Inflammatory milieu alterations associated with carcinogenesis persist in cirrhotic patients despite HCV cure

Background Chronic hepatitis C virus (HCV) infection can lead to cirrhosis, hepatocellular carcinoma (HCC) and extrahepatic manifestations. A sustained virological response (SVR) is achieved with direct-acting antivirals (DAA) in over 95% of the patients, but sequelae of chronic HCV infections do not improve in all patients, suggesting permanent biological alterations. Therefore, we investigated the influence of chronic HCV infection, viral elimination and cirrhosis on soluble immune mediators (SIM).

Methods In 102 chronic HCV patients, 46 with and 56 without cirrhosis, 92 SIM were measured in plasma samples at therapy start, end of treatment and long-term follow-up (median 96 weeks). 8 of the cirrhotic patients developed HCC after the last sampling point. Thirty-nine HBsAg positive persons with HBeAg negative infection served as controls.

Results At baseline, 42 SIM were altered in chronic HCV patients (adj.p<0.05). Notably, patients with cirrhosis displayed both a higher frequency and more severe alterations. At long-term follow-up, SIM of non-cirrhotic patients were restored, while 41 SIM remained altered in cirrhotic patients (adj.p<0.05). 33 of these SIM correlated with elastography at follow-up (adj.p<0.05), among them SIM linked to carcinogenesis as e.g. HGF, IL8 and IL6 (KEGG Pathways hsa05202, hsa05200). Patients developing HCC showed the lowest decline of HGF, uPA, IL8 and IL6.

Conclusions Persisting SIM alterations are closely linked to liver impairment and carcinogenesis. Our results emphasize the need for viral elimination before extended liver damage occurs and suggest the further evaluation of IL6, IL8, CXCL10, uPA and HGF as therapeutic targets.

Publication History

Article published online:
23 January 2024