Long-term renal safety between patients with chronic hepatitis B receiving tenofovir vs. entecavir therapy: A multicenter study
Young Eun Chon
Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
Search for more papers by this authorSoo Young Park
Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
Search for more papers by this authorSeung Up Kim
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorHan Pyo Hong
Big Data Center, Department of Statistics, Yonsei University Wonju College of Medicine, Wonju-si, Korea
Search for more papers by this authorJae Seung Lee
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorHye Won Lee
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorMi Na Kim
Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
Search for more papers by this authorJun Yong Park
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorDo Young Kim
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorSang Hoon Ahn
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Beom Kyung Kim
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Correspondence
Beom Kyung Kim, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul 03722, Korea.
Email: [email protected]
Search for more papers by this authorYoung Eun Chon
Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
Search for more papers by this authorSoo Young Park
Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
Search for more papers by this authorSeung Up Kim
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorHan Pyo Hong
Big Data Center, Department of Statistics, Yonsei University Wonju College of Medicine, Wonju-si, Korea
Search for more papers by this authorJae Seung Lee
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorHye Won Lee
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorMi Na Kim
Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
Search for more papers by this authorJun Yong Park
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorDo Young Kim
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorSang Hoon Ahn
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Beom Kyung Kim
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Korea
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Correspondence
Beom Kyung Kim, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul 03722, Korea.
Email: [email protected]
Search for more papers by this authorYoung Eun Chon and Soo Young Park contributed equally to this work as co-first authors.
Abstract
Renal safety is a critical issue in chronic hepatitis B (CHB) patients receiving long-term entecavir (ETV) or tenofovir disofuroxil fumarate (TDF) therapy. We investigated their effects on estimated glomerular filtration rate (eGFR). Treatment-naive CHB patients receiving ETV or TDF for ≥1 year were recruited. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. We calculated average annual percent change (AAPC) in eGFR using Joinpoint regression. At the beginning of the observation, the ETV group had more unfavorable conditions than the TDF group: lower eGFR and higher FIB-4 and APRI than the TDF group (all p < .001). After 6 years of antiviral therapy, the mean eGFR in the ETV group (n = 1793) was maintained (96.0 at first year to 95.6 ml/min/1.73 m2 at sixth year; AAPC −0.09%; p = .322), whereas that in the TDF group (n = 1240) significantly decreased annually (101.9 at first year to 96.9 ml/min/1.73 m2 at sixth year; AAPC −0.88%; p < .001). Notably, in the TDF group, even patients without diabetes (AAPC −0.80%; p = 0.001) or hypertension (AAPC −0.87%; p = .001) experienced significant decrease in eGFR. Expectably, accompanying diabetes (AAPC −1.59%; p = .011) or hypertension (AAPC −1.00%; p = .002) tended to accelerate eGFR decrease. TDF treatment (odds ratio 1.66, p < .001), along with eGFR<60 ml/min/1.73 m2, serum albumin<3.5 mg/dl, and hypertension, were independently associated with ongoing renal dysfunction, defined as a negative slope of the mean eGFR change. In conclusion, compared with ETV, long-term TDF treatment induced slow, but progressive renal dysfunction. Although the annual eGFR change by TDF was small, careful monitoring is necessary, especially in patients requiring life-long therapy.
CONFLICT OF INTEREST
None.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author, if appropriate. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information
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REFERENCES
- 1Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018; 3(6): 383-403.
- 2Chen YC, Chu CM, Yeh CT, Liaw YF. Natural course following the onset of cirrhosis in patients with chronic hepatitis B: a long-term follow-up study. Hepatol Int. 2007; 1(1): 267-273.
- 3Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006; 130(3): 678-686.
- 4Lampertico P, Agarwal K, Berg T, et al. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017; 67(2): 370-398.
- 5KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol. 2019; 25(2): 93-159.
- 6Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018; 67(4): 1560-1599.
- 7Yim HJ, Kim JH, Park JY, et al. 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. 2020; 26(4): 411-429.
- 8Liang LY, Wong GL. Unmet need in chronic hepatitis B management. Clin Mol Hepatol. 2019; 25(2): 172-180.
- 9Oh H, Jun DW. Increasing comorbidities in a South Korea insured population-based cohort of patients with chronic hepatitis B. Aliment Pharmacol Ther. 2020; 52(2): 371-381.
- 10Bucsics T, Krones E. Renal dysfunction in cirrhosis: acute kidney injury and the hepatorenal syndrome. Gastroenterol Rep (Oxf). 2017; 5(2): 127-137.
- 11Hwang HS, Park CW, Song MJ. Tenofovir-associated Fanconi syndrome and nephrotic syndrome in a patient with chronic hepatitis B monoinfection. Hepatology. 2015; 62(4): 1318-1320.
- 12Viganò M, Brocchieri A, Spinetti A, et al. Tenofovir-induced Fanconi syndrome in chronic hepatitis B monoinfected patients that reverted after tenofovir withdrawal. J Clin Virol. 2014; 61(4): 600-603.
- 13Koksal AR, Alkim H, Boga S, et al. Value of cystatin C-based e-GFR measurements to predict long-term tenofovir nephrotoxicity in patients with hepatitis B. Am J Ther. 2019; 26(1): e25-e31.
- 14Ha NB, Ku K, Ha NB, Chaung KT, Trinh HN, Nguyen MH. Renal function in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or entecavir monotherapy: a matched case-cohort study. J Clin Gastroenterol. 2015; 49(10): 873-877.
- 15Mallet V, Schwarzinger M, Vallet-Pichard A, et al. Effect of nucleoside and nucleotide analogues on renal function in patients with chronic hepatitis B virus monoinfection. Clin Gastroenterol Hepatol. 2015; 13(6): 1181-1188.e1181.
- 16Tsai MC, Chen CH, Tseng PL, et al. Does nucleos(t)ide analogues treatment affect renal function in chronic hepatitis b patients who have already decreased eGFR? A longitudinal study. PLoS One. 2016; 11(3):e0149761.
- 17Koklu S, Gulsen MT, Tuna Y, et al. Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B. Aliment Pharmacol Ther. 2015; 41(3): 310-319.
- 18Wong GL, Chan HL-Y. Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment. Aliment Pharmacol Ther. 2018; 48(9): 984-992.
- 19Esfeh JM, Hajifathalian K, Ansari-Gilani K. Sensitivity of ultrasound in detecting hepatocellular carcinoma in obese patients compared to explant pathology as the gold standard. Clin Mol Hepatol. 2020; 26(1): 54-59.
- 20Yang JD. Detect or not to detect very early stage hepatocellular carcinoma? The western perspective. Clin Mol Hepatol. 2019; 25(4): 335-343.
- 21Shin H, Jung YW, Kim BK, et al. Risk assessment of hepatocellular carcinoma development for indeterminate hepatic nodules in patients with chronic hepatitis B. Clin Mol Hepatol. 2019; 25(4): 390-399.
- 22Maruyama H, Kato N. Advances in ultrasound diagnosis in chronic liver diseases. Clin Mol Hepatol. 2019; 25(2): 160-167.
- 23Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150(9): 604-612.
- 24Park J, Jung KS, Lee HW, et al. Effects of entecavir and tenofovir on renal function in patients with hepatitis B virus-related compensated and decompensated cirrhosis. Gut Liv. 2017; 11(6): 828-834.
- 25López Centeno B, Collado Borrell R, Pérez Encinas M, Gutiérrez García ML, Sanmartin FP. Comparison of the effectiveness and renal safety of tenofovir versus entecavir in patients with chronic hepatitis B. Farm Hosp. 2016; 40(4): 279-286.
- 26Gitman MD, Hirschwerk D, Baskin CH, Singhal PC. Tenofovir-induced kidney injury. Expert Opin Drug Saf. 2007; 6(2): 155-164.
- 27Jafari A, Khalili H, Dashti-Khavidaki S. Tenofovir-induced nephrotoxicity: incidence, mechanism, risk factors, prognosis and proposed agents for prevention. Eur J Clin Pharmacol. 2014; 70(9): 1029-1040.
- 28Chen YC, Su YC, Li CY, Hung SK. 13-year nationwide cohort study of chronic kidney disease risk among treatment-naïve patients with chronic hepatitis B in Taiwan. BMC Nephrol. 2015; 16: 110.
- 29Maggi P, Montinaro V, Leone A, et al. Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study. J Antimicrob Chemother. 2015; 70(4): 1150-1154.
- 30Jung CY, Kim HW, Ahn SH, Kim SU, Kim BS. tenofovir is associated with higher risk of kidney function decline than entecavir in patients with chronic hepatitis B. Clin Gastroenterol Hepatol. 2021.
10.1016/j.cgh.2021.05.032 Google Scholar
- 31Park SH, Plank LD, Suk KT, et al. Trends in the prevalence of chronic liver disease in the Korean adult population, 1998–2017. Clin Mol Hepatol. 2020; 26(2): 209-215.
- 32Lim TS, Lee JS. An observational study on long-term renal outcome in patients with chronic hepatitis B treated with tenofovir disoproxil fumarate. J Viral Hepatitis. 2020; 27(3): 316-322.
- 33Carvalho JR, Verdelho Machado M. New insights about albumin and liver disease. Ann Hepatol. 2018; 17(4): 547-560.
- 34EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010; 53(3): 397-417.
- 35Inoue T, Tanaka Y. Novel biomarkers for the management of chronic hepatitis B. Clin Mol Hepatol. 2020; 26(3): 261-279.
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