Background: Increasing evidence suggested that hepatitis C virus (HCV) infection was associated with non-Hodgkin’s lymphoma (NHL). However, no clear consensus has been reached about the clinical features and the effective treatment in HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effect of antiviral treatment or rituximab administration in NHL patients with HCV infection.
Methods: PubMed, Embase, Web of Science, and OVID database were searched for eligible studies up to Feb 28, 2021. Hazard ratio (HR) or odds ratio (OR) corresponding to 95% confidence interval (CI) were calculated to estimate outcomes. Publication biases were assessed by Egger's test and Begg's test. Statistical analysis was performed by software RevMan 5.4 and Stata version 15.
Results: There were 27 shortlisted articles out of a total of 13368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection showed significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42-2.51, P<0.0001) and progress-free survival (PFS: HR 1.58; 95% CI 1.26-1.98, P<0.0001), lower overall response rate (ORR: OR 0.58, 95% CI 0.46-0.73, P<0.00001) and higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61-13.62, P<0.0001) compared with NHL patients without HCV infection. HCV-positive NHL patients exhibited advanced disease stage, elevated level of LDH, high-intermediate and high IPI/FLIPI risk as well as higher incidence of spleen and liver involvement. Moreover, antiviral treatment could prolong survivals (OS: HR 0.38; 95% CI 0.24-0.60, P<0.0001), reduce disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46-0.86, P=0.003] and reinforce treatment response (ORR: OR 2.62; 95% CI 1.34-5.11, P=0.005) in HCV-infected NHL patients. Finally, rituximab administration was associated with a favorable OS while liver cirrhosis and low levels of albumin were inferior prognostic factors of OS for HCV-positive NHL patients.
Conclusions: The current study provided the compelling evidence about an inferior prognosis and distinct clinical characteristics in HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimes were shown to be efficacious to improve clinical outcomes of NHL patients with HCV infection.