Predictors of hepatocellular carcinoma recurrence associated with the use of direct‐acting antiviral agent therapy for hepatitis C virus after curative treatment: A prospective multicenter cohort study

Abstract

Background Previous studies have suggested an association between the use of direct‐acting antiviral agents (DAAs) for treating hepatitis C virus (HCV) infection and the resulting decrease in the incidence of hepatocellular carcinoma (HCC); however, it is unclear whether DAAs prevent the recurrence of HCC after curative treatment for HCC. This study aimed to prospectively investigate HCC recurrence and its predictors after curative treatment for HCC. Methods A total of 3012 patients with chronic HCV infection, with or without cirrhosis, who were treated with DAAs were enrolled between January 1, 2015 and January 31, 2017 as per the institutional review board approved study protocol at 15 institutions, including 10 university hospitals and five high‐volume centers in the Kyusyu area of Japan. Of the 3012 patients, 459 patients who had HCC but were cured with surgery or ablation therapy (curative treatment) before the use of DAAs were included in the analysis. Results During a mean follow‐up period of 29.4 months, 217 (47.2%) patients developed HCC recurrence. The median time to recurrence was 34.0 months, and the 1‐, 2‐, and 3‐year cumulative HCC recurrence rates were 27.1%, 43.4%, and 50.8%, respectively. The risk factors for HCC recurrence were the α‐fetoprotein (AFP) level before DAA therapy ( P = 0.0047) and the number of curative treatments for HCC before DAA therapy ( P < 0.0001). Conclusions A high AFP level and multiple occurrences of HCC before DAA therapy are associated with a high risk for HCC recurrence after curative treatment. Follow‐up after DAA therapy should include special attention to the abovementioned risk factors.

Residual risk of liver disease after hepatitis C virus eradication

“…50 After therapy, HCC risk has been associated with persistently increased GGT15, 62 or AFP levels. These are frequently lowered during therapy with DAAs, possibly due to reduced necroinflammation, but they may remain high in some patients despite viral clearance and normalisation of liver enzymes, preceding the development of either de novo 63,64 or recurrent 60 HCC. Non-invasive markers of liver fibrosis are also very promising, because pre-and/ or post-treatment, elevated values of Fibro-scan®, 65,66 FIB-4 44,54,60 and aspartate aminotransferase-to-platelet ratio index (APRI) 60,67 also seem to predict HCC after SVR in patients with lower degrees of liver fibrosis.…”

Hepatic benefits of HCV cure

“…Lack of SVR and high alpha-fetoprotein (AFP) were independent predictors of HCC recurrence. A large group of patients (459 patients whose HCC was cured by surgery or ablation before DAAs) was analysed by Nakano et al 52 Akin to previous studies, they found that high AFP level and multiple recurrences of HCC before DAA therapy were associated with a high risk of HCC recurrence after curative treatment.…”

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

“…Similar results were achieved by Imai et al [ 65 ], who identified the SVR by DAA as an independent factor for the prevention of HCC recurrence. Nakano et al [ 66 ] evaluated 459 patients who had HCC for the recurrence rate and to identify the predictors of HCC recurrence after DAAs treatment. In a median time of 29.2 months, 47.2% of patients developed HCC recurrence.…”

“…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 ].…”