TITLE: Prediction of Hepatocellular Carcinoma in Entecavir treated Patients: Results from 744 Chronic Hepatitis B patients in a European Multicenter Study (VIRGIL)
AUTHORS (FIRST NAME, LAST NAME): Pauline Arends1, Roeland Zoutendijk1, Ivana Carey2, Ashley S. Brown3, Massimo Fasano4, David J. Mutimer5, Katja Deterding6, Jurrien G. Reijnders1, Ye H. Oo5, Joerg Petersen7, Florian van Boemmel8, Robert J. de Knegt1, Thomas Berg8, Tania M. Welzel9, Teresa Santantonio4, Bettina E. Hansen1, 10, Heiner Wedemeyer6, Maria Buti11, Pierre Pradat12, Fabien Zoulim12, Harry L. Janssen13, 1
Institutional Author(s):
INSTITUTIONS (ALL): 1. Gastroenterology and Hepatology, Erasmus MC university medical center, Rotterdam, Netherlands.
2. Institute of Liver Studies and Transplantation, King’s College London school of Medicine, London, London, United Kingdom.
3. Hepatology and Gastroenterology, Imperial College London, London, United Kingdom.
4. Clinic of Infectious Diseases, University of Foggia, Foggia, Italy.
5. NIHR Biomedical Research Unit and Centre for Liver Research, Queen Elizabeth Hospital, Birmingham, United Kingdom.
6. Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany.
7. Liver Unit, IFI Institute, Asklepios Klinik St. Georg, Hamburg, Germany.
8. Hepatology, University Clinic Leipzig, Leipzig, Germany.
9. Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
10. Public Health, Erasmus MC university medical center, Rotterdam, Netherlands.
11. Hepatology, Hospital Vall de Hebron, Barcelona, Spain.
12. Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
13. Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada.
ABSTRACT BODY: BACKGROUND The goal of HBV treatment is to reduce disease progression to (decompensated) cirrhosis, HCC and death. Entecavir (ETV) inhibits HBV replication and reduces HCC. Recently, CU-HCC, GAG-HCC, and REACH-B HCC-risk scores showed to predict HCC in Asian ETV treated patients. The aim of this study was to investigate risk factors for development of HCC under ETV treatment.
METHODS We studied all HBV monoinfected patients treated with ETV monotherapy from 11 European referral centers within the Virgil Network. Patients with HCC at baseline or within the first 3 months of FU were excluded.
RESULTS A total of 744 patients treated with ETV were included (mean age 44±14 years; 77%male; 42%Caucasian/29%Asian/20%Black; 31%HBeAg+; HBV DNA 5.3±2.2log IU/ml; ALT 2.9xULN; 77%NA naive and 82%IFN naive; 164 patients (22%) had cirrhosis (by ultrasound or histology) at baseline. During a median FU of 167 (IQR 82-213) weeks, 14 patients were diagnosed with HCC of whom 9 (64%) had cirrhosis at baseline. Median time to development of HCC was 125 (IQR 59-188) weeks. The 5-year cumulative incidence rate of HCC was 4.4% (95% CI 1.7%–7.1%). Cumulative probability of HCC was higher in cirrhotic (p<0.001), older patients (p<0.001) and patients with lower platelet counts (p=0.02). Occurrence of HCC was not influenced by sex, HBeAg status, previous NA or IFN, baseline ALT, HBV DNA, or MELD score (p>0.11). All but one patient who developed HCC achieved virological response (VR) within 18 months of therapy. Early VR appeared protective for HCC development (HR0.63, 95%CI 0.15-2.63, p=0.52). At baseline, higher CU-HCC and GAG-HCC, but not REACH-B scores were associated with HCC. GAG-score was best in predicting HCC development. Cut-off values of 5 for the CU-HCC score and 101 for the GAG-HCC score were predictive for HCC development.(table) Hazard ratios of GAG-HCC score for development of HCC were less discriminative in Caucasians compared to Asians and Black (c-stat=0.72, 0.89 & 0.95 respectively).
CONCLUSION Cumulative incidence of HCC in ETV treated patients is low and early VR may be protective for HCC. Baseline CU-HCC and GAG-HCC, but not REACH-B scores predicted HCC in our population. Risk-scores were less discriminative in Caucasians, thus new risk-scores for this population are warranted.