Hepatology 8 ORIGINAL ARTICLE Comparison of tenofovir and entecavir on the risk of OPEN ACCESS hepatocellular carcinoma and mortality in treatment- naive patients with chronic hepatitis B in Korea:a large-scale,propensity score analysis Sung Won Lee2 Jung Hyun Kwon.2 Hae Lim Lee,1.2 Sun Hong Yoo,1. Hee Chul Nam,12 Pil Soo Sung,2Soon Woo Nam,2 Si Hyun Bae, 138610113 ong Young Kew Yoon,Nam Ik Han,Jeong Won Jang ABSTRACT Objective The use of tenofovir (TDF)and entecavir Significance of this study 318947 %19e10136 on this subject on 31 Catho Octobe 2019 s are reported to agents nthe wnloaded fror 659iRepubicotcead wcted cohort (%model ETV in the incidence rates of HCC and all-cause ndETV in the chronic hepatitis and cirhosis. incid How might it impact on cinical practice in the com/on 0.622 model p=0.763).and patients with fore ble future? demonstrated the clinical HB who r ut arm all patients with CHB. 2020 周Check for updates INTRODUCTION the first herapy ir Prote ted by by BMI. n of fib and improved ive ersion and normalisatio alanin in a lard tothe d and immune-active disease. BMJ e5 N.etal..G20190.:1-8.d10.11350unl2019318947Lee SW, et al. Gut 2019;0:1–8. doi:10.1136/gutjnl-2019-318947 1 Hepatology Original article Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and mortality in treatment￾naïve patients with chronic hepatitis B in Korea: a large-scale, propensity score analysis Sung Won Lee ,1,2 Jung Hyun Kwon ,1,2 Hae Lim Lee,1,2 Sun Hong Yoo,1,2 Hee Chul Nam,1,2 Pil Soo Sung,1,2 Soon Woo Nam,1,2 Si Hyun Bae,1,2 Jong Young Choi,1,2 Seung Kew Yoon,1,2 Nam Ik Han,1,2 Jeong Won Jang 1,2 To cite: Lee SW, Kwon JH, Lee HL, et al. Gut Epub ahead of print: [please include Day Month Year]. doi:10.1136/ gutjnl-2019-318947 ► Additional material is published online only. To view, please visit the journal online (http://dx.doi.org/10.1136/ gutjnl-2019-318947). 1 Division of Hepatology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea 2 The Catholic University Liver Research Center, Seoul, Republic of Korea Correspondence to Dr Jeong Won Jang, Division of Hepatology, Department of Internal Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea; garden@catholic.ac.kr SWL and JHK contributed equally. This study was previously presented as part of a poster presentation at The International Liver Congress 2019. Received 23 April 2019 Revised 25 September 2019 Accepted 18 October 2019 © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-­NC. No commercial re-use. See rights and permissions. Published by BMJ. Significance of this study What is already known on this subject? ► The treatment with highly potent antiviral drugs tenofovir (TDF) and entecavir (ETV) for patients with chronic hepatitis B (CHB) has led to a decrease in the incidence of hepatocellular carcinoma (HCC) and liver-related events. ► Although there has been no head-to-head randomised controlled trial that directly compared TDF and ETV, virologic, serologic and biochemical responses are reported to be similar but whether there is a difference between the two agents in the extent of decreasing incidence rates of HCC and mortality has not been clarified thus far. What are the new findings? ► No difference was observed between TDF and ETV in the incidence rates of HCC and all-cause mortality or liver transplantation in the entire cohort and in the subgroups of patients with chronic hepatitis and cirrhosis. How might it impact on clinical practice in the foreseeable future? ► HCC develops consistently even after treatment with highly potent antiviral drugs and in patients without cirrhosis, which indicate the importance of regular surveillance for HCC in all patients with CHB. Abstract Objective The use of tenofovir (TDF) and entecavir (ETV) in patients with chronic hepatitis B (CHB) has led to a decrease in the incidence of hepatocellular carcinoma (HCC) and liver-related events. However, whether there is a difference between the two agents in the extent of improving such outcomes has not been clarified thus far. Therefore, we aimed to compare TDF and ETV on the risk of HCC and mortality. Design A total of 7015 consecutive patients with CHB who were treated with TDF or ETV between February 2007 and January 2018 at the liver units of the Catholic University of Korea were screened for study eligibility and 3022 patients were finally analysed. Study end points were HCC and all-cause mortality or liver transplantation (LT) within 5 years after the initiation of antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting methods were used. Results No difference was observed between TDF and ETV in the incidence rates of HCC in the entire cohort (HR 1.030; 95% CI 0.703 to 1.509, PSM model, p=0.880) and subgroups of patients with chronic hepatitis and cirrhosis. Also, no difference was observed between TDF and ETV in the incidence rates of all-cause mortality or LT in the entire cohort (HR 1.090; 95% CI 0.622 to 1.911, PSM model, p=0.763), and patients with chronic hepatitis and cirrhosis. Conclusion This study has demonstrated the clinical outcomes in patients with CHB who received TDF or ETV treatment. There was no difference in the intermediate￾term risk of HCC and mortality or LT between the two drugs. Introduction The treatment with highly potent antiviral drugs for patients with CHB has led to a decrease in the incidence of HCC and liver-related events.1 2 The main factors associated with the improvement in such clinical outcomes are reported to be complete virologic (VR) and biochemical responses (BR).3 4 Regression of fibrosis and improved liver function with long-term antiviral treatment, which have been verified in a prospective study, may also be related to the decreased risk of HCC and mortality.5 ETV and TDF, which were approved for use in Korea since 2007 and 2012, respectively, are currently recommended as the first-line therapy in patients with CHB. Both drugs display high genetic barriers with very low rates of resistance and high rates of viral suppression. Although there has been no head-to-head randomised controlled trial that directly compared the two drugs, the rates of HBV DNA suppression, Hepatitis B e Antigen (HBeAg) seroconversion and normalisation of alanine aminotransferase (ALT) are reported to be compa￾rable in treatment-naïve adult patients with CHB and immune-active disease.6 on January 28, 2020 by guest. Protected by copyright. http://gut.bmj.com/ Gut: first published as 10.1136/gutjnl-2019-318947 on 31 October 2019. Downloaded from