Simple scoring system for prediction of hepatocellular carcinoma occurrence after hepatitis C virus eradication by direct‑acting antiviral treatment: All Kagawa Liver Disease Group Study

Abstract

Direct acting antivirals (DAA) have recently been developed to treat patients with hepatitis C virus (HCV) infection, and interferon-free DAA treatment has improved the cure rate of patients. However, the occurrence rate of hepatocellular carcinoma (HCC) following HCV eradication remains unknown. Therefore, the present study aimed to identify predictors of HCC occurrence following DAA treatment. Among 1,454 patients infected with HCV, 1,088 patients who achieved sustained virologic response and who had no history of HCC treatment were recruited between September 2014 and November 2018. The incidence of HCC in patients infected with HCV following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinicopathological characteristics and blood test results. During the present study, 26 patients developed HCC. The incidence of HCC was 0.61, 1.88, 2.82 and 3.71% at 6, 12, 18 and 24 months after treatment with DAA, respectively. The results of multivariate analysis identified age [hazard ratio (HR), 1.0729; P=0.0044] and α-fetoprotein (AFP) level after DAA treatment (HR, 1.0486; P=0.0486) as independent factors that may contribute to HCC occurrence following DAA treatment. By using these two factors, a novel scoring system (0-2 points) was established to predict HCC occurrence following HCV eradication by DAA treatment. The incidence of HCC at 2 years was 0.3% in the 0 points group, 6.27% in the 1 point group and 18.37% in the 2 points group. In conclusion, AFP level after DAA treatment and age at DAA administration were identified as independent predictors of HCC occurrence in patients that were treated with DAA. The scoring system that was established in the present study is simple and easy, and using pre-treatment factors may be a convenient tool to predict the risk of HCC occurrence in HCV-free patients following DAA treatment.

Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis

“…The 1-, 2-, 3-, and 4-year incidence rates of HCC for the low-score group (0 points or 1 point) were 0.7%, 2.2%, 3.1%, and 3.1% compared to 12.5%, 15.2%, 33.9%, and 41.2%, respectively, in the high-score group (2 or 3 points). Previous studies reported the stratification of HCC incidence by FIB-4 scores and AFP levels after SVR and by scores composed of patient sex and age, with and without cirrhosis [11,12]. On the other hand, the score established in this study is useful for patients with compensated cirrhosis who still have an absolute risk of residual HCC.…”

“…On the other hand, another study demonstrated that in patients without cirrhosis, higher FIB-4 scores, the presence of DM, and alcohol use were risk factors for developing HCC after DAA treatment [3]. In addition, recent studies reported that male sex, increased FIB-4 scores, decreased ALB levels, older age, and increased AFP levels were independent risk factors identified by multivariate analysis [11][12][13]. In the present study, a longterm observation period of more than 3 years was used, and the HCC risk factors after HCV eradication were identified in patients with compensated cirrhosis or without cirrhosis.…”

Characterization of gut microbiota in patients with primary hepatocellular carcinoma received immune checkpoint inhibitors

“…Many risk factors, including primary hepatitis C virus, hepatitis B virus, smoking, cirrhosis and obesity, are involved in HCC. [ 21 , 22 ] The gut microbiota is involved in protection against or promotion of different diseases, including various cancers. The gut microbiota composition differs in several diseases, including obesity, inflammatory bowel disease, and hepatocellular carcinoma (HCC), suggesting a distinct intestinal metabolism and immune response in each patient.…”

Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics

“…Recently, Tani et al [ 39 ], who followed for 24 months 1084 HCV patients who achieved an SVR, showed that the incidence of HCC was 0.61%, 1.88%, 2.82% and 3.71% at 6, 12, 18 and 24 months after treatment with DAAs, respectively. Furthermore, they identified age and alfa-fetoprotein levels as the independent predictors of HCC occurrence.…”

“…Several studies have shown that the male sex, diabetes and elevated serum alpha-fetoprotein levels before and after DAAs treatment are significant predictors of the onset or recurrence of HCC [ 34 , 39 , 66 , 67 , 102 ].…”