Abstract Background Medical treatment of decompensated cirrhosis due to hepatitis C virus (HCV) remains a clinical challenge even in the era of direct-acting antiviral drugs (DAAs). We evaluated the efcacy and safety of DAAs in the management of HCV genotype 4-related decompensated cirrhosis. Methods The study included a treatment group (n=160) composed of HCV patients with decompensated cirrhosis who received DAAs for 3 months and a matched control group (n=80) who preferred not to receive DAAs, follow-up was for 24–31 months. Results In treatment group; there were improvements in platelet count, albumin, CTP (p=0.001) and MELD scores (p=0.03), a signifcant reduction in the frequency of hepatic encephalopathy (HE). SVR was achieved in 90%. Hepatocel￾lular carcinoma (HCC) developed in 10% (n=18) within 6.8±2.5 months after DAAs, survival was higher in the treated vs. the control group (28.9±0.95 vs. 11.4±2.2 months, p=0.001). Liver volume by ultrasound at a cutof 495 ml was predictive of complications after DAAs therapy mainly HCC and reduced survival with sensitivity 93.2%, specifcity 72%. Conclusion HCV with decompensated cirrhosis and adequate liver volume had a 90% SVR with improved CTP&MELD and survival. Clinical trial: (NCT03547895)