Hepatitis C infection was a serious problem. Over 50 million individuals were successfully screened, and 4 million people were treated.

Hepatitis C Virus (HCV) also affects lymphocytes, which explains why non-Hodgkin lymphoma, primarily diffuse large B cell lymphoma (DLBCL), often accompanies HCV infection. Direct Acting Antivirals (DAAs) treatment of HCV has dramatically resolved this problem, but there has been debate about its relationship to the accompanying lymphoma. Cell-free DNA (cfDNA) is a reliable non-invasive biomarker for multiple malignancies, primarily lymphoma. It can aid in prognosis and drug-tailored treatment plans, especially with HCV and DAAs.

Objective: This study aimed to evaluate cfDNA as a prognostic biomarker for DLBCL patients.

Method: The study was conducted on three groups of subjects: Group 1: DLBCL patients positive for HCV, this group was subdivided to: Group (1A): DLBCL patients positive for HCV [receiving DAAs].Group (1B): DLBCL patients positive HCV [did not receive any treatment for HCV]. Group 2: DLBCL patients negative HCV. Group 3: Control group. All participants underwent full history, clinical examination, routine laboratory investigations and quantitative measurement of cfDNA by real-time PCR.

Results: Our study reveals that cfDNA levels are significantly higher in DLBCL patients positive for HCV who did not receive any treatment for HCV (Group 1B), as well as in advanced lymphoma stages. Additionally, we found a high mortality rate among patients with elevated cfDNA. These findings highlight the complex relationship between DLBCL, HCV, and DAA treatment, emphasizing the need for tailored management strategies and increased surveillance in this patient population.

Conclusion: cfDNA has a valuable prognostic and monitoring role in DLBCL, particularly with HCV infection.