Residual hepatitis C virus in peripheral blood mononuclear cell as a risk factor for hepatocellular carcinoma after achieving a sustained virological response: a dogma or fiction.

Abstract

Clinical worsening after achieving a sustained virological response (SVR) needs to be clarified and explained. Persistence of hepatitis C virus (HCV) core antigen interacts with the host proteins to interfere with signaling pathways and increases the susceptibility to hepatic carcinogenesis. This study aimed to investigate the risk factors that increase the progression of liver disease and hepatocellular carcinoma in a subgroup of HCV patients who achieved a SVR. Eighty-nine HCV patients with hepatic decompensation were selected 8.2 ± 1.8 months after achieving SVR24. HCV core antigen and HCV RNA were detected in peripheral blood mononuclear cells. Matched control (n = 100) and training (n = 200) groups were recruited. Eighty-five patients showed a progression of Child-Turcotte-Pugh and model for end-stage liver disease scores, with positive RNA in peripheral blood mononuclear cell (357.4 ± 42.1 IU/million cell) and positive hepatitis C virus core antigen (n = 73); four patients were excluded. Susceptibility to decompensation and hepatocellular carcinoma after direct-acting antiviral drugs increased with age [odds ratio (OD) = 1.87], and was associated with male sex (OD = 1.65), diabetes (OD = 3.68), thrombocytopenia (OD = 2.44), pretreatment Alfa-fetoprotein (OD = 3.41), and occult HCV (OD = 4.1). Clinical deterioration after SVR could be explained by occult HCV mainly in older male patients with diabetes and thrombocytopenia.