Characteristics and Prognosis of De Novo Hepatocellular Carcinoma After Sustained Virologic Response

Abstract

Hepatocellular carcinoma (HCC) can de novo develop in patients with chronic hepatitis C even after the achievement of sustained virologic response (SVR). We characterized de novo HCC after SVR, comparing it with HCC that developed in patients during persistent hepatitis C virus (HCV) infection. Characteristics, survival rates, and recurrence rates after curative treatment in 178 patients who developed initial HCC after SVR diagnosed between 2014 and 2020 were compared with those of 127 patients with initial HCC that developed during persistent HCV infection diagnosed between 2011 and 2015; HCC was detected under surveillance in both groups. HCC was less advanced and liver function worsened less in patients with SVR than in patients with persistent HCV. The survival rate after diagnosis was significantly higher for patients with SVR than for patients with persistent HCV (1‐, 3‐, and 5‐year survival rates, 98.2%, 92.5%, and 86.8% versus 89.5%, 74.7%, and 60.8%, respectively; P < 0.001). By contrast, the recurrence rate after curative treatment was similar between groups (1‐, 3‐, and 5‐year recurrence rates, 11.6%, 54.6%, and 60.4% versus 24.0%, 46.7%, and 50.4%, respectively; P = 0.7484). Liver function improved between initial HCC diagnosis and recurrence in patients with SVR ( P = 0.0191), whereas it worsened in the control group ( P < 0.001). In addition, patients with SVR could receive curative treatment for recurrence more frequently than patients with persistent HCV (80.4% versus 47.8%, respectively; P = 0.0008). Conclusion: Survival of patients with de novo HCC after SVR was significantly higher than that of patients in whom HCC developed during persistent HCV infection, despite similar rates of recurrence after curative treatment. A higher prevalence of curative treatment for recurrent HCC and improved liver function contributed to this result.

The Impact of Cirrhosis and History of Hepatocellular Carcinoma on All-Cause Mortality After Eradication of Hepatitis C Virus in Patients With Chronic Hepatitis C

“…Unlike post-SVR HCC recurrence in patients with a history of HCC, post-SVR HCC in patients with no history of HCC, ie, de novo HCC, only modestly increased mortality after SVR. The survival rate of patients with de novo HCC after SVR was significantly higher than that of patients with HCC that developed during persistent HCV infection, 14 which was associated with a decreased unfavorable influence of post-SVR HCC on mortality in patients with no history of HCC. Consequently, patients with compensated cirrhosis and those without cirrhosis showed no difference in either liver-related or nonliver-related mortality after PSM.…”

Prospective Comparison of Hepatocellular Carcinoma Behavior and Survival of Patients who Did or Did not Receive HCV Direct-Acting Antivirals

“…Liver function improved between initial HCC diagnosis and recurrence in these patients but declined in controls. SVR patients thus received more frequent curative treatment for recurrence (Toyoda et al, 2021). Montasser (2021) reported that tumor size in DAA-treated patients was statistically larger than in patients without a history of such treatment (p = 0.03), but types of intervention, BCLC stage, and survival had no impact (Montasser et al, 2021).…”

“…Three-year OS was 76% in DAA-HCC patients versus 88.93% in control HCC subjects (Brozzetti et al, 2021). Conversely, other studies found a higher survival rate in SVR achievers who developed de-novo HCC lesions during surveillance, despite similar recurrence rates after curative HCC management (Toyoda et al, 2021). Tumors were more extensive in patients that received DAA treatment, but no difference in survival was reported in another study (Montasser et al, 2021).…”

Improved survival of viral hepatocellular carcinoma but not non‐viral hepatocellular carcinoma from 2000 to 2020: A multi‐centre cohort study of 6007 patients from high‐volume academic centres in Japan

“…This might be because of poor awareness regarding the risk of HCC in patients without viral hepatitis, and, more importantly, difficulty in identifying patients with non-viral liver diseases who are at risk of HCC and who should, therefore, undergo HCC surveillance.Assessment with the ALBI score showed that liver function at HCC diagnosis improved over time in both groups, and this improvement was greater in the viral HCC group than in the non-viral HCC group. In the viral HCC group, the clinical use of oral antiviral therapy for HBV infection (nucleos[t]ide analogues, NAs) and for HCV (direct-acting antivirals, DAAs) contributed to preventing liver function deterioration over the course of chronic infection, resulting in an increase in the percentage of patients with better liver function at the development of HCC 10. Whereas NAs for HBV were available and used in most patients throughout the study period, the percentage of HCV patients who achieved SVR increased significantly over time due to the emergence of DAAs.…”