Noninferiority Outcomes of Besifovir Compared to Tenofovir Alafenamide in Treatment-Naïve Patients with Chronic Hepatitis B
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Background/Aims: Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. Methods: We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. Results: A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (–0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. Conclusions: BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.
Abstract
Background/Aims: Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. Methods: We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. Results: A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (–0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. Conclusions: BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.
참고문헌 (33)
- "Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021" (2021)[URL]
- Kim DY, "History and future of hepatitis B virus control in South Korea", Clin Mol Hepatol, 27, pp.620~622 (2021)
- Yim HJ, "Comparison of clinical practice guidelines for the management of chronic hepatitis B : when to start, when to change, and when to stop", Clin Mol Hepatol, 26, pp.411~429 (2020)
- Agarwal K, "96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection", J Hepatol, 68, pp.672~681 (2018)
- Ahn SH, "Efficacy and safety of besifovir dipivoxil maleate compared with tenofovir disoproxil fumarate in treatment of chronic hepatitis B virus infection", Clin Gastroenterol Hepatol, 17, pp.1850~1859 (2019)
- Chon HY, "Efficacy of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide in treatment-naive hepatitis B patients", Hepatol Int, 15, pp.1328~1336 (2021)
- Kim SH, "Comparison of biochemical response during antiviral treatment in patients with chronic hepatitis B infection", Liver Int, 42, pp.320~329 (2022)
- Lee HW, "Impact of tenofovir alafenamide vs. entecavir on hepatocellular carcinoma risk in patients with chronic hepatitis B", Hepatol Int, 15, pp.1083~1092 (2021)
- Yuen MF, "Two-year treatment outcome of chronic hepatitis B infection treated with besifovir vs. entecavir : results from a multicentre study", J Hepatol, 62, pp.526~532 (2015)
- Ginès P, "Liver cirrhosis", Lancet, 398, pp.1359~1376 (2021)
- Kim TH, "Determinants of re-compensation in patients with hepatitis B virus-related decompensated cirrhosis starting antiviral therapy", Aliment Pharmacol Ther, 55, pp.83~96 (2022)
- Korean Association for the Study of the Liver(KASL), "KASL clinical practice guidelines : management of alcoholic liver disease", Clin Mol Hepatol, 19, pp.216~254 (2013)
- Maiwall R, "Incidence, risk factors, and outcomes of transition of acute kidney injury to chronic kidney disease in cirrhosis : a prospective cohort study", Hepatology, 71, pp.1009~1022 (2020)
- Yim HJ, "Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B(ACE study) : a 2-year follow-up randomized controlled trial", Liver Int, 33, pp.244~254 (2013)
- European Association for the Study of the Liver, "EASL 2017Clinical Practice Guidelines on the management of hepatitis B virus infection", J Hepatol, 67, pp.370~398 (2017)
- Korean Association for the Study of the Liver(KASL), "KASL clinical practice guidelines for management of chronic hepatitis B", Clin Mol Hepatol, 25, pp.93~159 (2019)
- Yoo JJ, "Estimation of renal function in patients with liver cirrhosis : impact of muscle mass and sex", J Hepatol, 70, pp.847~854 (2019)
- Angeli P, "News in pathophysiology, definition and classification of hepatorenal syndrome : a step beyond the International Club of Ascites(ICA)consensus document", J Hepatol, 71, pp.811~822 (2019)
- Wong F, "Acute kidney injury in liver cirrhosis : new definition and application", Clin Mol Hepatol, 22, pp.415~422 (2016)
- Hahn S, "Understanding noninferiority trials", Korean J Pediatr, 55, pp.403~407 (2012)
- Yim HJ, "Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients", J Gastroenterol Hepatol, 37, pp.378~386 (2022)
- Yim HJ, "Besifovir dipivoxil maleate 144-week treatment of chronic hepatitis B : an open-label extensional study of a phase 3 trial", Am J Gastroenterol, 115, pp.1217~1225 (2020)
- Murata K, "Induction of IFN-λ3 as an additional effect of nucleotide, not nucleoside, analogues : a new potential target for HBV infection", Gut, 67, pp.362~371 (2018)
- Toyoda H, "Treatment and renal outcomes up to 96 weeks after tenofovir alafenamide switch from tenofovir disoproxil fumarate in routine practice", Hepatology, 74, pp.656~666 (2021)
- Jung CY, "Similar risk of kidney function decline between tenofovir alafenamide and besifovir dipivoxil maleate in chronic hepatitis B", Liver Int, 42, pp.2408~2417 (2022)
- Zheng HL, "L-Carnitine protects against tacrolimus-induced renal injury by attenuating programmed cell death via PI3K", AKT, Acta Pharmacol Sin, pp.2021, 42[DOI]
- Koohpeyma F, "The effects of L-carnitine on renal function and gene expression of caspase-9 and Bcl-2 in monosodium glutamate-induced rats", BMC Nephrol, 22, pp.162~ (2021)
- Choi J, "Risk of hepatocellular carcinoma in patients treated with entecavir vs tenofovir for chronic hepatitis B : a Korean nationwide cohort study", JAMA Oncol, 5, pp.30~36 (2019)
- Kim SU, "A multicenter study of entecavir vs. tenofovir on prognosis of treatment-naïve chronic hepatitis B in South Korea", J Hepatol, 71, pp.456~464 (2019)
- Lee SW, "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", Gut, 69, pp.1301~1308 (2020)
- Oh H, "No difference in incidence of hepatocellular carcinoma in patients with chronic hepatitis B virus infection treated with entecavir vs tenofovir", Clin Gastroenterol Hepatol, 18, pp.2793~2802 (2020)
- Lee HW, "Effect of tenofovir alafenamide vs. tenofovir disoproxil fumarate on hepatocellular carcinoma risk in chronic hepatitis B", J Viral Hepat, 28, pp.1570~1578 (2021)
- Yang HI, "Real-world effectiveness from the Asia Pacific Rim Liver Consortium for HBV Risk Score for the prediction of hepatocellular carcinoma in chronic hepatitis B patients treated with oral antiviral therapy", J Infect Dis, 221, pp.389~399 (2020)