12 weeks of treatment. The highest level of NAFLD score was in group C, and the lowest was in group B. The BMI mean decreased from 28.31 ± 1.53 at baseline to 28.07 ± 1.52 at SVR12. HbA1C level mean decreased from 5.73 ± 0.23 at baseline to 5.40 ± 0.24 at SVR12. In addition, liver enzymes, cholesterol, triglycerides, APRI score (AST-platelet ratio index), and HBA1C decreased after 12-week treatment with a statistically significant difference, while the mean LDL increased after 12 weeks of treatment. Conclusions DAAs affect the metabolic profile of the treated patients. There is a noticed improvement in the FibroScan, NAFLD score, and lipid profile after achieving the SVR-12 weeks. However, LDL is increased after viral cure, mostly due to viral-host molecular interaction.