Changes in the Liver Fibrosis of Patients Who Develop Hepatocellular Carcinoma After a Sustained Virologic Response to Hepatitis C Virus Infection

The risk of developing hepatocellular carcinoma (HCC) persists in patients with cirrhosis and a sustained virologic response (SVR, the eradication of hepatitis C virus [HCV]), and therefore surveillance for HCC is recommended. However, patients with mild or no fibrosis are usually at low risk and HCC surveillance is not recommended in many guidelines. Nevertheless, some patients experience post-SVR HCC despite having low degree liver fibrosis. We characterized the changes in liver fibrosis in patients in whom HCC developed after SVR. We performed a nationwide multicenter study, during which HCC developed in 332 of 6047 patients (5.5%) with no history of HCC who achieved SVR. FIB-4 index, the laboratory index of liver fibrosis, was calculated at the start of anti-HCV therapy and at a diagnosis of HCC, and the changes were characterized. Most patients who developed HCC after SVR had cirrhosis or advanced liver fibrosis (FIB-4 index > 3.25) before anti-HCV therapy, including some whose liver fibrosis regressed after SVR. Some patients (3.6%) without substantial fibrosis (FIB-4 index ≤ 3.25) before anti-HCV therapy developed HCC with the progression of liver fibrosis after SVR. Finally, 5 patients (1.6%) had mild or no fibrosis (FIB-4 index < 1.45) both before anti-HCV therapy and when HCC developed. Most HCCs in patients who achieve SVR develop in association with liver cirrhosis or advanced fibrosis, but some develop in livers without substantial fibrosis. In addition, post-SVR HCC can develop in patients with mild or no fibrosis both before anti-HCV therapy and after SVR.