Journal of Hepatocellular Carcinoma (Jun 2021)

Rates of Hepatocellular Carcinoma After Start of Treatment for Chronic Hepatitis C Remain High with Direct Acting Antivirals: Analysis from a Swiss Liver Transplant Center

  • Karbeyaz F,
  • Kissling S,
  • Jaklin PJ,
  • Bachofner J,
  • Brunner B,
  • Müllhaupt B,
  • Winder T,
  • Mertens JC,
  • Misselwitz B,
  • von Felten S,
  • Siebenhüner AR

Journal volume & issue
Vol. Volume 8
pp. 565 – 574

Abstract

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Fatih Karbeyaz,1 Seraphina Kissling,2 Paul Julius Jaklin,1 Jaqueline Bachofner,1 Barbara Brunner,1 Beat Müllhaupt,1 Thomas Winder,3 Joachim C Mertens,1 Benjamin Misselwitz,1,4 Stefanie von Felten,5 Alexander R Siebenhüner6,7 1Division of Gastroenterology and Hepatology, University Hospital Zurich and Zurich University, Zurich, Switzerland; 2Master Program in Biostatistics, University of Zurich, Zurich, Switzerland; 3Division of Oncology, Landeskrankenhaus Feldkirch, Feldkirch, Austria; 4Department of Visceral Surgery and Medicine, Inselspital Bern and Bern University, Bern, Switzerland; 5Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; 6Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland; 7Department of Medical Oncology, Cantonal Hospital Schaffhausen, Schaffhausen, SwitzerlandCorrespondence: Alexander R SiebenhünerKlinik für Medizinische Onkologie und Hämatologie, Universitätsspital Zürich, Rämistrasse 100, Zürich, CH-8091, SwitzerlandEmail [email protected]: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood.Patients and Methods: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis.Results: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5– 4.7) for DAA and 9.3 years (IQR: 6.6– 12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20– 18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤ 0.001, depending on covariates). A HR of 6.62 (CI: 2.01– 21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups.Conclusion: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.Keywords: hepatocellular carcinoma, chronic hepatitis C, direct-acting antivirals, PEG-interferon and ribavirin, viral load, liver transplantation, sustained virological response

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