George V Papatheodoridis1, George N Dalekos2, Ramazan Idilman3, Vana Sypsa4, Florian Van Boemmel5, Maria Buti6, Jose Luis Calleja7, John Goulis8, Spilios Manolakopoulos9, Alessandro Loglio10, Margarita Papatheodoridi11, Nikolaos Gatselis2, Rhea Veelken5, Marta Lopez-Gomez7, Bettina E Hansen12, Savvoula Savvidou8, Anastasia Kourikou13, John Vlachogiannakos11, Kostas Galanis2, Cihan Yurdaydin14, Rafael Esteban6, Harry L A Janssen15, Thomas Berg5, Pietro Lampertico16. 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 Internal Medicine, Thessalia University Medical School, Larissa, Greece. 3. Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey. 4. Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece. 5. Division of Hepatology, Clinic for Oncology, Gastroenterology, Hepatology, Infectious Diseases and Pneumology, University Clinic Leipzig, Leipzig, Germany. 6. Hospital General Universitario Valle Hebron and CIBERehd, Barcelona, Spain. 7. Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain. 8. 4th Department of Internal Medicine, Aristotle University of Thessaloniki Medical School, Thessaloniki, Greece. 9. 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. 10. Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy. 11. Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. 12. Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada. 13. 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital of Athens, Athens, Greece. 14. Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey; Department of Gastroenterology and Hepatology, Koc University Medical School, Istanbul, Turkey. 15. Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada. 16. Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Abstract
BACKGROUND & AIMS: A recent study in Asian patients with chronic hepatitis B (CHB) reported that the incidence of hepatocellular carcinoma (HCC) was lower in patients treated with tenofovir disoproxil fumarate (TDF) than entecavir (ETV), but this finding remains controversial. We aimed to identify any differences in HCC incidence, or other patient outcomes, between patients receiving TDF or ETV in the well monitored, multicenter European PAGE-B cohort. METHODS: We included 1,935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n = 772) or TDF (n = 1,163) monotherapy. Mean follow-up was 7.1 ± 3.0 years from ETV/TDF onset. RESULTS: The 5-year cumulative HCC incidence was 5.4% in ETV- and 6.0% in TDF-treated patients (log-rank, p = 0.321), with no significant difference in any patient subgroup (with or without cirrhosis, naïve or experienced to oral antiviral(s) [total, with or without cirrhosis]). In multivariable Cox regression analyses, the hazard of HCC was similar between ETV- and TDF-treated patients after adjustment for several HCC risk factors. ETV- and TDF-treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis, being more frequent in TDF- than ETV- treated patients (73.8% vs. 61.5%, p = 0.038). CONCLUSION: In Caucasian patients with CHB, with or without cirrhosis, long-term ETV or TDF monotherapy is associated with similar HCC risk, rates of biochemical/virological remission, HBsAg loss and liver transplantation or death, but elastographic reversion of cirrhosis at year 5 was more frequent with TDF. LAY SUMMARY: In a large cohort of Caucasians with chronic hepatitis B treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) monotherapy, cumulative rates of hepatocellular carcinoma did not differ (up to 12 years). Nor did rates of biochemical/virological remission, HBsAg loss and liver transplantation or death. However, elastographic reversion of cirrhosis at year 5 was more frequent in TDF- than ETV-treated patients with pretreatment cirrhosis.
BACKGROUND & AIMS: A recent study in Asian patients with chronic hepatitis B (CHB) reported that the incidence of hepatocellular carcinoma (HCC) was lower in patients treated with tenofovir disoproxil fumarate (TDF) than entecavir (ETV), but this finding remains controversial. We aimed to identify any differences in HCC incidence, or other patient outcomes, between patients receiving TDF or ETV in the well monitored, multicenter European PAGE-B cohort. METHODS: We included 1,935 Caucasians with CHB, with or without compensated cirrhosis, treated with ETV (n = 772) or TDF (n = 1,163) monotherapy. Mean follow-up was 7.1 ± 3.0 years from ETV/TDF onset. RESULTS: The 5-year cumulative HCC incidence was 5.4% in ETV- and 6.0% in TDF-treated patients (log-rank, p = 0.321), with no significant difference in any patient subgroup (with or without cirrhosis, naïve or experienced to oral antiviral(s) [total, with or without cirrhosis]). In multivariable Cox regression analyses, the hazard of HCC was similar between ETV- and TDF-treated patients after adjustment for several HCC risk factors. ETV- and TDF-treated patients had similar rates of on-therapy biochemical and virological remission, HBsAg loss, liver transplantation and/or death. Elastographic reversion of cirrhosis at year 5 (liver stiffness <12 kPa) was observed in 245/347 (70.6%) patients with pretreatment cirrhosis, being more frequent in TDF- than ETV- treated patients (73.8% vs. 61.5%, p = 0.038). CONCLUSION: In Caucasian patients with CHB, with or without cirrhosis, long-term ETV or TDF monotherapy is associated with similar HCC risk, rates of biochemical/virological remission, HBsAg loss and liver transplantation or death, but elastographic reversion of cirrhosis at year 5 was more frequent with TDF. LAY SUMMARY: In a large cohort of Caucasians with chronic hepatitis B treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) monotherapy, cumulative rates of hepatocellular carcinoma did not differ (up to 12 years). Nor did rates of biochemical/virological remission, HBsAg loss and liver transplantation or death. However, elastographic reversion of cirrhosis at year 5 was more frequent in TDF- than ETV-treated patients with pretreatment cirrhosis.
Authors: Francesco Paolo Russo; Alberto Zanetto; Elisa Pinto; Sara Battistella; Barbara Penzo; Patrizia Burra; Fabio Farinati Journal: Int J Mol Sci Date: 2022-01-02 Impact factor: 5.923
Authors: Satinder P Kaur; Arslan Talat; Hamidreza Karimi-Sari; Andrew Grees; Hao Wei Chen; Daryl T Y Lau; Andreea M Catana Journal: J Clin Med Date: 2022-02-21 Impact factor: 4.241