Author information
1Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse, 3010 Bern, Switzerland.
2Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, 9000 St. Gallen, Switzerland.
3Division of Gastroenterology and Hepatology, Cantonal Hospital St. Gallen, 9000 St. Gallen, Switzerland.
4Gastroenterology und Hepatology, University Hospital Zürich, 8091 Zürich, Switzerland.
5Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland.
6Division of Gastroenterology and Hepatology, University Hospitals Geneva, 1211 Geneva, Switzerland.
7Division of Gastroenterology and Hepatology, University Hospital Basel, 4031 Basel, Switzerland.
8Department of Internal Medicine and Infectious Diseases, Pourtalès Hospital, 2000 Neuchâtel, Switzerland.
9Institute of Global Health, University of Geneva, 1205 Geneva, Switzerland.
Abstract
Introduction: The use of direct-acting antivirals (DAAs) has drastically changed the management of HCV-infected patients by achieving a 95-98% sustained virologic response (SVR) and reducing morbidity and mortality in this population. However, despite their effectiveness, controversy exists concerning the occurrence of oncologic events following DAA therapy. Aims and Methods: A retrospective analysis was conducted on data from the Swiss Hepatitis C Cohort Study, a prospective cohort involving patients with positive HCV viremia upon inclusion, enrolled in various Swiss centers from September 2000 to November 2021. To examine potential differences in the risk of intrahepatic tumor (IHT) occurrence and death among patients treated with direct-acting antivirals (DAAs), untreated patients, and those receiving interferon (IFN)-based therapy, a semiparametric competing risk proportional hazards regression model was used. Results: Among 4082 patients (63.1% male, median age 45 years; genotype 1: 54.1%; cirrhosis: 16.1%), 1026 received exclusive treatment with IFN-based regimens, and 1180 were treated solely with DAAs. Over a median follow-up of 7.8 years (range: 3.8-11.9), 179 patients (4.4%) developed intrahepatic tumors (IHT), and 168 (4.1%) experienced extrahepatic tumors (EHT). The 5-year cumulative incidence of IHT was 1.55% (95% CI 0.96-2.48) for IFN-based therapy, 4.27% (95% CI 2.93-6.2) for DAA and 0.89% (95% CI 0.4-1.99) for untreated patients. There was no statistically significant difference in the risk of developing IHT (HR = 1.34; 95% CI = [0.70; 2.58]; p = 0.380) or death (HR = 0.66; 95% CI = [0.43; 1.03]; p = 0.066) between patients treated with DAAs and those treated with IFN. Conclusions: The DAAs reduced the risk of death and were not associated with an increased risk of extrahepatic tumors (EHT). In the adjusted model, accounting for cirrhosis and high liver stiffness, the DAA treatment was associated with a higher risk of IHT occurrence compared with untreated patients, emphasizing the relevance of implementing standardized hepatocellular carcinoma (HCC) screening post-DAA treatment.