BACKGROUNG: Type 1 herpes simplex virus (HSV1) is a ubiquitous pathogen and is known to induce liver dysfunction. Seroprevalence and clinical implications of HSV-1 among chronic hepatitis C virus (HCV)-infected patients are poorly defined OBJECTIVE: The study goal was to evaluate HSV1 seroprevalence in chronic HCV patients and healthy controls as well as to demonstrate the clinical outcomes of HCV/HSV-1 co-infection, focusing on the relationship between HSV1 antibodies and liver fibrosis and cirrhosis progression. METHODS: The current study involved 120 participants (80 chronic HCV patients and 40 controls). All participants underwent the measurements of HCV RNA and baseline clinical parameters. Serum samples were investigated for HSV1 IgG and HSV1 IgM antibodies by ELISA. The APRI score was calculated to evaluate liver fibrosis and cirrhosis. RESULTS: A significant increase in the incidence of seropositivity of HSV1 IgG antibodies (P 0.004) was detected in HCV patients (80/80,100%), compared to controls (36/40, 90%), whereas the tendency of the increase in seropositivity of HSV1 IgM antibodies was detected in HCV patients (HCV/HSV1 co-infection, 20/80, 25%), compared to controls (4/40,10%). In HCV/HSV1 co-infection, a significant increase in GGT and ALP as well as a tendency of increase in ALT was reported beside a significant decrease in PLC compared to HCV mono-infected patients. At APRI score cutoff ≥ 1.5, HCV patients were identified with late fibrosis (≥ F2, n = 40). However, at the APRI score cutoff > 2, HCV patients were identified with cirrhosis (F4, n = 24). At high APRI score cutoff values, a non-significant change in seropositivity of HSV-1 IgM antibodies between HCV patients with early fibrosis and those with late fibrosis was observed (P > 0.05). At high and low APRI score cutoff values, non-significant changes in seropositivity of HSV1 IgM antibodies among the groups of HCV patients in relation to liver fibrosis and cirrhosis were observed (P > 0.05). However, at a low APRI score cutoff value of 1, a significant increased incidence of higher HSV1 IgG antibody titre (> mean value) was observed to be associated with the lower probability of ruling out cirrhosis among chronic HCV patients (Odd's ratio 0.20, 95% C.I. 0.0606 to 0.6604, and P 0.008). CONCLUSION: Our results shed light on the establishment of HSV-1 reactivation among chronic HCV patients. Increased incidence of HSV-1 IgG antibodies is observed in chronic HCV infection. In the studied cohort of HCV patients, the seroprevalence of HSV1 IgM antibodies is not associated with liver fibrosis and cirrhosis progression. However, the increased incidence of higher HSV1 IgG titre is associated with a lower probability of ruling out cirrhosis.