Treatment with direct‐acting antivirals for HCV decreases but does not eliminate the risk of hepatocellular carcinoma

Abstract

Background & Aims Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. Methods This was a prospective multicentre cohort study from Latin America including 1400 F1‐F4‐treated patients with DAAs (F3‐F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. Results During a median follow‐up of 16 months (IQR 8.9‐23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02‐0.05) at 12 months and 0.06 (CI 0.04‐0.08) at 24 months of follow‐up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non‐responder, Child‐Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%‐91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. Conclusions Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.

Comparison of the efficacy and safety of direct-acting antiviral therapy with or without hepatitis C-related hepatocellular carcinoma

“…A previous study on the associated factors of HCC recurrence showed that SVR 12 rate, time between the last HCC treatment and DAA therapy initiation, noncurative HCC treatment, more than one HCC treatment before DAA therapy, tumor size, LC, and AFP-L3% were relevant factors [15,20,22]. A recent study reported that patients with previous IFN experience have a high risk of de novo HCC, and the same results were found in our study [23]. As a theory supporting this result, it was estimated that this is due to the immunomodulatory and antitumor properties of IFN rather than antiviral activity alone [24].…”

Advantage of liver stiffness measurement before and after direct‐acting antiviral therapy to predict hepatocellular carcinoma and exacerbation of esophageal varices in chronic hepatitis C

“…The present study could shed light on the relationship between HCC and portal hypertension. A previous report showed that HCC risk after SVR is still high in the case of portal hypertension complicated with advanced fibrosis . We also previously reported that EV is the significant independent predictor of HCC .…”

B.A.R.C.O.S. (Brazilian Argentine Hepatitis C Collaborative Observational Study): Effectiveness and clinical outcomes of HCV treatment with daclatasvir and sofosbuvir with or without ribavirin

“…Cumulative incidence of death, liver decompensation, LT and HCC was not compared to an untreated population, but results were alike to those published in similar studies . In a larger cohort with long‐term follow‐up, we reported a reduced incidence of HCC in HCV‐treated patients with various DDAs regimens . Also, a recent study from France showed an improvement in all evaluated clinical outcomes …”