The impact of cirrhosis on the inflammatory milieu before and long-term after hepatitis C virus elimination by direct-acting antiviral therapy

Background and AimsChronic hepatitis C virus (HCV) infection can lead to cirrhosis, development of hepatocellular carcinoma (HCC) and several extrahepatic manifestations. A sustained virological response (SVR) is achieved with direct-acting antivirals (DAA) in over 95% of the patients, but sequelae do not improve in all patients, suggesting permanent biological alterations induced by HCV infection. Therefore, we investigated the influence of chronic HCV infection, viral elimination and cirrhosis on inflammatory immune mediators. Approach and ResultsIn 102 chronic HCV patients, 46 with and 56 without cirrhosis, 92 soluble immune mediators (SIM) were measured in plasma samples at therapy start, end of treatment and long-term follow-up (median 96 weeks). 39 HBsAg positive persons with HBeAg negative infection served as controls. At baseline, 42 SIM were altered in chronic HCV patients (adj.p <0.05). Notably, patients with cirrhosis displayed a higher frequency and severity of alterations. At long-term follow-up, the SIM profile of the non-cirrhotic patients recovered to the level of the control group, while 41 SIM remained altered in cirrhotic patients. 33 of these SIM correlated with elastography, among them SIM linked to carcinogenesis as e.g. HGF, IL8 and IL6 (KEGG Pathways hsa05202, hsa05200). ConclusionsHCV-related changes in the inflammatory milieu can persist even after HCV elimination, specifically in cirrhotic patients. These changes are closely associated with liver damage and carcinogenesis. Our findings underscore the need for HCV elimination before extensive liver injury occurs and suggest further investigation of the relationship between persistent inflammatory milieu changes and long-term sequelae after HCV elimination. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/23297828v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@3a885borg.highwire.dtl.DTLVardef@ce3eb1org.highwire.dtl.DTLVardef@7601f6org.highwire.dtl.DTLVardef@17ad655_HPS_FORMAT_FIGEXP M_FIG C_FIG