Aim To analyse the impact of the length of antiviral therapy with tenofovir disoproxil fumarate (TDF) on the renal function in patients with chronic hepatitis B (CHB). Methods A cross-sectional study included 75 patients with CHB treated with tenofovir, who had a normal renal function at the beginning of the treatment. Renal function was determined based on glomerular filtration rate (eGFR) value using the Modification of Diet in Renal Disease formula (MDRD). Measurement of serum creatinine concentration and urinary protein excretion were performed using standard laboratory analyses. Viral load quantification (HBV-DNA) was determined by polymerase chain reaction (PCR). The degree of liver fibrosis was determined using fibrosis4 (FIB-4) and aspartate transaminase to platelet ratio index (APRI) fibrosis score. Results Out of 75 CHB patients, 37 were on antiviral treatment for up to 2 years (group 1) and 38 patients on antiviral treatment longer than two years (group 2). Mean age of patients was not significantly different between the groups (p=0.076), nor was the gender distribution. There was no statistically significant difference between the mean values of the eGFR in the two groups (91.89±9.24 vs. 88.42±7.84 mL/min/1.73m2 ; p=0.42), as well as between the mean values of serum creatinine (p=0.360) and 24-hour urine protein excretion (p=0.380). There was no statistically significant correlation between renal parameters and viral load, APRI and FIB-4 fibrosis score. Conclusion Results of our study did not show significant changes in the measured parameters of renal function in group 1 and group 2 of patients, regardless of the length of antiviral treatment, indicating a good renal safety profile of TDF.
Cai D, Pan C, Yu W, Dang S, Li J, Wu S, et al. Comparison of the long-term efficacy of tenofovir and entecavir in nucleos(t)ide analoguenaïve HBeAg-positive patients with chronic hepatitis B: A large.
2.
Wang T, Smith DA, Campbell C, Mokaya J, Freeman O, Salih H, et al. Hepatitis B virus (HBV) viral load, liver and renal function in adults treated with tenofovir disoproxil fumarate (TDF) vs. untreated: a retrospective longitudinal UK cohort study. BMC Infect Dis. 2021;21(610).
3.
Wong GL, Chan HL, Tse YK, Yip TC, Lam KL, Lui GC, et al. Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment. Aliment PharmacolTher. 2018;48:984–92.
4.
Ascher SB, Scherzer R, Estrella MM. Association of urinary biomarkers of kidney injury with estimated GFR decline in HIV-infected individuals following tenofovir disoproxil fumarate initiation. CJASN. 2018;13:1321–9.
5.
Waal R, K C, MP F, K S, G M, A B, et al. Changes in estimated glomerular filtration rate over time in South African HIV-1- infected patients receiving tenofovir: a retrospective cohort study. J Int AIDS Soc. 2017;20(21317).
6.
Mtisi TJ, Ndhlovu CE, Maponga CC, Morse GD. Tenofovir-associated kidney disease in Africans: a systematic review. AIDS Res Ther. 2019;16(12).
7.
Suzuki S, Nishijima T, Kawasaki Y, Kurosawa T, Mutoh Y, Kikuchi Y, et al. Effect of tenofovir disoproxil fumarate on incidence of chronic kidney disease and rate of estimated glomerular filtration rate decrement in HIV-1-infected treatment-naïve Asian patients: results from 12-year observational cohort. AIDS Patient Care STDS. 2017;31:105–12.
8.
Chan L, Asriel B, Eaton EF, Wyatt CM. Potential kidney toxicity from the antiviral drug tenofovir: new indications, new formulations, and a new prodrug. Curr Opin Nephrol Hypertens. 2018;27:102–12.
9.
Maggi P, Montinaro V, Leone A, Fasano M, Volpe A, Bellacosa C, et al. Bone and kidney toxicity induce by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study. J Antimicrob Chemother. 2015;70:1150–4.
10.
Milazzo L, Gervasoni C, Falvella FS, Cattaneo D, Mazzali C, Ronzi P, et al. Renal function in HIV/HBV co-infected and HBV mono-infected patients on a long-term treatment with tenofovir in real life setting. Clin Exp Pharmacol Physiol. 2017;44:191–6.
11.
Gu J, Yu G, Zhang X, Zhang S, Cai H, Ye C, et al. Cross-sectional retrospective analysis of clinical characteristics of chronic hepatitis B patients with oral antiviral treatment in eastern China. Virol J. 2021;18(19).
12.
Marcellin P, Zoulim F, Hezode C, Causse X, Roche B, Truchi R, et al. Effectiveness and safety of tenofovir disoproxil fumarate in chronic hepatitis B: a 3-year, prospective, real-world study in France. Dig Dis Sci. 2016;61:3072–83.
13.
Lee IC, Chao Y, Li CP, Su CW, Lan KH, Lin HC, et al. Risk of renal events during tenofovir disoproxil fumarate and entecavir antiviral prophylaxis in HBsAg-positive cancer patients undergoing chemotherapy. J Viral Hepat. 2018;25:1599–607.
14.
Kim SJ, Rhu J, Lee SH, Kim JM, Choi GS, Kim K, et al. Tenofovir does not induce renal dysfunction compared to entecavir in post-liver-transplant hepatitis B virus patients. Ann Surg Treat Res. 2020;99:180–7.
15.
Riveiro-Barciela M, Tabernero D, Calleja JL, Lens S, Manzano ML, Rodríguez FG, et al. Effectiveness and safety of entecavir or tenofovir in a Spanish cohort of chronic hepatitis B patients: validation of the page-B score to predict hepatocellular carcinoma. Dig Dis Sci. 2017;62:784–93.
16.
Trinh S, Le AK, Chang ET, Hoang J, Jeong D, Chung M, et al. Changes in renal function in patients with chronic HBV infection treated with tenofovir disoproxil fumarate vs entecavir. Clin Gastroenterol Hepatol. 2019;17:948–56.
17.
Petersen J, Heyne R, Mauss S, Schlaak J, Schiffelholz W, Eisenbach C, et al. Effectiveness and safety of tenofovir disoproxil fumarate in chronic hepatitis B: a 3-year prospective Field Practice Study in Germany. Dig Dis Sci. 2016;61:3061–71.
18.
Jung WJ, Jang JY, Park WY, Jeong SW, Lee HJ, Park SJ, et al. Effect of tenofovir on renal function in patients with chronic hepatitis B.
19.
Lim TS, Lee JS, Kim BK, Lee HW, Jeon MY, Kim SU, et al. An observational study on long-term renal outcome in patients with chronic hepatitis B treated with tenofovir disoproxil fumarate.
20.
Zheng S, Liu L, Lu J, Zhang X, Shen H, Zhang H, et al. Efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B virus infection: A 2-year prospective study.
21.
Du Y, Zhang S, Hu M, Wang Q, Liu N, Shen H, et al. Association between hepatitis B virus infection and chronic kidney disease: a cross-sectional study.
22.
Fabrizi F, Cerutti R, Donato FM, Messa P. HBV infection is a risk factor for chronic kidney disease: systematic review and meta-analysis. Rev ClinEsp (Barc. 2021;221:600–11.
23.
Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, et al. Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) Study. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 2016;3:e23-32.
24.
Terrault NA, Lok A, McMahon BJ, K‐M C, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560–99.
25.
Gallant JE, Deresinski S. Tenofovir disoproxil fumarate. Clin Infect Dis. 2003;37:944–50.
26.
Li J, Hu C, Chen Y, Juan L, Chunhua H, Yi C, et al. Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acuteon-chronic liver failure associated with hepatitis B. BMC Infect Dis. 2021;21(567).
27.
Kearney BP, Flaherty JF, Shah J. Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics. ClinPharmacokinet. 2004;43:595–612.
28.
Jeon HJ, Jung SW, Park NH, Yang Y, Noh JH, Ahn JS, et al. Efficacy of tenofovirbased rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir. Clin Mol Hepatol. 2017;23:230–8.
29.
Trinh S, Le AK, Chang ET, Hoang J, Jeong D, Chung M, et al. Changes in renal function in patients with chronic HBV infection treated with tenofovir disoproxil fumarate vs entecavir. Clin Gastroenterol Hepatol. 2019;17:948–56.
30.
Tsai HJ, Chuang YW, Yang SS, Chang YZ, Chang HR, Lee TY. Evaluating the renal safety of tenofovir disoproxil fumarate in hepatitis B patients without chronic kidney disease. J Viral Hepat. 2021;28:1579–86.
31.
Lampertico P, Berg T, Buti M, Pathil A, Petersen J, Ryder SD, et al. Viread) Investigators’ Group. Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus-infected patients with renal impairment: results from a 7-year, multicentre retrospective cohort study. Aliment Pharmacol Ther. 2020;52:500–12.
32.
Koksal AR, Alkim H, Boga S, Iyisoy MS, Sen I, Tekin Neijmann 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:e25-e31.
33.
Jung WJ, Jang JY, Park WY, Jeong SW, Lee HJ, Park SJ, et al. Effect of tenofovir on renal function in patients with chronic hepatitis B.
34.
Campbell C, Wang T, Burrow R, Mandal S, Hippisley-Cox J, Barnes E, et al. Estimating the epidemiology of chronic Hepatitis B Virus (HBV) infection in the UK: what do we know and what are we missing? Wellcome Open Res. 2023;7(203).
35.
ZhangS R, DuRX SWL, ML F, ZhangXC. Global, regional, and national burden of kidney dysfunction from 1990 to 2019: a systematic analysis from the global burden of disease study 2019.BMC Public Health. Vol. 23. 2023.
36.
Tsai HJ, Chuang YW, Yang SS, Chang YZ, Chang HR, Lee TY. Evaluating the renal safety of tenofovir disoproxil fumarate in hepatitis B patients without chronic kidney disease. J Viral Hepat. 2021;28:1579–86.
37.
Chon YE, Parl SY, Ki SU, Hong HP, Lee JS, Lee HW, et al. Kim BK.Long-term renal safety between patients with chronic hepatitis B receiving tenofovir vs. entecavir therapy: A multicenter study. J Viral Hepat. 2022;29:289–96.
38.
E.A.S.L. Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–98.
39.
Graham RDJ. Seyed KI.Validation of the revised MDRD formula and the original Cockcroft and Gault formula for estimation of the glomerular filtration rate using Australian data. Pathology. 2009;41:379–82.
40.
Nagata I, Colucci G, Gregorio GV, Cheeseman P, Williams R, Mieli-Vergani G, et al. The role of HBV DNA quantitative PCR in monitoring the response to interferon treatment in chronic hepatitis B virus infection. J Hepatol. 1999;30:965–9.
41.
Kim SM, Sohn JH, Kim TY, Roh YW, Eun CS, Jeon YC, et al. Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease. Korean J Hepatol. 2009;15:454–63.
42.
Rungta S, Kumari S, Verma K, Akhtar G, A D, Swaroop S. A Comparative analysis of the APRI, FIB4, and FibroScanscore in evaluating the severity of chronic liver disease in chronic hepatitis B patients in India. Cureus. 2021;13:e19342.
43.
Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann HW, et al. Tenofovir disoproxil fumarate (TDF) vs.
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.