George V Papatheodoridis1, Vana Sypsa2, George N Dalekos3, Cihan Yurdaydin4, Florian Van Boemmel5, Maria Buti6, Jose Luis Calleja7, Heng Chi8, John Goulis9, Spilios Manolakopoulos10, Alessandro Loglio11, Theodoros Voulgaris12, Nikolaos Gatselis3, Onur Keskin4, Rhea Veelken5, Marta Lopez-Gomez7, Bettina E Hansen13, Savvoula Savvidou9, Anastasia Kourikou14, John Vlachogiannakos12, Kostas Galanis3, Ramazan Idilman4, Rafael Esteban6, Harry L A Janssen15, Thomas Berg5, Pietro Lampertico11. 1. Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. Electronic address: gepapath@med.uoa.gr. 2. Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece. 3. Department of Internal Medicine, Thessalia University Medical School, Larissa, Greece. 4. Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey. 5. Division of Hepatology, Clinic and Polyclinic for Gastroenterology, Hepatology, Infectiology and Pneumology, University Clinic Leipzig, Germany. 6. Hospital General Universitario Valle Hebron and Ciberehd, Barcelona, Spain. 7. Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain. 8. Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands. 9. 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece. 10. Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece; 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital of Athens, Athens, Greece. 11. CRC "AM e A Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy. 12. Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. 13. Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada. 14. 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital of Athens, Athens, Greece. 15. Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada.
Abstract
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting. METHODS: Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5. RESULTS: In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups. CONCLUSIONS: In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy. LAY SUMMARY: In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.
BACKGROUND & AIMS:Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting. METHODS: Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5. RESULTS: In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups. CONCLUSIONS: In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy. LAY SUMMARY: In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.
Authors: Hye Won Lee; Hyun Woong Lee; Jae Seung Lee; Yun Ho Roh; Hyein Lee; Seung Up Kim; Jun Yong Park; Do Young Kim; Sang Hoon Ahn; Beom Kyung Kim Journal: J Hepatocell Carcinoma Date: 2021-05-25
Authors: George V Papatheodoridis; George N Dalekos; Ramazan Idilman; Vana Sypsa; Florian Van Boemmel; Maria Buti; Jose Luis Calleja; John Goulis; Spilios Manolakopoulos; Alessandro Loglio; Margarita Papatheodoridi; Nikolaos Gatselis; Rhea Veelken; Marta Lopez-Gomez; Bettina E Hansen; Savvoula Savvidou; Anastasia Kourikou; John Vlachogiannakos; Kostas Galanis; Cihan Yurdaydin; Rafael Esteban; Harry L A Janssen; Thomas Berg; Pietro Lampertico Journal: JHEP Rep Date: 2021-04-20