Impact of viral eradication by direct‐acting antivirals on the risk of hepatocellular carcinoma development, prognosis, and portal hypertension in hepatitis C virus‐related compensated cirrhosis patients

Abstract

We analyzed the impact of hepatitis C virus eradication by direct-acting antiviral (DAA) therapy on the risk of development of hepatocellular carcinoma (HCC), prognosis, and portal hypertension in patients with liver cirrhosis. Methods: The rate of HCC development and overall survival after achievement of sustained virological response (SVR) in 173 DAA-treated compensated cirrhosis patients without HCC history were retrospectively compared with that of 125 cirrhosis patients who achieved SVR by interferon (IFN)-based therapy or that of 85 cirrhosis patients who failed to respond to anti-HCV therapy. Changes in esophagogastric varices (EGV) and incidence of portosystemic encephalopathy were analyzed in 87 consecutive cirrhosis patients. Results: The cumulative HCC development rates at 1, 3, and 5 years were 2%, 7%, and 7% for the DAA-SVR group, significantly lower than the 3%, 7%, and 18% for the non-SVR group (log-rank, P <0.001). The cumulative overall survival rates were also significantly improved in the DAA-SVR group compared to the non-SVR group (log-rank, P <0.001). These rates were similar between DAA-SVR and IFN-SVR groups (P =0.121 and 0.261, respectively). Esophagogastric varices were aggravated, and portosystemic encephalopathy occurred in a subset of cirrhosis patients who achieved SVR by DAA therapy. These events were more frequent in patients with large feeding vessels for EGV and portosystemic shunts at the time of SVR. Conclusion: Achievement of SVR by DAA therapy reduces the risk of HCC development and prolongs survival, similar to theresults achieved with IFN-based therapy, but portal hypertension is not immediately improved in compensated liver cirrhosis patients.

Absence of differences in the recurrence rates of hepatitis C virus‑associated hepatocellular carcinoma between direct‑acting antivirals and interferon‑based treatments: A multicenter study

“…In conclusion, the present study demonstrated that the HCC recurrence rate following curative treatment for HCC was equivalent in patients treated with DAAs and those treated with an IFN-based regimen. The present study supports previous results (7)(8)(9) showing that DAA treatment did not accelerate HCC recurrence. In addition, multivariate analysis of factors affecting HCC recurrence in the DAA group identified the number of previous HCC treatments (≥3) and the Forns index as significant independent risk factors.…”

“…A previous multicenter study of the HCC recurrence rates in patients treated with DAAs or an IFN-based regimen following treatment for HCC in hospitals belonging to the Japan Red Cross Hospitals group also found no significant difference in the HCC recurrence rate in patients who achieved SVR (8). Furthermore, other Japanese research groups have also performed studies involving patients extracted by propensity score matching, and, similar to the present results, they reported that there was no significant difference in the HCC recurrence rate between patients treated with DAAs and those treated with an IFN-based regimen (9,12).…”

“…The results demonstrated that, following adjustment for background factors, there was no significant difference in the HCC recurrence rate between DAA monotherapy and other treatments (6). Furthermore, Japanese studies have found that when patients who received treatment with IFN-based regimens or DAAs were matched by background characteristics, there was no difference in the HCC recurrence between the two groups who achieved SVR (7)(8)(9).…”

Should we continue surveillance for hepatocellular carcinoma and gastroesophageal varices in patients with cirrhosis and cured HCV infection?

“…As follow-up of patients cured with DAAs extends, more data concerning their effect on the development of GEV is emerging (Supplementary table 2) [90][91][92][93][94][95][96]. In a large French cohort including 246 patients with Child-Pugh A cirrhosis due to chronic viral hepatitis (70% HCV), the cumulative rates of de novo large GEV at 1, 3 and 5 years after SVR were 2%, 4% and 4%, respectively [92].…”

“…In a large French cohort including 246 patients with Child-Pugh A cirrhosis due to chronic viral hepatitis (70% HCV), the cumulative rates of de novo large GEV at 1, 3 and 5 years after SVR were 2%, 4% and 4%, respectively [92]. In contrast, incidences of de novo small or large GEV following viral eradication varied between 9% and 13% after 18 to 36 months of follow-up in three smaller studies, each including approximately 60 patients with cirrhosis [93,95,96]. Among 176 patients with Child-Pugh A cirrhosis who used a maximum tolerable NSBB dosage following ligation of their GEV, the reported recurrence of GEV (size not reported) following DAA-based HCV eradication was 30% after 4 years [94].…”