De Re V, Tornesello ML, De Zorzi M, et al. - Since genetic variants of IFNL4 and PDCD1 genes have been shown to affect the spontaneous clearance of hepatitis C virus (HCV) infection, researchers sought to examine the IFNL4 rs12979860 and the PDCD1 polymorphisms in 734 HCV‐positive patients, including 461 cases with liver disease of varying severity and 273 patients with lymphoproliferative disorders to determine the correlation of these genes with patient’s outcome. In patients with HCV‐related diseases, the frequency of IFNL4 rs12979860 C/T or T/T genotypes was significantly higher than blood donors. PBMCs of mixed cryoglobulinemia (MC) patients expressed low levels of PD‐L1 in CD19+IgM+ B cells and of PD‐1 in CD4+ T cells indicating the involvement of regulatory B‐T cell interaction to the pathogenesis of MC. Collectively, the data show a significant contribution of IFNλ4 expression to the development of HCV‐related HCC and an epistatic contribution of IFNL4 and PDCD1 in MC.